>> WAYS THAT TO IMPROVING HEALTH
OF THE POPULATION AND WE'RE SO
THANKFUL THAT YOU'RE SPENDING
SOME OF THAT WITH US.
DURING THIS WORKSHOP WE'LL
UNDERSTAND THE OPPORTUNITIES
THAT WE FACE IN THIS SCIENTIFIC
REALM.
THESE DISCUSSIONS ARE IMPORTANT
TO US AT THE INSTITUTE AND
ESPECIALLY TO THE DIVISION OF
CARDIOVASCULAR SCIENCES AND THE
NATIONAL CENTER FOR SLEEP
DISORDERS RESEARCH.
WE RELEASED OUR IMPLEMENTATION
PLAN AND ONE OF THE SIX PILLARS
IS TO UNDERSTAND RESILIENCE AN
SOME INDIVIDUALS DO VERY WELL
DESPITE BEING EXPOSED TO THE
SAME HARMFUL EXPOSURES IN THE
ENVIRONMENT THAT CAUSE OTHER
PEOPLE TO HAVE MEDICAL PROBLEMS.
AND IF WE CAN UNDERSTAND WHY
SOME INDIVIDUALS ARE MORE
RESILIENT TO THESE HARMFUL
EXPOSURES THAN OTHERS WE SHOULD
ABLE TO LEVERAGE THAT
UNDERSTANDING TO IMPROVE HEALTH
OF THE POPULATION MORE BROADLY.
SO THIS FOCUS ON RESILIENCE IS
CRITICAL TO ALL ASPECTS OF OUR
PORTFOLIO.
WHEN WE STARTED THINKING ABOUT
HOW TO PURSUE RESILIENCE
RESEARCH, IT BECAME OBVIOUS VERY
EARLY NO MATTER WHICH PART OF
THE CARDIOVASCULAR PORTFOLIO
CONDITIONS CAN YOU THINK ABOUT
WHETHER IT'S HYPERTENSION OR
DYSLIPIDEMIA OR HEART FAILURE OR
ATHEROSCLEROSIS AND ON AN ON,
RESILIENCE IS A KEY UNDERLYING
CHARACTER CAN -- CHARACTERISTIC
THAT MAKES A DIFFERENCE IN THE
WAY INDIVIDUALS HEALTH
TRAJECTORY PROGRESSES ACROSS THE
LIFE SPAN.
AND OF COURSE WHEN WE'RE
THINKING ABOUT THE LIFE SPAN,
RESILIENCE IS A CRITICAL
COMPONENT OF THE TRAJECTORIES OF
HEALTH AND DISEASE ACROSS THE
LIFE SPAN FOR DIFFERENT
INDIVIDUALS.
ONE OF OUR OTHER IMPORTANT
STRATEGIC PRIORITIES IS TO
ADDRESS SOCIAL DETERMINATES OF
CARDIOVASCULAR HEALTH AND HEALTH
INEQUITIES AND AGAIN RESILIENCE
PLAYS A MITIGATING FACTOR IN THE
IMPACT OF SOCIAL DETERMINATES ON
INDIVIDUAL HEALTH.
SO WHEREVER WE LOOK IN OUR
MISSION, WE SEE RESILIENCE AS A
MAJOR ISSUE FOR US TO UNDERSTAND
BETTER AND LEVERAGE TO IMPROVE
HEALTH OF THE POPULATION.
SO I HOPE I SHARED WITH YOU THE
IMPORTANCE THAT WE AT THE
INSTITUTE DO THIS TOPIC.
SO THEN WHAT WOULD BE THE
OUTCOME OF A WORKSHOP LIKE THIS
ON AN IMPORTANT TOPIC?
WELL, WE ANTICIPATE SEVERAL
OUTCOMES.
THE FIRST AND PERHAPS MOST
IMPORTANT IS THAT AFTER THE
WORKSHOP YOU ALL GO BACK TO YOUR
WORK INVIGORATING TO PURSUE THIS
LINE OF INQUIRY AND SEND US YOUR
BEST IDEAS FOR SUBSEQUENT
RESEARCH PROJECTS.
THE VAST MAJORITY OF THE
RESOURCES THAT NHLBI AND REALLY
ALL OF NIH INVEST IN RESEARCH
GOES TO INVESTIGATOR INITIATED
DISCOVERY SCIENCE.
SO WE HOPE YOU'LL GO HOME AND
WRITE WONDERFUL APPLICATIONS
THAT GET GREAT PEER REVIEW AND
WE'RE ABLE TO SUPPORT MORE
RESEARCH IN THIS SPACE.
OF COURSE THERE WILL BE REPORTS
FROM THIS WORKSHOP.
WE'LL PUT AN EXECUTIVE SUMMARY
ON OUR WEBSITE WE WANT THAT
WITHIN A COUPLE WEEKS MO NO MORE
THAN A MONTH SO IT COULD BE
SHARED WITH THE BIOMEDICAL
COMMUNITY RAPIDLY.
YOU MAY DECIDE YOU WANT TO WRITE
A WHITE PAPER FOR PUBLICATION
AND PEER-REVIEWED JOURNAL.
IF YOU DECIDE TO DO THAT, WE'LL
SUPPORT THAT EFFORT AND WOULD
AGAIN ENCOURAGE THE GROUP TO BE
TIMELY IN GETTING THE MATERIAL
OUT TO THE PUBLIC AND THE
BIOMEDICAL RESEARCH COMMUNITY SO
PEOPLE CAN BENEFIT FROM THE
WONDERFUL THINK THAT'S GOING TO
BE SHARED IN THE NEXT HOURS AND
DAYS.
THEN FINALLY THE RECOMMENDATIONS
FOR YOUR OPPORTUNITIES TO INFORM
THE OPPORTUNITIES WE SUPPORT.
WE'LL DO THAT IN A COUPLE WAYS.
FIRST, WHILE WE USE MOST OUR
FUNDS FOR INVESTIGATOR INITIATED
RESEARCH, WE RESERVE A SMALL POT
OF FUNDS FOR WHAT WE CALL OUR
SELECT PAY PROCESS.
SO APPLICATIONS THAT DON'T QUITE
GET UNDER THE PAY LINE BUT ARE
STRATEGICALLY ALIGNED WITH
IMPORTANT AREAS FOR THE
INSTITUTE CAN BE FUNDED AS
SELECT PAY APPLICATIONS.
AND WE USE THE OPPORTUNITIES
THAT ARE IDENTIFIED IN THE
STRATEGIC OPPORTUNITIES IN THE
WORKSHOP LIKE THIS ONE TO HELP
GUIDE OUR SELECT PAY PROCESS
WHEN THOSE OPPORTUNITIES ARE
AVAILABLE.
SOMETIMES WE WRITE A NOTICE OF
FUNDING OPPORTUNITY THAT'S BASED
ON THE INPUT WE GET FROM
WORKSHOP.
WE DON'T DO THAT FOR EVERY
WORKSHOP.
WE CAN'T DO THAT FOR EVERY
WORKSHOP BECAUSE AS I MENTIONED
BEFORE, MOST OF OUR RESOURCES GO
TO INVESTIGATOR INITIATED
PROJECTS BUT WHEN THE
OPPORTUNITIES ARE COMPELLING AND
THE NEED FOR INSTITUTE
INVESTMENT IS CLEAR, WE DO PUT
OUT FUNDING OPPORTUNITIES AND
THAT'S A POSSIBILITY.
CERTAINLY CAN'T COMMIT TO THAT
TODAY BUT ONE OF THE THINGS
WE'LL BE THINKING ABOUT
SERIOUSLY WHEN WE SEE THE
OPPORTUNITIES THAT YOU IDENTIFY.
SO THIS WORKSHOP'S REALLY
IMPORTANT TO US AND THE SCIENCE
UND
UNDERLIES OUR ENTIRE MISSION AND
WANT IT CLOSE WHERE I STARTED IN
THANK YOU FOR COMMITTING YOUR
TIME AND EFFORT TO THIS AREA AS
PART NEUTRAL ZONE IN THIS
JOURNEY TO UNDERSTAND RESILIENCE
BETTER TO LEVERAGE IT TO IMPROVE
HEALTH FOR ALL.
THANK YOU VERY MUCH, BACK TO
YOU.
>> THANK YOU, DR. GOFF.
NEXT IS DR. GALIS THE CHIEF OF
VASCULAR BIOLOGY IN THE
HYPERTENSION BRANCH OF THE
DIVISION OF CARDIOVASCULAR
SUNSUNS
S -- SCIENCES OF THE NHLBI AND
FACILITATED RESEARCH FROM BASIC
RESEARCH TO CLINICAL TRIALS
INCLUDING TECHNOLOGY V AND THE
TRANSLATION.
SHE PLAYS A KEY ROLE IN THE
TRANS-NIH RESILIENCE WORKING
GROUP AND WILL PROVIDE ALL OF
YOU OF THE TRANS-NIH RESILIENCE
PROGRAM.
WELCOME, DR. GALIS.
>> THANK YOU, DR. GAO.
I WANT TO ECHO DR. GAO'S THANKS
TO THE ORGANIZERS.
THE RESILIENCE WORKING GROUP
WHICH I CO-CHAIR AND THE SLEEP
INTEREST GROUP.
I AM ALSO VERY HONORED BY THE
DISTINGUISHED SPEAKERS AND
CHAIRS WHO ARE GOING TO SHARE
THEIR INSIGHTS AND I WANTED TO
THANK EVERYONE FOR SPENDING
THEIR TIME WITH US SO DR. GAO
NOTICED THE RECORDING WILL BE
AVAILABLE AFTER THE WORKSHOP SO
FEEL FREE TO SPREAD THE WORD AND
LISTEN TO PRESENTATIONS THAT YOU
MAY MISS.
MY DUTY TODAY AND HONOR IS TO
SPEAK ON BEHALF OF THE TRANS-NIH
WORK GROUP AND OUR INSTITUTE
BECAME ONE OF THE FOUNDING
MEMBERS OF THIS GROUP, THERE ARE
MANY INSTITUTES ACROSS THE NIH
AND YOU SEE THEM LISTED HERE.
THEY ARE COMING TOGETHER IN A
TRANS-NIH RESILIENCE WORKING
GROUP AND A WANT TO GIVE A
SPECIAL SHOUT OUT TO DR. LA
VERNE BROWN THE CHAIR OF OUR
TRANS-NIH WORKING GROUP FOR HER
LEADERSHIP AND COLLABORATING ON
THE SLIDES I'M GOING TO SHOW
YOU.
I WANTED TO BRIEFLY SAY WHAT WE
THINK ABOUT RESILIENCE ACROSS
THE NIH.
NEXT SLIDE.
THE TITLE IS A LITTLE BIT OFF SO
ONE OF THE FIRST THINGS THAT WE
DID AND THIS WAS A MEETING JUST
BEFORE SHUTTING DOWN FOR COVID
WAS COME TOGETHER FOR A COMMON
INFORMATION OF RESILIENCE.
IT'S OF NO SURPRISE TO THIS
AUDIENCE THAT RESILIENCE HAS SO
MANY DIFFERENT LEVELS AND
PERSPECTIVES WE WANT TO MAKE
SURE THAT WE'RE ALL SPEAKING
ABOUT THE SAME THING.
SO ONE THING THAT CAN HELP US IS
TO DEFINE CRITERIA.
SO THE IDEA IS THAT OUR
DEFINITION HAS TO ENCOMPASS ALL
THE HEALTH AND DISEASE OUTCOMES.
ALL THE TYPES OF CHALLENGES THAT
WE ARE POTENTIALLY SUBMITTED TO
AND ALL THE PROCESSES THAT ARE
INVOLVED IN THE RESPONSE TO
THESE CHALLENGES.
IT HAS TO BE APPLICABLE TO FROM
THE CELLULAR LEVEL TO THE
POPULATION AND PLANETARY HEALTH
AND OBVIOUSLY HAS TO ALIGN WITH
OUR MISSION TO TURN DISCOVERY
INTO HEALTH AND TAKE INTO
CONSULT CAN EVERYTHING WE
ALREADY KNOW ABOUT THE
RESILIENCE.
SO THE NEXT TASK WAS TO COME UP
ONE A WORKING DEFINITION AND
WHILE THIS MAY VERY SLIGHTLY
BASED ON PEOPLE'S PERSPECTIVE,
WE BELIEVE THIS SHOULD REFLECT
THE SYSTEM'S CAPACITY TO RESIST,
RECOVER OR EVEN GROWTH OR ADAPT
TO CHALLENGE AND THE FACT THE
CHALLENGE COULD BE A DIFFERENT
TYPES OR MAGNITUDES OF DURATION.
THE SYSTEM GOES ACROSS SCALES
FROM MOLECULES TO ENVIRONMENT.
AND THE RESPONSE CAN BE
REFLECTIVE OF RESILIENCE WHEN
THE SYSTEMS ADAPT OR EVEN GROW
AS A RESPONSE TO CHALLENGE OR
REFLECTS LACK OF RESILIENCE WHEN
THERE IS MALADAPTATION OR EVEN
COLLAPSE.
WE ALSO HAVE A USEFUL TOOL WE
THINK TO USE INTERNALLY TO
ASSESS WHETHER SOME AWARDS WE'RE
ALREADY FUNDING ARE
INVESTIGATING THE SIGNS OF
RESILIENCE BUT PEOPLE FROM
OUTSIDE CAN ALSO TEST THEIR
PROPOSAL WHETHER THEY WOULD FALL
WITHIN THE SIEFDZ RESILIENCE.
SO IN ORDER TO ACCESS THE
RESOURCES YOU CAN GO TO THE
TRANS-NIH WORKING GROUP WEBSITE
WHICH YOU CAN FIND BY GOOGLING,
MY FAVORITE WAY TO FIND THINGS,
OR YOU COULD READ IN MORE DETAIL
IN A COUPLE APPLICATIONS THAT WE
PUT TOGETHER AS PART OF A
SPECIAL ISSUES AND THIS
OPERATIONAL TOOL INCLUDES A LOT
OF DIFFERENT TYPES OF RESEARCH
THAT IS RELATED TO RESILIENCE
FROM THE SPIRITUAL TO THE
PHYSIOLOGIC TO THE SLEEP HEALTH
ACTIVITY WITH STRESS ON
PERSONNEL AND INTEGRITY OF OUR
HEALTH AND SO FORTH.
SO THIS AGAIN CAN BE FOUND
EASILY ON OUR WEBSITE OR BY
SEARCHING FOR STRESS AND HEALTH
SPECIAL ISSUE ON RESILIENCE NIH.
IT LOOKS LIKE ALL MY SLIDES HAVE
BEEN REFORMATTED VERY NARROW.
WE HAVE A VARIETY OF TOOLS THAT
ARE OPEN TO THE PUBLIC WE HAVE
PUBLIC WEBINARS THAT CAN AGAIN
BE FOUND EVEN AFTER THEY ARE
HAPPENING ON THE NIH VIDEOCAST.
ONE IMPORTANT WORKSHOP THAT IS
COMING UP IS A WORKSHOP ON
MEASURES AND METRICS OF
RESILIENCE.
WE THINK IT'S VERY IMPORTANT TO
DISCUSS TO HAVE A CRITICAL
EVALUATION OF THE MEASURES OF
RESILIENCE AND IDENTIFY THE BEST
PRACTICES THAT CAN HELP US
ADVANCE THE STUDY OF RESILIENCE
SO THE DATES ARE 24 TO 25 AND
THE DETAILS OF THE AGENDA AND SO
FORTH WILL BE POSTED ON THE
TRANS-NIH RESILIENCE WORKING
GROUP.
ALSO OF POTENTIAL INTEREST TO
THE OUTSIDE IS THE NEW
RESILIENCE RESEARCH INTEREST --
SCIENTIFIC INTEREST GROUP OPENED
TO OUTSIDE BY INVITATION YOU
HAVE TO EXPRESS THE REQUEST BY
RIGHTING TO LAVERN BROWN AND
HAVE INTERACTIONS WITH THEM AND
OUTSIDE NIH AND SHARE DATA AND
RESOURCES AND POTENTIALLY LINK
THE LONGITUDINAL DATA ON HEALTHY
INDIVIDUAL TO TRIAL DATA.
AGAIN, YOU CAN WRITE TO
DR. LAVERNE BROWN EVERYBODY IS
FULL NAME AT NIH.gov AND WE'LL
ALSO SHARE THESE IN THE CHAT.
HERE'S OUR OPEN INVITATION TO
JOIN OUR OPEN WEBINARS AND JOIN
THE SCIENTIFIC INTEREST GROUP
AND TO JOIN THE FUTURE WORKSHOP
THAT'S GOING TO HAPPEN SEPTEMBER
24 AND 25.
WE'LL BE HAPPY TO TAKE ANY
QUESTIONS YOU HAVE BY CHAT.
THANK YOU VERY MUCH.
>> THANK YOU, DR. GALIS.
I'LL LET THE OTHER WORKSHOP
ORGANIZE ERS TO INTRODUCE
DR. BROWN.
>> THANK YOU, DR. GAO.
IT'S GREAT HONOR TO INTRODUCE
DR. MARISHKA BROWN ON SLEEP
DISORDERS RESEARCH LEADING THE
SCIENCE FOR INNOVATIVE DISCOVERY
TO IMPROVE HEALTH AND
PARTNERSHIP BUILDING HAS HELPED
SUSTAIN A ROBUST NETWORK
BRINGING THE BENEFITS OF THE NIH
SCIENTIFIC RESEARCH INTO
MEDICINE AND PUBLIC HEALTH.
DR. BROWN WILL HIGHLIGHT THE
SLEEP AND CIRCADIAN RHYTHM
ACROSS NIH AND THE CONTRIBUTIONS
TO UNDERSTANDING HOW TARGETING
SLEEP AND CIRCADIAN RHYTHMS MAY
STRENGTHEN THE CARDIOVASCULAR
SYSTEM.
WELCOME, DR. BROWN.
>> I'LL BE QUICK WITH MY REMARKS
BECAUSE WE KNOW TIME IS A FACTOR
IN THIS AND WE'RE ALREADY
GETTING CLES TO THE START OF THE
FIRST SET SO AGAIN WELCOME,
EVERYONE TO THE WORKSHOP.
SLEEP AND CIRCADIAN RHYTHMS AND
CARDIOVASCULAR RESILIENCE.
OVER THE NEXT TWO DAYS, THIS
WORKSHOP WILL EXAMINE THE
POTENTIAL SYNERGIES AND
BI-DIRECTIONAL RELATIONSHIPS
BETWEEN SLEEP, CIRCADIAN RHYTHMS
AND CARDIOVASCULAR RESILIENCE.
A TERM WE HOPE THIS WORKSHOP
WILL ASSIST IN HELPING DEFINE.
WE REALIZE THE REASON WE HAVE
THESE WORKSHOPS IS THAT THERE'S
AN AREA THAT WE SEE A POTENTIAL
GAP IN THE PORTFOLIO IN THE
RESEARCH WE'D LIKE TO HAVE
STIMULATE.
WE HOPE THE CONVERSATION WILL
POINT TO THOSE DIRECTIONS FOR
US.
THE INFLUENCE ON THE SPECTRUM OF
CHRONIC CONDITIONS BOTH CAN BE
TARGETED TO ENHANCE THE BODY'S
ABILITY TO RESIST, ADAPT AND
GROW FROM CARDIOVASCULAR
DISORDERS.
THE OVER ARCHING GOAL OF THE
WORKSHOP IS TO DELINEATE THE
SLEEP AND CARDIOVASCULAR
RESILIENCE AND IDENTIFY THE
POTENTIAL MECHANISMS AND
UNDERPINNING OF THE
RELATIONSHIPS AND PROMOTE
STRATEGY FOR CARDIOVASCULAR
RESILIENCE BY OPTIMIZING SLEEP
AND CIRCADIAN RHYTHMS IN GENERAL
AT CRITICAL POINTS THROUGHOUT
THE LIFE SPAN WITH THE RISK IN
CARDIOVASCULAR DISEASE
PARTICULARLY INCREASED.
IF YOU WANT TO KNOW OF THE
ACTIVITIES AND ACTIONS AND
RESEARCH DIRECTION FOR THE
NATIONAL CENTER ON SLEEP
DISORDERS RESEARCH AS WELL AS
SLEEP AND CIRCADIAN RESEARCH
ACROSS NIH WE ENCOURAGE YOU TO
CHECK OUT OUR SLEEP RESEARCH
PLAN THAT IS EASILY GOOGLEABLE
AND WITH THAT I'LL STOP TO BE
COGNIZANT OF THE TIME TO MOVE
FORWARD WITH THE WORKSHOP.
THANK YOU.
>> THANK YOU, DR. BROWN.
I'LL TURN IT BACK OVER TO
DR. GAO TO INTRODUCE OUR FIRST
CO-CHAIR.
IT'S MY HONOR TO INTRODUCE
DR. LLOYD JONES.
HE HOLDS NUMEROUS PRESTIGIOUS
ROLES ALLOW ME TO BRIEFLY
INTRODUCE HIM AS THE CHAIR AND
PROFESSOR OF PREVENTIVE MEDICINE
AT PEDIATRICS AT NORTHWESTERN
UNIVERSITY.
HE SERVED AS THE AMERICAN OF THE
AMERICAN HEART ASSOCIATION FROM
2021 TO 2022.
HE FOCUSES ON THE LIFE COURSE
AND MECHANISMS OF CARDIOVASCULAR
HEALTH, HEALTHY AGING AS WELL AS
EPIDEMIOLOGY, RISK ASSESSMENT
AND THE PREVENTION OF
CARDIOVASCULAR DISEASE.
HE'LL LEAD US TO START SESSION 1
THE INTERPLAY OF SLEEP,
CIRCADIAN RHYTHMS AND
CARDIOVASCULAR RESILIENCE.
>> THANK YOU.
I THINK WE HAVE AN EXCITING
LINEUP AND AGENDA AND LOOK
FORWARD TO THE GREAT TALKS AND
LEAD US TO A BETTER PLACE IN
DEFINING CARDIOVASCULAR
RESILIENCE AND THE ROLE OF SLEEP
AND IMPROVING CARDIOVASCULAR
RESILIENCE.
I WANT TO ALSO THANK MY
CO-CHAIRS, WHO ARE MAJOR THOUGHT
LEADERS IN THE AREAS OF SLEEP
AND CIRCADIAN SCIENCE AND LOOK
FORWARD TO HEARING FROM THEM
SOON AS WELL.
I'LL DO BRIEF INTRODUCTIONS OF
OUR SPEAKERS BUT KEEP US MOSTLY
ON TIME.
LOOKS LIKE MY SLIDES GOT SHRUNK
AS WELL AND TALK ABOUT
CARDIOVASCULAR RESILIENCE AND
SLEEP.
I HAVE NO RELATIONSHIPS WITH
INDUSTRIES.
I HOPE TO TALK ABOUT HOW WE
MIGHT THINK OF DEFINING
CARDIOVASCULAR RESILIENCE AND
HOW WE'VE DONE IT TO DATE AND
INTRODUCE A CONCEPT CALLED
CARDIOVASCULAR HEALTH THAT MIGHT
SERVE AS A BASIS FOR FUTURE
DEFINITION OF CARDIOVASCULAR
RESILIENCE.
AND I'LL REVIEW SOME OF THE DATA
THAT WE'VE GENERATED LOOKING AT
HOW CARDIOVASCULAR HEALTH ACROSS
THE LIFE COURSE MIGHT BE
INTERPRETED AS A FORM OF
RESILIENCE AGAINST NOT ONLY
CARDIOVASCULAR DISEASE BUT ALSO
OTHER MANY CHRONIC DISEASES OF
AGING.
AND WE'LL EXPLORE SOME ASPECTS
OF CARDIOVASCULAR RESILIENCE AND
HOW SLEEP FITS IN THE CONSTRUCT
OF CARDIOVASCULAR HEALTH.
I THINK WHEN YOU DEFINE
CARDIOVASCULAR RESILIENCE AND
I'M A CARDIOLOGIST AND
CARDIOVASCULAR CARDIOLOGIST AND
WE'VE LOOKED AT RISK IN THE
POPULATION AND WE'VE PICKED OUT
THE PEOPLE AT THE TOP END OF
RISK AND I'M WORRIED THIS MAY
NOT BE MY MOST UP TO DATE SLIDE
DECK BUT ANYWAY WE OFTEN SEE
BEHAVIORS OR PHYSIOLOGIC FACTOR
OR SINGLE SEVERELY ADVERSE RISK
FACTORS IN THE UPPER END OF RISK
DISTRIBUTION.
BUT WHO ACTUALLY DON'T DEVELOP
CLINICAL CARDIOVASCULAR DISEASE
AND ALSO MAY APPEAR NOT TO HAVE
SUB CLINICAL CARDIOVASCULAR
DISEASE.
THERE'S SOMETHING ABOUT THEM
THAT MAKES THEM RESISTANT TO THE
ADVERSE EXPOSURES OR SEVERELY
ELEVATED RISK FACTORS.
THE PROBLEMS WITH THIS KIND OF A
DEFINITION I THINK ARE THE
BENEFIT IS THAT WHEN WE STUDY
OUTLIERS WE LEARN A LOT AND TEND
TO BE INDIVIDUALS IN THE
POPULATION.
THE PROBLEMS ARE SEVERAL.
FIR
FIRST, THIS IS A RETROSPECTIVE
DEFINITION.
WE HAVE TO HAVE TIME GO BY FOR
PEOPLE NOT TO DEVELOP
CARDIOVASCULAR TODAY TO DEFINE
THEMSELVES AS RESILIENT.
THAT'S LESS OPERATIONALLY
HELPFUL PARTICULARLY IF WE'RE
LOOKING AT A PATIENT OR PERSON
SITTING IN FRONT OF US TODAY.
IF WE HAVE STRONG INTERMEDIATE
MARKERS THAT CAN INDICATE THAT
RESILIENCE THAT HELPS US BUT
OFTEN THAT REQUIRES NON-STANDARD
CLINICAL MEASUREMENTS AND NOT
EASY IF WE HAVE TO DO SPECIAL
IMAGING OR TESTING OF BLOOD
BIOMARKERS OR OTHER THINGS.
FINALLY, A DEFINITION LIKE THIS
RETROSPECTIVE IN ITS NATURE HAS
QUESTIONS IS WHAT WOULD WE DO
ABOUT IT?
WHAT CAN WE DO TO IMPROVE
CARDIOVASCULAR RESILIENCE TODAY
I HOPE TO INTRODUCE YOU TO A
DEFINITION OF CARDIOVASCULAR
RESILIENCE.
THIS FORMAL
MISSION WAS PROPOSED BY THE
AMERICAN HEART ASSOCIATION IN
2010.
I WAS PRIVILEGED TO LEAD A GROUP
OF OUTSTANDING VOLUNTEERS AND
STAFF MEMBERS TO MAKE THOSE
WORDS COME ALIVE NOT JUST A TERM
OF CARDIOVASCULAR HEALTH BUT HOW
CAN WE MEASURE THAT IN
INDIVIDUALS AND POPULATIONS IN A
WAY THAT WAS MEANINGFUL.
SO AS WE THOUGHT HOW WE MIGHT
DEFINE CARDIOVASCULAR HEALTH WE
DEFINE HEALTH IS A BROADER
CONSTRUCT AND MORE POSITIVE THAN
THE ABSENCE OF ANY DISEASE AND
AT THE NHLBI WE NEED EVIDENCE
BASE IT LOOK AT WHAT WAS LINKED
TO LONG-TERM HEALTH SURVIVAL AND
LONGEVITY AND QUALITY OF LIFE
AND IMPORTANT AS SPEBLTS OF
HEALTH.
AND WE ALSO WANTED TO FRAME THIS
AS SOMETHING THAT COULD BE
MEASURED AND MONITORED TODAY NOT
JUST IN TERMS OF FUTURE RISK.
IT HAD TO BE SIMPLE, ACTIONABLE
FOR INDIVIDUALS AND PAYERS AND
PROVIDERS AND CONSUMERS ALLOWING
ALL SUBSETS OF THE POPULATION TO
IMPROVE AND IMPORTANT
CONSIDERATIONS I THINK HERE AND
MOST IMPORTANTLY AGAIN NEED TO
BE MEASURABLE, MONITORABLE AND
MODIFIABLE IN ORDER TO BE A
DEFINITION THAT WAS WORTHWHILE
AND USABLE.
WE CAME UP WITH THE SEVEN HEALTH
BEHAVIORS AND FACTORS YOU SEE ON
THE SLIDE.
OPTIMAL LEVEL OF ALL THOSE WERE
DEFINED AS IDEAL CARDIOVASCULAR
HEALTH AND ONLY A VERY SMALL
PROPORTION OF THE POPULATION AT
ANY AGE HAS ALL SEVEN OF THESE
FACTORS AT IDEAL LEVELS
SIMULTANEOUSLY.
SO WE PROVIDED THIS DEFINITION
ACROSS THE SEVEN METRICS THAT
ALLOWS FOR CHARACTERIZATION OF
POOR, INTERMEDIATE AND IDEAL
CARDIOVASCULAR HEALTH FOR EACH
METRIC THAT CAN THEN BE SUM --
SUMMARIZED OR ASSIGNING ZERO
POINTS AND TWO POINTS TO IDEAL
METRIC AND SUMMING THAT ACROSS
THE SEVEN DIFFERENT
CARDIOVASCULAR HEALTH DISEASE
METRICS.
LETS TAKE A QUICK TOUR OF
CARDIOVASCULAR HEALTH ACROSS THE
LIFE COURSE AND YOU'LL START TO
SEE WHY IT'S A DEFINITION OF
CARDIOVASCULAR RESILIENCE.
FIRST, IN OLDER ADULTS IN THE
MULTI-ETHNIC STUDIES OF ATHEIR
OWE SCLEROSIS AND DEVELOPING IT
IN THE NEXT 10 YEARS AND SEE THE
NICE LOG LINEAR RELATIONSHIP THE
HIGHER THE CARDIOVASCULAR HEALTH
THE BETTER THE CARDIOVASCULAR
HEALTH AND LOWER RISK FOR
DEVELOPING CARDIOVASCULAR
DISEASE IN OLDER AGE.
AND FROM THE ATHEROSCLEROSIS
DOSE RESPONSE RELATIONSHIP WAS
LOWER AND LOWER HAZARDS RATIOS
THE MORE IDEAL CARDIOVASCULAR
HEALTH METRICS YOU HAVE EVEN TO
THE POINT WHERE PEOPLE WITH ALL
SEVEN METRICS AT IDEAL LEVELS
THOUGH THEY WERE RARE IN THIS
POPULATION HAD ZERO
CARDIOVASCULAR EVENTS OVER THE
NEXT 20 YEARS.
THAT'S SEVERAL HUNDRED PEOPLE IN
MIDDLE AGE AND ADULTHOOD OVER 20
YEARS.
REMARKABLE STATEMENT.
HERE YOU SEE THEM DEFINED ADD 12
TO 14 POINTS AS YOUNG AS 18 TO
24 WAS ASSOCIATED AS WITH LOW
CARDIOVASCULAR EVENT RATES IN
THE BLUE OVER THE NEXT 30 YEARS
OF FOLLOW UP.
THEY'RE ALL PREMATURE
CARDIOVASCULAR EVENT RATES AND
PEOPLE HAD LOW EVENTS OF
PREMATURE CARDIOVASCULAR DISEASE
AND THOSE WITH LOW
CARDIOVASCULAR HEALTH STATUS HAT
HIGHER RATES.
SO THESE ARE DATA AT MY
INSTITUTION WHO DID A NICE JOB
CREATING A SYNTHETIC COHORT
ACROSS THESE INDIVIDUALS AND
KNITTED TOGETHER COHORTS AND
FOUND TRAJECTORIES OF
CARDIOVASCULAR HEALTH SCORES IN
THIS CASE STARTING AS EARLY AS
THIRD GRADE AND SEE FIVE
PATTERNS OF CHANGE IN
CARDIOVASCULAR HEALTH SCORE FROM
EARLY LIFE INTO MIDDLE AGE.
AND YOU CAN SEE THERE WAS
ALREADY STRATIFICATION AS EARLY
AS AGE EIGHT.
PEOPLE WERE ALREADY DECLARING
THEIR MEMBERSHIP IN THIRD GRADE
INTO SOME OF THESE TRAJECTORY
GROUPS.
WHEN YOU HAVE THICKENING OF THE
CAROTID ARTERY WALL MEASURED IN
35 OF THE COHORT THERE'S WAS A
STRONG GRADIENT OF THICKNESS
MEANING ATHEROSCLEROSIS
DEVELOPMENT ACROSS THE GROUPS
RELATED TO MEMBERSHIP IN THE
DIFFERENT TRAJECTORY GROUPS FROM
EARLY LIFE.
THAT DIFFERENCE MAY SEEM VERY
MUCH BUT IF YOU APPLY IT TO A
55-YEAR-OLD POPULATION IT'S AN
INCREASE OF RISK IN THE FUTURE.
THIS IS A RISK EVEN AT A YOUNGER
AGE.
THEN TAKE IT BACK TO THE
EARLIEST PART OF LIFE, THESE ARE
DATA FROM THE HYPERGLYCEMIA
OUTCOME STUDY AND WE WERE ABLE
TO LOOK AT CARDIOVASCULAR HEALTH
STATUS AT THE SECOND TRIMESTER
OF GESTATION AND MOM'S HEALTH
STATUS AND LINK IT TO OFFSPRING
STATUS AGE 10 TO 14 AND FOUND
MOMS WITH HIGH CARDIOVASCULAR
HEALTH WERE EIGHT TIMES MORE
LIKELY TO HAVE CHILDREN WITH
HIGH CARDIOVASCULAR HEALTH AND
VICE VERSA.
MOMS WITH POOR CARDIOVASCULAR
HEALTH WERE TEN TIMES MORE
LIKELY TO HAVE CHILDREN WITH
POOR CARDIOVASCULAR HEALTH.
SO THIS TABLE PROVIDES A BRIEF
SUMMARY OF SOME OF THE OUTCOMES
ASSOCIATED LINKING HIGH
CARDIOVASCULAR HEALTH TO HEALTH
OUTCOMES.
THERE ARE THINGS ON THE SLIDE
THAT CERTAINLY WOULD BE EXPECTED
IN TERMS OF CARDIOVASCULAR
HEALTH OUTCOMES, TOTAL MORTALITY
BUT I THINK A NUMBER OF THINGS
ALSO REALLY IMPORTANT IN
THINKING ABOUT WHY YOUR HEALTH
STATUS IS SOMETHING TO FOCUS ON,
FUTURE DEMENTIA, FUTURE
DEPRESSION, FUTURE QUALITY OF
LIFE AND I'LL TALK ABOUT
COMPRESSION OF MORBIDITY.
SO LOOKING AT THIS COHOST 40,000
MEN AND WOMEN CHARACTERIZED
MOSTLY IN MIDDLE AGE AT AGE 40
WE WERE ABLE TO LOOK AT WHAT THE
OUTCOMES WERE IN MEDICARE
SEVERAL DECADES LATER.
AND GIVE ME TWO CLICKS AHEAD.
YOU'LL SEE THE TOTAL BAR
REPRESENT THE LIFE SPAN OF
INDIVIDUALS DURING MEDICARE AND
THE GREEN BAR REPRESENTS THEIR
HEALTH SPAN.
THAT IS HOW LONG THEY LIVE
WITHOUT MAJOR CARDIOVASCULAR
COMORBIDITIES.
THE YELLOW WITH ONE AND ORANGE
WITH TWO AND RED BAR WITH THREE
OR MORE CARDIOVASCULAR
COMORBIDITIES AND WE STRATIFIED
THEM BY THEIR HEALTH STATUS OF
ABOUT AGE 40 COMPARED WITH THOSE
OF TWO OR MORE MAJOR RISK
FACTORS.
PEOPLE WITH TWO OR MORE MAJOR
RISK FACTORS HAVE A HEALTH SPAN
OF 86 AND 84.
THEY SPEND ABOUT EIGHT YEARS
WITH CARDIOVASCULAR
COMORBIDITIES AND THOSE WITH
CARDIOVASCULAR HEALTH AT 40 HAVE
A HEALTH SPAN THAT EXPANDS AGE
83 AND HEALTH TO AGE 88.
THEY ONLY SPEND FIVE YEARS.
AND EVERYBODY WILL DIE BUT GET
SICKER CLOSE TO THE END OF THE
LIFE SPAN.
SOW LOOKING AT THIS APPROACH
THINKING ABOUT COMPRESSION
MORBIDITY AND HEALTH SPAN, THESE
DATA ARE ACTUALLY FROM THE
NATIONAL HEALTH AND NUTRITION
EXEMPTION SURVEYS AND LOOKED AT
DIFFERENT TYPES OF CHRONIC
DISEASE OF AGING RELATED TO
CARDIOVASCULAR HEALTH STATUS.
SORRY, THE DATA FROM THE U.K.
BIO BANK.
WHAT THEY FOUND IT OBVIATES
LONGER HEALTH SPAN AND LIFE
SPAN.
WHAT YOU SEE IS THOSE PEOPLE
WITH HIGH CARDIOVASCULAR HEALTH
ACTUALLY WITHIN THE LOW
EDUCATION GROUP HAVE A LONGER
HEALTH SPAN AND ALSO ACROSS
EDUCATION STATUS THE PRESENCE OF
HIGH CARDIOVASCULAR HEALTH SEEMS
TO OBVIATE THE RISK ASSOCIATED
WITH POOR EDUCATION.
THEY FOUND THIS FOR A SOCIAL
DEPRIVATION INDEX SCORE AS WELL
AS PERSONAL INCOME LEVELS.
HOUSEHOLD INCOME LEVELS.
YOU CAN SEE THE HEALTH SPAN IS
THE SAME FOR PEOPLE WITH LOWER
AND HIGHER HOUSEHOLD INCOME
LEVELS.
THIS CARDIOVASCULAR HEALTH
STATUS SEEMS TO BE NULLIFYING
THE EFFECTS OF SOCIAL
DETERMINATES OF HEALTH.
THIS A PARTICULARLY INTERESTING
STUDY WHERE I THINK WE'RE SEEING
RESILIENCE IN IMPARTED BY
CARDIOVASCULAR HEALTH IN THIS
STUDY FROM ATHEROSCLEROSIS RISK
SCORE LOOKED AT PEOPLE WIN SNIPS
OF CARDIOVASCULAR DISEASE AND
HEALTH SCORE.
AND WHAT YOU SEE HERE IS AT THE
TOP YOU SEE PEOPLE WITH GOOD
GENES BUT POOR CARDIOVASCULAR
HEALTH AND IN THE VERY BOTTOM
BAR YOU SEE PEOPLE WITH BAD
GENES BUT GOOD CARDIOVASCULAR
HEALTH.
THE PEOPLE WITH BAD GENES DON'T
LIVE OUT THEIR DESTINY IF THEY
HAVE GOOD CARDIOVASCULAR HEALTH.
NOTICE THIS DIFFERENT, 12 YEARS
LONGER LIFE SPAN, 19 YEARS
LONGER HEALTH SPAN AND SEVEN
YEARS LESS ON AVERAGE SPEND WITH
CORONARY HEALTH DISEASE IF THEY
HAD IDEAL HEART HEALTH EVEN WITH
BAD GENES AND GOOD
CARDIOVASCULAR HEALTH.
IT'S A NICE DEMONSTRATION OF
RESILIENCE.
THAT'S BEEN RE-REPLICATED IN THE
U.K. BIO BANK.
IN SOME OF OUR IT'S NOT THAT
THESE PEOPLE DON'T DEVELOP
ATHEROSCLEROSIS OR
CARDIOVASCULAR PEOPLE WITH HIGH
HEALTH SCORES STILL HAVE SOME
ATHEROSCLEROSIS BUT CLEARLY NOT
AS MUCH IT'S NOT JUST
QUANTITATIVE BUT QUALITATIVE.
AND IN THE DATA LOOKING AT
CROSS-SECTIONAL LEFT MAIN CORE
NARY ARTERY AND DECRESCENDING A
SLICES FROM A 72-YEAR-OLD MAN
WHO HAD CARDIOVASCULAR RISK
FACTORS 40 YEARS AGO YOU CAN SEE
IRREGULARITIES IN THE WALL OF
THE CORONARY ARTERY AND IN THE
LEFT MAIN THE LIPID RICH CORE
DARK SPOT OF PLAQUE IN THE
INDIVIDUAL'S ARTERY.
CONTRAST THAT WITH AN INDIVIDUAL
WHO HAD IDEAL CARDIOVASCULAR
HEALTH ABOUT 40 YEARS AGO, HE
HAS MORE UNIFORM WALL OF HIS
CORONARY ARTERIES AND YOU DON'T
SEE THE LOW ATTENUATION LIPID
RICH AREAS IN THE WALLS OF HIS
CORONARY ARTERIES.
IN FACT WE'RE SEEING WHILE THE
ARTERIES OF PEOPLE WITH
CARDIOVASCULAR HEALTH IN YOUNG
AGE ARE NOT NORMAL LATER IN LEIF
THEY STILL HAVE THICKENING AND
REMODELLING OF THEIR CORONARY
ARTERIES BUT THERE'S MUCH MORE
THERE THAN THERE WOULD BE IF
THEY WERE HEALTHY OLD INDIVIDUAL
AND THEY'RE DEVELOPING
ATHEROSCLEROSIS BUT DEVELOPING
MORE SCLEROSIS AND LESS ATHERO.
IT'S A MORE BENIGN DEPOSITION IN
THE WALLS OF THE ARTERIES.
IS WE KWUPDATED THE DEFINITION
INCLUDE SLEEP WHICH IS WHY IT'S
RELEVANT TO OUR TOP EKZ TODAY.
-- TOPICS.
SO LIFE'S SIMPLE SEVEN HAS
BECOME LIFE'S ESSENTIAL EIGHT.
AND IN CRAFTING THIS BY ADDING
SLEEP AS A NEW METRIC WE ALSO
ACKNOWLEDGE AS YYOU SEE THE
CRITICAL IMPORTANCE OF SOCIAL
DETERMINATES OF HEALTH AND ALSO
THE CRITICAL IMPORTANCE OF
PSYCHOLOGICAL HEALTH AND WELL
BEING AS STRONG CONTEXTUAL
FACTORS FOR ONE'S ABILITY TO
ACHIEVE THEIR HIGHEST
CARDIOVASCULAR HEALTH.
>> EXCUSE ME, DOCTOR, TWO-MINUTE
WARNING.
>> I APPRECIATE THAT.
WE UPDATE THE SCORING ALGORITHM
WHICH ALLOWS NOW FOR A BROADER
SENSE OF SCORING THAT ALLOWS
BETTER SENSE OF INTERINDIVIDUAL
AND INTRAINDIVIDUAL DIFFERENCES
AND CHANGE.
BUT AGAIN WE ALSO ADDED SLEEP
HEALTH WHICH THE SIMPLE
DEFINITION ONLY LOOKS AT THE
DURATION OF AVERAGE SLEEPER
NIGHT.
WE NOW HAVE THESE EIGHT HEALTH
BEHAVIORS AND HEALTH FACTORS
DEFINING CARDIOVASCULAR HEALTH
IN A MORE GRANULAR WAY BECAUSE
OF THE SCORING CHANGES.
THE CORRELATION COEFFICIENT FOR
THE SLEEP SCORE WITHIN THE
HEALTH METRICS WITH EACH OF THE
OTHER SEVEN MET OF -- METRICS
IS STATISTICALLY CORRELATED AND
SLEEP IS ADDING INDEPENDENT
INFORMATION IN CORRELATION WITH
OTHER METRICS.
THE TAKE HOME POINTS ARE CLEARLY
HIGHER CARDIOVASCULAR HEATH AT
ANY LIFE SPAJ IS A CRITICAL
FACTOR ASSOCIATED WITH HEALTHY
LONGEVITY.
REDUCTION OF MORBIDITY IN THE
FUTURE AND COMPRESSION OF
MORBIDITY AND HIGHER QUALITY OF
LIFE.
WE'VE SEEN FROM OTHER STUDIES
IMPROVING CARDIOVASCULAR HEALTH
WHICH IS VERY ACHIEVABLE
IMPROVES HEALTH OUTCOMES AND
IT'S NEVER TOO LATE IN LIFE TO
IMPROVE CARDIOVASCULAR HEALTH
BUT THE SOON THEIR BETTER.
THE BIGGER THE IMPACT IF YOU
CHANGE SOONER AND HIGHER
CARDIOVASCULAR HEALTH THROUGH
HEALTHIER LIFE STYLE TRUMPS
GENETICS A WORKING DEFINITION OF
CARDIOVASCULAR RESILIENCE.
I'LL STOP THERE IN THE INTEREST
OF TIME AND IT'S A REAL PLEASURE
NOW INTRODUCE OUR NEXT SPEAKER,
WHO DR. STEPHANIE COOK FROM NEW
YORK UNIVERSITY AND SHE'S GOING
TO SPEAK ON SOCIAL DETERMINATES
OF SLEEP HEALTH FROM 2017 TO
2020: EXPLORING THE INTERSECTION
OF RACE AND GENDER.
DR. COOK, OVER TO YOU.
>> THANK YOU FOR THE WONDERFUL
INTRODUCTION AND OVERVIEW.
I'LL TALK ABOUT RACE AS A SOCIAL
DETERMINATE OF HEALTH OF SLEEP
HEALTH AND I'M GOING USE THE ALL
OF US DATA TO DO SO AND MOST
IMPORTANTLY TALK ABOUT
INTERSECTIONALITY.
MY POSITION STATEMENT I'M A
BLACK CISGENDER WOMAN WHO WORKED
IN COMMUNITY FOR YEARS AND I
STRIVE TO MAKE A DIFFERENCE AND
ALSO ACKNOWLEDGE THAT I WORK
MORE IN THE COMMUNITIES I SERVE
AND I BELIEVE REPRESENTATION IS
VITALLY IMPORTANT.
WE HAD A NICE OVERVIEW OF
CARDIOVASCULAR DISEASE BUT WHAT
I WANT TO HIGHLIGHT IS THAT
THERE ARE STAR AND WE SAW A
DECREASE BUT THERE'S DISPARITIES
BASED ON RACE ARE MAINTAINED AND
FROM 2018 AND 2021 WE SEE THE
STUDY OF CARDIOVASCULAR WITH
SMALL DECREASES BUT AGAIN THE
DISPARITIES REMAIN.
SO WE KNOW CARDIOVASCULAR
DISEASE IS THE LEADING CAUSE OF
DISEASE AND THERE'S FACTORS
INCLUDING SMOKING AND HIGH
CHOLESTEROL AND BLOOD PRESSURE
AND AMONG BLACK INDIVIDUALS
CARDIOVASCULAR DISEASE IS VERY
HIGH AND WE SEE INCREASING RATES
AMONG BLACK WOMEN AND THIS
FORCES US TO THINK MORE
CRITICALLY ABOUT THE ROLE OR
INTERSECTION OF GENDER AND RACE.
I ENTERED IN THINK OF SOCIAL
DETERMINATES OF CARDIOVASCULAR
DISEASE THERE WAS A WONDERFUL
SCIENTIFIC STATEMENT THAT CAME
OUT LED BY GIANTS IN THE FIELD
AND THERE'S AN UPDATE IN A 2020
PAPER THAT TALKS ABOUT THE
SOCIAL DETERMINATES OF
CARDIOVASCULAR DISEASE AND RACE
AND ETHNICITY AND THERE'S A
SOCIAL CONSTRUCT AND WHEN WE
TALK ABOUT RACE AND ETHNICITY
WE'RE TALKING ABOUT RACISM.
WHEN WE THINK OF RACISM AS A
SOCIAL DETERMINATE OF HEALTH WE
HAVE TO THINK HOW STRESSORS FROM
BEING IN CONSTELLATIONS OF
RACIST ENVIRONMENTS REALLY
INFLUENCE CARDIOVASCULAR DISEASE
IS NEGATIVE.
WE HAVE TO THINK WHEN WE START
THINKING ABOUT THE INTERSECTION
OF RACE AND ETHNICITY IS SO WHEN
WE START THINK
SOCCEREDS OF HEALTH WE NEED TO
THINK ABOUT OTHER ACCESSES OF
INEQUALITY AND USING
INTERSECTIONAL FRAMEWORK USING
AN INTERSECTIONAL FRAMEWORK IS
IMPORTANT IN HOW TO WE THINK OF
SOCIAL DETERMINATES MUCH HEALTH
AND THINK CARDIOVASCULAR DISEASE
RISK AND SLEEP I'LL TALK ABOUT
IN A MINUTE.
INTERSECTIONALITY IS MOVING AWAY
FROM THE SUB GROUP ANALYSES AND
SAYING FOR EXAMPLE BLACK WOMEN
HAVE INCREASING RATES OF
CARDIOVASCULAR DISEASE INSTEAD
FRAMING IT IN THE CONTEXT OF
PRIVILEGE AND POWER.
SO THESE IDENTITIES ARE LINKED
AND REFLECTIVE OF THE LARGER
SOCIAL POWER DYNAMICS.
STARTING WITH THE INTERSECTIONAL
FRAMEWORK HELPS GUIDE OUR
SCIENTIFIC INQUIRY IN THIS AREA.
TOE GIVE EXAMPLES HOW
INTERSECTIONALITY AND HOW HAIR
DISCRIMINATION AFFECTS WOMEN AND
IT'S NOT REALLY ABOUT BLACKNESS
INSTEAD IT'S ABOUT THE CRITICAL
INTERSECTION OF BEING A BLOCK
WOMAN.
-- BLACK WOMAN.
SO WE UTILIZE MANY STATISTICAL
METHODS IN IDENTIFYING THESE
GROUP PHENOMENA USING
INTERSECTIONAL PERSPECTIVE AND A
LOT OF THE WORK I DO IS THE
MET
METHODOLOGICAL AREA AND I
IMPLORE US TO THINK HOW WE USE
INTERSECTIONALITY AS AN
ORGANIZING FRAMEWORK FOR OUR
WORK EVEN OUTSIDE OF THE ROLE OF
BUILDING THESE STATISTICAL
MODELS.
I'M GOING TO TALK ABOUT THE WORK
WITH "ALL OF US" IN
UNDERSTANDING DISPARITIES.
SO SHORT SLEEP DURATION IS ONE
CRUDE METRIC OF SLEEP HEALTH.
A LOT OF EXPERTS SAY THAT PEOPLE
SHOULD HAVE ON AVERAGE SEVEN
HOURS OF SLEEP IN A 24 HOUR
PERIOD AND THIS IS A KEY
INDICATOR IF YOU HAVE LESS THAN
THAT OF POOR SLEEP HEALTH.
WE KNOW THAT LACK OF SLEEP IS
ASSOCIATED WITH CARDIOVASCULAR
DISEASE AND WE HAVE PAPERS AND
SCIENTIFIC INQUIRIES TO
DEMONSTRATE THAT BY NOW.
AND AS EARLY AS 2014 AND EARLIER
THE CHICAGO SLEEP STUDY, FOR
EXAMPLE, STARTED TO IDENTIFY
DISTINCT DIFFERENCES BASED ON
RACE AND SLEEP HEALTH
IDENTIFYING SL BLACK, HISPANIC D
ASIANS AND SLEEP HEALTH THAN
WHITE INDIVIDUALS.
IN ADDITION, THE NIEHS IN A 2022
PAPER INDICATED THAT BLACK WOMEN
IN PARTICULAR HAD EVEN GREATER
DISPARITIES IN SLEEP HEALTH OR
DURATION OF SLEEP COMPARED TO
WHITE WOMEN.
SO WE'RE ALREADY STARTING TO SEE
THE DIFFERENCES IN SLEEP HEALTH
AT THE INTERSECTION BUT THE
FINDINGS ARE RATHER MIXED.
IN THIS STUDY I WAS TAKING AN
INTERSECTIONAL APPROACH AND
HYPOTHESIZED IN THE CATEGORY OF
RACE AND ETHNICITY MINORITY
WOMEN WOULD HAVE LESS MINUTES OF
SLEEP THAN WHITE WOMEN AND
WITHIN THE CATEGORY OF RACE AND
ETHNICITY WE HYPOTHESIZED ETHNIC
MINORITY MEN WOULD HAVE LESS
MINUTES OF SLEEP THAN WHITE MEN
AND OVER ALL WE HYPOTHESIZED
NON-WHITE WOMEN WOULD HAVE
INCREASING TRAJECTORIES OF SLEEP
DURING DURATION COMPARED TO
WHITE WOMEN.
THESE DATA COME FROM NIH ALL OF
US WHICH IS A RICH DATA SOURCE
AND WE SPECIFICALLY USED THE
FITBIT AND WE WERE LOOKING AT
SLEEP TRAJECTORIES.
LOOKING FROM 2017 TO 2022 FOR
THOSE WHO HAD FITBIT DATA.
SO MINUTES OF SLEEP WAS
CHARACTERIZED BY LESS THAN SEVEN
MINUTES OF SLEEP AN 24 HOUR
PERIOD.
IN ADDITION WE MEASURED
SELF-REPORTED RACE OR ETHNICITY
AND REPORTED GENDER BY
SELF-REPORT AND USED A FEW
COVARIATES INCLUDING HEART
CONDITIONS OR HISTORY OF ANY
KIND OF HEART CONDITION AND
FAMILY HISTORY OF HEART
CONDITION AND SUBSTANCE USE
BEHAVIOR.
WE DID BASIC BI-VARIATE
STATISTICS AND CONDITIONAL AND
LINEAR MIXED MODELS AND ACTION
TERMS TO TALK ABOUT
INTERSECTIONALITY AND ALL THIS
IN OUR WORK BENCH.
SO THE FIRST THING I WANT TO
TALK ABOUT IS JUST KIND OF THE
GENERAL RESULTS.
IN TERMS OF RACE, WE SEE THE
RESULTS THAT WE HAVE SEEN AND
THE GENERAL LITERATURE.
WE SEE OVER ALL THAT BLACKS
EXPERIENCE ABOUT 50 LESS MINUTES
OF SLEEP AT BASELINE COMPARED TO
OTHER GROUPS.
WE SEE THE OVER ALL TRAJECTORIES
LOOK SIMILAR BETWEEN RACIAL
GROUPS BUT PARTICULARLY BLACK
AND ASIAN OVER ALL EXPERIENCE
LESS SLEEP THAN THE OTHER RACIAL
ETHNIC GROUPS.
IN ADDITION WE SEE THE SAME
PATTERN WHEN WE LOOK AT GENDER
ALONE BETWEEN MALES AND FEMALES
AND WE SEE SIMILAR PATTERNS AND
WITH MORE TIME WE COULD TALK
ABOUT THE COVID EFFECT OR WHAT
WE THINK IS GOING ON FROM COVID
BUT OVER ALL WHAT I WANT TO
HIGHLIGHT IS THAT THESE
DISPARITIES CONTINUE.
AND THEN IF WE LOOK -- THE
PREVIOUS SLIDE -- SOW -- SO
THIS IS A SLIDE I WANT TO SPEND
TIME ON.
WITHIN THE FEMALE CATEGORY ALL
THE ETHNIC GROUP DECREASE IN
MINUTES OF SLEEP BETWEEN 2017
AND 2022 EXCEPT FOR THOSE IN THE
OTHER GROUP AND THE BLACK
CATEGORY WHERE WE SAW AN
INCREASE IN MINUTES OF SLEEP TO
THE 2020 AND 2022 EN THESE
GROUPS OF WOMEN.
AND THEN WHITE WOMEN THAT'D MOST
MINUTES OF SLEEP OVER ALL
CONSISTENT IN THE ACADEMIC
LITERATURE.
AND BLACK AND HISPANIC AND ASIAN
AND OTHER WOMEN ALL HAD
STATISTICALLY SIGNIFICANT
DECREASING TRAJECTORIES OF WOMEN
OF SLEEP COMPARED TO WHITE
WOMEN.
THE LARGEST DIFFERENCE WAS
BETWEEN BLACK AND WHAT WOMEN AND
ASIAN AND WHITE WOMEN THOUGH
WE'RE USING THE PERSPECTIVE
UPLIFTING THE INTERSECTION OF
RACE AND GENDER THE DRIVER IN
THE FIRST TWO SLIDES ARE BY THE
BLACK AND ASIAN CATEGORIES.
AND WITHIN THE MAIL GROUP BLACK
EXPERIENCE A DECREASE IN MINUTES
OF SLEEP COMPARED TO WHITE MALES
AND THEN IF WE'RE JUST LOOKING
AT WITHIN RACE OVER ALL, BLACK
MALES EXPERIENCE A DECREASE IN
MINUTES OF SLEEP BY .15 FOR
EVERY INCREASE IN CUBIC UNIT OF
TIME AND EXPERIENCE DIFFERENT
SLEEP THAN FEMALES.
AND OVER ALL COMPARED TO MALES
OVER ALL, WOMEN OF THE SAME RACE
JUST SLEPT LONGER.
SO OUR HYPOTHESES WERE PARTIALLY
SUPPORTED AMONG RACIAL ETHNIC
AND MINORITY MALES.
THEY HAD LESS MINUTES OF SLEEP
COMPARED TO FEMALES AND WITHIN
THE CATEGORY OF RACIAL GENDER
MINORITY FEMALES THEY HAD LESS
MINUTES OF SLEEP OVER ALL THAN
WHITE FEMALES.
HOWEVER, WE KNOW THAT THERE ARE
BIOLOGICAL SEX DIFFERENCES IN
CARDIOVASCULAR DISEASE AND THERE
MIGHT BE SOME HINTS IN TERMS OF
SLEEP AND CIRCADIAN RHYTHM.
WE HAVE TO THINK MORE GENERALLY
HOW THIS USING THE BASIC
INTERACTION TERM POINTS TOWARDS
THIS SOCIAL DETERMINATES OF
HEALTH FRAMEWORK.
SO BEYOND JUST LOOKING AT THESE
DIFFERENCES THAT MIGHT BE HINTH
AT SOME BIOLOGY WITHIN THE
CATEGORY MUCH WOMEN AND MEN
DISTINCT DIFFERENCE TO PAY
ATTENTION TO AND MADE MORE
VISIBLE BY DOING SO IN THIS KIND
OF PROCESS.
NOW WE CAN DO FUTURE WORK THAT
FOCUSES ON THE ROLE OF RACISM
AND DISCRIMINATION AND OTHER
SOCIAL DETERMINATES OF HEALTH
AND GETTING CLOSER TO THE
TRAJECTORIES USING THE
INTERSECTIONAL APPROACH.
WHAT DOES RESILIENCE HAVE TO DO
WITH ANY OF THIS?
BASED ON THE CONVERSATION JUST
NOW AND OVER ALL WE KNOW
RESILIENCE CAN BE PROTECTIVE
WHEN WE TALK ABOUT
CARDIOVASCULAR DISEASE RISK AND
CARDIOVASCULAR HEALTH IN
GENERAL.
HOUR RESILIENCE CAN BE
CONCEPTUALIZED IN A MYRIAD OF
WAYS.
THE WORKING GROUP HAS DONE GREAT
WORK AND HAS HELPED ORGANIZE THE
FRAMEWORK THAT REALLY POINTS TO
LOOKING AT THE PSYCHOLOGICAL,
SOCIOLOGICAL AND ENVIRONMENTAL
AND EVEN BIOLOGICAL RESILIENCE
FACTORS THAT HELP BRING
CARDIOVASCULAR HEALTH BACK TO
HOMEOSTASIS.
I WANT TO PRESENT TO YOU IN
ADDITION TO THIS TRAIT-LEVEL
RESILIENCE WE TALK A LOT ABOUT
IN PSYCHOLOGY AND THE SOCIAL
SCIENCES WE CAN LOOK AT THE
SOCIAL SAFETIES OF OUTCOME
RESILIENCE.
SO RESOURCES USED TO COPE WITH
RESILIENCE LIKE SOCIAL SUPPORT
AND BEYOND THAT SOCIAL SAFETY
REFERS TO THE CONSISTENT SOCIAL
INCLUSION AND PROTECTION THAT
CAN BE SEEN IN A RESILIENT
MECHANISM.
>> YOU HAVE TWO-MINUTE WARNING.
>> THANK YOU.
WE KNOW AN RECENT REVIEW THAT
INDIVIDUAL LEVEL RESILIENCE,
THEY WERE ALL VITALLY IMPORTANT
TO SPEAKING ABOUT A LOWER
ADVERSE CARDIOVASCULAR OUTCOME
HOWEVER, RACE AND ETHNICITY AND
GENDER CAN IMPACT CARDIOVASCULAR
HEALTH DRASTICALLY DIFFERENT.
FOR EXAMPLE, WE SEE IN A STUDY
THAT RESILIENCE DID NOT
ATTENUATE THE ASSOCIATION
BETWEEN LIFE STRESS AND CVD RISK
AMONG BLACK WOMEN AND HOW CAN WE
THINK DIFFERENTLY ABOUT
RESILIENCE?
I WANT TO LEAVE YOU WITH THE
THEORETICAL FRAMEWORK I'M WORK
AT IN THE CARDIO METABOLIC
BEHAVIORS THAT LOOK PARTICULARLY
AT SLEEP AS ONE OF THE
CARDIOVASCULAR HEALTH OUTCOME
VARIABLES.
AND HERE WE TAKE AN
INTERSECTIONAL APPROACH TO
INFORMATION IT'S RELATIONSHIP
AND LOOK AT SOCIAL PROTECTIVE
AND SOCIAL SAFETY.
THIS IS A COMPLEX SYSTEM.
AND WHAT I WOULD LIKE TO LEAVE
YOU WITH IS THAT IDENTIFYING
RESILIENCE FACTORS IN
CARDIOVASCULAR HEALTH AND SLEEP
ESPECIALLY USING INTERSECTIONAL
FRAMEWORK IS COMPLEX.
SO WHAT WE'RE DOING IS
STATISTICAL WORK IN THIS AREA
AND WE'RE TRYING TO BUILD OUT
THE THEORETICAL LINKAGES TO SHOW
HOW USING THE INTERSECTIONAL
FRAMEWORK WITHIN THE CONTEXT OF
CARDIOVASCULAR DISEASE RESEARCH
AND THE SOCIAL PROTECTIVE
FACTORS FEATURED IS REALLY
IMPORTANT TO MOVING THE FIELD
FORWARD.
SO THANK YOU SO MUCH AND PARDON
THE INTERRUPTIONS FROM MY
CHILDREN.
THAT'S THE WAY IT GOES SOMETIMES
AND LET ME KNOW IF YOU HAVE ANY
QUESTIONS.
MY E-MAIL'S RIGHT THERE.
>> THANK YOU SO MUCH WE HAVE ALL
BEEN IN YOUR SHOES.
THAT WAS A WONDERFUL OVERVIEW I
THINK OF THE IMPORTANCE OF
SOCIAL DETERMINATES AND THE
INTERSECTIONALITY.
I AGREE AND LOOK FORWARD TO TALK
MORE DURING THE Q&A SESSION AT
THE END OF THIS.
I'LL MOVE US AHEAD.
THE NEXT SPEAKER IS DR. JOSÉ
ORDOVAS FROM TUFTS UNIVERSITY
TALKING ABOUT INTEGRATING CROHNO
NUTRITION AND SLEEP A PATHWAY TO
ATHEROSCLEROSIS MANAGEMENT AND
CARDIOVASCULAR RESILIENCE.
>> I DON'T HAVE CONFLICTS OF
INTEREST.
WHAT I'M GOING DO IS TALK ABOUT
THE SLEEP RHYTHM.
AND SO IN TERMS OF THE
DEFINITION OF CHRONONUTRITION
INVOLVES THE TIMING OF FOOD
INTAKE TO ALIGN WITH THE
CIRCADIAN RHYTHM WHICH WILL
CHANGE FROM ONE PERSON TO
ANOTHER OPTIMIZING MELT --
METABOLIC PROCESSES AND WILL
BRING METABOLIC HEALTH AND AND
INTERPLAY BETWEEN SLEEP AND
ATTENTION.
AND JUST TO BRING OUT THE
IMPORTANCE OF CHRONO BIOLOGY AND
CARDIOVASCULAR DISEASES, AND FOR
EXAMPLE CARDIOVASCULAR EVENTS OR
IT DOES NOT TAKE PLACE IN THAT
WAY AND TEND TO BE CONCENTRATED
IN THE EARLY HOURS OF THE DAY.
IN THE MORNING IS THE
PERSPECTIVE AND WE CAN WE CAN GO
FURTHER AND SEE HOW
CARDIOVASCULAR DISEASE HAS AN
IMPACT AND WE SEE EFFECTS BY
MANY MEASURES AND SEE IN THE
NORTHERN HEMISPHERE THE
CARDIOVASCULAR MORTALITY
INCREASES WITH TIME OR COLD
WEATHER AND DECREASES IN THE
SUMMERTIME OR WARMER WEATHER.
AND IF WE GO TO THE SOUTHERN
HEMISPHERE WE SEE THE SAME THING
IN TERMS OF LIGHT AND RHYTHM.
AND RHYTHMS ARE IMPORTANT WHEN
IT COMES CARDIOVASCULAR DISEASE.
THIS IS A SLIDE WE SEE OVER AND
OVER AND EVERY TIME OF THE DAY
OUR HORMONE LEVELS ARE DIFFERENT
AND MOOD AN HORMONES AND OTHER
FACTORS.
PART OF THE TIME IS OCCUPIED BY
SLEEP BUT SLEEP IS DISRUPT
SEVERAL TYPES AND ONE THAT IS
THE ACTUAL JET LAG AND THE OTHER
ONE IS WORK IS DIFFERENT AND
ALSO WHERE KIDS START SCHOOL
HOURS TOO EARLY FOR THEIR NORMAL
CIRCADIAN RHYTHM.
AND WITHIN HOURS OF SLEEP AND
OVERLAP AND THE ONE MARK IN RED.
THERE IS VARIETY AROUND THE
WORLD.
THERE ARE PLACES LIKE
SCANDINAVIAN COUNTRIES WHERE
THEY HAVE DINNER BETWEEN 4:00
AND 5:00 AND MY TYPICAL EXAMPLE
IS MY HOME COUNTRY OF SPAIN
WHERE THE TYPICAL HOURS OF
HAVING DINNER IS BETWEEN 9:00
AND 11:00 BUT YOU WILL SEE THE
DIFFERENT PARTS OF THE WORLD
THEY HAVE DIFFERENT TIMES OF
EATING.
THAT PERIOD OF SLEEP AND PERIOD
IS DIFFERENT ACROSS THE WORLD
AND IT'S INTERESTING TO SEE HOW
THEY LINK TO CARDIOVASCULAR
DISEASE OR RISK.
THOUGH WE THINK ABOUT THE
CURRENT RHYTHMS AND KIRKED
CLOCKS BEING TRAINED OR
REGULATED BY SLIGHT, ALSO FOOD
IS IMPORTANT.
NUTRITION IS IMPORTANT.
AND IT'S NOT LIGHT OR DARK BUT
FOOD.
SO CROHRONONUTRITION HAS BEEN
LINKED AND IF WE THINK OF THE
MATERNAL MILK YOU WILL SEE HERE
THE COMPOSITION OF THE MILK IS
NOT HOMOGENEOUS ALONG THE DAY
AND IT DEPENDS ON THE TIME OF
DAY.
THE TIMING OF WHICH THE MOTHER
IS TRAINING THE BABY IN
CIRCADIAN AND THIS IS THE FIRST
ENCOUNTER WITH THE REGULATION
AND WE CAN SEE LIPIDS AND SO ON
IN THE MATERNAL MILK.
AND WE HAVE ABANDONED THE
PRACTICE RECENTLY ON FOR EXAMPLE
YOU CAN PROVIDE MATERNAL MILK
BUT SOMETIMES MATERNAL MILK IS
FROZEN FOR A LATER TIME BUT YOU
DON'T PUT THE TIME OF DAY AND
COULD BE PROVIDING THE BABY WITH
MILK THAT WAS FOR THE MORNING IN
THE NIGHT AND THAT COULD CONFUSE
THAT TRAINING OF THE CIRCADIAN
RHYTHM.
THERE'S BEEN DEMONSTRATION FOR
EVERY PARAMETER OF SLEEP BREAST
MILK PERFORM MUCH BETTER THAN
FORMULA IN TERMS OF OUR SLEEP
AND LATENCY AND SO UPON -- ON.
IT'S IMPORTANT FOR MATERNAL
NUTRITION AND IS PROBABLY THE
FIRST ENCOUNTER OF THE BABY WITH
THAT CIRCADIAN RHYTHM.
AND IN THE CASE OF THE ELDERLY
WE ALSO HAVE SLEEP DISTURBANCES
AND LEADING TO RHYTHMS IN LIFE
THEY CAN GET FLOODED IN THE
ELDERLY WHICH MEANS THAT WE CAN
TEND TO REMAIN AND HAVE GOOD
QUALITY OF SLEEP DURING THE
NIGHT.
AND THERE'S BEEN EXPERIMENTS
LOOKING AT HOW SLEEP IMPROVE THE
QUALITY OF THE SLEEP IN THE
ELDERLY.
SIMILARLY TO WHAT WE HAVE SEEN
IN BABIES WITH THE MATERNAL
MILK.
WE DON'T HAVE -- WE HAVE
DIFFERENT PATTERNS OF EATING.
SOME PEOPLE EAT EARLY, SOME
PEOPLE EAT LATE, SOME PEOPLE
GRAZE ALL THE TIME AND THEN I'M
GOING TO -- GIVE YOU AN EXAMPLE
ALSO HOW THE TIME OF EATING MAY
HAVE INFLUENCED FACTORS
ASSOCIATED WITH CARDIOVASCULAR
DISEASE AND THIS IS WORK IN
COLLABORATION IN SPAIN THAT
BROUGHT TO ME THE IMPETUS FOR
CHRONONUTRITION AND SLEEP.
WHAT WE SEE HERE IS THAT IT'S A
PROGRAM IN WHICH PEOPLE WANTED
TO GROW AND THERE WAS
MEDITERRANEAN DIET AND GROUP
THERAPY AND SO FORTH AN THERE'S
DIFFERENT PATTERNS.
SOME WERE MORE SUCCESSFUL THAN
OTHERS.
WHEN WE EXAMINE WHAT THESE
PEOPLE WERE EATING AND THEY WERE
ABLE TO LOSE MORE WEIGHT THAN
THE OTHERS AND THEY WERE EATING
THE SAME THING.
THEY WERE DEVELOPING THE SAME
LIFESTYLE PATTERN AND THERE WAS
ONE DIFFERENCE.
THE TIME WHEN THEY WERE EATING
THEIR MAIN MEAL OF THE DAY IN
SPAIN AROUND MIDDAY.
SO WHAT HAPPENED IF YOU EAT YOUR
MAIN MEAL EARLY?
WE SAW THE PEOPLE WERE
SUCCESSFUL IN LOSING WEIGHT.
WHAT HAPPENS IF YOU EAT AFTER
3:00?
THESE PEOPLE DESPITE THE FACT
THEY WERE EATING THE SAME THING
WERE LESS SUCCESSFUL IN LOSING
WEIGHT.
TO THAT WE HAVE TO INCLUDE THAT
THEY HAVE WORSE DIABETES AND THE
CHRONOTYPE WAS WORSE ALSO IN THE
CASE OF THE LATE EATING.
INTERESTING ALSO ONE OF THE MAIN
OR CENTRAL GENES THE FREQUENCY
OF GENOTYPES WERE DIFFERENT.
THERE WAS A GENETIC COMPONENT
EMBEDDED HERE.
WE COULD SAY AS A PUBLIC HEALTH
MEASURE WE COULD ASK PEOPLE TO
EAT EARLY BUT IN ADDITION TO
CHRONONUTRITION, WE HAVE THE
CONCEPT AND INTERVIEWED THE
CONCEPT OF PRECISION
CHRONONUTRITION PEOPLE EAT AT
THE MOST OPTIMAL TIME TO KEEP
THE CLOCKS IN BALANCE, CENTRAL
AND PERIPHERAL CLOCKS AND SO
FORTH.
LET'S SEE WHAT HAPPENS IN THE
NEXT SLIDE WHEN WE INTRODUCE
MORE.
THIS IS THE EXPERIMENT.
WE'RE GOING INTRODUCE THE
CONCEPT OF PRECISION
CHRONONUTRITION EARLY AND WE
HAVE EXAMINED THIS IN THE
CONTEXT OF OBESE.
WE HAVE FOUND IT'S ASSOCIATED
WITH OBESITY AND ONE THING IS
THAT HAS BEEN BROUGHT UP IF WE
HAVE CONCLUSIONS THAT MAY NOT
APPLY TO THE ENTIRE POPULATION.
MEANING MOST WERE BIFFED --
BASED ON THESE AND HOW DIFFERENT
THEY'RE ON AFRICAN AND ASIAN AND
WHATEVER INFORMATION WE INSTRUCT
HAS TO BE THROUGH ALSO THE
RACIAL ETHNICITY.
LET'S GO TO THE RIGHT WHAT IS
IMPORTANT HERE.
HERE IN THE POLYMORPHISM YOU CAN
BE AND LOOK HOW DIFFERENT IS THE
BEHAVIOR IN TERMS OF WEIGHT
LOSS.
IF YOU ARE AN A IT DOESN'T
MATTER THE TIME YOU EAT.
FROM THIS YOU CAN SEE YOU ARE
RESILIENT TO THE EFFECT OF TIME
OF EATING.
HOWEVER, IF YOU'RE ON A
HOMOZYGOUS A YOU CAN SEE IT
INCREASES THE EFFECT WE HAVE
DEMONSTRATED IN WHICH WE EAT AND
CONTRIBUTES TO BE LESS
SUCCESSFUL LOSING WEIGHT.
THIS IS A NICE EXAMPLE OF
PRECISION CHRONONUTRITION IT AND
RESILIENCE.
I ALREADY MENTIONED THE CLOCK
BEFORE AND IT WAS ASSOCIATED
WITH THE CIRCADIAN RHYTHM AND
THERE'S A GROUP I MENTIONED
BEFORE.
YOU CAN SEE DEPENDING ON THIS
YOU EAT MORE CALORIES PER DAY
AND IT RESULTS NOT ONLY IN
INCREASE IN WAIST CIRCUMFERENCE
BUT ELEVATED SLEEP AND WEIGHT
AND IF YOU'RE LESS RESILIENT AND
HAVE AN INCREASE IN THE RISK OF
CARDIOVASCULAR DISEASE.
LOOK AT THE DIFFERENCE BETWEEN
AFRICAN AMERICAN, ASIANS AND IN
SOME PLACES THIS GENES MAY BE
MORE IMPORTANT IN TERMS OF
NUTRITIONAL OR BEHAVIORAL
RECOMMENDATIONS.
I'M GOING TALK ABOUT THE STUDY
IN THE LONG-TERM INTERVENTION
STUDY SEVEN YEARS.
WE LOOK AT LOW-FAT DIET.
A VERY IMPORTANT CONCEPT, VERY
EASY TO ACQUIRE AS PART OF THE
CHRONOTYPE ARE YOU AN OWL AND
WHY IS THIS IMPORTANT?
BECAUSE YOUR CHRONOTYPE VERY
IMPORTANT WHEN IT COMES RISK
FACTORS HERE IN THE STUDY WE SEE
THE MORNING TIME TEND TO HAVE
CARDIOVASCULAR RISK FACTOR THAT
ARE MORE PROTECTIVE THAN THE
EVENING TYPE AND THAT INCLUDES
WAKE TIME AND BED TIME.
SO MEASURING THE EARLY PERSON OR
EVENING PERSON IS IMPORTANT WHEN
IT COMES TO CARDIOVASCULAR
RESILIENCE AND OBVIOUSLY PART OF
THE CIRCADIAN RHYTHM THAT WE
WERE TALKING ABOUT.
>> TWO-MINUTE WARNING.
>> THANK YOU.
NEXT IS GENETICS.
YES, IN PART IT'S GENETIC AND
BEING AN OWL OR LARK THE GENETIC
CONTRIBUTION IS INTERESTING TO
SEE THE GENES THAT COME ARE MORE
IMPORTANT THAN THOSE THAN ARE
EXPRESSED IN THE BRAIN AND TYPE.
CAN WE CHANGE THAT?
WE CAN CHANGE IT.
HERE WE HAVE AN EXAMPLE OF
SOMETHING THAT WAS IMPOSED ON US
A FEW YEARS AGO THAT WAS THE
CONFINEMENT DURING COVID.
THAT SENSE OF LIFESTYLE IN WHICH
OUR SLEEP HABIT AND EATING HABIT
CHANGED FOR THE WORSE WAS ENOUGH
TO CHANGE THE CHRONOTYPE OF THE
INDIVIDUALS AND THEY SAID IN THE
TIME OF THE CONFINEMENT WE SAW
AN INCREASE IN BODY MASS IN BODY
WEIGHT.
AND I COULD CONTINUE SAYING MORE
INTERESTING THINGS ABOUT THESE
RELATIONSHIPS WITH NUTRITION AND
SLEEP AND CARDIOVASCULAR
RESILIENCE BECAUSE OF THE TIME.
THANK YOU SO MUCH FOR YOUR
ATTENTION.
>> THANK YOU, DR. ORDOVAS.
SORRY I'M IN THE ABLE TO TURN MY
CAMERA ON.
WONDERFUL REVIEW OF PRECISION
CHRONONUTRITION AND I THINK THAT
WILL FEED NICELY THAT OUR
DISCUSSION SO I LOOK FORWARD TO
NA AS WELL.
OUR NEXT SPEAKER IS DR. PAMELA
LUTSEY FROM UNIVERSITY OF
MINNESOTA TALKING ON THE
INTERSECTION OF AGING, SLEEP AND
CARDIOVASCULAR RESILIENCE.
PLEASE TAKE IT AWAY.
>> THANK YOU FOR THE OPPORTUNITY
TO SPEAK HERE TODAY.
THESE ARE NOT MY SLIDES YET.
CAN YOU PLEASE ADVANCE?
AND AGAIN.
I'LL TALK ABOUT THE INTERSECTION
OF AGING AND SLEEP RESILIENCE.
IN AGING WE'LL TALK ABOUT
CHRONOLOGICAL AND BIOLOGICAL AGE
AND FOR SLEEP WE'LL TALK ON
SLEEP DISTURBANCES AND CIRCADIAN
RHYTHMS.
YOU CAN GO AHEAD TO THE NEXT
ONE.
AGE IS A STRONG RISK FACTOR FOR
CARDIOVASCULAR DISEASE SO I
WON'T TAKE TIME TO BELABOR THIS
FURTHER.
AGING HAS IMPORTANT ASSOCIATIONS
WITH SLEEP ACROSS THE LIFE
COURSE.
ONE EXAMPLE IS DISPLAYED IN THIS
FIGURE WHICH COMES FROM A
META-ANALYSIS OF 65 STUDIES THAT
INCLUDED OVER 3500 PARTICIPANTS
AND WHERE SLEEP ARCHITECTURE WAS
ASSESSED USING POLY SONOGRAPHY.
PARTICIPANTS IN THIS ANALYSIS
WERE BETWEEN THE AGES OF 5 AND
102 YEARS.
ON THE X AXIS 5 IS ON THE FAR
LEFT AND 85 IS YEARS ON THE FAR
RIGHT.
SO AGE IS ACROSS THE BOTTOM IN
TIME IN SLEEP TIME IN MINUTES ON
THE Y AXIS.
FIRST IMPRESSIONS THERE'S A
CLEAR DECLINE IN TOTAL TIME
SLEEPING ACROSS THE LIFE COURSE
HOWEVER, IT'S IMPORTANT TO TAKE
A CLOSER LOOK.
I'VE SEPARATED OUT
CHARACTERISTICS WITH SLEEP
ARCHITECTURE.
IN THE TOP SECTION ABOVE THE
BLUE LINE I ADDED IS SLEEP
LATENCY THE AM OF TIME IT TAKES
TO FALL ASLEEP AND THAT'S
CONSISTENT ACROSS THE LIFE
COURSE.
IMMEDIATELY ABOVE THE BLUE LINE
IS WAKE AFTER SLEEP ONSET IT
INCREASES DRAMATICALLY WITH AGE.
OLDER INDIVIDUALS HAVE MORE
AWAKENINGS DURING THE NIGHT.
WHEN YOU THINK OF TOTAL SLEEP
TIME IT INCREASES MORE
DRAMATICALLY IF YOU LOOK AT
TRAJECTORY OF THE BLUE LINE THAN
THE FIGURE OVER ALL.
ANOTHER SPECIFIC ASPECT OF SLEEP
ARCHITECTURE I WANT TO CALL OUT
ARE SLOW WAVE SLEEP SHOWN BELOW
THE BLUE LINE IN BLACK HERE AND
AS YOU CAN SEE THAT DECREASES
DRAMATICALLY ACROSS THE LIFE
COURSE.
NOTE SURPRISING SLEEP COMPLAINTS
ARE RELATIVELY COMMON AMONG
OLDER ADULTS.
40% TO 70% OLDER ADULTS REPORT
SLEEP PROBLEMS AND INSOMNIA AND
DAYTIME SLEEPINESS ARE THE MOST
COMMON SLEEP COMPLAINTS AND DATA
SHOW 46% OF ADULTS 65 TO 74
YEARS REPORT INSOMNIA AND 75 TO
84 YEARS REACHES 50%.
SOME CHANGES ARE NORMAL.
THERE ARE OTHER FACTORS MORE
COMMON IN OLDER ADULTS THAT CAN
EXACERBATE THE SITUATION BY
SLEEP ARCHITECTURE.
SOME ARE PATHOLOGICAL FACTORS
LIKE ARTHRITIS, DIGESTIVE
DISEASE AND HEART FAILURE AND
OLDER ADULTS ARE LIKELY TO TAKE
MEDICATIONS AND DEPRESSANTS AND
STIMULANTS HAVE IMPACT AND
SUBSTANCE USE AND DEPRESSION OR
ANXIETY AND EVEN PSYCHOSOCIAL
FACTORS SUCH AS WAKING UP TO
HELP IF YOU'RE IN A CAREGIVING
ROLE TO HELP SOMEONE ELSE CAN
INFLUENCE SLEEP IN OLDER
INDIVIDUALS.
SIMILARLY OBSTRUCTIVE SLEEP
APNEA PREVALENCE IS KNOWN TO
CHANGE WITH AGE AND OSA RELATE
TO INTERMEDIATE AND PAUSES IN
BREATHING DURING SLEEP.
DATA ARE FROM THE SLEEP HEART
STUDY.
AGE IS ON THE Y AXIS FROM 35 TO
85 YEARS AND PREVALENCE OF AGE
ARE GREATER THAN GREATER THAN
15, MODERATE OR SEVERE SLEEP
APNEA ON THE Y AXIS.
YOU SEE AN INCREASE IN THE
PREVALENCE OF OSA UNTIL ABOUT 65
YEARS WHERE IT PLATEAUS.
WE'VE TALKED ABOUT HOW SLEEP AND
AGE WHAT SORTS OF PATTERNS YOU
SEE.
HOWEVER, THERE'S ALSO EVIDENCE
THAT SLEEP OR FORCED SLEEP MAY
HAVE A DIRECT IMPACT ON
BIOLOGICAL AGING.
WHEN WE THINK ABOUT AGING, WE
THINK IT AS A PHYSIOLOGICAL
DISTURBANCE LEADING TO GREATER
FUNCTIONAL DECLINE AND INCREASE
OF DEATH.
HOWEVER, INDIVIDUALS WITH THE
SAME CHRONOLOGICAL AGE OR SAME
YEARS OF BEING ALIVE CAN HAVE
DIFFERENT PHYSIOLOGICAL STATUS
AND THIS CAN BE REFERRED TO AS
BIOLOGICAL AGING.
SO TO PUT IT SIMPLY,
CHRONOLOGICAL AGING REFERS TO
THE NUMBER OF YEARS SINCE BIRTH
AND BIOLOGICAL AGING REFERS TO
PHYSIOLOGIC CHANGES THAT OCCURS
IN THE CELLS.
AGE ACCELERATION IS AN IMPORTANT
CONCEPT AND THIS IS THE
DISCREPANCY BETWEEN AGE AND
BIOLOGICAL MARKERS AN THIS SHOWS
BIOLOGICAL AGE ON THE Y AND THE
DOTTED LINE ABOVE THE SOLID
DIAGONAL LINE INDICATES AGE
ACCELERATION.
AN INDIVIDUAL THERE WOULD HAVE
GREATER BIOLOGICAL AGE RELATIVE
TO THEIR ACTUAL CHRONOLOGICAL
AGE.
THERE ARE MANY PATHWAYS THROUGH
WHICH POOR SLEEP MAY IMPACT
BIOLOGICAL AGING SOME ARE
RELATED TO DNA DAMAGE, TELOMERE
SHORTENING AND MYOCON DRIAL
FUNCTIONING AND THE NEXT FEW
SLIDES I'LL TALK ABOUT SOME DATA
IN HUMANS RELATING TO THE FIRST
THROW PATHWAYS HIGHLIGHTED.
SOME RELATE TO SLEEP APNEA MAY
HAVE REPETITIVE AROUSALS AND
SLEEP FRAGMENTATION AND THESE
ARE THOUGHT TO SIMULATE
OXIDATIVE STRESS, INFLAMMATION
AND SYMPATHETIC STRESS AND
ENDOTHELIAL DYSFUNCTION.
SO THE FIRST DATA I'M SHOWING
FROM THE MULTI-ETHNIC STUDY OF
ATHEROSCLEROSIS.
THERE ARE TWO PAPERS USING MAY
TA DATA I'LL SHARE.
BOTH INCLUDE A CROSS-SECTIONAL
ANALYSIS OF 600 TO 700
INDIVIDUALS AND THE PARTICIPANTS
HAD A MEAN AGE OF 69 YEARS WITH
A RANGE OF 45 TO 93.
THE FIRST STUDY FOUND SLEEP
APNEA WAS ASSOCIATED WITH
SHORTER LEUKOCYTE TELOMERE LINK.
ON THE Y IS THE LEUKOCYTE
TELOMERE LINK AND REPRESENT
DIFFERENT DEGREES OF SLEEP
APNEA.
DARK GRAY AND MODERATE IN LIGHT
GRAY AND THEN THE ZEBRA DIAGONAL
STRIPPED BAR SHOWS SEVERE SLEEP
APNEA.
INDIVIDUALS WITH SEVERE SLEEP
APNEA HAS SIGNIFICANTLY SHORTER
TELOMERES IN THE CROSS SECTIONAL
ANALYSIS.
THE OTHER PAPER FOUND A HIGHER
HYPONEA INDEX WERE ASSOCIATED
WITH HIGHER EPIGENETIC AGE AND
THERE WASN'T A CLEAR EXPLANATION
WHY IT WAS HIGHER IN WOMEN.
AND THE INITIATIVE LOOKED AT
INSOMNIA SYMPTOMS IN AN ANALYSIS
CROSS-SECTIONAL AGAIN OF ABOUT
2,000 WOMAN WITHIN THE AGMEAN A
OF 69 YEARS AND INSOMNIA
SYMPTOMS WERE ASSOCIATED WITH
LATE DIFFERENTIATED T CELLS
FOCUSSING ON AGE ACCELERATION IN
THE FIGURE, YOU SEE AGE
ACCELERATION ON THE Y AXIS AND
THEN YOU CAN LOOK COMPARED TO
INDIVIDUALS WITH NO INSOMNIA
SYMPTOMS, THOSE WITH 1 TO 2 OR 3
IT 4 HAD ABOUT A ONE-YEAR
ACCELERATION IN EPIGENETIC AGING
AND THOSE WITH FIVE SYMPTOMS HAD
ABOUT A 1.8 YEAR ACCELERATION IN
EPIGENETIC AGING.
THEY LOOKED AT SHORT SLEEP
DURATION AND IT HAD NO
ASSOCIATION WITH THE T CELLS.
AS MENTIONED EARLIER, IMMUNITY
AND INFECTION IS ANOTHER PATHWAY
WHICH MAY LINK AGE, SLEEP AND
CARDIOVASCULAR RESILIENCE.
WE KNOW THAT AGING AND POOR
SLEEP ARE BOTH ADVERSELY
ASSOCIATED WITH IMMUNITY AND
INFLAMMATION AND INDIVIDUALS
WITH OSA ARE LIKELY TO
EXPERIENCES SILENT EXAS
PAIRATIONS AND LIKELY TO HAVE
GASTROINTESTINAL REFLEX
POTENTIAL LEADING TO ORGANISMS
IN THE AIRWAYS.
SO FAIRLY RECENTLY WE DAYEDED TO
EVALUATE WHETHER SEVERE OSA WAS
ASSOCIATED WITH RISK OF
DEVELOPING PNEUMONIA IN THE
CONTEXT OF ATHEROSCLEROSIS
STUDY.
INDIVIDUALS WITH SEVERE OSA WERE
AT 90% GREATER RISK OF PNEUMONIA
AND DOSE RESPONSE RELATIONSHIP
WHEREBY THOSE WITH SEVERE OSA
WERE AT GREATEST RISK OF
PNEUMONIA DEPICTED ON THE RIGHT.
AND CIRCADIAN RHYTHMS AS WAS
MENTIONED IN THE PRIOR LECTURE
ALSO CHANGE WITH AGE.
AND WHAT WE SEE IS THAT AS AN
INDIVIDUALS AGE THERE TENDS TO
BE A SHIFT IN PREFERENCE TOWARDS
MORNING CHRONOTYPE AND OLDER
ADULTS PREFERRING BED TIMES ONE
TO TWO HOURS EARLIER THAN
YOUNGER ADULTS AND NOT ALL THIS
IS PATHOLOGICAL BUT IT CAN BE
AND ADVANCED SYNDROME DISORDERS
MORE COMMON IN OLDER ADULTS NOW
THERE'S SEVERAL FACTORS
UNDERLYING AGE-RELATED SHIFTS IN
CIRCADIAN RHYTHMS.
SOME INCLUDE DECREASES IN
MELATONIN SECRETION AND
METABOLIC AND TEMPERATURE
RHYTHMS, CHANGES IN THE
CIRCADIAN CLOCK GENE EXPRESSION
AND ALSO A REDUCED SENSITIVITY
TO ENVIRONMENTAL CUES THAT
TRIGGER WHEN WE SHOULD GO TO
SLEEP OR NOT SUCH AS LIGHT.
SO THINKING SPECIFICALLY ABOUT
AGE-RELATED LATE AND POTENTIAL
IMPLICATIONS FOR CARDIOVASCULAR
RESILIENCE, WE SEE THAT AS
PEOPLE AGE THERE TENDS TO BE
LENS YELLOWING WHICH REDUCES
SENSITIVITY TO LIGHT AND THE
DEGREE OF DENSE YELLOWING HAS
BEEN ASSOCIATED WITH SLEEP
DISTURBANCES IN OLDER ADULTS.
ADDITIONALLY INDIVIDUALS WITH
CATARACTS TEND TO HAVE POORER
SLEEP QUALITY RELATIVE TO THOSE
WITHOUT CATARACTS.
THERE'S BEEN STUDY LOOKING AT
THOSE WITH CATARACT STUDY BUT
THEY'VE BEEN INCONCLUSIVE TO
DATE.
THERE'S SEVERAL PATHWAYS TO
WHICH THIS CAN HAPPEN.
CIRCADIAN RHYTHMS ARE KNOWN TO
IMPACT THE CORTEX AND THEREFORE
COULD HAVE A ROLE ON COGNITIVE
FUNCTIONS AND ALSO IT'S INVOLVED
WITH METABOLISM THROUGH ACTIONS
ON THE LIVER, KIDNEY AND
PANCREAS AND ADDITIONALLY IT HAS
ASSOCIATIONS WITH IMMUNITY AND
INFLAMMATION.
SO ALL OF THESE PATHWAYS MAY
COME TOGETHER RESULTING IN
CIRCADIAN RHYTHMS HAVING A ROLE
IN RELATION TO CARDIOVASCULAR
RESILIENCE IN OLDER POPULATIONS.
SO TO BRING IT TOGETHER THERE'S
CLEAR SECTIONS BETWEEN AGING,
SLEEP AND CARDIOVASCULAR
RESILIENCE.
AND THAT'S BEEN DEMONSTRATED
EVEN WITH THE MOST DESCRIPTIVE
DATA SHOWING THE CHANGES IN
AGING THAT OCCUR WITH SLEEP AND
CARDIOVASCULAR RISK.
THIS IS A STATEMENT PUBLISHED IN
2024 I WAS VICE CHAIR WHERE WE
LOOKED AT THE IMPACT OF SLEEP
DISORDERS AND SLEEP DISTURBANCES
ON BRAIN HEALTH.
AND IN THE FIGURE FROM THE PAPER
YOU SEE MANY PATHWAYS WE'VE BEEN
TALKING ABOUT RELATING TO
CEREBRAL VASCULAR DISEASE OR
HEALTH.
HIGHER INFLAMMATION WITH HIGHER
DISORDERS.
HOWEVER, THERE ARE OTHER
PATHWAYS THAT LINK DIRECTLY
POTENTIALLY TO ALZHEIMER'S
DISEASE AND RELATED DEMENTIAS.
SO IN SUM, I THINK THERE ARE
CLEAR INTERSECTIONS BETWEEN AGE,
SLEEP AND CARDIOVASCULAR
RESILIENCE AND I BELIEVE
RIGOROUS RESEARCH IS NEEDED TO
EVALUATE WHETHER TREATMENT OF
SLEEP DISORDERS AND OPTIMIZING
SLEEP HIYGIENE CAN IMPROVING
CARDIOVASCULAR RESILIENCE AND
IMPROVED AMONG INDIVIDUALS.
THANK YOU AND ARE THERE ANY
QUESTIONS?
>> THANK YOU.
I THINK WE'LL TAKE QUESTIONS
DURING THE Q&A COMING UP AT THE
TOP OF THE HOUR SO PLEASE STICK
AROUND FOR THAT AND I'LL HAVE
QUESTIONS FOR YOU AS WELL.
SO THE LAST SPEAKER IN THIS
MORNING'S SESSION WILL BE
DR. VICTORIA BAUTCH FROM THE
UNIVERSITY OF NORTH CAROLINA
SPEAKING ON CONCEPTUALIZING
CARDIOVASCULAR RESILIENCE AND
FOR OUR FOLKS JOINING, PLEASE DO
STAY AT THE TOP OF THE HOUR
WE'LL HAVE 30 MINUTES FOR
QUESTION AND ANSWER SESSION AND
DON'T FORGET TO PUT YOUR
QUESTIONS IN THE Q&A IN THE ZOOM
WHICH YOU SHOULD SEE AT THE
BOTTOM OF YOUR SCENE AND WE'LL
ABLE
ABLE TO CURATE THOSE FROM
THERE.
PLEASE TAKE IT AWAY.
>> THANK YOU VERY MUCH.
I'D LIKE START OUT BY THINKING
THE ORGANIZERS FOR ALLOWING ME
TO PRESENT A FEW THOUGHTS ON
CONCEPTUALIZING CARDIOVASCULAR
RESILIENCE.
I ALSO WANT TO APOLOGIZE FOR
COMING IN A LITTLE BIT LATE.
SO SOME OF MY INFORMATION MAY
HAVE OVERLAP.
AND I WANT TO START OUT BY
SAYING I'M GOING PRESENT A FEW
THOUGHTS AND IDEAS FROM THE
PERSPECTIVE OF MY PLACE AS A
CELL MOLECULAR GENETIC VASCULAR
BIOLOGIST AND THINKING MORE
ABOUT CELLS AND TISSUES AND
MOLECULAR PATHWAYS AND HOW THOSE
CAN INTEGRATE INTERN WITH
SMALLER AND LARGER SCALES IN
TERMS OF THINK ABOUT THIS.
I'D LIKE TO START BY GIVING A
QUICK OVERVIEW.
WE'LL QUICKLY DEFINE
CARDIOVASCULAR RESILIENCE WITH
AN EMPHASIS AND ASPECTS AND
DISCUSS BRIEFLY THE CONCEPT OF
SCALING AND BIOLOGY AND
CARDIOVASCULAR BIOLOGY AND GO
OVER RESILIENCE CONCEPTS FROM
THE PERSPECTIVE OF THE CELL AND
SPECIFICALLY WHAT WE WORK ON THE
VASCULAR ENDOTHELIAL CELLS THAT
LINES THE BLOOD VESSELS IN OUR
BODY AND END UP WITH INTERESTING
VIGNETTE ON SCALING CIRCADIAN
RHYTHMS IN BIOLOGIES.
SO IF THIS IS ALREADY -- I'D
LIKE TO EITHER DEFINE OR
REDEFINE IF IT'S ALREADY BEEN
DISCUSSED THE CONCEPT OF
RESILIENCE THAT WAS DEFINED BY
AN NHLBI WORKSHOP.
RESILIENCE IS THE ABILITY OF
LIVING SYSTEMS TO SUCCESSFULLY
MAINTAIN OR RETURN TO
HOMEOSTASIS IN RESPONSE TO
PHYSICAL, MOLECULAR, INDIVIDUAL,
SOCIAL, SOCIETAL OR
ENVIRONMENTAL STRESSORS OR
CHALLENGES.
SO THAT'S A PRETTY BIG BUCKET.
THERE'S A LOT OF THINGS IN
THERE.
IT INCLUDES EVERYTHING AND
RIGHTFULLY SO THERE MOLECULAR
INTERACTIONS TO SOCIAL AND
SOCIETAL.
WE SEE COMPLEXITY IN HOW WE
DEFINE BIOLOGICAL RESILIENCE.
WHEN WE THINK ABOUT BIOLOGICAL
SYSTEMS THERE'S NUMEROUS SYSTEMS
WITH RESPONSES AND OUTPUTS TO
THOSE RESPONSES FROM ADAPTATION
TO TOLERATION AND EVENTUALLY
LEADING TO EITHER THE
PRESERVATION OF HOMEOSTASIS OR
COMING BACK TO HOMEOSTASIS.
THESE ARE BIG TERMS.
AGAIN, PART OF THE REASON IS
BECAUSE WE'RE RUNNING INTO THE
CONCEPT OF SCALE.
SCALE AND BIOLOGY.
THE SCALE IN GENERAL GOES
THROUGH A NUMBER OF DIFFERENT
SCENARIOS FROM MOLECULES TO
STRUCTURED WITHIN CELLS TO THE
CELLS THEMSELVES.
TO BUILDING UP TISSUES AND
BUILDING HOME TO ORGANS AND
ORGANISMS.
THAT'S JUST IN THE BIOLOGICAL
REALM.
THOSE ARE VAST DIFFERENCES IN
SCALES.
IF YOU LOOK AT THE LEFT YOU'LL
SEE THE ORGANISM AND THE ORGANS.
IF YOU LOOK IN THE MIDDLE YOU'LL
SEE THOSE ARE BLOOD VESSELS WITH
VASCULAR ENDOTHELIAL CELLS AND
YOU'LL SEE STRUCTURES WITHIN THE
ENDOTHELIAL CELLS THAT ARE
IMPORTANT FOR THEIR FUNCTION AND
BLOOD VESSELS.
THE CONCEPT OF SCALE, WHICH IS
VERY DIFFICULT THEN TO IMPOSE A
SINGLE DEFINITION, I THINK, OF
CARDIOVASCULAR RESILIENCE
BECAUSE IT NEEDS TO BE DEFINED
BY THE SCALE ALSO EXTENDS TO
VARIATIONS IN THE TIMING.
SO THERE'S SCALES IN TIMING.
ONE EXAMPLE OF CARDIOVASCULAR
RESILIENCE AGAIN FROM THE
PERSPECTIVE OF THE BLOOD VESSELS
IS VASO DIALATION AND
CONSTRICTION.
THE ABILITY TO REGULATE BLOOD
FLOW BY VESSELS BECOMING LARGER
OR SMALLER IN DIAMETER AND THIS
IS A PROCESS THAT OCCURS OVER
SECONDS OR MINUTES.
AND ONE QUESTION THAT COMES UP
WITH THIS IS WHY IS VASCULAR
TONE DIMINISHED AS IT NORMALLY
IS WITH AGE?
ANOTHER TYPE OF CARDIOVASCULAR
RESILIENCE IS INFLAMMATION AND
AGAIN THAT MAY HAVE BEEN TALKED
ABOUT EARLIER.
BUT THERE ARE BOTH ACUTE
RESPONSES INFLAMMATORY RESPONSES
AND RETURN TO HOMEOSTASIS AND
RESILIENCE IS BUILT IN AND THEN
THERE'S CHRONIC RESPONSES WHERE
IT DOESN'T HAPPEN.
ONE QUESTION THAT COMES FROM NA
IS WHY DO COVID-19 PATIENTS SUM
SUCCUMB TO THE RUN AWAY
INFLAMMATION WE ALL LEARNED
ABOUT DURING THE PANDEMIC.
I'M GOING TO DISCUSS A COUPLE
VIGNETTES THAT DEMONSTRATE
CARDIOVASCULAR RESILIENCE AND
CARDIOVASCULAR RESILIENCE AGAIN
FROM THE PERSPECTIVE OF THE
CELLS IN THE VASCULATURE AND
SPECIFICALLY THE ENDOTHELIAL
CELLS THAT LINE ALL THE BLOOD
VESSELS.
SO I'M GOING TO TRY TO CONVINCE
YOU THAT RESILIENCE IS OCCURRING
AT THE CELLULAR LEVEL BEFORE WE
BUILD ON THE OTHER SCALES GOING
OUTWARD AND EVEN BEFORE WE DELVE
MORE INTO OTHER SCALES THAT ARE
GETTING EVEN MORE MOLECULAR.
THE FIRST VIGNETTE I'D LIKE TO
PRESENT SAY CONCEPT OF SET
POINTS IN FLOW RESPONSES.
IN TERMS OF THE ORGANISM OR IN
TERMS OF THE VASCULATURE.
THE CONCEPT WHERE INCREASES OR
DECREASES IN BLOOD FLOW WILL
LEAD TO CHANGES IN THE DIAMETER
OF THE BLOOD VESSEL TO
ACCOMMODATE THAT BLOOD FLOW AND
KEEP THE SHEER FACTOR OR THE
FORCE OF THE BLOOD GOING OVER
THE ENDOTHELIAL CELLS IN THE
LUMEN OF THE BLOOD VESSELS AND
KEEP THAT THE SAME.
YOU CAN SEA ON THE LEFT THE
TYPICAL VASCULATURE AND WITH AN
OCCLUSION YOU GET COLLATERAL
VESSELS INCREASE IN THEIR TIME
TER AND EVENTUALLY THE GOAL FOR
THE VESSEL IS FOR THE SHEER FLOW
TO GO BACK TO HOMEOSTASIS TO GO
BACK TO WHERE IT WAS BEFORE.
WORK BY MANY PEOPLE IDENTIFIED
THE SET POINT IN THE CONTEXT OF
THE INDIVIDUAL ENDOTHELIAL CELLS
AND I'LL SHOW YOU THE DATA THAT
SUPPORTS THE IDEA THAT
INDIVIDUAL ENDOTHELIAL CELLS
HAVE AN INTERNAL SET POINT THAT
S TO BLOOD FLOW.
SO ON THE TOP LEFT ARE LYMPHATIC
ENDOTHELIAL CELLS THAT NORMALLY
SEE LOW SHEER LAMMI -- LAMITER
FLOWS AND THE RED CIRCLES SHOW
THE POINT AT WHICH THE CELLS
BEGIN ALIGNING TO THE FLOW IS
VERY LOW FOR LYMPHATIC
ENDOTHELIAL CELLS AND HIGHER FOR
VENUS ENDOTHELIAL CELLS WHERE
WHERE THEY RESPOND TO THE FLOW
IS DIFFERENT FOR THE DIFFERENT
CELL TYPES.
WHAT'S DIFFERENT ABOUT THEM?
IT TURNS OUT A RECEPTOR THAT IS
PART OF A MECHANO TRANSDUCTION
COMPLEX IS EXPRESSED AT HIGHER
LEVELS IN THE LYMPHATIC ENDO
THAN VENUS ENDOTHELIAL CELLS.
AND ON THE TOP WHEN MARTIN
SCHWARTS AND HIS COLLEAGUES
REMOVE THAT MECHANO TRANSDUCTION
RECEPTOR FROM THE LYMPHATIC THE
SET POINT CHANGE TO BECOME MORE
LIKE VENUS ENDOTHELIAL CELLS AND
WHEN THE RECEPTOR WAS
UPREGULATED THEIR SET POINT
SHIFTS DOWN TO BE BECOME LIKE
LYMPHATIC ENDOTHELIAL CELLS.
THIS IS EVIDENCE WITHIN THE
CELLS THERE'S A RESPONSE TO FLOW
THAT'S ULTIMATELY PROBABLY
PROPAGATING TO THE PHYSIOLOGICAL
LEVEL.
SO, SOME QUESTIONS THAT ARISE
FROM THIS VIGNETTE ARE HOW DO
INTRINSIC EPITHELIAL CELLS
TRANSLATE TO RESPONSES AND WHAT
REGULATES EXPRESSION OF SET
POINT MACHINERY AT THE LEVEL OF
THE CELLS.
WE LOOKED AT THE ONE RECEPTOR
BUT THERE'S MORE THERE.
I'M LEAVING THE QUESTIONS FOR
MAYBE THE DISCUSSION PERIOD AND
I'LL MOVE ON.
SO THE NEXT THING I WOULD LIKE
TO DISCUSS BRIEFLY IS THE
CONCEPT OF ENDOTHELIAL CELLS AND
QUIESCENCE.
VASCULAR QUIESCENCE IS THE IDEA
THAT MOST OF THE TIME, MOST THE
ENDOTHELIAL CELLS ARE ALIGNED TO
THE FLOW FACTOR AND HAVE A LOT
OF PROPERTIES IN THE PHASE WHICH
INCLUDES BEING
ANTI-INFLAMMATORY.
ALL AS THE ASPECTS ARE IMPORTANT
FOR NORMAL FUNCTION AND NORMAL
VASCULAR HOMEOSTASIS AND FOR
VASCULAR RESILIENCE.
ONE ASPECT MY GROUP HAS RECENTLY
STARTED TO INVESTIGATE IS THE
QUALITY OF THE QUIESCENCE THAT
CURBS IN DIFFERENT BLOOD VESSELS
AND UNDER DIFFERENT CONDITIONS.
ONE QUALITY IS CALLED QUIESCENT
DEPTH THE TIME IT TAKES FOR THE
CELLS TO RE-ENTER THE CELL CYCLE
ONCE THE STIMULUS IS CHANGED OR
REMOVED.
THIS PROPERTY HAS IMPLICATIONS
IN TERMS OF THE EXCITABILITY OR
THE PROLIFERATIVE CAPACITY BUT
FOR WHICH WE KNOW VIRTUALLY
NOTHING AT THE LEVEL OF THE
VASCULATURE AND THE ENDOTHELIAL
CELLS.
THE RECENT WORK SHOWSYY -- SHOW
THIS VARIES AND YOU CAN SEE THE
CARTOON AND IF YOU LOOK AT THE
BOTTOM YOU CAN SEE QUIESCENCE
DEPTH WHICH IS -- SORRY WHAT'S
HAPPENING TO THE SLIDES.
QUIESCENCE DEPTH WHICH GOES UP
ON THE Y AXIS STARTS OUT THE
SAME FOR CELLS EXPOSED TO EITHER
ARTERIAL FLOW WHICH IS MUCH
STRONGER FLOW THAN VENUS FLOW.
IF YOU LOOK A THIRD OF THE WAY
ACROSS THE LINES ARE EQUIVALENT
AND THEN YOU SEE THE ARTERIAL
LINES START TO GO DOWN.
IF YOU GO OUT FOR 72 HOURS WE
SEE A DIFFERENCE IN THE
PARTICULAR PARAMETER PROBABLY AS
A RESULT OF MOLECULAR FLOW
MEDIATED INTERACTIONS THAT ARE
DIFFERENTIAL BETWEEN THE FLOW
RATES.
WE HAVE NO IDEA HOW THE
QUIESCENT STEP AVENFFECTS THE
PHYSIOLOGY OF THE SYSTEM.
SO SOME OF THE QUESTIONS THAT
WE'RE LEFT WITH, HOW DOES
QUIESCENCE DEPTH AFFECT
CARDIOVASCULAR RESILIENCE?
WE KNOW THERE'S A DIFFERENTIAL
PARAMETER BUT DON'T YET
UNDERSTAND HOW IT AFFECTS THE
OUTPUTS OF THE ENDOTHELIAL CELLS
AND VASCULAR TURE IN GENERAL AND
WANT KNOW WE'RE MORE OR LESS
LEAST AND THERE'S DIFFERENCES
POTENTIALLY HERE EVEN WITHIN THE
BLOOD VESSELS AND CELLS WITHIN
THE BLOOD VESSELS.
A THIRD VIGNETTE IS THE CONCEPT
OF ENDOTHELIAL CELL NUCLEAR
MECHANO TRANSDUCTION.
THE IDEA THE NUCLEUS WITHIN THE
ENDOTHELIAL CELL SAY SENSOR
IMPARTED BY BLOOD FLOW AND
PRESSURE.
WE KNOW THAT THIS SUBCELLULAR
STRUCTURE IS INVOLVED IN
RESILIENCE TO AGE-RELATED
VASCULAR INSULTS.
WE KNOW THIS BECAUSE BEAUTIFUL
WORK HAS SOUGHT TO UNDERSTAND
THIS DISEASE PROGERIA THAT
LEAVES PATIENTS WITH A
STRUCTURALLY DEFICIENT NUCLEI
ALL OVER THE BODY EARLY ONSET
VERY SEVERE CARDIOVASCULAR
DISEASE.
UNFORTUNATELY VERY EARLY DEATH
ALONG WITH OTHER ASPECTS OF
AGING.
THE RESILIENCE CAPACITY OF THESE
INDIVIDUALS IS VERY VERY MUCH
REDUCED.
SOME OF THE WORK UNDERSTANDING
HOW GET FROM THIS MUTATION IN
THE INNER NUCLEAR STRUCTURE
CALLED THE LAMINS AND THEY LINK
TO A COMPLEX THAT GOES OUT TO
THE REST OF THE CELL CALLED THE
LINK COMPLEX SHOWN ON THE FAR
LEFT AND THERE'S A NUMBER OF
COMPONENTS INCLUDING SOME
PROTEINS AND NESPRINS AND
MUTATING THE EFFECTS THROUGHOUT
THE CELLS AND THROUGH THE REST
OF THE BODY EVENTUALLY.
AND SOME OF THE WORK DONE IN
OTHER LABS IN THE MIDDLE SHOW
ONE OF THE COMPONENTS OF THE
LINK COMPLEX ACCUMULATES
ABNORMALLY AROUND THE NUCLEUS OF
CELLS OVEREXPRESSING THE LAMIN
CALLED PROGERIN AND FIBROBLASTS
FROM PROGERIA PATIENTS GO INTO
PERMANENT CELL CYCLE ARREST.
YOU CAN SEE WITH THE BLUE CELLS
IN THE UPPER RATE AND WHEN A
LINK COMPLEX COMPONENT IS
DELETED OR REDUCED, THAT
SENESCENCE PHENOTYPE IS
ABROGATED.
THIS SUGGESTS THERE'S
COMMUNICATION THERE.
WE'VE RECENTLY STARTED TO
UNDERSTAND HOW THE LINK COMPLEX
OPERATES IN THE VASCULATURE
BEFORE THE PROGERIN COMES ALONG
TO START LEADING TO DYSFUNCTION.
WE FOUND THERE ARE EFFECTS WITH
NORMAL ANGIOGENESIS WITH LACK OF
PROGRESSION YOU CAN SEE IN THE
BOTTOM SLIDES IN THE POST NATAL
RETINA WHEN ONE LINK COMPLEX
COMPONENTS IS SPECIFICALLY
DELETED FROM THE VASCULAR
ENDOTHELIAL CELLS.
THERE'S IMPORTANT MOLECULAR
MECHANISMS WE WOULD LIKE TO
BETTER UNDERSTAND AND THEN OF
COURSE PULL OUT TO THE BIGGER
ARENA.
IF I COULD HAVE THE NEXT SLIDE.
SO SOME OF THE QUESTIONS THAT
WE'RE LEFT WITH IS HOW DO
PROGERIN LINK ACTIONS COMPROMISE
ENDOTHELIAL CELL RESILIENCE?
I THINK IT'S PRETTY DAM --
DRAMATIC BUT DON'T KNOW HOW AND
THERE ARE AFFECTS REGARDING
ENDOTHELIAL CELLS THAT LINE THE
LUMEN BLOOD VESSELS AND THERE'S
AFFECTS THAT ARE IMPORTANT FOR
THE PATHOLOGY.
WHAT I'D LIKE TO DO IS FINISH BY
PRINTING A FINAL VIGNETTE THAT
HAS TO DO WITH LOOKING AT THE
PERSPECTIVES IN THE BLOOD
VESSELS IN THE BODY AND WHAT'S
GOING ON WITH CIRCADIAN RHYTHM.
IS THERE EVIDENCE OF THIS SORT
OF PROCESS AT THE CELLULAR
LEVEL.
THIS BEAUTIFUL PAPER
INVESTIGATES THE ROLE OF
TRANSCRIPTION FACTOR AND ITS
AFFECT ON VASCULAR ENDOTHELIAL
CELLS AND PROCESSES.
IF YOU LOOK AT THE LOWER LEFT
YOU'LL SEE THE TRANSCRIPTION
FACTOR IS EXPRESSION IS
REGULATED ACCORDING TO TIME AND
CYCLE AND IF YOU LOOK OVER
ACROSS ON THE BO BOTTOM YOU'LL
SEE SEVERAL GENES INVOLVED IN
THE CELL CYCLE ARE ALSO
CO-REGULATED OR REPRESSED BY THE
UP REGULATION OF THE
TRANSCRIPTION FACTOR AND IT'S
REGULATING CELL CYCLE GENES.
AND THEN FINALLY WHEN THIS
PARTICULAR TRANSCRIPTION FACTOR
WAS REMOVED FROM THE DEVELOPING
VASCULATURE IN THE POST NATAL
RETINA IN THE UPPER RIGHT YOU'LL
SEE THE RESPONSE IS A LACK OF
VASCULAR PROGRESSION SIMILAR TO
THE LINK OF THE COMPONENT
THERE'S CLEARLY AN EFFECT ON
VASCULAR PROCESSES OF THIS
TRANSCRIPTION FACTOR OF COURSE
AT THIS LEVEL IT ISN'T KNOWN
WHETHER THAT'S ENTRAINED BY THE
NORMAL CIRCADIAN RHYTHMS AND IF
SO HOW THAT HAPPENS.
>> TWO-MINUTE WARNING, SAESPEAK.
>> THANK YOU VERY MUCH.
THE QUESTIONS WE'RE LEFT WITH
HERE IS HOW IS THE CELLULAR
CIRCADIAN CLOCK SET UP IN
VASCULAR ENDOTHELIAL CELLS.
THIS IS AMAZING BECAUSE THESE
ARE NOT CELLS IN THE BODY PER
SE.
THEY'RE SITTING IN A DISH IN
TERMS OF THE FIRST WORK I
PRESENTED.
AND THEN FINALLY, AND VASCULAR
CELLS TRAINED IN OUR BLOOD
VESSELS TO THE ORGANISM AND TO
THE ENVIRONMENT THAT THE
ORGANISM IS EXPERIENCING AT ANY
PARTICULAR POINT IN TIME.
AND THEN WHAT ARE THOSE
ENTRAINMENT MECHANISMS.
THESE ARE INTERESTING QUESTIONS
FROM THE SCALE OF THE CELL AND
MOLECULAR PATHWAYS.
THE CHALLENGE IS TO MOVE FROM
THIS VERSION FROM THE HIGHER
LEVELS TO THE LOWER LEVELS.
TO THE CONCLUSIONS IS
CARDIOVASCULAR RESILIENCE
STRATEGIES SPAN NUMEROUS
BIOLOGICAL SCALES AND I THINK
THESE OUTCOMES NEED TO BE
DEFINED BY THE SCALE YOU'RE
WORKING WITH.
SO I DON'T THINK THERE IS A ONE
SIZE FITS ALL SPECIFIC
RESILIENCE DEFINITION.
I THINK THERE'S THE GENERIC ONE
AND NEED TO PULL THESE OUT TO
SPECIFIC SCALES BUT WE DO NEED
TO INTEGRATE THESE EVENTUALLY.
IT DOESN'T WORK IF WE STAY IN
OUR SILOS.
I'M HOPING THE WORKSHOP WHICH
I'M EXCITED ABOUT WILL HELP US
BRIDGE SOME OF THOSE SPACES.
AND ENDOTHELIAL CELLS ARE
CONTROL NODE FOR CARDIOVASCULAR
RESILIENCE WHICH I FIND EXCITING
AND CIRCADIAN RHYTHMS ARE
OPERATIONAL IN THE CELL SCALE
AND I'D LIKE TO THANK MY
COLLEAGUES WHOSE WORK I
PRESENTED HERE TODAY AND I'M
HOOP WHERE HE TO TAKE QUESTIONS
OR MOVE THINGS ALONG.
THANK YOU.
>> THANK YOU.
LET ME JUST SAY AN IF IT'S
POSSIBLE TO GET ALL FOUR OF THE
OTHER SPEAKERS BECAUSE WE'LL
HAVE A LITTLE BIT OF A
ROUNDTABLE AND DISCUSSION.
THAT WOULD BE GREAT.
I'M GOING GIVE A BRIEF COMMENT
AND OVERVIEW AND THANK YOU TO
OUR SPEAKERS FOR TALKS FROM THE
POPULATION LEVEL TO THE
INDIVIDUAL LEVEL EVEN THE
COMMUNITY LEVEL AS WELL AND THE
INDIVIDUAL LEVEL.
OF COURSE DOWN TO THE TISSUE,
CELLULAR AND MOLECULAR LEVEL AND
MAYBE A LITTLE BIT DEEPER.
I THINK WE ACCOMPLISHED THE GOAL
TO INK OF THE WHOLE SPAN OR
SCOPE OF CARDIOVASCULAR
RESILIENCE AND HOW SLEEP
INTERACTS OF DOMAINS OF HOW WE
DEFINE CARDIOVASCULAR DISEASE
AND THE CLOSE INTERACTION WITH
AGING.
I THINK WE HEARD FROM DR. COOK
SOME WONDERFUL DATA AND
PERSPECTIVES ON THE SOCIAL
DETERMINATES OF HEALTH AND
PARTICULARLY HOW THE
INTERSECTIONALITY OF RACE AND
GENDER CONSTRUCTS AND THE THINGS
THAT TRAVEL WITH THEM MAY BE
VERY IMPORTANT DETERMINATES OF
OUR ABILITY TO ACHIEVE OPTIMAL
SLEEP AND HOW IT MAY ULTIMATELY
IMPACT OUR CARDIOVASCULAR
RESILIENCE AND OPENS UP
QUESTIONS AROUND THE POLICY
ANGLES WE MIGHT USE AS LEVERS TO
IMPROVE SLEEP AND CARDIOVASCULAR
RESILIENCE.
WONDERFUL DATA LOOKING AT
CHRONONUTRITION AND THE
GENE-ENVIRONMENT INTERACTION.
THERE'S DIFFERENT GENOTYPES THAT
RESPOND TO DIFFERENT DESIGNS TO
HELP PEOPLE ACHIEVE OR MAINTAIN
OPTIMAL WEIGHT LEVELS AND BY
EXTENSION LEADING TO
CARDIOVASCULAR HEALTH AND
RESILIENCE.
LOVELY DATA FROM DR. ORDOVAS
THERE.
AND THINKING ARE THERE CLINICAL
LEVERS WE MIGHT USE TO TRY TO
IDENTIFY THOSE INDIVIDUALS WHO
WOULD RESPOND TO DIFFERENT TYPES
OF EATING PATTERNS IN TERMS OF
TIME.
FROM DR. LUTSEY WE SAW CHANGES
THAT HAPPEN WITH SLEEP AND AGING
AND THE INTERSECTIONS BY
EXTENSION HAPPEN WITH DIFFERENT
TYPES OF CARDIOVASCULAR DISEASE
AND LOVELY DATA LOOKING AT
BIOLOGICAL VERSUS CHRONOLOGICAL
AGING AND HOW WE CAN TEASE THOSE
OUT AND A QUESTION I HAD WAS CAN
WE DISSECT AGING FROM
CARDIOVASCULAR AGING?
ARE THEY DIFFERENT THINGS OR
SAME THINGS?
KNOW THE CARDIOVASCULAR SYSTEM
IS IMPORTANT FOR THE ENTIRE
BODY.
AND FINALLY, A LOVELY TALK AT
THE END FROM DR. BAUTCH WHO
ANTICIPATED SOME QUESTIONS OF
COURSE CARDIOVASCULAR RESILIENCE
HAS TO BE DIFFERENT DEPENDING ON
YOUR PERSPECTIVE.
ARE YOU THINKING AT THE
POPULATION LEVEL OR COMMUNITY OR
INDIVIDUAL OR ORGAN SYSTEM OR
TISSUE OR CELL OR MOLECULE.
AND I THINK THAT MAY BE ONE OF
THE BEST THINGS THAT COULD COME
OUT OF THIS WORKSHOP TO HAVE AN
INTEGRATIVE RESILIENCE OF
CARDIOVASCULAR RESILIENCE THAT
CAN EXPAND AND CONTRACT
DEPENDING ON THE SCOPE OR SCALE.
I WANT TO THANK ALL THE
SPEAKERS.
I THINK OUR TEAM IS LOOKING
FORWARD TO CURATING YOUR
QUESTI
QUESTIONS FOR OUR PARTICIPANTS
TO PUT YOUR QUESTIONS IN THE Q&A
AND WE'LL BE SURE TO ADDRESS
THEM.
I PUT TOGETHER A FEW THINGS I
THOUGHT MIGHT JUICE THE
DISCUSSION AND DO A ROUND ROBIN
ON THE PANEL.
THINKING HOW MUCH OF
CARDIOVASCULAR RESILIENCE IS
INTRINSIC AND HOW MUCH IS
MODIFIABLE AND WHAT LEVERS DO WE
HAVE TO ADDRESS ANY MODIFIABLE
PORTIONS.
>> SO I'VE BEEN THINKING ABOUT
THIS A LOT SINCE THE REPORT FROM
THE WORKING GROUP CAME OUT.
I THINK THAT THERE'S TWO LEVELS
WHEN YOU THINK BIT AND A LOT OF
THE WORK WE SAW OR THE
PRESENTATIONS WE SAW TODAY
PEOPLE TALKED ABOUT A LOT OF
THESE MORE INTRINSIC, LESS
MODIFIABLE RESILIENCE FEATURES.
IT DOESN'T MEAN THEY'RE LESS
IMPORTANT.
I THINK IF
[NO AUDIO]
>> BUT IT'S STILL IMPORTANT AND
THE PATHWAYS ARE COMPLEX AND WE
NEED TO EMBRACE THE COMPLEXITY
AND HAVE INTRINSIC FEATURES AS
WELL AS MODIFIABLE RESILIENCE
FEATURES.
AND FOR ME AS A BIO STATISTICIAN
AND SOCIAL BEHAVIORAL SCIENTIST,
I'M TRYING TO INCREASE OUR
ABILITY TO MEASURE AND
UNDERSTAND THAT COMPLEXITY SO WE
CAN INTERVENE ON MULTIPLE
LEVELS.
IN OUR LAST PRESENTATION
TOMORROW WE'LL TALK MORE ABOUT
THIS MULTI-LEVEL APPROACH.
I KNOW IT SEEMS GENERAL BUT AND
GETTING US TO THINK OF EMBRACING
THE COMPLEXITY INSTEAD OF THE
MORE SIMPLISTIC MATH WE'VE BEEN
DOING SO FAR.
IN TERMS OF INTERVENTIONS MY
CURRENT ROV -- RO1 IS STRUCTURAL
FEATURES OF CARDIO METABOLIC
RISK INCLUDING SLEEP WITH
INDIVIDUAL LEVEL SO DAILY.
HOW DO DAILY SOCIAL DETERMINATES
OF HEALTH LIKE THE THINGS YOU
WERE TALKING ABOUT LIKE HAVING A
SUPPORTIVE STRUCTURE BUFFER THE
NEGATIVE EFFECTS.
I'M TRYING TO STRESS THERE'S
MULTIPLE LAYERS BUT WE NEED
BETTER METRICS AND NEED AN
UNDERSTANDING ABOUT AS A
SCIENTIFIC COMMUNITY EMBRACING
THIS COMPLEXITY.
SORRY THAT, WAS A LONG ANSWER
IT.
DR. ORDOVAS INTRINSIC
MODIFIABLE.
YOUR DATA SHOWS MODIFIABILITY
HERE WITH CHRONONUTRITION BUT WE
MAY NEED TO KNOW SOMETHING ABOUT
THE INDIVIDUAL BEFORE WE CAN
OPTIMIZE OUR INTERVENTION.
>> ABSOLUTELY.
WE COME BACK TO THE ONE SIZE
DOES NOT FIT ALL FOR SOME AND
THERE'S A DOMINANT FACTOR AND WE
SAW THE EXAMPLE OF THE MONOGENIC
DISORDERS AND FOR THE MOST PART
EARLY STATUS TAKE ABOUT 20%, 25%
AND THE REST IS UP TO US IN THE
WORKSHOP AND WE HAVE SEEN
ALREADY AND GOING TO SEE THE
FACTORS THAT ARE MOD FINALLYING.
THERE WAS THE TIME OF COVID.
THAT WAS AN IMPACT TO MAKE
RESILIENCE MODIFIABLE SO WE HAVE
ROOM TO WORK ON THE MODIFIABLES.
>> PERFECT, THANKS SO MUCH.
SO DR. LUTSEY, YOUR THOUGHTS ON
INTRINSIC OR MODIFIABLE.
AND IS AGING RESILIENCE THE SAME
AS CARDIOVASCULAR RESILIENCE OR
ARE THEY DIFFERENT SOMEHOW?
>> FIRST, REGARDING MODIFIABLE
OR NOT MODIFIABLE, ABSOLUTELY
MODIFIABLE AND THERE'S
OPPORTUNITIES TO SLEEP AND
CARDIOVASCULAR RESILIENCE
THINKING ABOUT AGE AND THE OTHER
SEVEN METRICS HAVE MORE RESEARCH
AND CLINICAL TRIALS EXPERIMENTAL
RESEARCH DEMONSTRATING CLEAR
CAUSAL RELATIONS AND CLINICAL
TRIALS IS AN OPPORTUNITY TO TEST
SOME OF THESE THROUGH
ENCOURAGING EXTENDING SLEEP
TIME, CORRECTING CIRCADIAN
RHYTHM AND TRAINING SLEEP APNEA
AND OTHER CONDITIONS THAT ARE
HAVE CLEAR ROLES IN
CARDIOVASCULAR RESILIENCE BUT
WHERE MAYBE YOU DON'T HAVE AS
MUCH AS TRIAL DATA AS YOU WOULD
LIKE.
TO YOUR QUESTION THEY'RE
DIFFERENT BUT INTERRELATED.
THERE'S COMMON FOUNDATIONS IN
TERMS OF SLEEP, DITE, PHYSICAL
OBESITY AND THEY LINK WITH AGING
AND IN GENERAL I THINK THERE'S
SPECIFIC THINGS TO
CARDIOVASCULAR DISEASE AND IF
YOU LOOK AT SOME OF THE AGING
THAT HAVE BEEN CREATED SOME ARE
FOR AGING IN GENERAL AND SOME DO
FOCUS ON SPECIFIC ORGANS AND
HAVE DIFFERENT ASSOCIATIONS.
I THINK DIFFERENT BUT
INTERRELATES AND THERE'S
INTERESTING WORK IN THIS RIGHT
NOW.
>> I COMPLETELY AGREE.
YOU'RE ALLOWED TO SAY BOTH ENDS
SO NO PROBLEM.
DR. BAUTCH, I LOVE YOUR
PERSPECTIVE AND WHY DON'T YOU
ANSWER THE MAIN QUESTION ABOUT
INTRINSIC OR MODIFIABLE AND IF
MODIFIABLE CAN WE CHANGE THE
FLOW TO ENHANCE CARDIOVASCULAR
RESILIENCE?
>> THAT'S AN INTERESTING IDEA.
ALONG WITH MOST OTHERS THE
GENERAL THEME IS YES, THERE IS
INTRINSIC RESILIENCE AND THAT'S
LOUD AND CLEAR WHEN YOU LOOK THE
MECHANISMS THEY'RE HARD WIRED IN
THE CELLS AND GO OUT FROM THERE.
THERE'S MODIFIABLE ASPECTS.
ONE OF THE GOALS OF THE LEVEL AT
WHICH WE AND OTHERS WORK IS
TRYING TO UNDERSTAND TRYING TO
UNDERSTAND WHAT IS MODIFIABLE
AND HOW TO MODIFY IT.
AND YOU BROUGHT UP THE IDEA OF
PERHAPS TRYING TO SOMEHOW MODIFY
THE STIMULUS AND FLOW AND
PULSITIVITY AND THERE'S WAYS TO
DO THAT AND THERE'S ALSO WAYS TO
THINK ABOUT FROM THE CELL
PERSPECTIVE CAN WE MODIFY THE
RESPONSE OF THE CELL AND THE
FIRST VIGNETTE I SHOWED CHANGING
THE CELLS IS ONE CONCEPT AND
THERE MAY BE SITUATION WHERE'S
IF YOU CHANGE THE SET POINT YOU
WOULD DEFLECT A RESPONSE OR
BRING IT BACK TO HOMEOSTASIS
MORE QUICKLY AND GOING UNDER THE
HOOD AND LOOKING AT THE
DIFFERENT PATHWAYS AND WHAT THEY
CONTRIBUTE TO THOSE RESPONSES
THEN BECOMES THE STARTING POINT
FOR THINK ALSO ABOUT HOW TO DO
MODIFIABLE THINGS WITH DRUG
TARGETS, ETCETERA.
>> PERFECT.
SO WE HAVE A QUESTION FROM THE
AUDIENCE.
I'M GOING TO GO AHEAD AND PIVOT
TO THAT.
AGAIN, I THINK WONDERFUL TALKS
AND I WANT TO MAKE SURE OUR GET
TO ENGAGE.
A QUESTION FOR YOU, I'M
WONDERING HOW ENDOTHELIAL CELLS
IN SET POINT MAY BE AFFECTED OR
ALTERED IN THE CONTEXT OF SLEEP
APNEA WHERE THERE'S INTERMITTENT
HYPOXIA DURING SLEEP.
THE SET POINTS AND HOW THEY
RESPOND IS RELATIVELY NEW.
>> I THINK THOSE ARE SOME OF THE
QUESTIONS WE WANT TO ASK AND IS
GOING REQUIRE MOVING THROUGH
DIFFERENT SCALES TO BE ABLE TO
ASK ABOUT THAT BUT AGAIN IF WE
HAVE ANIMAL MODELS AND WE CAN
MANIPULATE THE SET POINTS IN
VARIOUS WAYS, WE CAN TRY TO
ADDRESS THAT VERY INTERESTING
QUESTION.
THANK YOU.
>> THANK YOU.
DR. COOK, I SEE A QUESTION THAT
IS PROBABLY BEST TAILORED TO
YOU.
THE OCCUPATIONAL SEGREGATIONAL
ASPECT IS A SUBSET OF SOCIO
ECONOMIC DECISION AND THINGS YOU
WERE TALKING ABOUT AND ADVERSE
OPPORTUNITIES FOR SLEEP AND
EXERCISE INCLUDE SHIFT WORK,
WORKING TWO PLUS PART-TIME JOBS
AND SO ON.
HOW CAN WE MODIFY THOSE THINGS,
IF WE MODIFY THOSE THINGS CAN
EXPECT IMPROVEMENTS IN
CARDIOVASCULAR HEALTH AND
RESILIENCE?
I FORGOT WHO ALLUDED TO THE
COVID SITUATION EARLIER AND WE
SAW STRESSORS TO THE RACE AND
RACISM AND OCCUPATION PLAY OUT
CLEARLY DURING TIMES OF COVID.
ONE THING WE HAVE TAKEN FROM
THIS TIME IS HOW CHANGES IN THAT
AREA CAN HELP IN TERMS OF HEALTH
AND WELL BEING AN IN TERMS OF
SLEEP, HOPEFULLY SLEEP HEALTH AS
WELL.
WHEN YOU ASK THAT QUESTION
YOU'RE RIGHT WE NEED TO MODIFY
SOCIO POLITICAL STRUCTURES IF
WE'RE GOING TO CHANGE THESE
THINGS AND SEE AFFECTS IN SLEEP
HEALTH AND WE HAVE SO MUCH
RESEARCH ON OTHER ASPECTS OF
THIS BUT THINGS WE'RE LACKING ON
IS SLEEP AND SOCIO POLITICAL
PROTECTIVE OR RESILIENCE FACTORS
WE NEED TO FOCUS ON SO WE KNOW
SHIFT WORK IS DEFINITELY IF
YOU'RE THIRD SHIFT DETRIMENTAL
TO SLEEP HEALTH BUT WHAT'S THAT
MEAN AND FOR WHOM AND WHY AND
WHAT CULTURAL SHIFTS DO WE NEED
TO MAKE?
ALL THIS WORK WE STILL NEED TO
DO AND THE PEOPLE IN THIS AREA
THAT I'M WORKING ON ARE TRYING
TO DO MORE OF THAT WORK
ESPECIALLY IN A MORE CAUSAL
FRAMEWORK.
>> THE QUESTIONER NOTES THERE'S
SOME SNIPS BUT CAN CHANGE WITH
AGE AND WHAT'S THE SENSE OF THE
CHRONOTYPE SHOULD IDENTIFY
INDIVIDUALS WITH OLDER AGE BASED
ON THEIR CHRONOTYPE.
ARE WE ALWAYS EVENING OR MORNING
TYPES AND IS THERE A NORM THAT
NEEDS TO BE SPECIFIC IS WHAT THE
QUESTIONER'S I THINK IS GETTING
AT.
>> THANK YOU FOR THE QUESTION.
FOR SOME PEOPLE SHIFTING A FEW
HOURS MAY BE FINE BUT FOR OTHERS
THERE'S A GREATER LIKELIHOOD OF
PATHOLOGY AND SO LOOKING AT
SYMPTOMS AND HOW IT'S AFFECTING
A PERSON'S LIFE AND CHANGES
ACROSS THE LIFE COURSE AND MUCH
WORK HAS BEEN CROSS SECTIONAL
AND ADDITIONAL EXPLORATION IS
NEEDED.
>> THANKS, PAM.
>> CAN WE FIGHT OUR INTRINSIC
CHRONOTYPE?
SHOULD A NIGHT OWL BE ENCOURAGED
TO FIGHT THEIR CHRONOTYPE OR
BETTER TO ENSURE OUR BEHAVIORS
ALIGNED WITH OUR INTRINSIC
CHRONOTYPE?
YOUR THOUGHTS ABOUT THAT.
>> SOME PREFER THE NIGHT SHIFT
AND OTHER PREFER THE MORNING
SHIFT.
OUR HYPOTHESIS IS THE NIGHT
SHIFT POORER CARDIOVASCULAR
HEALTH BUT IT'S NOT ENTIRELY
CORRECT BECAUSE THE PEOPLE WITH
POORER CARDIOVASCULAR HEALTH ARE
THE SHIFTERS THE ONES THAT SPEND
ONE MONTH IN THE MORNING SHIFT
AND ANOTHER MONTH IN THE EVENING
SHIFT.
AND THESE PEOPLE HAVE WORSE
CARDIOVASCULAR DISEASE.
PROBABLY DUE TO GENETICS MORE
WORK TO BE DONE BUT IT'S
DIFFICULT TO SWIM UPSTREAM
AGAINST YOUR NATURAL INTRINSIC
CHRONOTYPE IS WHAT YOU'RE
SAYING.
>> YES.
>> TWO MORE QUESTIONERS ARE
GETTING TO THE MEAT OF THE ISSUE
AND IT'S GETTING TO GENERAL
HEALTH RESILIENCE AND
CARDIOVASCULAR HEALTH
RESILIENCE.
DO WE NEED DIFFERENT DEFINITIONS
DEPENDING ON WHETHER WE'RE
THINKING ABOUT THE HEART, BRAIN,
KIDNEY OR ARE THERE COMMON
THREADS HERE.
AND IF SO, WHAT ARE THE SPECIFIC
THINGS THE CARDIOVASCULAR SYSTEM
THAT MIGHT INDICATE TO US THESE
ARE CRITICALLY IMPORTANT METRICS
FOR CARDIOVASCULAR RESILIENCE.
YOU MAY SEE ONE OF THESE IN THE
CHAT WHICH MIGHT HELP GUIDE YOU
BUT A COROLLARY THAT'S AN
INTERESTING QUESTION IS CAN WE
DEFINE RESILIENCE WITHOUT A
PERTURBATION?
DOES RESILIENCE REQUIRE
PERTURBATION OR IS THERE ALL THE
TIME AND DOESN'T MATTER WHAT THE
PERTURBATION IS GOING TO BE AND
THAT'S AN INTERESTING CONCEPT AS
WELL.
MUST THERE BE AN INSULT FOR TO
US SAY THIS PERSON IS RESILIENT
OR CAN WE DEFINE THIS EVEN
EARLIER THAN THAT OCCURRENCE.
I'LL OPEN THAT UP TO ANYBODY WHO
HAS THOUGHTS ON ALL THESE
ISSUES.
SPECIFICITY TO CARDIOVASCULAR
RESILIENCE AND CAN WE DEFINE
SOMETHING AT ANY LEVEL THAT
DOESN'T REQUIRE IN STULT TO
PROVE IT?
MEATY QUESTIONS.
DOES ANYBODY WANT TO TAKE THAT
ON?
>> IT DEPENDS ON WHAT YOU CALL
INSULT.
WE HAVE DEFINED IT FROM THE
PHASE THAT'S AN INFLAMMATORY
STATE AFTER ALL AND TEND TO USE
THAT AS A MEASURE OF
CARDIOVASCULAR RESILIENCE AND
LOOKING AT PARTICLES AND
ASSOCIATED THE CONCEPT OF THE
PHENOTYPIC OF METABOLIC
REFLEXIVITY AND HOW FAST WE'RE
ABLE TO RETURN TO THE BASELINE
AFTER THE INSULT.
>> OTHER THOUGHTS ABOUT THE
ISSUE?
AGAIN, PRETTY LARGE PHILOSOPHY I
THINK HERE.
>> YOU HEAR THE ANECDOTES OF
SOMEONE WHO SMOKED A PACK A DAY
AND LIVED TO 95.
CLEARLY, THEY HAD THE INSULT AND
THEY WERE RESILIENT.
IF SOMEONE'S HEALTHY BUT DON'T
HAVE SMOKING INSULT AS IT HARD
TO KNOW WHERE THEY STAND IN
TERMS OF CARDIOVASCULAR
RESILIENCE.
>> IT'S OF IT MAY EASY TO DEFINE
IN RETROSPECT.
GREAT, MAYBE I'LL PIVOT TO
ANOTHER SPECIFIC QUESTION AND
DR. COOK, CAN YOU SPEAK TO THE
BALANCE BETWEEN LEVERAGING
RESILIENCE AMONG BLACK ADULTS
WITH THE IDEA RESILIENCE CAN
HAVE A NEGATIVE EFFECT ON BLACK
ADULTS AND CERTAIN TYPES OF
RESILIENCE SPECIFICALLY.
>> YES.
FOR PEOPLE IN THE PSYCHOLOGICAL
RESILIENCE FIELD IT'S
COMPLICATES BECAUSE WE HAVE MANY
MIXED FINDINGS RELATED TO THE
AFFECTS OF RESILIENCE AND A
PERSONALLY THINK THAT'S RELATED
TO THE DIFFERENCES IN THE WAYS
IN WHICH WE MEASURE RESILIENCE
AND THAT'S WHY AS A SOCIAL
BEHAVIORAL SCIENTIST I MOVED
AWAY FROM SOME OF OUR RESILIENCE
SCALES THAT HAVE SHOWN THESE
KIND OF NEGATIVE EFFECTS WHEN WE
TALK ABOUT BLACK AMERICANS TO
THINKING MORE ABOUT THE OUTCOME
RESILIENCE WHICH IS REALLY ABOUT
SOCIAL SAFETIES AND SUPPORTS AND
PROTECTIVE FACTORS WHY WE KNOW
THEY'RE MODIFIABLE AND TWO, AND
FIRST, RESEARCHERS IN THE FIELD
AND TWO WE NEED TO THINK ABOUT
THE WAYS WE TALK AND THINK ABOUT
RESILIENCE AND NUMBER THREE, I
THINK ALSO THE CONCEPT OF
RESILIENCE IN TERMS OF
CARDIOVASCULAR METABOLIC HEALTH
BEHAVIOR AND SLEEP SPECIFICALLY
CAN BE POWERFUL.
IF WE TAKE THE APPROACH OF THE
WORKING GROUP USE IN THEIR
DEFINITION TO TACKLE IT AT
MULTIPLE LEVELS INCLUDING THE
RESILIENCE AND I WOULD ARGUE
MAYBE NOT SO MUCH PSYCHOLOGICAL
RESILIENCE AND MORE
ENVIRONMENTAL AND BIOLOGICAL IF
WE WANT TO HAVE A BETTER
UNDERSTANDING OF WHAT THIS LOOKS
LIKE FOR DIFFERENT AMERICANS AND
BLACK AMERICANS HIGHLY AFFECTED
BY CARDIOVASCULAR DISEASE AND
NUMBER TWO, IF WASN'T TO PREVENT
MORBIDITY AND MORTALITY.
I HOPE THAT KIND OF ANSWERS YOUR
QUESTION WITHOUT GOING DOWN THE
RABBIT HOLE OF DEBATE AMONGST
RESILIENCE RESEARCHERS AT THE
MOMENT.
>> I THINK YOU DRAW AN IMPORTANT
DISTINCTION BETWEEN THE SOCIO
AND PHYSIOLOGICAL AND
PHYSIOLOGICAL RESILIENCE AND
THEY REQUIRE DIFFERENT
INTERVENTIONS I WOULD SAY.
WE MAY HAVE TO THINK ABOUT THESE
IN LESS INTEGRATIVE WAYS BUT
IT'S A GREAT ANSWER.
AND THEN ONE OTHER QUESTION THAT
CAME IN ABOUT OPTIMAL STRATEGIES
FOR AMERICA CARDIOVASCULAR
RESISTANCE IN HUMANS IN AN
OUT-PATIENT COMMUNITY SETTING
AND WHAT ARE THE MOST ACCEPTED
VARIABLES IN RESILIENCE IN
RESEARCH.
I HOPE I ADDRESSED SOME OF SINCE
MY TALK BUT I THINK ONE WAY IS
SOMETHING THE AMERICAN HEART
ASSOCIATION HAS DEVELOPED IS THE
LIFE ESSENTIAL EIGHTS THE
CARDIOVASCULAR HEALTH SCORE
WHICH IN TURN HAS BEEN
ASSOCIATED WITH UP STREAM
FACTORS SOCIAL AND OTHER
BEHAVIORAL DETERMINATES OF
HEALTH AND IMPORTANTLY IT'S BEEN
ASSOCIATED WITH DOWN STREAM
HEALTH OUTCOMES IN TERMS OF
CHRONIC DISEASE OF AGING AND
LONGER HEALTH SPAN AND
COMPRESSION, MORBIDITY, LOWER
HEALTH CARE COSTS AND BETTER
QUALITY OF HEALTH.
THINGS WE DEFINE AS SUCCESSFUL
AGING ULTIMATELY IN SOMETHING
YOU CAN MEASURE TODAY, MODIFY
WITH BOTH SMALL AND LARGE
CHANGES AND THOSE CHANGES HAVE
BEEN SHOWN TO MAKE AN IMPORTANT
DIFFERENCE.
IF YOU GOOGLE LIFE ESSENTIAL'S
EIGHT IT TAKES YOU TO THE TOOL
FROM THE AMERICAN HEART
ASSOCIATION AND THE COMPONENTS
SHOULD NOT BE A SURPRISE.
THERE'S FOUR HEALTH BEHAVIORS,
AND THERE'S FOUR PHYSIOLOGIC OR
HEALTH S THAT ARE BLOOD
PRESSURE, BLOOD GLUCOSE AND
BLOOD CHOLESTEROL LEVELS AND
BODY WEIGHT THAT OF COURSE ALSO
SHOULDN'T A SUPPLIES BUT THE
FRAMEWORK THERE ALLOWS YOU TO
THINK ABOUT WHAT ONE THING CAN I
WORK ON TODAY TO KNOW IT'S GOING
TO BE ASSOCIATED WITH IMPROVED
HATH WHICH MAY BE AN EQUIVALENCE
TO RESILIENCE.
WE'RE AT THE BOTTOM OF THE HOUR.
I WANT TO RESPECT PEOPLE'S LUNCH
TIME.
I WANT TO EXPRESS MY GRATITUDE
TO OUR WONDERFUL SPEAKERS AND
PANELISTS THIS MORNING.
I THINK YOU'VE KICKED THIS
WORKSHOP OFF PERFECTLY.
AND RAISED MORE QUESTIONS THAN
ANSWERS WHICH IS PERFECT.
YOU HAVE THREE MORE SESSION TO
GO AND GROUND TO COVER
MECHANISTICALLY AND
INTERVENTIONALLY IN THE COMING SESSIONS.
ENJOY YOUR LUNCH AND COME BACK AT 1:00 EASTERN, 12:00 CENTRAL
AND LOOK FORWARD TO SAYING WHEN
YOU COME BACK. THANK YOU SO MUCH.
>> I'D LIKE TO START THE SESSION
BY GIVING AN OVERVIEW OF THE
POTENTIAL MECHANISMS LINKING
SLEEP AND CIRCADIAN RHYTHMS AND
CARDIOVASCULAR RESILIENCE.
THESE ARE MY DISCLOSURES IN
TERMS OF GRANT FUNDING AND
PROGRAM SUPPORT.
SO THIS IS WHAT WE HOPE TO
ACCOMPLISH TODAY.
WE WILL BE DETERMINING THE
PATHWAYS IN WHICH SLEEP AFFECTS
CARDIOVASCULAR RESILIENCE AND
HOW IT'S RELATED TO OTHER
INDICATORS OF RESILIENCE AND
WHETHER THEY CAN SERVE AS
POTENTIAL THERAPEUTIC THAT ARE
GETS FOR ENHANCING
CARDIOVASCULAR RESILIENCE.
THEY COULD AFFECT MULTIPLE
ASPECTS OF CARDIOVASCULAR
RESILIENCE.
AS WE HEARD THIS MORNING IT'S
THE ABILITY TO GROW OR ADAPT OR
RECOVER FROM A STRESSOR OR
CHALLENGE AND CARDIOVASCULAR
HEALTH AS REPRESENTED HERE COULD
IMPART CARDIOVASCULAR
RESILIENCE.
SO WHEN WE THINK ABOUT
MECHANISMS THROUGH WHICH SLEEP
AND CIRCADIAN RHYTHMS CAN AFFECT
RESILIENCE THERE'S SEVERAL BROAD
CATEGORIES.
WE HAVE BEHAVIORAL MECHANISMS,
FOR EXAMPLE, DIET IS ONE
BEHAVIORAL MECHANISM.
PHYSIOLOGICAL MECHANISM.
BLOOD PRESSURE REGULATION AND WE
HAVE MOLECULAR MECHANISM
MOLECULES THAT AFFECT
ENDOTHELIAL FUNCTION AND
PSYCHOLOGICAL MECHANISMS, STRESS
AND DEPRESSION.
I'LL BE TALKING ABOUT EACH OF
THESE CATEGORIES TODAY AND
GIVING AN EXAMPLE OF EACH.
DIET IS AN IMPORTANT RISK FACTOR
FOR CARDIOVASCULAR DISEASE.
DIET COULD AFFECT CARDIOVASCULAR
RESILIENCE THROUGH THE TYPES OF
FOOD WE EAT AFFECTING
INFLAMMATION AND CAN ALSO AFFECT
CARDIOVASCULAR RESILIENCE IN
DIRECTLY BY INCREASED ENERGY
INTAKE THROUGH DIET.
IT COULD LEAD TO OVER WEIGHT AND
OBESITY A RISK FACTOR FOR
CARDIOVASCULAR DISEASE.
THIS WAS A NICE FIGURE.
DEPICTING THE CYCLICAL NATURE OF
THE DIET IN RELATIONSHIP BY
DR. FARAKAT.
WHILE WE RECOGNIZE RELATIONS
WITH SLEEP IS BI-DIRECTIONAL
TODAY I'LL FOCUS ON THE LEFT
SIDE OF THE FIGURE WHICH IS THE
FIGURE A PART.
HOW POOR SLEEP QUALITY MAY
AFFECT DIET.
WHEN SOMEONE DOESN'T SLEEP
SENSITIVITY TO FOOD REWARD
CHANGES AND IS INCREASES OUR
PREFERENCE FOR FOODS HIGHER IN
FAT, SWEETS LEADING TO UNHEALTHY
FOOD CHOICES.
WE CAN ALSO AFTER POOR SLEEP
INCREASE OUR FOOD INTAKE WHICH
WOULD LEAD TO INCREASED ENERGY
INTAKE OVER ALL AND AGAIN THAT
COULD LEAD TO OVERWEIGHT AND
OBESITY AND THE PREFERENCES
COULD LEAD TO POOR DIET QUALITY.
THIS REVIEW OF INDIVIDUALS IN
META-ANALYSIS OF 11 STUDIES OF
172 INDIVIDUALS FOUND AFTER
PARTIAL SLEEP DEPRIVATION IT
INCREASES BY 385 CALORIES PER
DAY.
IN THIS REVIEW IT WAS SHOWN THAT
INCREASED ENERGY INTAKE WAS
ACCOMPANIED BY NO CHANGE IN
ENERGY EXPENDITURE OR RESTING
METABOLIC RATE AND THAT LED TO A
NET POSITIVE ENERGY INTAKE OVER
ALL.
I SHOULD SAY THERE'S BEEN OTHER
STUDIES WHICH HAVE SHOWN AFTER
SLEEP DEPRIVATION THERE'S AN
DECREASED FPHYSICAL ACTIVITY AN
LOWER INTENSITIY THE NEXT DAY.
AND PARTICIPANTS HAD HIGHER
PREFERENCE FOR HIGHER FAT INTAKE
AND LOWER PROTEIN INTAKE AFTER
PARTIAL SLEEP DEPRIVATION.
THE WAY IT IMPACTS
CARDIOVASCULAR RESILIENCE HAS A
GREATER SENSITIVITY TO FOOD AS A
REWARD AND GREATER PREFERENCE
FOR FOODS HIGH IN FAT AND SUGAR
AND SENSITIVITY CHANGES AND
DYSREGULATION OF APPETITE
HORMONES INCLUDING LEPTIN AND
GHRELIN AND OTHER APPETITE
REGULATING HORMONES INCLUDING
AD
ADIPENECTIN.
IF WE KNOW POOR SLEEP QUALITY
COULD LEAD TO POOR DIET QUALITY
IS THE REVERSE ALSO TRUE?
SO GOOD DOES SLEEP LEAD TO DOWN
STREAM EFFECTS AND IMPROVING
CARDIOVASCULAR RESILIENCE?
WE HAVE A SIGNAL HERE.
THIS WAS A RANDOMIZED CONTROL
PILOT STUDY AND IT LASTED FOUR
WEEKS AND SHORT SLEEPERS.
21 PARTICIPANTS WERE RANDOMIZED
TO A SLEEP EXTENSION AND THEY
WERE ACTUALLY ABLE TO INCREASE
TIME IN BED AND SLEEP DURATION.
SLEEP DURATION INCREASED BY AN
AVERAGE OF 21 MINUTES PER NIGHT
IN THE SLEEP EXTENSION GROUP AND
LED TO REDUCED INTAKE OF ADDED
SUGARS IN THE DIET.
THIS SUGGESTS IMPROVING SLEEP
MAY SLEEP TO PRODUCTION IN
EXCESS SUGAR AND INFLAMMATION
AND CARDIOVASCULAR RISK.
NOW I'LL TURN TO PHYSIOLOGICAL
MECHANISMS AND EXAMPLE OF BLOOD
PRESSURE.
HYPERTENSION IS THE LEADING
MODIFIABLE RISK FACTOR FOR
CARDIOVASCULAR DISEASE AND LAST
MONTH THIS NICE REVIEW A
FRAMEWORK FOR CIRCADIAN,
BEHAVIORAL AND ENVIRONMENTAL
MECHANISMS THAT INFLUENCE THE
CARDIOVASCULAR SYSTEM AND BLOOD
PRESSURE REGULATION UNDER NORMAL
CONDITIONS WHICH IS SHOWN ON THE
LEFT SIDE HEALTHY INDIVIDUAL AND
DURING DISEASE STATES FOR
CIRCADIAN MISALIGNMENT ON THE
RIGHT.
IF YOU LOOK ON THE BOTTOM LEFT
YOU CAN SEE BLOOD PRESSURE
NORMALLY FOLLOWS A DAILY RHYTHM
AND THERE'S A PEAK DURING THE
DAY AND AT NIGHT THE BLOOD
PRESSURE DIPS BY 10% TO 20%.
ON THE RIGHT SIDE YOU CAN SEE
THE BLOOD PRESSURE REGULATION IS
DISRUPTED AND SO INDIVIDUALS MAY
NOT DIP AT ALL AT NIGHT AND MAY
BE NON-DIVERSE AND MAY BE
REVERSE DIVERSE.
THEY CAN EXPERIENCE A GREATER
MAGNITUDE THAN ONE WOULD EXPECT
ASSOCIATED WITH ACUTE
HYPERTENSION.
THE CONDITIONS OF CIRCADIAN
MISALIGNMENT THAT
AFFECT REGULATION ARE SHIFT
WORK, SOCIAL JET LAG WHEN PEOPLE
HAVE SHORTER SLEEP DURATION
DURING THE WEEK AND CATCH UP ON
THE WEEKENDS.
CHRONOTYPE WHICH WE TALKED ABOUT
EARLIER TYPE ESPECIALLY LATE OR
PREFERENCE FOR EVENING S IN
PEOPLE WITH CIRCADIAN SLEEP
DISORDERS THAT COULD AFFECT THIS
DYSREGULATION AND AGING.
HERE'S AGE EXAMPLE OF HOW SLEEP
COULD BE AFFECT.
THERE WERE RADIOLOGY RESIDENTS
AND ONE 24 HOUR ON-CALL SHIFT.
THEY SLEPT AN AVERAGE OF THREE
CALLS PER NIGHT AND THIS THE
FIRST STUDY TO USE
RESONANCE-BASED IMAGING TO LOOK
AT CARDIOVASCULAR STRAIN AFTER A
24-HOUR SHIFT.
AND THEY DID THE IMAGING BEFORE
THE RESIDENTS WENT ON THEIR CALL
AND THIS SHIFT RESULTED IN
INCREASED BLOOD PRESSURE AND
HEART RATE AND CORTISOL AND
INCREASED CARDIOVASCULAR AND NOW
MECHANISMS SLAEP AND CIRCADIAN
RHYTHMS MAY BE LINKED TO AND
MOLECULES RELATED TO ENDOTHELIAL
FUNCTION.
WE RECRUITED A COHORT OF WOMEN
FROM NEW YORK CITY AND IN A
SUBSET WE WERE ABLE TO EXTRACT
ENDOTHELIAL CELLS FROM A VEIN IN
THE ARM.
WE FOUND WOMEN WHO REPORTED
POORER SLEEP QUALITY THOUGH THEY
WERE SLEEPING IN ADEQUATE NUMBER
OF HOURS PER NIGHT ALL SEVEN TO
EIGHT HOURS PER NIGHT THEY HAD
INCREASED ENDOTHELIAL
INFLAMMATION AS REPRESENTED BY
NUCLEAR FACTOR KAPPA B A
PRO-INFLAMMATORY TRANSCRIPTION
FACTOR AND IT'S INCREASED WHEN
PARTICIPANTS REPORTED HIGHER
SCORES ON THE INSOMNIA SEVERITY
INDEX.
GRAPH B SHOWS IT WAS INCREASED
UNDER DIRECT OBSERVATION WHEN
PARTICIPANTS REPORTED WORSE
SLEEP QUALITY SCORES AND FINALLY
GRAPH C SHOWS IT WAS INCREASED
AS TIME TO SLEEP ONSET
INCREASED.
WOMEN WITH INSOMNIA HAVE HIGHER
MEASURES AND THESE ARE
COMPLETELY HEALTHY WOMEN.
NOW THE PSYCHOLOGICAL REASONS
WHERE IT MAY IMPACT SLEEP,
CIRCADIAN RHYTHMS AND DEPRESSION
AND IN THIS STUDY 62
PARTICIPANTS MOSTLY WOMEN
AVERAGE AGE WAS 36 YEARS OLD
COMPLETED A SLEEP RESTRICTION
INTERVENTION CONSISTING OF TWO
SIX-WEEK INTERVENTION PHASES
SEPARATE A SIX-WEEK WASH OUT
PHASE.
IN ONE PHASE THEY HAD HABITUAL
SLEEP AND MAINTAINED THEIR
NORMAL WAKE TIMES AND IN THE
OTHER PHASE THEY COMPLETED SLEEP
RESTRICTION AND THEIR BED TIME
WAS DELAYED BY ONE AND A HALF
HOURS A NIGHT BUT MAINTAINED THE
WAKE TIME.
THEY SHOWED A SIGNIFICANT
REDUCTION IN SLEEP DURING THE
SLEEP RESTRICTION SLEEP AND THE
MEAN TOTAL TIME DURING HABITUAL
SLEEP WAS 7.4 AND DURING
RESTRICTION 6.2 HOURS.
HIGHER PERCEIVED STRESS AND
ANXIETY WERE BOTH OBSERVED AFTER
SLEEP RESTRICTION COMPARED TO
HABITUAL SLEEP.
THIS SUGGESTS EVEN PROLONGED
INSUFFICIENT SLEEP CAN LEAD TO
PERCEIVED STRESS AND ANXIETY IN
OLDER ADULTS.
IN TERMS OF SLEEP IN RELATION TO
DEPRESSION THIS IS A
META-ANALYSIS OF ASSOCIATIONS
BETWEEN SLEEP DURATION AND
DEPRESSION AND HERE WAS SHOWN
BOTH SHORT SLEEP DURATION AND
LONG SLEEP DURATION IS
ASSOCIATED WITH INCREASED RISK
OF DEPRESSION AND ASSOCIATED
WITH CARDIOVASCULAR RISK.
IT WAS 31% INCREASED ODDS OF
HAVING DEPRESSION FOR SHORT
SLEEP DURATION AND 42% INCREASED
ODDS OF HAVING DEPRESSION FOR
LONG SLEEP DURATION.
THE KEY POINTS TO SUMMARIZE IS
THEIR LINKED TO CARDIOVASCULAR
RESILIENCE THROUGH A VARIETY OF
MECHANISMS.
AND MOSTLY TALKED ABOUT SLEEP
DURATION BUT THERE'S MULTIPLE
DIMENSION AFFECT CARDIOVASCULAR
RESILIENCE THROUGH INCREASED
BLOOD PRESSURE REGULATION AND
STRESS AND REGULATION AND
CIRCADIAN MISALIGNMENT MAY
IMPACT BEHAVIORS FOR DIET AND
PHYSICAL ACTIVITY AND
PSYCHOSOCIAL RISK FACTORS SUCH
AS DEPRESSION, ANXIETY, STRESS
HAVE BEEN ON THE TO INCREASE
AFTER PERIODS OF EVEN MILD SLEEP
DEPRIVATION OR DISTURBANCES
COMMON IN THE POPULATION.
IN TERMS OF FUTURE DIRECTION
THESE ARE QUESTIONS I'D LIKE TO
POSE TO OUR PANEL DURING
DISCUSSION TODAY.
ONE OF THEM IS HOW CAN WE BETTER
INCORPORATE THE CARDIOVASCULAR
RESILIENCE SPECIFICALLY IN
MECHANISTIC RESEARCH ON SLEEP
AND CIRCADIAN RHYTHMS AND WHAT
ARE GAPS WE NEED TO FILL IN THIS
AREA.
?
-- AND NOW MIGHT WE SHIFT
CARDIOVASCULAR DISEASE EVENTS OR
RISK TO IMPROVING CARDIOVASCULAR
RESILIENCE?
HOW CAN WE BETTER INTEGRATE
SCIENCE IN RESEARCH THAT'S
FOCUSSED ON SLEEP AND
CARDIOVASCULAR RESILIENCE AND
CONNECT AND PROMOTE
CROSS-COLLABORATION RESEARCH TO
ADDRESS SOME GAPS?
TODAY WE'LL HAVE THREE SPEAKERS
FOLLOWED BY Q&A AND SHORT BREAK.
FIRST THREE ARE DR. BROUSSARD
ABOUT SLEEP AND DR. CHENG WILL
TALK ABOUT CIRCADIAN HEALTH AND
APPLICATION INS CARDIOVASCULAR
RESILIENCE AND DR. LIPTON WILL
TALK ABOUT MECHANISMS OF
CIRCADIAN RESILIENCE IN CELLS
AND AFTER THE Q&A AND BREAK
WE'LL HAVE THREE ADDITIONAL S,
TALKING ABOUT MECHANISMS AND
INCREASED CARDIOVASCULAR RISK IN
SLEEP AND SLEEP AND LEUKOCYTE
DIYNAMICS AND WITH A LITTLE TAL
ABOUT MULTI-LEVEL CARDIOVASCULAR
DISPARITY AND ANOTHER Q&A AND
END THE DAY.
FEEL FREE TO ENTER YOUR
QUESTIONS IN THE CHAT WHILE S
GIVE THEIR TALKS TO COME BACK TO
THAT DURING THE Q&A SESSION.
THANK YOU VERY MUCH AND NOW I'D
LIKE TO INTRODUCE OUR NEXT
SPEAKER DR. JOSIAN BROUSSARD
TALKING ABOUT THE IMPACT OF
SLEEP ON CIRCADIAN DISRUPTION ON
CARDIOVASCULAR OUTCOMES AND
STUDIES.
>> THANK YOU.
THANK YOU TO THE ORGERS FOR THE
INVITATION AND DR. AGGARWAL FOR
THE GREAT INTRODUCTION WHICH
HELPS ME IN THE PRESENTATION.
I WANT TO SEND A SHOUT OUT TO
THE SAM LAB, THE SAMIS WE CALL
OURSELVES IN MY LAB AND I'LL BE
SHOWING DATA FROM OUR CONTROLLED
IN-PATIENT CLINICAL STUDIES
WHICH REQUIRES THIS LARGE TEAM
OF DEDICATED AND PASSIONATE
TRAINEES LED BY OUR FANTASTIC
LAB MANAGER IN THE BOTTOM LEVEL,
ELLEN LYON.
AND YOU HEARD FROM THE GREAT
INTRODUCTION I THINK WE CAN ALL
AGREE SLEEP AND CIRCADIAN
DISRUPTION ARE FACTORS FOR
CARDIO METABOLIC DISEASES.
I'LL FOCUS ON EXPERIMENTAL
EVIDENCE FROM OUR CONTROLLED IN
PATIENT CLINICAL TRIALS AND TALK
ABOUT TRANSLATABILITY BUT I'M
MORE HERE TO DISCUSS THE EARLY
HOME ON -- HOMOGENOUS TO LOOK AT
CIRCADIAN DISRUPTION ASSOCIATED
TO DISEASE RISK.
I'LL TALK ABOUT TWO TYPES OF
PROTOCOLS WE RUN IN THE LAB.
PROTOCOLS OF INSUFFICIENT SLEEP
AND DIFFERENT PROEL -- PROTOCOLS
OF MISALIGNMENT AND ASPECTS OF
BOTH OR THE OTHER.
FOR ME MOST PART FOR OF THE OF
THE DATA I'LL DISCUSS THESE ARE
INCLUSION CRITERIA AND
RECRUITING AND STUDYING YOUNG
HEALTHY PARTICIPANTS 18 TO 35
YEARS OLD ARE THE ABLE RANGES
AND BELOW 26 KILOGRAMS PER METER
SQUARED AND RECRUITING HEALTHY
SLEEPERS TO UNDERSTAND WHAT OUR
MANIPULATION DOING AND
RECRUITING IN THE SEVEN TO NINE
HOUR PER NIGHT RANGE AND CONDUCT
HISTORY AND CONFIRM NO SURGICAL
CONDITIONS, NO SLEEP DISORDERS
WE CONFIRM THEY'RE MEDICATION
AND DRUG FREE.
THIS IS IMPORTANT IN STATES
WHERE RECREATIONAL MARIJUANA
EXISTS.
WE CONDUCT DRUG SCREENS AND MAKE
SURE THEY'RE NOT TRAVELLING
OUTSIDE THE TIME ZONE AND IN THE
STUDIES IN OUR AREAS THE
DENVER/Ft. COLLINS AREA AND THEY
LIVE AT THE ALTITUDE ABOUT A
MILE BECAUSE THAT'S IMPORTANT IN
OUR STUDIES GIVEN KNOWN
METABOLIC CHANGES WHEN COME TO
ACUTE ALTITUDE.
AND CONFIRM STABILITIES.
WE ACCEPT ORAL CONTRACEPTIVES
AND RULE OUT EXCESSIVE CAFFEINE
OR ALCOHOL USERS AND CONFIRM
REGULAR MENSES FOR FEMALE
PARTICIPANTS.
THIS IS FROM OUR LAB BUT MANY OF
YOU ARE OUT DOING SIMILAR
STUDIES.
IT'S AN EXAMPLE OF THE TYPE OF
LAB THAT WE TYPICALLY CONDUCT
THESE IN EFFICIENT STUDIES IN
OUR LAB IS SET UP FOR A
DORM-LIKE FEEL WHERE
PARTICIPANTS CAN LIVE
COMFORTABLY IN THE LAB WHERE IT
DOESN'T FEEL LIKE A SLEEP LAB
SETTING YOU MAY FIND IN A
HOSPITAL.
AND YOU CAN SEE THE PAPER TO
DISCUSS THE METHOD THROUGH THE
WALL BLOOD SAMPLING.
IF YOU'RE LISTENING AND SAY WE
DO THAT EXACT SAME METHOD, IF
YOU DON'T MIND PINGING ME I'D
LOVE TO CITE YOU IN THE PAPER.
FOR THE FIRST PART I'LL DIVE
INTO OUR INSUFFICIENT SLEEP
PROTOCOLS.
THIS IS AN EXAMPLE OF ONE TYPE
OF PROTOCOL WE RUN.
THIS IS A RANDOMIZED CROSSOVER
DESIGN STUDY.
WHERE ON THE LEFT FROM TOP TO
BOTTOM YOU SEE THE DAYS OF IN
PATIENT STAY WHERE THE WHITE
INDICATES THE SLEEP OPPORTUNITY
AND THE SAME PARTICIPANTS COME
BACK AND PARTICIPANTS WILL SPEND
A CERTAIN NUMBER OF DAYS IN THIS
CASE FOUR IN INSUFFICIENT SLEEP
AND THIS WAS FIVE HOURS PER
NIGHT IN BED FOLLOWED BY
RECOVERY SLEEP AND I'LL SHOW
DATA BY THE YELLOW DOTTED LINE
WHEN THE OVERNIGHT OR 24-HOUR
BLOOD SAMPLING OCCURRED.
THESE ARE INTERSTITIAL GLUCOSE
DATA FROM ONE OF OUR
INSUFFICIENT SLEEP PROTOCOLS.
HERE WE SEE THE WHITE LINE IS
THE SUFFICIENT OR HABITUAL SLEEP
WHERE PARTICIPANTS WERE IN BED
FOR IN THIS CASE NINE HOURS PER
SLEEP AND YOU SEE THE WHITE BAR
TO SHOW SLEEP OPPORTUNITY.
AND YOU CAN SEE CLEAR EXERTIONS
THIS IS INTERSTITIAL GLUCOSE.
YOU CAN SEE IN THIS CASE WE'RE
GETTING SAMPLES EVERY 15 MINUTES
AND MEALS ARE INDICATED IN THE
WHITE AND RED ARROW FOR
INSUFFICIENT SLEEP.
DURING INSUFFICIENT SLEEP THEY
HAVE HIGHER GLUCOSE ON AVERAGE
IN RESPONSE TO THE FIRST MEAL OF
THE DAY THE AREA UNDER THE CURVE
IS LARGER AND SEE AN OVERSHOOT
WITH LOWER GLOW -- GLUCOSE AND
WE CAN DISCUSS THIS IN THE
QUESTION AND ANSWER BIT DON'T
HAVE INSULIN IN THIS PARTICULAR
STUDY.
HERE DURING SUFFICIENT SLEEP IN
WHITE AND THIS WAS A STUDY
CONDUCTED AT UNIVERSITY OF
CHICAGO AND IT WAS LED BY A
SPEAKER IN THE SECOND DAY AND
SEE THE NOCTURNAL SURGE AND
PRE-FATTY ACID AND THIS IS
DURING SUFFICIENT SLEEP.
AND DURING INSUFFICIENT SLEEP
YOU SEE THE BOTTOM BARS INDICATE
THE SLEEP OPPORTUNITY DURING
INEFFICIENT SLEEP.
THE SAME PARTICIPANTS HAVE A
HIGHER FATTY ACIDS DURING THE
LATE NIGHT AND EARLY MORNING
PERIODS.
THIS IS NOT A DRASTIC INCREASE
BUT CERTAINLY PRESENT OVER THE
THIRD NIGHT OF INSUFFICIENT
SLEEP.
WE NEXT ASK WHETHER THE
CIRCULATING LIPIDS GET IN THE
MUSCLE BECAUSE IN THE CONTEXT OF
DIABETES AND OBESITY WE KNOW
LIPIDS ARE GETTING IN THE MUSCLE
AND PLAYING A ROLE IN INDUCING
INSULIN RESISTANCE.
THIS IS HOW WE CONDUCT BIOPSY OF
THE THYMUSAL.
-- THIGH MUSCLE.
IF YOU LOOK AT THE LEFT GRAPH
WITH THE TURQUOISE WE'RE
INTERESTED IN A FORM OF LIPID
FORUM AFTER THE HYDROLYZATION OF
FATTY ACIDS FROM TRIGLYCERIDE.
WE DO FIND FROM THE MUSCLE
BIOPSIES THEY'RE INCREASED IN
SOME OF THE CHAIN LINK OF
LIPIDS.
ACROSS THE BOTTOM THEY'RE
DIFFERENT SIZES OF FATTY ACIDS.
THESE HAVE BEEN OTHER CONTEXT OF
METABOLIC DISEASE.
MOVING INTO MORE BLOOD PRESSURE
RESULTS THE NEXT TWO PIECES OF
DATA WERE GENERATED AND LED BY
Ph.D. STUDENT IN THE LAB.
AND THAT'S SOON TO BE DR. SOPHI
SEWARD ON THE CALL.
AND HERE DR. AGGARWAL NICELY
SHOWED DURING HABITUAL SLEEP
THERE WAS A CLEAR DIPPING
PATTERN FOR SYSTOLIC BLOOD
PRESSURE.
AND DURING SLEEP AND CIRCADIAN
DISRUPTION WE LOSE THIS DIPPING
BECAUSE YOU CAN SEE AGAIN
THEY'RE STAYING AWEAK LONGER
WHEN IN THE OTHER CONDITION THEY
WERE ASLEEP.
YOU CAN SEE THE SIGNIFICANT
ELEVATION IN BLOOD PRESSURE.
HERE WE HAVE DIASTOLIC PATTERN
AND YOU SEE THE SLEEP AND
CIRCADIAN DISRUPTION.
FOLLOWING A SIMILAR PATTERN IN
SYSTOLIC AND DIASTOLIC BLOOD
PRESSURE AND CONDUCTED WITH A
BLOOD PRESSURE MONITORING DEVICE
WE USED TO ASSESS BLOOD PRESSURE
EVERY 30 MINUTES.
THIS IS HABITUAL SLEEP AND
INSUFFICIENT SLEEP SEEING A
REDUCTION IN VASCULAR FUNCTION
WITH FLOW METER DILATION.
AND SEE THESE ARE INCREASED
DURING INSUFFICIENT SLEEP.
WE DON'T SEE ANY CHANGES IN T
TAU BUT THIS ALONG WITH OUR
PREVIOUS DATA SHOWED SHOWING
NEURO VASCULAR CHANGES AND
THEY'RE I AM IMPLEMENTING TRANS
CRANIAL DOPPLER IMAGING.
TO REITERATE FOR OUR PURPOSES I
WANTED TO DEFINE CIRCADIAN
MISALIGNMENT FOR THE NEXT COUPLE
OF SLIDES.
WE'D LOOK AT SLEEP, WAKE AND
ASSOCIATED BEHAVIORS.
WHEN THINK OF BEING AWAKE AND
ACTIVE WE CONSIDER THAT TO OCCUR
IN DIURNAL SPECIES LIKE
OURSELVES AND AT DARK BEING
ASLEEP AND FASTING AND INACTIVE
AND CIRCADIAN MISALIGNMENT IS
ANY MISMATCH BEFORE YOUR
HABITUAL WAKE TIME OR EATING IN
MY EXAMPLE GETTING UP EARLY TO
CATCH A FLIGHT WE COULD CALL
THAT MORNING CIRCADIAN
MISALIGNMENT.
THERE'S A SLAM SHIFT PROTOCOL
BEFORE DAYS ARE SPENT IN THE LAB
WHERE PARTICIPANTS COME IN IN
THE EVENING AND D INDICATES
DINNER I HAVE TWO NIGHTS OF A
DAY SHIFT MIMICKING SCHEDULE
WHERE THEY SLEEP AT NIGHT AND
AWAKE DURING THE DAY.
ON THE THIRD DAY WE USE THAT AS
A TRANSITION DAY INTO SIMULATED
NIGHT SHIFT WORK WHERE
PARTICIPANTS WOULD TRY TO GET A
DAYTIME NAP OPPORTUNITY WHICH IS
PRETTY TYPICAL IN SHIFT WORKERS
FOLLOWED BY TWO DAYS OF
SIMULATED NIGHT SHIFT WORK.
I'LL SHOW DATA FROM THE RED
DOTTED LINES FROM BLOOD SAMPLES
OVER 24 HOURS ON WHAT I'LL CALL
ALIGNMENT AND MISALIGNMENT.
THESE ARE INTERSTITIAL GLUCOSE
DATA AND WE SEE A PATTERN WHERE
WE HAVE NICE GLUCOSE EXERTIONS
IN RESPONSE TO THE MEALS WHICH
ARE INDICATED IN THE WHITE
ARROWS.
WE SEE THE SIGNIFICANT ELEVATION
IN GLUCOSE LEVELS ESPECIALLY IN
RESPONSE TO THE FIRST MEAL OF
THE DAY WHICH IN THIS CASE IS
ADD A DIFFERENT CIRCADIAN TIME.
THE X AXIS IS TIME AND WEIGHT
AND MISALIGNMENT CONDITION
PARTICIPANTS WAKE UP IN THE
BIOLOGICAL EVENINGL THIS IS AN
IDENTICAL MEAL AND YOU CAN SEE
IN THE MISALIGNMENT CONDITION
THERE'S A MEAL LATER IN THE DAY
THAT'S WHAT THAT LITTLE SURGE IS
THERE.
YOU CAN SEE THEY'RE SUPPRESSED
AND INSULIN SECRETION AND IN THE
YELLOW ARROWS YOU CAN SEE
FOLLOWING THAT PERIOD YOU HAVE A
PRE-FATTY ACID SUPPRESSION.
AND THEY'RE ELEVATED WHEN
PARTICIPANTS ARE AWAKE AND
EATING DURING THE BIOLOGICAL
NIGHT.
ON THE LEFT YOU CAN SEE THESE
ARE DATA FROM LABS USING A
SIMILAR PROTOCOL YOU CAN SEE
DURING CIRCADIAN MISALIGNMENT IN
THE RED LINES WE CAN SEE THAT
BLOOD PRESSURE ARE SIGNIFICANTLY
ELEVATED WHEN PARTICIPANTS ARE
SLEEPING DURING THE BIOLOGICAL
DAY AND THEN ON THE RIGHT SLIDE
THESE ARE DATA SHOWING THE
INHIBITER WHICH INHIBITS FIB
FIBRINOLYSIS AND YOU CAN SEE THE
COLOR IS IN DAY TWO WHICH IS IN
YELLOW YOU CAN SEE IT'S HIGH
OVER HABITUAL SLEEP BUT WHEN
PARTICIPANTS IN THE SIMILAR
PROTOCOL ARE CIRCADIAN
MISALINED, WE SEE AN ALMOST
FLATTENING OF IT.
THIS DATA WERE PUBLISHED AS A
SUPPLEMENT BUT I CHECKED IN WITH
DR. DEPNER AND THE DATA UNDER
REVIEW CURRENTLY HOPEFULLY IT
WILL BE OUT PRETTY SOON.
THINKING ABOUT COUNTER MEASURES
AND AS WAS NICELY MENTIONED
CHRONONUTRITION AND DIVE INTO
PRELIMINARY DATA LOOKING AT
EATING AT NIGHT AND HOW THAT MAY
PLAY A ROLE IN CIRCADIAN
MISALIGNMENT.
WE HEARD EATING AT BIOLOGICAL
NIGHT IS ASSOCIATED WITH
DISTURBING CIRCADIAN RHYTHMS IN
PERIPHERAL CLOTS AND WE KNOW
IT'S ASSOCIATED WITH IMPAIRED
METABOLIC FUNCTION AND INCREASED
DISEASE RISK.
TO DIVE IN MORE AND ASSESS THE
IMPACT OF TIME-RESTRICTED
FEEDING OR EATING DURING EYE
SHORTER PERIOD DURING THE
BIOLOGICAL MORNING WE
ASSESSED -- I'LL SHOW YOU DATA
FROM THE FACTORS WE LACKED AT
BEFORE.
-- LOOKED AT BEFORE LIKE GLUCOSE
AND LIPIDS AND BLOOD PRESSURE.
FOR THIS WE RECRUITED HEALTHY
YOUNG PARTICIPANTS FOR ONE WEEK
EATING WITH 13 HOURS ON THE LEFT
AND THEN RESTRICTED IT WITH ISO
CALORIC CONDITIONS.
YOU'RE FAMILIAR WITH THE PATTERN
OF GLUCOSE DURING THE CONTROL 13
HOUR EATING WINDOW IN WHITE.
AND --
>> TWO-MINUTE WARNING.
>> THREW.
THE PARTICIPANTS WERE SUCCESSFUL
IN SHIFTING TO AN EIGHT-HOUR
WINDOW AND THAT RESULTED IN A
SIGNIFICANT REDUCTION IN
INTERSTITIAL GLUCOSE DURING THAT
TIME PERIOD.
WE'VE NOW DONE SOME LIPID OMICS
AND FOUND THE DAGS ARE REDUCED
SHOWN IN RED.
THIS IS THE FINAL DATA SLIDE
FAIRLY PRELIMINARY BUT SHOWING A
CONSISTENT PATTERN OF REDUCED
BLOOD PRESSURE SYSTOLIC AND
DIASTOLIC AFTER THE CONDITION IN
THE STUDY.
SOME CONCLUSIONS AND WE COULD DO
THREE CLICKS AND PUT THE
CONCLUSIONS UP.
HOPEFULLY I HAVE CONVINCED YOU
CIRCADIAN DISRUPTION AND INCLUDE
HOMEOSTASIS I DIDN'T MAKE THE
LINK TO VASCULAR COMPLICATIONS
BUT WE KNOW ELEVATED GLUCOSE IS
RESPONSIBLE FOR A LOT OF
VASCULAR PROBLEMS IN PEOPLE WITH
DIABETES.
WE ALSO FOUND INCREASED FATTY
ACIDS CIRCULATING LIPID SPECIES
AND INCREASED BLOOD PRESSURE AND
REDUCED VASCULAR FUNCTION AS
ASSESSED BY FMG.
TIME RESTRICTED EATING WAS
ASSOCIATED WITH LOWER GLUCOSE
AND LOWERED LIPID SPECIES AND
BLOOD PRESSURE.
SO MOVING FORWARD WE ARE
INTERESTED IN WHETHER OPTIMIZING
CIRCADIAN TIMING DURING
CIRCADIAN MISALIGNMENT WHICH I
DOESN'T SHOW YOU, THAT'S KIND OF
OUR FUTURE DIRECTION AND WHETHER
THAT COULD MITIGATE SOME
CARDIOVASCULAR AND METABOLIC
COMPLICATIONS.
WITH THAT THE LAST CLICK IS
FUNDING ACKNOWLEDGEMENTS.
AND FEEL FREE TO PUT QUESTIONS
IN THE CHAT AND Q&A FOR THE
FINAL SESSION WHERE WE'LL TALK
ABOUT IT AT THE END.
THANK YOU.
>> INTERESTING TALK AND LOOKING
FORWARD TO ASKING QUESTIONS
LATER.
NOW WE'LL TURN TO OUR NEXT TALK
WHICH IS FROM DR. PHILIP CHENG
TALKING ABOUT CONCEPTUALIZING
CIRCADIAN HEALTH AND APPLICATION
TO CARDIOVASCULAR RESILIENCE.
COULD THE A/V TEAM UNMUTE HIM.
>> I COULDN'T UNMUTE MYSELF.
>> WELCOME.
THANK YOU.
>> I'M EXCITED TO BE HERE.
LIKED TO THINK OF THE
OPPORTUNITIES TO PUSH THE HEALTH
AND RESILIENCE.
IN THIS TALK I REALLY AM GOING
TO TRY AND GROUND THE CONTENT IN
RESILIENCE AND IN DEFINITION OF
RESILIENCE THAT HAS COME UP.
I'LL FLY THROUGH THE RESILIENCE
PIECES SO WE'RE ON THE SAME PAGE
AND ALSO ONE COMMONALITY BETWEEN
CIRCADIAN HEALTH AND RESILIENCE
IS WE DON'T HAVE A GOOD STRONG
SHARED DEFINITION SO I'D LIKE TO
UNPACK A LITTLE BIT AND GET TO
KEY QUESTIONS.
WE'LL GET INTO OVERVIEW OF THE
EVIDENCE AND SOME OF WHICH GETS
TO THE KEY QUESTIONS.
THEN END WITH FUTURE DIRECTIONS.
LET'S START WITH THE TERM
RESILIENCE.
THIS WAS AN IMAGE GENERATED BY
CHAT GPT WHICH IS AS VAGUE AS WE
CAN GET IN THINKING ABOUT
RESILIENCE.
I WANT TO SURFACE THE THREE
COMPONENT RESIST OR ADAPT FROM A
STRESSOR.
ON THE Y AXIS YOU HAVE
FUNCTIONING AT NORMAL LEVELS OR
HIGHER AND THE BLUE LINE IS
THRESHOLD FOR CLINICALLY
SIGNIFICANT IMPAIRMENT.
EVERYONE'S MOVING AT NORMAL
FUNCTIONING.
WE HAVE A STRESSOR AS INDICATED
IN THE ORANGE AND YOU GET SOME
PEOPLE WHO GET IMPAIRMENT AND
SOME OF WHOM ARE CLINICALLY
SIGNIFICANT, OTHERS LESS SO
THOSE RESISTANT ARE TYPICALLY
THOSE WE THINK OF BEING ABLE TO
BEND BUT NOT BREAK.
THE APPROPRIATE ANALOGY IS YOU
WALK ALONG AND QUICKLY REGAIN
YOUR BALANCE AND SUSTAIN AN
INJURY.
ON THIS SLIDE WE'LL TALK ABOUT
RECOVERY.
THIS SHOWS UP IN RESILIENCE AND
WHEN WE ASK PEOPLE HOW RESILIENT
THEY ARE AND HOW QUICKLY THEY
RECOVER FROM STRESS.
AND THE IDEA HERE IS THAT YOU
CAN HAVE A SLOW RECOVERY IN THE
BLUE OR PURPLE OR FASTER
RECOVERY LIKE YOU SEE IN THE RED
AND SO THOSE ARE FOLKS WE MIGHT
CONSIDER BEING MORE RESILIENT.
ON THE NEXT SLIDE YOU'LL SEE
ADAPTATION WHICH I THINK IS MORE
COMPLEX BUT PERHAPS MORE
INTERESTING COMPONENT.
SO MY CONCEPTUALIZATION OF
ADAPTATION OPPOSED TO THE ORANGE
LINE WHERE YOU HAVE A STRESSOR A
RESPONSE AND MAYBE A DIP IN
FUNCTIONING AND RECOVER AND WHAT
HAPPENS WHEN YOU HAVE A REPEATED
STRESSOR.
I THINK ADAPTATION GETS AT
CHANGE OR GROWTH THAT LEADS TO
RESIST IN THE LONG RUN IN THE
STRESS INOCULATION MODEL OR HOW
THE IMMUNE SYSTEM CAN CREATE
ANTIBODIES TO FIGHT EXPOSURE TO
THE SAME PATHOGENS.
AND YOU SEE CIRCADIAN HEALTH.
I'LL ALSO JUST QUICKLY GO
THROUGH THIS YOU'LL SEE THE
POINT WHICH IS WE'VE ALMOST ALL
ORGANISMS HAVE EVOLVED UNDER
THIS 24 HOUR CYCLE AND CIRCADIAN
RHYTHM AFFECTS FUNCTIONING.
HOW LONG A RHYTHM TAKES AND
AMPLITUDE GETTING TO THE
MAGNITUDE THEIR SIGNAL.
LET'S START WITH PHASE.
ONE COMMON EVENT IS CIRCADIAN
HEALTH IS THE ONSET OF MELATONIN
SECRETION AS A MARKER FOR WHEN
OUR BODY IS PREPARED FOR SLEEP.
MOST OF US WILL VIT AT NIGHTTIME
AND GO TO WORK DURING THE DAY
AND THAT ALLOWS US TO AB -- BE
ALERT DURING THE DAY AND IN
TERMS OF SHIFT WORK IS WHEN OUR
WORK SCHEDULE NOW IS OVERLAPPING
WITH THE PHYSIOLOGICAL PERIOD
WHERE OUR BODY IS EXPECTING
SLEEP AND THE BAD THINGS THAT
CAN HAPPEN.
YOU'LL SEE CIRCADIAN
MISALIGNMENT HAS BEEN WELL
ESTABLISHED AS A RISK FACTOR FOR
CARDIOVASCULAR ILLNESS.
THE ODDS RATIO BEING 1.4 IN THE
STUDIES.
THIS MODEL SPEAKS TO HOW
MISALIGNMENT COULD BE A RISK FOR
BLOOD PRESSURE AND OTHER
CARDIOVASCULAR ISSUES.
ON THE NEXT SLIDE A KEY QUESTION
IS CIRCADIAN MISASSIGNMENT --
MISALIGNMENT AS A WAY TO CONFER
DISEASE RESISTANCE OR ENHANCE
RECOVERY.
IF SO, WHAT ARE WE ALIGNING TO?
THIS GETS AT CHRONOTYPE I'LL SAY
MORE ABOUT LATER.
ANOTHER QUESTION IS IS
MISALIGNMENT A PHYSIOLOGICAL
CHALLENGE WE OUGHT TO BE
RESILIENT AGAINST?
WE'LL TALK ABOUT PERIOD WE ALL
HAVE RHYTHMS THERE VARY AND IF
THEY'RE 24 HOURS THAT IS NICE
BECAUSE IT ALLOWS PREDICTABLE IN
PHASE.
SO IN THIS CASE WE'RE TRACKING
THE RED TRIANGLE SAY WE'RE
TRACKING PEAK RESISTANCE AND
PERIODS LONGER THAN 24 HOURS,
YOU'LL SEE THE THING WE'RE
TRACKING WILL SHIFT LATER AND
PERIODS SHORTER WILL SOMETIMES
GET TWO EVENTS DURING THE DAY.
NEXT SLIDE YOU'LL SEE MY POINT
BEING MOST OF US ARE IN THIS
CATEGORY.
THIS IS A DISTRIBUTION AS YOU
CAN SEE 24.0 IS THE THIRD TICK
MARK THERE.
THE MAJORITY OF US ARE LONGER
THAN 24 HOURS WITH A 24.2
ESSENTIAL MEAN IN THE
POPULATION.
WHICH THEN ON THE NEXT SLIDE
SHOULD SUGGEST THAT WE SHOULD BE
WALKING AROUND THE CLOCK BUT
THAT'S NOT WHAT HAPPENS BECAUSE
ON THE NEXT SLIDE YOU'LL SEE
FULL EN TRAINMENT BEING ABLE OR
PHYSIOLOGICAL BUILT INTO LOCK IN
TO OUR ENVIRONMENT MOSTLY
THROUGH THE LIGHT-DARK CYCLE IS
AN IMPORTANT PIECE OF THAT.
IN THE NEXT SLIDE OF BOTH
EXTREMES YOU'LL SEE A NIGHT OWL
MORE MORNING LARK AND IT
SUGGESTS NIGHT OWLS HAVE BEEN
SHOWN FOR INCREASED RISK AT
ADVERSE OUTCOMES.
TO PUSH THAT FORWARD IN THE NEXT
SLIDE ONE KEY QUESTION ARE
CHRONOTYPES CONFER RESISTANCE
ARE MORNING TYPES MORE LIKELY TO
EXPERIENCE DISEASE RESISTANCE AN
ARE LATE CHRONOTYPE INHERENT
RISK OR ARE THEY A VICTIM OF
MORNING BIAS?
WE HAVE ALL THESE EVENTS THAT
HAPPEN IN THE MORNING SO THE
PROBLEM IS THE EVENTS WE
SCHEDULE OPPOSED TO THEIR
UNDERLYING CHRONOTYPE.
IF WE CAN INCREASE THE SPEED OF
EN TRAINMENT DOES THAT DRIVE
RESILIENCE?
CAN THAT CONFER DISEASE
RESISTANCE.
FINALLY, OUR THIRD COMPONENT IS
AMPLITUDE.
AMPLITUDE IS INTERESTING.
HIEFRZ DATA TO SHOW IN THE LEFT
HAND PANEL PEOPLE WHO ARE
ACTIVELY IN A DEPRESSIVE EPISODE
IN YELLOW FROM REDUCED AMPLITUDE
AND THOSE WITH A HISTORY OF
DEPRESSION WHO HAVE SINCE
RECOVERED.
ON THE RIGHT-HAND SIDE YOU'LL
SEE SAME THING ON THE Y AXIS IS
MELATONIN AND IN THE RED YOU SEE
HEALTHY CONTROLS IN THE BLACK
WITH PARKINSON'S DISEASE AND
AMPLITUDE AND WHEN YOU TAKE THAT
GROUP AND FURTHER PARS IT BY
THOSE WITH AND WITHOUT EXCESSIVE
DAYTIME SLEEPINESS YOU SEE THOSE
IN THE BLACK ARE PARKINSON'S
WITH EXCESSIVE DAYTIME
SLEEPINESS.
AMPLITUDE MAY BE IMPORTANT.
A COUPLE KEY QUESTIONS, CAN WE
BOOST AM PPLITUDE TO CREATE MOR
ROBUST HEALTH TO CONFER
RESISTANCE AND/OR CAN WE BOOST
AMPLITUDE IN ORDER TO CONFER
BETTER RECOVERY?
COULD MISALIGNMENT A STRESSOR WE
WANT TO BE RESILIENT AGAINST AND
SLEEP CONSTRUCT IS THE IDEA THE
SLEEP SYSTEM CAN HAVE VARYING
DEGREES OF VULNERABILITY LIKE
OTHER SYSTEM ORGANS.
ON THE NEXT SLIDE WE'LL PREVENT
LIKE SLEEP IS ITSELF AN ORGAN
THAT CAN SHOW VULNERABILITIES.
WE HAVE THE IDEA OF THE SLEEP
SYSTEM IS VULNERABLE TO
DISRUPTIONS IN THE ENVIRONMENT.
MAYBE IT'S STRESS BUT COULD BE
NOISE.
AND IT COULD EVEN BE POSITIVE
STRESSORS LIKE A VERY COOL STRIP
TO A FUN DESTINATION.
A VACATION.
IT'S HOW VULNERABLE OUR SLEEP
SYSTEM IS AND WE SEE WHAT
HAPPENS IN PEOPLE WITH LOW SLEEP
REACTI
REACTIVITY.
THIS IS EVIDENCE SPEAKING TO THE
FIRST LINE OF FACTORS WHEN YOU
GO TO A HOTEL ROOM OR NEW
ENVIRONMENT IT'S NORMAL FOR
SLEEP DISRUPTION AND WE SEE 38
PLUS MINUTES OF LATENCY TO
PERSISTENCE SLEEP AND LOW
EFFICIENCY ON THE RIGHT AND ON
THE NEXT SLIDE THOSE WITH SLOW
SLEEP REACTIVITY ARE RESISTANT.
THEY SLEEP MORE EFFICIENTLY.
THIS SLIDE SHOWS CAFFEINE.
WE ALSO THINK CAFFEINE HAVING AN
IMPACT IS A NORMAL EXPERIENCE
AND YOU SEE THIS IN THE HIGH
SLEEP REACTIVITY GROUP AND IN
BLACK YOU SEE A BIG RESPONSE IN
TERMS OF LATENCY TO PERSISTENT
SLEEP AND THE LOW SLEEP ACTIVITY
GROUP DOESN'T SHOW THAT.
THEY'RE RESISTANT TO EVEN CA CAN
FEEN WHICH IS INTERESTING.
AND SPEAK TO A STRESS RESPONSE
TO COVID.
YOU SEE HIGH SLEEP ACTIVITY.
THIS IS MEASURED P
AND THESE HAVE HIGHER ACTIVITY
AND THESE WERE AT LOWER RISK NOR
HAVING CLINICALLY SIGNIFICANT
STRESS RESPONSE.
WE SEE RESISTANCE TO CIRCADIAN
MISALIGNMENT.
THIS TOOK HEALTHY SLEEPERS AND
MOVED THEIR SLEEP EARLIER BY
THREE AND SIX HOURS.
IN THE ROUND GROUP IN THE BOTTOM
YOU SEE A REACTION THAT IS
NORMAL.
WE EXPECT TO SEE MISALIGNMENT
CAUSING MORE SLEEP PROBLEMS BUT
THOSE IN THE DARK SQUARES DON'T
DIFFER.
ON THE NEXT SLIDE THERE'S
EVIDENCE WE'VE SHOWN BEING
INDICATING THIS IS LINKED TO
YOUR PHYSIOLOGICAL STRESS
RESPONSE.
THOSE WITH LOWER REACTIVITY ARE
ABLE TO MOUNT A MORE SIGNIFICANT
STRESS RESPONSE LEADING TO
IMPROVEMENT IN FUNCTIONING.
THOSE WITH LESS OF A BLUNTED
CORTISOL EFFECT SHOW HIGHER
AVOIDANCE AND COGNITION AND
GREATER FEELINGS OF CONSTRAINT
AND ON THE NEXT SLIDE THERE'S
DATA TO LINK THIS TO HEART RATE
VARIABILITY WITH THOSE WITH
LOWER HEART RATE VARIABILITY AS
BEING CONNECTED TO HAVING WORSE
SLEEP IN RESPONSE TO VARIOUS
STRESSORS.
ANOTHER QUESTION IS CAN BOOSTING
AMPLITUDE CONFER RESISTANCE OR
RECOVERY?
IN NORTHERN EUROPE IN A
PSYCHIATRIC UNIT THEY LOOKED AT
ROOMS NORTH VERSUS SOUTH FACING.
YOU SEE ROOMS SOUTH FACING AND
YOU CAN SEE FROM THE TIME LAPSE
THAT SOUTH FACING ROOMS HAD
BRIGHTER LIGHT DURING THE DAY.
THEY HAVE A GREATER DAY-NIGHT
QUADRANTS.
THEY FIND PATIENTS IN THE
BRIGHTER ROOM HAD AN AVERAGE
LENGTH OF STAY THAT WAS ROUGHLY
HALF AS LONG AS THOSE IN THE
NORTH FACING ROOM.
IT SPEAKS TO OFFICIALLY FASTER
RECOVERY.
YOU SEE A SIMILAR STUDY OR STUDY
WITH A SIMILAR IDEA EXCEPT IN
THE CARDIOVASCULAR INTENSIVE
CARE UNIT AND THEY COMPARED
ROOMS WITH AND WITHOUT WINDOWS.
YOU SEE SIMILAR RESULTS THOSE
WITH MORE LIGHT AND WINDOWS HAD
SHORTER STAYS.
THE NEXT SLIDE YOU SEE THIS IS
NEW DATA FROM THE PAPER SHOWING
THAT AMPLITUDE MAY ALSO REDUCE
SLEEP FRAGMENTATION.
THE AMOUNT OF LIGHT DURING TE
DAY AND DURING THE TIME WHERE WE
TYPICALLY CONSIDER IT THE QUOTE
UNQUOTE DEAD ZONE HELPS PROTECT
PEOPLE FROM SLEEP FRAGMENTATION.
SO WE KNOW SLEEP IS IMPORTANT SO
THE NEXT SLIDE I'D LIKE TO SHOW
YOU SOME DATA SPEAKING TO
CIRCADIAN HEALTH THROUGH ROBUST
SLEEP.
THIS IS ANIMAL DATA LOOKING AT
THE INFARCT CATEGORY SORRY,
EVERYONE -- ALL THE ANIMALS WERE
IN THE IN FARC CATEGORY BUT WERE
EITHER EXPOSED TO SLEEP
DISRUPTION OR NOT AND YOU CAN
SEE IN THE LIGHTER GRAY MARKERS
GREATER RECOVERY IN THOSE
WITHOUT SLEEP DISTURBANCE.
WE'LL MOF -- MOVE QUICKLY TO
LU
HUMANS AND WHEN WE ASK PEOPLE
HOW RESILIENT THEY FEEL, THEY
TEND TO REPORT THEY FEEL MORE
RESILIENT WITH AFFECTS LASTING
ONE YEAR.
ON THAT NEXT SLIDE WE DID AN
ANALYSIS AND PROSPECTIVE STUDY
AND CONFIRMED IMPROVED
RESILIENCE CAN MAKE PEOPLE MORE
RESISTANT TO THE RISK FACTORS.
YOU CAN IMPROVE RESILIENCE WHICH
THEN REDUCES RISK FACTORS AND
PROTECTS AGAINST RELAPSE ONE
YEAR LATER.
AP WE SAY THE SAME RESULT EXCEPT
FOR IN DEPRESSION.
>> YOU HAVE TWO MINUTES.
>> THANK YOU.
SAME RESULT FOR DEPRESSION AND
WE TOOK OUT THE SLEEP ITEMS.
THIS IS NOT A SLEEP FINDING.
WHEN WE LOOK THROUGH TIME WE CAN
SEE THOSE WHO GOT CBTI WE CAN
REDUCE THEIR RISK OF DEPRESSION
BY 50%.
EVEN MORE INTERESTINGLY AND LOOK
AT THE SECOND STRESSOR RESPONSE
WHAT WE SEE IS THOSE WHO GOT
CBTI ARE ACTUALLY PROTECTED
AGAINST AND SHOW MORE
RESISTANCE.
YOU'VE SEEN THE DATA EXCEPT FOR
I'M SHOWING YOU THE ACTIVE
CONTROL IS ACTIVE GROUP HERE AS
WELL.
AND IN THE HIGH CATEGORY YOU SEE
THEY DON'T SHOW THE SAME
INCREASE THAT THE OTHER GROUP
DOES SO THEY'RE SHOWING
RESISTANCE AND THE NEXT SLIDE
YOU SEE REDUCED ODDS OF
RESURGENT INSOMNIA.
PEOPLE WHO PREVIOUSLY RECOVERED
AND COVID HIT AND WE LOOKED
WHETHER OR NOT THEY HAD
RESURGENT INSOMNIA AND THOSE WHO
RECEIVED TREATMENT WERE TWICE AS
RESISTANT COMPARED TO THE SHAM
TREATMENT CONDITION.
YOU SEE THE SAME RESULT EXCEPT
FOR DEPRESSION.
WE'RE ABLE TO SHOW CCGI SHOWED
THE RISK OF DEPRESSION DURING
COVID WHICH WAS THERE'S TO FOUR
YEARS AFTER TREATMENT.
WE WERE ABLE TO REDUCE THIS BY
30%.
LET'S MOVE THROUGH FUTURE
DIRECTION.
IT'S IMPORTANT TO BE CLEAR WITH
WHAT OUR CONCEPTUALIZATION IS OF
RESILIENCE.
WHAT IS CIRCADIAN HEALTH AND
MORE IMPORTANTLY BEING ABLE TO
MACHINE CIRCADIAN HEALTH AND
RESILIENCE IN THIS SPACE
THINKING ABOUT FEASIBLE
ASSESSMENT WITH WEARABLE
TECHNOLOGY AND THINK ABOUT
RESILIENCE IN A SOCIO ECOLOGICAL
CONTEXT BECAUSE THESE ARE
COMPLEX IDEAS.
MY LAST SLIDE IS AN
ACKNOWLEDGEMENT SLIDE AND I'LL
END IT THERE.
>> THANK YOU.
I SEE FANTASTIC IN THE CHAT AND
GET TO THOSE AFTER THE NEXT
SPEAKER.
I'D LIKE TO INTRODUCE
DR. JONATHAN LIPTON FROM HARVARD
UNIVERSITY TALKING ABOUT
MECHANISMS OF RESILIENCE IN
CELLS AND SYNOPSIS.
-- SYNAPSIS.
>> I'M A BIT OF A BLACK SLEEP OR
DARK HORSE IN THE GROUP BECAUSE
I'M NOT A CARDIOLOGIST I'M A
PEDIATRIC NEUROLOGIST AT HARVARD
MEDICAL SCHOOL AND STUDY THE
INTERFACE BETWEEN NEUROLOGICAL
DISEASES AND CIRCADIAN TIME
KEEPING MECHANISM AND MY
LABORATORY USES BIO CHEMISTRY
AND CELL BIOLOGY AND MOUSE
MODELS SO FOR THOSE NOT
INTERESTED IN THE BRAIN YOU MAY
WANT A COFFEE.
I HOPE THIS WILL HAVE RELEVANCE
TO HOW CIRCADIAN CLOCKS AFFECT
DISEASE.
I HAVE NO DISCLOSURES.
WE LIVE ON A ROTATING PLANET AND
IT RENDERS A LIGHT/DARK CYCLE
THAT PROVIDE THE SOURCE OF OUR
BASIS AND ENERGY AND
PHOTOSYNTHESIS AND LIVING
ORGANISMS THAT GET THEIR ENERGY
FROM PHOTOSYNTHESIS HAVE EVOLVED
SYSTEMS THAT ALLOW THEM TO
SYNCHRONIZE AND ANTICIPATE THIS
ENERGY SOURCE AND THAT
ORGANIZING US TO SLEEP AND WAKE
AND ENERGETIC STATES AND OTHER
PROCESSES.
INDEED THE CIRCADIAN TIME
KEEPING SYSTEM IS REALLY THE
MULTISCALE TALKED ABOUT BEFORE
AND THE MULTI-SCALE PROCESS
THROUGH WHICH TIME KEEPING IS
ORGANIZED IN THE BRAIN AND BODY.
IN MAMMALS THE CIRCADIAN SYSTEM
IS ORGANIZE IN WHICH LIGHTEN --
LIGHT ENTERS TO THE RETINA AND
THE NUCLEUS WHICH ACTS AS A
CONNOR -- CONDUCTOR OR MASTER
CLOCK FOR ALL CELLS IN THE BODY
INCLUDING THE BRAIN.
REMARKABLY THERE'S QUITE LITTLE
KNOWN ABOUT HOW CLOCKS ARE
ORGANIZED OR WORK IN THE BRAIN.
UNFORTUNATELY, MOST THE
LITERATURE IN THE BRAIN IS
REFERRED TO LIKE EVERY OTHER
ORGAN AS THE PERIPHERY IF IT'S
OUTSIDE THE SCN.
THE CIRCADIAN RHYTHM IS KNOWN IN
THE SLEEP/WAKE CYCLES AND
THERE'S BEHAVIORS INCLUDING
ATTENTION, LEARNING AND MEMORY,
MOOD AND OTHER ASSOCIATIVE AND
ADAPTIVE BEHAVIORS.
TO THE CIRCADIAN REGULATION
SEEMS TO BE EVOLUTIONARY
CONSERVED BUT IDENTIFIED IN
ANIMALS HIGHLY EVOLUTIONARY
DIVERSE GOING BACK TO FLIES AND
EVEN INVERTEBRATE SEA SLUGS.
I LIKE THIS SLIDE FROM A MOVIE
FROM A FAMOUS SWEDISH DIRECTOR
AND THE MOVIE OPENS WITH A
GENTLEMAN FALLING ASLEEP AND
SEES THE CLOCK WITH NO HANDS AND
SETS HIM ON AN EXISTENTIAL
CRISIS.
THAT'S BECAUSE WE NEED CLOCKS AS
PREDICTION TOOLS TO ORIENT
OURSELVES TO THE EARTH AND TO
OTHER INDIVIDUALS.
THERE IS NO SENSATION -- WE
SENSE TIME BUT THERE'S NO ACTUAL
MOLECULE THAT ALLOWS US TO SENSE
TIME UNLIKE ODOR OR MECHANO
TRANDUCTION.
THERE'S NO PHOTONS OF TIME.
THERE'S SOMETHING WE MEASURE
TIME AGAINST.
THE CLOCK IN OURSELVES HELPS US
DO THAT.
WE KNOW IT'S IMPORTANT BECAUSE
THERE'S A STRONG ASSOCIATION IN
MY BUSINESS AND I'M FOCUSSING ON
NEURODEVELOPMENT DISORDERS BUT
MOST NEUROPSYCHIATRIC DISORDERS
HAVE ASSOCIATIONS WITH CIRCADIAN
DYSFUNCTION.
HERE'S A FEW FORMS OF AUTISM
ASSOCIATED STRONGLY WITH SLEEP
DISRUPTION AND CIRCADIAN
DISRUPTION SOME OF WHICH I'VE
STUDIED IN MY GROUP.
WHEN YOU DISRUPT CIRCADIAN RI
RHYTHMS WE HAVE AND METABOLIC
DISRUPTION AND TRUANCY AND LOWER
QUALITY OF LIFE.
THE MAIN QUESTION FOR OUR GROUP
AND FOR THE FIELD IS DOES THE
DISRUPTION OF CIRCADIAN CLOCKS
CONTRIBUTE DIRECTLY TO DISEASE
PROCESSES OR IS IT THE PRODUCT
OF' BAD BRAIN OR UNDERLYING
SYSTEM OR BOTH?
WHAT'S THE INTERFACE?
IN MM -- MANY HAVE ALLUDED TO
THAT.
WE NEED TO GET TO THE UNDERLYING
MACHINE THAT ALLOWS IT TO TICK.
AND THAT IS REALLY THIS
BEAUTIFUL UNDERLYING CLOCK
MECHANISM WHICH WAS AWARDED THE
NOBEL PRIZE IN 2017.
WITHOUT GETTING INTO TOO MANY
DETAILS AND THIS IS A PARED
VERSION YOU HAVE THE
TRANSCRIPTION FACTORS THAT DRIVE
EXPRESSION OF A SERIES OF GENES
INCLUDING THE INHIBITERS AND
THEY GOOD OUT IN THE CYTOPLASM
AND COME BACK IN THE NUCLEUS AND
SHUT DOWN THE MACHINE THAT
TURNED THEM ON.
YOU HAVE AN UPSWING AND DOWN
SWING OF AN OSCILLATOR.
IN PREVIOUS WORK I DEMONSTRATED
THE PROTEIN RESPONSIBLE FOR
CIRCADIAN RHYTHM UNDER GOES A
PHOSPHORYLATION EVENT AT AN A
SPECIFIC SEARING PHOSPHORYLATED
BY PRO -- PROTEINS IMPORTANT
LATER MIN TALK.
AND AT THE HEART OF THE
SYMPOSIUM AND WORK IN MY LAB IS
TRYING TO UNDERSTAND WHAT ABOUT
THIS CORE OSCILLATING MACHINE
ALLOWS IT TO PROVIDE RESILIENCE
TO CELLS AND SYSTEMS.
HOW DOES A CELL AND BRAIN AND
BODY CONSTANTLY EXPOSED TO
DIFFERENCES IN TEMPERATURE AND
PH FROM CHANGES IN OXYGEN OR
OXIDATION REDUCTION IN THE AGING
PROCESS HOW DOES IT GET
MAINTAINED AND WHAT ARE THE
MECHANISMS THAT GET RUDISRUPTED
AND RESULT IN DISEASE.
WE TRIED TO UNDERSTAND HOW IT
WORKS IN THE BRAIN.
WE HAD TO CONSIDER WHAT IS NOT
WELL UNDERSTOOD IN THE BRAIN
WHICH IS THAT THE BRAIN IS MADE
OF DIFFERENT CELL TYPES
INCLUDING HUNDREDS OF TYPES OF
NEURONS AND NEURONS ARE THESE
BEAUTIFUL HIGHLY RAMIFIED CELLS
WHERE MOST THE CYTOPLASM IS
SPREAD OUT IN THE PROCESSES
THROUGH WHICH NEURONS
COMMUNICATE TO OTHER CELLS.
THE QUESTION FOR US WAS HOW IS
CIRCADIAN INFLAMMATION THOUGHT
TO BE ENCODED IN THE
TRANSCRIPTIONAL SYSTEM IN THE
NUCLEUS, HOW IS DOES THAT END UP
IN SYNAPSES WHICH ARE CONTAINED
IN THE PROCESSES AND JUST TO
REMIND THOSE WHO HAVEN'T THOUGHT
BIT THE WAY THE BRAIN COMPUTES
INFORMATION IS THROUGH SYNAPTIC
MACHINES AND SYNAPSES ARE THE
FUNDAMENTAL COMMUNICATION UNIT
OF THE BRAIN AND HOW IS
CIRCADIAN INTEGRATED WITH
SYNAPTIC INFORMATION?
THIS WAS TAKEN BEEN BY A
TALENTED FORMER POSTDOC IN MY
LAB AND MOST THE WORK I'LL SHOW
YOU IS SPEARHEADED BY HER.
THE QUESTION WE WANTED TO ASK IS
HOW DOES THIS CLOCK SYSTEM WHICH
I RECENTLY PREVIOUSLY FOUND HAD
A ROLE IN THE CYTOPLASM WHERE
IT'S PHOSPHORYLATED WHAT IS IT
DOING IN THE CYTOPLASM OF A
NEURON?
THE PROTEIN THIS AND THIS UNDER
GOES THE SAME PHOSPHORYLATION
EVENT AND TIMING IN THE SYNAPSE
AND HOW IT AFFECTED CORE
COMPONENTS TO ALLOW THE BRAIN TO
RESPOND IN PLASTICITY AND
RESILIENCE AND I'M SUMMARIZING
MANY YEARS OF WORK BUT WE FOUND
USING THE HIPPOCAMPAL NEURON AND
ISOLATED SYNAPSES AND THEN
STAINED THE SAMPLES WITH GOLD
AND ABLE TO IDENTIFY PARTICLES
IN PRE AND POST SYNAPTIC TER
TERMINI.
WHEN WE DID THIS IN SAMPLES
TAKEN IN CIRCADIAN TIME WE FOUND
THE DIURNAL VARIANT IN THE
PARTICLES IN SYNAPTIC TERMINI.
SUGGESTING THE RHYTHM WE THEN
SHOWED THIS IN VARIOUS OTHER
WAYS.
THIS IS A SUPER RESOLUTION
MICROSCOPY WITH NEURONS PLATED
IN A DISH AND YOU SEE THE TOP
STRIPS ARE THE PROCESSES.
THEN WE'RE LOOKING NOW AT A NANO
SCALE AT THE BMAL COLOCALIZING
WITH THE MARKER ON THE LEFT OR
ACTIVE ZONE MARKER OF THE
STRUCTURAL COMPONENT OF THE
PRESYNAPTIC TERMINIS.
YOU SEE IT SUGGESTS THE
SYNAPSES.
BMAL ARE FORM IN THE HIPPOCAMPAL
SUGGESTIONS AND WE LOSE THE
OVERLAP SUGGESTING A TRUE
OVERLAP OF SIGNAL.
WE HAVE BIO CHEMICAL FRACTIONS
OF MEMBRANES THAT ALLOW US TO
ENRICH SYNAPSES AND WE FIND IT
CORROBORATED WHAT WE FOUND BY
THE GOLD LABELLING OF THE
ELECTRON MICROGRAPH SHOWS THE
DIURNAL RHYTHM AND THE
PHOSPHORYLATED FORM SUGGESTS THE
PHOSPHORYLATED FORM I FOUND PAY
BE IMPORTANT IN REGULATING THE
SYNAPSE.
SORRY ABOUT THAT, AND I'LL TELL
EVERYONE WHAT THIS SHOWS.
MY APOLOGIES.
BUT WE ABLATE THE
PHOSPHORYLATION SITE.
INSTEAD OF SS42, THE SEARING WAS
CONVERTED AND CAN'T GET
PHOSPHORYLATED.
THE MOUSE IS IDENTICAL TO
REGULAR MICE EXCEPT THE ONE
POINT DEFICIENT AND THE BMAL
KNOCKOUT MICE LOSES CIRCADIAN
BEHAVIOR AND THESE MICE HAVE
NORMAL CIRCADIAN BEHAVIOR THAT'S
DEPENDENT ON THE TRANSCRIPTIONAL
RHYTHM.
SO THAT IS CONSISTENT WITH
PREVIOUS WORK WE HAD SHOWED THIS
PHOSPHORYLATION WHILE IMPORTANT
IN RHYTHMIC TRANSLATION AND SITO
PLASMIC IS NOT CRUCIAL TO THE
CORE TRANSCRIPTIONAL OSCILLATOR.
REMARKABLY TO US, THIS IS ONE OF
THE MORE EXCITING FINDINGS IS
WHEN YOU LOOK AT THE RHYTHM OF
BMAL IN THE SYNAPSE IN THE WILD
TYPE VERSUS MUTANT MOUSE IN THE
WILD TYPE WE SEE THE DIURNAL
DIFFERENT BETWEEN MORNING AND
EVE THING THAT WAS GONE IN THE
MUTANT.
THAT SUGGESTED THOUGH THE GLOBAL
OSCILLATOR, MECHANISMS
REGULATING GLOBAL BEHAVIOR ARE
IN FACT IN THE HOUSE BUT THE
LOCAL MECHANISMS IN SYNAPSE ARE
LOST.
WE CORROBORATED THE SAME FINDING
BY ELECTRON MICROSCOPY.
NOT ONLY BY SYNAPTOSOMES BUT THE
PHOSPHO MUTANT ANIMAL HAD IT
LOST.
HOUSE THIS WORK?
-- HOW'S THIS WORK?
GOOD QUESTION.
ONE THING WE DID WAS DID BIO
CHEMISTRY AND TOOK BMAL FROM THE
SYNAPSES AND IMMUNOPRECIPITATED
IT AND WERE ABLE FROM MA MASS SC
AND THIS IS IMPORTANT FOR HEART
FUNCTION THOUGH I WON'T TALK
ABOUT THAT.
AND WE WERE EXCITED BY THIS
BECAUSE THERE'S WORK SUGGESTING
IMPORTANCE OF IT IN SLEEP
REGULATION AND PLASTICITY AND
CIRCADIAN TIME.
THIS WAS INTERESTING TO US.
TO CORROBORATE THE MASS SPEC
DATA WE DID EXPERIMENTS AND LET
ME QUICKLY REVIEW HOW CAM K II A
WORKS BY FORMING THE TWO RINGS
AND FORMS A HOLLOW DECAMER BY A
LINKER DOMAIN AND HUB DOMAIN.
AND MAINTAINS A RHYTHM OF BIO
CHEMICAL ACTIVATION.
IF YOU USE REPORTERS TO
DEMONSTRATE THAT YOU CAN SEE AS
YOU ADD CALCIUM OR GLUTAMATE THE
KINASE INCREASES THE CALCIUM IN
THE CELL AND CONVERTS IT INTO A
BIO CHEMICAL EVENT.
IF YOU ABLATE THE AUTO
PHOSPHORYLATION EVENT THAT'S
CALCIUM DEPENDENT AND GO FROM
DARK GREEN TO LIGHT GREEN.
YOU LOSE THE ACTIVATION OF THE
KINASE.
IF YOU MAKE ONE THAT CAN'T CAN
EXCHANGE IT'S GIJIGIST -- JUST
ALL THE TIME IS BLAKE AND NEEDS
A DYNAMIC RANGE TO GO FROM OFF
TO ON TO COMPUTE AND YOU'LL SEE
WHY IT'S IMPORTANT IN A MOMENT.
>> YOU HAVE TWO MINUTES.
>> OKAY.
WHAT WE FOUND IS WE CORROBORATED
IT INTERACTS AND IT INTERACTS
WITH CAMKIIA IN THE PROXIMITY
LABELS AND THIS SHOWS THE BMAL
AND CAMKIIA CO-LOCALIZE AND WHAT
WE FOUND TO OUR IS BMAL WE
THOUGHT WOULD BE A SUBSTRATE BUT
IT TURNS IT ON AND THIS IS
SHOWING CELLS THE CAMKIIA IS
HIGH.
WE SHOWED IN CELLS WHERE WE USE
THE WILD TYPE ANIMALS OR 42A
PHOSPHO MUTANT THE KINASE IS
OPEN WHEN IT'S NOT
PHOSPHORYLATED.
THESE ARE FIBROBLASTS.
THAT'S REMARKABLY SIMILAR TO
WHAT WE DID WITH PLASTICITY ON
THE HIPPOCAMPUS AND YOU
STIMULATE WITH A TONIC STIMULUS
AND WERE ABLE TO SHOW A
CIRCADIAN RHYTHM TO THE
PLASTICITY SO HIGHER DURING THE
SLEEP PERIOD AND LOWER DURING
THE ACTIVE PERIOD AND IN OUR
MICE WITH NORMAL GLOBAL RHYTHM
THEY LOSE THE RHYTHM OF SYNAPTIC
PLASTICITY.
WE THINK IT'S IMPORTANT BECAUSE
THE MICE THOUGH THEY HAVE NORMAL
CIRCADIAN BEHAVIOR HAD IMPAIRED
MEMORY.
THEIR FEAR MEMORY KNOWN TO BE
CAMKIIA AND HIPPOCAMPUS
DEPENDENT WAS MARKEDLY IMPAIRED.
NEXT SLIDE.
I HOPE I TOLD YOU LIFE WITHOUT
KEEPING IS LIFE WITHOUT CONTEXT.
THE GOAL FOR US IS TO PUT THE
CONTEXT BACK.
WHAT CAN WE DO TO PUT THE ARROWS
BACK IN THE CLOCK?
NEXT SLIDE.
SO BMAL ORGANIZING SYNAPTIC
FUNCTION IN A CAMKIIA DEPENDENT
MANNER.
RHYTHMS OF PHOSPHORYLATION COULD
GO TO TIMING OF PLASTICITY.
I THINK INFORMATION NOT JUST
THESE CORE MECHANISMS IN THE
NUCLEUS BUT THE CYTOPLASMIC CAN
GO TO MORE THAN JUST THE GENES
THAT GET TURNED ON AND OFF AND I
WANT TO THANK THE PEOPLE IN MY
LAB AND FUNDING SOURCES AND MANY
COLLABORATORS.
MOST OF WHAT I TOLD YOU WAS DONE
BY MY POSTDOC.
THANK YOU.
>> THANK YOU SO MUCH,
DR. LIPTON.
THAT WAS WONDERFUL.
NOW WE HAVE ABOUT 24 MINUTES FOR
A Q&A SESSION.
IF WE CAN HAVE DR. CHENG AND
DR. BROUSSARD JOIN US AND I'LL
BRIEFLY SUMMARIZE WHAT WE HEARD.
I'D LIKE TO THANK OUR SPEAKERS
FOR FANTASTIC TALKS.
WE HEARD FROM DR. BROUSSARD
ABOUT HER IN PATIENT LAB STUDIES
SHOWING INSUFFICIENT SLEEP IS
RELATED TO INTERSTITIAL GLUCOSE,
BLOOD PRESSURE, VASCULAR
FUNCTION AND MARKERS OF BRAIN
INJURY AND NEUROINFLAMMATION AND
PRESENTED DATA ON CIRCADIAN
MISALIGNMENT AND A NEWER AREA
COUNTER MEASURES INCLUDING TIME
RESTRICTED EATING IN HEALTHY
YOUNG ADULTS AND HOW TIME
RESTRICTED EATING WAS ASSOCIATED
WITH PRODUCTIONS IN INTERSTITIAL
GLUCOSE AND ASSOCIATED WITH
LIPID OMICS WHICH IS
INTERESTING.
AND GAVE US PREVIEW OF WHAT
SHE'S GOING TO BE WORKING ON AND
HOW TO OPTIMIZE CIRCADIAN TIMING
OF EATING.
AND DR. CHENG GAVE A FANTASTIC
TALK AND HELPED US
OPERATIONALIZE RESISTANCE AND
CIRCADIAN HEALTH AND PHASE,
PERIOD AND AMPLITUDE.
I LIKED WHAT DR. CHENG SAID THAT
RESILIENCE IS THE ABILITY TO
BEND NOT BREAK.
WE TALKED ABOUT KEY QUESTIONS.
CAN WE IMPROVE ENTRAINMENT AND
HE ALSO SHOWED INTERESTING DATA
THAT PATIENTS IN BRIGHTER ROOMS
IN HOSPITALS HAD SHORTER LENGTHS
OF STAYS.
AND THOSE WHO LACKED CBTI
REDUCED DEPRESSION BY 50% AND
THIS FACILITATED ADAPTATION AND
REDUCED RESURGENT INSOMNIA AND
DR. LIPTON TALKED ABOUT
CIRCADIAN CLOCKS AND IMPACT OF
DISEASE FROM THE NEUROLOGICAL
PERSPECTIVE.
HE EXPLAINED HOW CIRCADIAN
CLOCKS ARE PREDICTION TOOLS AND
HELP TO ORIENT US TO THE EARTH
AND MOST NEUROLOGICAL DISORDERS
ARE ASSOCIATED WITH SOME
CIRCADIAN DYSFUNCTION.
AND B MAL1 AND HOW IT INTERACTED
WITH CAMKIIA ENZYME AND
IMPLICATIONS FOR CIRCADIAN
RHYTHMS.
THANK YOU AGAIN TO OUR SPEAKERS.
I'LL TURN TO THE QUESTIONS WE
HAVE NOW.
WE HAVE A FEW IN THE Q&A AND
CHAT AND A BROAD CHEQUESTION IN
APPLYING QUESTION TO HEALTH CARE
PROVIDERS OR FACILITIES WHERE
PATIENT SLEEP IS CONSTANTLY
DISRUPTED AND GETTING BLOOD WORK
DONE AND CHECK-INS.
IS THERE A WAY IN THE HEALTH
CARE SETTING YOU WOULD SUGGEST
TO IMPROVE SCHEDULES TO ALLOW
PATIENTS TO HAVE BETTER SLEEP
CYCLES OVER ALL?
>> THERE'S A FEW STUDIES ONGOING
THAT ARE TESTING THIS.
SOME FROM DR. KENAUR AND ANOTHER
GROUP HAS ALSO BEEN LOOKING AT
THIS BUT IT'S A HUGE AREA OF
NEED BECAUSE AS I UNDERSTAND IT
MISTAKE -- MOST SERVICES AT THE
HOSPITAL ARE NOT BASED ON
CIRCADIAN RHYTHM BUT WHEN STAFF
CAN GET THEIR LABS DONE.
THERE'S HUGE POTENTIAL TO DO
BETTER.
>> I DON'T THINK MANY OF US ARE
STUDYING THAT DIRECTLY IN THE
SETTING BUT I AGREE THERE'S MANY
SIGNIFICANT IMPLICATIONS OF THE
WORK TO BE APPLIED TO HEALTH
CARE SETTING.
AND EVEN INCLUDING TIMING OF
MEDICATION THERAPY WHICH WE
DIDN'T REALLY TALK ABOUT YET BUT
PROBABLY WILL ON DAY TWO.
THANK YOU FOR THAT.
THIS IS FOR DR. BROUSSARD SINCE
YOU TALKED A LITTLE BIT ABOUT
TIME RESTRICTED EATING AND
CIRCADIAN EATING.
THERE WAS A QUESTION ABOUT REAL
WORLD APPLICATION OF TIME
RESTRICTED EATING.
START EARLY AND UNTIL THEY'RE
DELAYED TO A MORE APPROPRIATE
HOUR, SHOULD WE BE ENCOURAGING
STUDENTS TO DELAY OR SKIP
BREAKFAST RATHER THAN EATING
EARLY MORNING WHEN GLUCOSE
TOLERANCE IS IMPAIRED AND MAKE
THEM MORE INTOLERANT TO THE
DIFFERENCES IN THE EARLY MORNING
AWAKENINGS.
DR. BROUSSARD IS MUTED.
THANK YOU FOR PUTTING THAT IN
THE CHAT.
COULD THE A/V TEAM UNMUTE
DR. BROUSSARD.
>> THAT WAS MY FAULT BECAUSE I
MUTED AND THEN LOST CONTROL.
THAT'S A GOOD QUESTION.
AS I POINTED OUT IN MY
DEFINITION OF CIRCADIAN
MISALIGNMENT EATING DURING THE
BIOLOGICAL NIGHT, IF THAT
REPRESENTS THE BIOLOGICAL NIGHT
IN KIDS AS YOU MENTIONED WOULD
BE A TYPE OF CIRCADIAN
MISALIGNMENT.
THE COOL PART ABOUT THAT
QUESTION IS I THINK THERE'S A
LOT OF MORE RESEARCH THAT CAN BE
DONE INTO WHAT IT MEANS TO BE
AWAKE AND FASTING PRIOR TO THE
FIRST MEAL BEFORE LIKE SLEEPING
UNTIL YOU'RE HABITUAL TIME AND
THEN EATING.
LIKE PERSONALLY, SO I TOTALLY
ANECDOTALLY I AVOID EATING
DURING MY BIOLOGICAL NIGHT.
IF I HAVE TO WAKE UP MORNING I
DO THAT BUT THAT'S NOT BASED ON
ANY EVIDENCE.
A LOT OF OUR IN-PATIENT STUDIOS
WE DO THE FIRST MEAL OF THE DAY
PLUS ONE HOUR AFTER WAKING BUT
IN OTHER STUDIES THAT I'VE
WORKED ON IN THE PAST WE DID IT
BASED ON CLOCK TIMES.
THE ACTUAL TIME OF THE MEAL WAS
MATCHED BUT PARTICIPANTS MAY
HAVE WOKEN UP FOR OR FIVE HOURS
EARLIER.
I THINK WE DON'T REALLY KNOW THE
IMPLICATIONS OF WHAT THAT AWAKE
FASTING MEANS.
>> RIGHT.
>> I THINK THE KEY IF I
UNDERSTAND IT, ONE OF THE
BIGGEST CHALLENGES FOR THE
APPLICATION OF THESE IDEAS TO
THE CLINIC AND THESE
IMPLICATIONS IS PHASE AND
MEASURE THEM THAT'S POSSIBLE
WITHOUT TAKING SOMETHING FROM
SOMEONE EVERY FOUR HOURS.
THERE'S LOTS OF GROUPS WORKING
ON THIS BUT THAT'S KEY.
YOU CAN'T ANSWER THE QUESTION IF
YOU DON'T KNOW THE INDIVIDUAL'S
PHASE AND THE VAST MAJORITY OF
PEOPLE ARE WITHIN A NARROW
WINDOW BUT THERE WILL BE
OUTLIERS FOR WHICH EARLY
INTERVENTIONS COULD POTENTIALLY
BE HARMFUL IF WE DON'T KNOW HOW
IT'S AFFECTING AND ARE THEY
MISALIGNED OR NOT OR MISALIGNED
IN A SIGNIFICANT WAY OR NOT.
>> GREAT POINT.
IT REQUIRES SOME DEGREE OF
PERSONALIZED MEDICINE TO
DETERMINE IF SOMEONE IS
MISALIGNED OR NOT.
THANK YOU FOR THAT.
DR. LIPTON THERE'S ANOTHER
QUESTION IN THE CHAT FOR YOU.
BASED ON YOUR RESEARCH, HOW CAN
WORK MEMORY BE IMPROVED IN
CHILDREN WITH ADHD AND CIRCADIAN
MISALIGNMENT?
>> GREAT QUESTION.
I DON'T KNOW THE ANSWER TO THAT.
I THINK VERY BRIEFLY THERE'S
PROBABLY VERY STRONG
INTERSECTION BETWEEN NEU
NEUROMODULATORY SYSTEM AND THE
CIRCADIAN CLOCK.
WE'VE EXTENDED SOME OF THE WORK
I SHOWED TO LOOK AT
NEUROMODULATOR SYSTEMS BUT IT'S
NOT READY FOR PRESENTATION YET.
I THINK VERY BROADLY SPEAKING,
WORKING MEMORY WOULD BE EXPECTED
TO BE IMPROVED BY BETTER
ALIGNMENT OF CIRCADIAN RHYTHMS
BECAUSE WORKING MEMORY BOTH
CERTAINLY IN ANIMAL MODELS FOR
SURE IS GATED BY THE CLOCK.
I THINK ANYTHING THAT'S GOING TO
HELP ALIGN THE CLOCK LIKE SOME
THINGS MY COLLEAGUES HAVE
PRESENTED WOULD BE EXPECTED TO
AFFECT WORK MEMORY.
WHETHER IT'S DIFFERENT FOR A
COHORT OF ADHD BECAUSE OF THE
CHANGES IN DOPAMINE AND
NEUROMODULATOR SYSTEMS IS A
LAYER OF COMPLEXITY WE'RE NOT
ABLE TO ADDRESS YET BUT
HOPEFULLY WE'LL GET THERE.
>> OKAY.
TO BE DETERMINED, THANK YOU.
A QUESTION FOR DR. BROUSSARD.
WHETHER MEALS DURING PROTOCOLS
WERE HIGHER IN PROTEIN OR CARBS
OR FAT AND AFFECTED METABOLIC
AFFECTS.
>> I LIKE THAT QUESTION BECAUSE
I'M HOPING THAT'S GOING TO BE
OUR RENEWAL.
WE ARE NOT TRYING TO MANIPULATE
MACRO NUTRIENTS.
WE ARE TRYING TO KEEP THEM OUT
OF THE NIGHT IN THE SHIFT WORK
PROTOCOLS.
I DO THINK FOR PEOPLE WHERE IT'S
NOT FEASIBLE OR MAY NOT WANT AN
EMERGENCY SERVICES WORKER
FASTING OVERNIGHT WHEN THEY NEED
TO MOBILIZE ENERGY QUICKLY,
THERE MAY BE OTHER WAYS TO
MANIPULATE MACRO NUTRIENTS AND
IS IT CARBOHYDRATES AT NIGHT
DRIVING IT AND HAVE A NIGHT
SCIENCE IDEA YOU CAN HAVE
SOMEONE SLEEP AND INFUSE
DIFFERENT MACRO NUTRIENTS SO
YOU'RE DISENTANGLING THAT TO
LOOK AT WHAT IS DRIVING THE
IMPAIRMENT.
WHEN THINKING ABOUT THE MACRO
NUTRIENTS THERE'S ANOTHER IDEA
SOMEONE COULD DO IS GIVEN THE
BACKGROUND THAT HIGH FAT DIET IN
MICE LEADS TO ARRHYTHMICITY AND
LEAD THAT TO MANIPULATE THE
CIRCADIAN SYSTEM?
I THINK THE IDEA OF MANIPULATING
THE MACRO NUTRIENTS IS A COOL
AREA FOR SURE.
>> AND ANOTHER QUESTION FOR
DR. LIPTON, I WONDER IF THE
EXPRESSION WAS TESTED IN DAY AND
NIGHT AND ACROSS LIFE SPAN OF
THE ANIMAL MODEL.
S
>> IT'S BEEN LOOKED AT BY A
NUMBER OF GROUPS AND THE SHORT
IS CLOCK AMPLITUDE IS SUPPRESSED
WITH AGING.
THAT'S THE BRIEF VIM SUMMARY
AND WE'RE LOOKING AT HOW THE
SYNAPTIC RHYTHM MAY BE AFFECTED
IN AGE AND AGE-RELATED DISORDER.
I'M EXCITED TO LOOK AT THAT.
WE HAVE A HINT THE
PHOSPHORYLATION MECHANISM MAYBE
DISRUPTED BUT WE DON'T KNOW YET.
BUT THANKS FOR THAT QUESTION.
>> THANK YOU.
THERE WAS ALSO A QUESTION
DR. CHENG ANSWERED IN THE CHAT.
I COULD ASK YOU LIVE AND IF
ANYONE ELSE WANTS TO CHIME IN.
FOR TE DATA PRESENTED TODAY,
WHICH CLINICAL TESTS COULD BE
DONE TO GET A ROUGH IDEA OF A
PATIENT'S CIRCADIAN REGION IF
THEY EXIST?
DR. CHENG DO YOU WANT TO START
WITH WHAT YOU ANSWERED?
>> SURE.
THERE ARE A NUMBER OF TOOLS LIKE
MY COLLEAGUES DESCRIBED.
WE HAVE NOW VALIDATED A PROCESS
TO TAKE ACTIVITY DATA FROM A
WATCH OR A WEARABLE LIKE AN
APPLE WATCH.
AND MAKE SOME PRETTY DECENT
PREDICTIONS OF MELATONIN ONSET
SO THIS WOULD BE DATA COLLECTED
IN THE FIELD BUT THEN REBRING
THEM INTO THE LAB AND DO
STANDARD TESTS FOR CONCORDANCE.
SO FAR WE'RE DOING PRETTY WELL.
IF YOU WANT TO GET ROUGH IDEAS
INTO MOSTLY HEALTHY OR ENTRAINED
POPULATIONS THEY'VE DONE A GOOD
JOB AND OTHER WORK SHOWS THE
MORNING AND EVENING AT SCALE AND
COMMUNITY POPULATIONS AND A
DECENT JOB TO FOR AN ESTIMATE.
THOSE ARE GOOD PLACES TO START.
THERE ARE BLOOD MARKERS, GENETIC
MARKERS WE'RE ALSO TESTING.
>> DOES ANYONE ELSE WANT TO
CHIME IN ON THAT QUESTION WAYS
TO GET A ROUGH IDEA OF PATIENT
CIRCADIAN RHYTHM?
>> I THINK THERE'S -- I THINK
AT
ATIGRAPHY IS GREAT AND THERE'S A
GENE EXPRESSION-BASED OUTPUT.
TAKING LIKE A HUMAN HAIR AND GET
FIBROBLASTS OR SKIN FIBROBLASTS
OR EVEN FROM A SMEAR FOR
EXAMPLE.
IT CAN ASSESS 40 OR 50 GENES YOU
CAN GET A FAIR ASSESSMENT OF
PHASE THE TIME YOU GET THE
ASSESSMENT.
IT DEPENDS ON WHEN YOU GET THE
BIOLOGICAL OR CELLULAR DATA.
>> THERE'S A WAY TO INTEGRATE
THE METHODS TO GET A PRECISE
MEASUREMENT.
>> AND A QUESTION FOR
DR. BROUSSARD.
I SAW THE DATA YOU SHOWED ON
TIME RESTRICTED FEEDING AND
OMICS AND BELIEVE YOU SHOWED
LIPID OMICS.
ARE YOU LOOKING AT ANY OMICS
LIKE METABOLOMICS AND WHAT WOULD
YOU PROPOSE THE AND PATHWAYS FOR
WHICH TIME RESTRICTED FEEDING
LEADS TO CARDIOVASCULAR
OUTCOMES.
IS THAT THE GOAL?
>> THAT'S THE GOAL OF THE LIPID
OMICS WE RAN.
WE DON'T HAVE ANY OTHER OMICS
RUN ON THOSE SAMPLES THOUGH I'M
OPEN TO IT.
IF WE'RE INTERESTED IN THE
PATHWAYS THAT MAY BE DRIVING
IMPROVEMENTS.
IT'S ALSO BECAUSE THE FASTING
TIME IS DIFFERENT IT'S -- IT'S
WHAT YOU'D EXPECT THE OMIC
OUTCOMES AND LIPIDS ARE DOWN
BECAUSE WHEN WE SAMPLED THEY HAD
BEEN FASTING LONGER.
I NEED TO BE MORE THOUGHTFUL WHY
WE'RE DOING THAT AND HOW TO
INTERPRET IT BECAUSE IT'S GOING
TO BE DRIVEN BY THE FASTING
DURATION.
AND LOOKING AT WHAT TYPE OF
LIPIDS.
WE COULD EXPECT LIPIDS TO GO
DOWN BUT THE COMPOSITION OF
LIPIDS AND FAMILIES AND SPECIES
THAT MIGHT BE CHANGING BASED ON
THE INTERVENTION.
>> QUESTION FOR DR. CHENG.
ONE OF THE OVER ARCHING GOALS OF
THE WORKSHOP IS TO THINK ABOUT
HOW SOME OF THE TRADITIONAL
OUTCOMES THAT WE HAVE BEEN
LOOKING AT IN TERMS OF SLEEP AND
CIRCADIAN RESEARCH AND
CARDIOVASCULAR RISK COULD BE
SHIFTED TO A MORE CARDIOVASCULAR
RESILIENCE FOCUS AND I SAW IN
SOME OF NUR DATA YOU SHOWED YOU
MEASURED THINGS LIKE INTRUSIVE
THOUGHTS WHICH WAS INTERESTING.
IS THAT SOMETHING YOU SUGGEST
RESEARCHERS WHO TRADITIONALLY DO
SLEEP AND CARDIOVASCULAR DISEASE
RESEARCH MAY START TO
INCORPORATE AS AN EXAMPLE OF AN
OUTCOME WE GET MORE RESILIENCE
OR OTHER OUTCOMES RESILIENT
FOCUS YOU SUGGEST WE
INCORPORATE?
>> GREAT QUESTION.
THANK YOU FOR THAT.
MY BIAS AS A PSYCHOLOGIST IS
STRESS AND VASCULAR FUNCTIONINGS
GO HAND IN HAND.
IT'S IMPORTANT TO HAVE A BIGGER
PICTURE OF WHAT IS GOING ON
BECAUSE IT ALSO HELPS US
UNDERSTAND GENERALIZABLE.
TO YOUR POINT A MORE POEFRL MOVE
WE SHOULD HAVE IS DIFFERENTIATE
RISK FROM RESILIENCE.
I THINK IT'S EASY TO THINK ABOUT
ON A CONTINUUM AND THEY MAY BE
DIFFERENT GOING BACK THAT
RESILIENCE IS NOT JUST THE
ABSENCE OF PATHOLOGY.
YOU COULD HAVE ABSENCE BY NOT
HAVING ANY STRESS EXPOSURES
LIVING A WELL PROTECTED LIFE
WITH LOTS OF RESOURCES.
OR YOU COULD BE RESILIENT IN HOW
YOU HANDLE CHALLENGES.
>> THAT'S INTERESTING TO THINK
ABOUT.
THANK YOU FOR THAT.
DR. LIPTON, ANOTHER GOAL IS WAYS
TO INCORPORATE DIFFERENT
DISCIPLINES.
AND DO YOU COLLABORATE WITH
OTHER TYPES OF SCIENCES IN YOUR
WORK AND IF YOU DO, COULD YOU
GIVE AN EXAMPLE HOW YOU DO THAT?
>> YEAH, I'M A PHYSICIAN
SCIENTIST.
I HAVE MANY COLLEAGUES WHO
ARE -- I SEE PATIENTS BUT ON A
VERY LIMITED BASIS.
I WOULD SAY YES, I COLLABORATE
WITH CLINICIANS.
WE'RE DOING A SERIES OF
TRANSLATIONAL PROJECTS.
I THINK ONE OF THE BEAUTIES OF
CIRCADIAN RHYTHMS AS I AND OTHER
SPEAKER HAVE SAID THEY'RE TRULY
MULTI-SCALED.
WHAT'S BEAUTIFUL IS YOU CAN
STUDY A SYSTEM THAT HAS
BEHAVIORAL OR EVEN SOCIAL
PHENOTYPES AND STUDY THEM AT A
MECHANISTIC LEVEL AND BECAUSE
THE SYSTEM IS MANIFEST AT THE
LEVEL OF COMPLEX CELLULAR
INTERACTIONS AND INDIVIDUAL
CELLS SO IT'S FUNDAMENTALLY A
CELLULAR SYSTEM.
WE CAN TAKE CELLS FROM PATIENTS
WITH UNDERLYING EXPOSURES OR
GENETIC DISORDERS AND UNPACK THE
INTERFACE BETWEEN THAT
BACKGROUND AND THE MECHANISM.
I THINK THIS NEEDS TO BE PART OF
THE FUTURE.
ONE OTHER THING I'LL MAKE A
QUICK PLUG, ONE THING THAT'S
CHALLENGING AS A PHYSICIAN IS I
THINK CHRONOBIOLOGY AND
CIRCADIAN RHYTHMS IS SOMETIMES
OFTEN AUTOMATICALLY ASSOCIATED
WITH SLEEP.
WHICH CAN FINE, IT'S OFTEN
ASSOCIATED WITH SLEEP BUT FAR
BROADER.
WE NEED TO THINK ABOUT HOW TO --
WHEN GO TO THE HOSPITAL AND
PEOPLE SAY WHAT DO YOU WORK ON
AND ASK WHAT DO YOU DO AND I SAY
CIRCADIAN RHYTHM AND THEY SAY
SLEEP.
YES, HOMEOSTATIC RESILIENT
SYSTEM THAT CAN BE APPLIED TO
THE HEART OR BEHAVIOR OR APPLIED
TO OBESITY, LIFE SPAN,
DEVELOPMENT, CANCER.
I THINK NOW'S THE TIME.
THE UNDERLYING MECHANISMS ARE
BEING WORKED OUT.
IT WON THE NOBEL PRIZE A FEW
YEARS AGO AND KNOW ABOUT THE
MECHANISMS.
NOW IT'S TIME TO GET EXCITED
ABOUT APPLYING IT.
YES, WE NEED TO COLLABORATE.
>> YOU MADE TERRIFIC POINTS THE
CIRCADIAN SYSTEM COULD BE
APPLIED BROADLY TO A NUMBER OF
DIFFERENT SYSTEMS.
I THINK WE HAVE TIME FOR ONE
MORE QUESTION AND THERE'S A
QUESTION IN THE CHAT ABOUT
GRAZING.
HOW OLD EATING FREQUENCY BE A
MODIFIABLE ?
>> I DON'T KNOW WE EVIDENCED
THAT FOOD INTAKE IS IMPACTING
THE INTERNAL CLOCK AND A GROUP
SHOWED AND IF LIGHT NIGHT
SNACKING COMES WITH LIGHT
EXPOSURE THERE'LL BE POTENTIAL
SHIFTING.
I LOVE DR. CHENG'S PRESENTATION
IN ENHANCING RHYTHMS IF CAN COME
OUT OF THE SYSTEM WITH DIFFERENT
WAYS WE COULD POTENTIALLY
ENHANCE THE SYSTEM AND THAT
MIGHT BE AN INTERESTING AND
IMPORTANT NEXT STEP AND WHAT
DOES AMPLITUDE MEAN
PHYSIOLOGICALLY?
DO WE KNOW AND LOOKING AT TIMING
AND PHYSICAL ACTIVITY COMING AT
DIFFERENT CLOCKS TO ENHANCE
RHYTHMS.
>> THAT'S A VERY EXCITING AREA.
NOW TO END THE SESSION RIGHT AT
2:50.
WE HAVE A 10-MINUTE BREAK AND
BACK AT 3:00 FOR NEXT HALF OF
OUR SESSION.
I WANT TO THANK OUR FIRST THREE
SPEAKERS AND HOPEFULLY WE'LL SEE
YOU BACK AT THEN OF TODAY FOR
THE PANEL DISCUSSION.
SEE EVERYONE ELSE AT 3:00.
THANK YOU.
WELCOME, DR. JELIC AND WE'LL GET
YOUR SLIDES UP AND YOU CAN TAKE
IT AWAY.
>> THANK YOU, BROOKE.
I WILL TALK ABOUT INSUFFICIENT
SLEEP AND CARDIOVASCULAR RISK.
I LIKE THE TERM BECAUSE IT
DESCRIBES BETTER WHAT'S
HAPPENING BECAUSE SHORT SLEEP
COULD BE OKAY FOR SOMEONE BUT
NOT FOR THE OTHER PERSON.
IT ALSO CHANGES DURING LIFE
SPAN.
I THINK INSUFFICIENT SLEEP WOULD
BE BETTER TERM TO USE FOR THESE
PURPOSES.
I'LL GO OVER INSUFFICIENT SLEEP
A
AND THIS BEHAVIOR IS MORE
PREVALENT IN HISPANIC AND
NON-HISPANIC BLACKS AS MENTIONED
IN MORE DETAIL THIS MORNING AND
THOSE WITH LOWER SOCIO ECONOMIC
STALTS.
THE PREVALENCE OF OF SHORT SLEEP
IS INCREASING OVER TIME.
THIS STUDY FOUND THE INCREASE
FROM 1970s TO 2010.
AND ALONG THE STUDIES SPANNING
THE ENTIRE 20th CENTURY FOUND
YOU SHORTEN SLEEP BY ONE HOUR
COMPARED TO THE BEGINNING OF THE
20th CENTURY.
THAT'S QUITE SIGNIFICANT.
THE TIME WE TAKE FROM SLEEP NOT
SPENT ON LEISURE OR ANYTHING
PLEASANT BUT UNPAID WORK AND
COMMUTE.
INSUFFICIENT SLEEP HAS BEEN
INCREASED CARDIOVASCULAR RISK
AND I HIGHLIGHT THE
OBSERVATIONAL TERM BECAUSE I
WILL MOSTLY TALK ABOUT SOME
CAUSAL EVIDENCE LATER UPON I
JUST LISTED HERE MANY STUDIES
SPANNING THE PAST 20 YEARS AND
HIGHLIGHTED THESE THREE WHICH
ARE FAMILIAR TO MOST OF YOU THAT
ARE ALSO OBSERVATIONAL
CROSS-SECTIONAL RETROSPECTIVE
AND TO SUMMARIZE THE POPULATION
VARE
VARED THOSE THAT SLEEP LE LESS
THAN SIX HOURS PER NIGHT HAVE
INCREASED ATHEROSCLEROTIC BURDEN
AND PREVALENCE IN ATRIAL FIBRIL
AND ASSOCIATED WITH ALL CAUSE
MORTALITY REPEATEDLY.
BASED ON THIS OBSERVATIONAL
EVIDENCE, AMERICAN HEARD
ASSOCIATION SAYS AS DR. JONES
EXPLAINED IN THE FIRST TALK
TODAY, SHORT SLEEP INCREASES
CARDIOVASCULAR RISK.
AND THEY INCLUDED AS THE EIGHTH
METRIC OF CARDIOVASCULAR HEALTH
AND WE'RE NOW IN ILLUSTRIOUS
COMPANY SUCH AS PHYSICAL
ACTIVITY AND CHOLESTEROL AND
SUCH.
WHAT IS THE CAUSAL EVIDENCE AND
WHY IS THIS HAPPENING?
SO THE CAUSAL EVIDENCE FOR THE
LINK BETWEEN INCREASED
CARDIOVASCULAR RISK AND
INSUFFICIENT SLEEP IS DERIVED
FROM MOSTLY EXTREME SHORT-TERM
EXPERIMENTAL STUDIES.
MOST STUDIES IN HUMAN USE SLEEP
LASTING 2 HOURS TO TWO WEEKS AND
ANOTHER ANOTHER CAVEAT IS MOST
STUDIES HAVE A SMALL SAMPLE SIZE
IN AN IN ANIMAL MODELS I'M
TALKING ABOUT BOTH MICE WHICH
ARE THE MOST COMMON MODELS ARE
GENETICALLY MANIPULATED AND IT
SHORTENED THE LIFE SPAN AND
CAUSING DISEASE AND BMAL
KNOCKOUT MICE SHOW ACCELERATED
AGING.
EXTREME SHORT TERM SLEEP HAS
LIMITED RELEVANCE TO THE PROM
POPULATION OF SLEEP PATTERN MILD
CURTAILMENT TO MAINTAINING
WORK-LIFE BALANCE.
MOST PEOPLE HAVE TO GET UP IN
THE MORNING TO GO TO SCHOOL OR
WORK.
THIS SLEEP CURTAILMENT OCCURS IN
THE EVENING AND DELAY OUR BED
TIME FOR AN HOUR OR TWO.
WHAT IS THE MECHANISM AND IT
FOCUSES ON OXIDATIVE STRESS
THOUGHT TO PROMOTE INFLAMMATION.
SO ONE MAJOR FUNCTION SUGGESTED
MAJOR FUNCTION OF HEALTHY SLEEP
IS TO CLEAR OXIDATIVE STRESS
ACCUMULATED DURING WAKE
FULLNESS.
IT'S AN IMPORTANT CONTRIBUTOR TO
INFLAMMATION IN GENERAL AND ALSO
ENDOTHELIAL CELL INFLAMMATION
THIS RESULTS IN ENDOTHELIAL
DYSFUNCTION AND THAT IS KNOWN TO
BE A KEY STEP IN THE DEVELOPMENT
AND PROGRESSION OF
CARDIOVASCULAR DISEASES.
SO IN MODEL ORG FIXES SLEEP
RESTRICTION INFECTIOUSES
OXIDATIVE STRESS AND UPREGULATES
RESPONSE AND EXPERIMENTAL ORGAN
EXPRESSION SHOWS MIXED RESULT.
SO WE ASKED DOES MILD CHRONIC
SLEEP RESTRICTION OR CURTAILMENT
AFFECT ENDOTHELIAL OXIDATIVE
STRESS AND OXIDATIVE RESPONSE
AND OXYGEN?
WE WANTED TO STUDY THAT DIRECTLY
IN THE ENDOTHELIAL.
WE DEVELOPED METHODS TO HARVEST
ENDOTHELIAL CELLS FROM PEOPLE.
THIS IS MINIMALLY INVASIVE OUT
PATIENT PROCEDURE WHERE WE LOOK
AT VASCULAR WIRES AND ABLE TO
RETRIEVE ENDOTHELIAL CELLS THIS
WAY.
WE FIRST LOOKED AT WOMEN AND THE
RATIONALE IS THAT WOMEN REPORT
SLEEP DISTURBANCES MORE OFTEN
THEN MEN INCLUDING IN MULTIPLE
SURVEYS SLEEP A FEW MINUTES
LONGER THAN MEN HOWEVER WE LIKE
TO COMPLAIN MORE ABOUT IT.
WOMEN HAVE MORE PRONOUNCED
INFLAMMATORY RESPONSE TO SLEEP
RESTRICTION COMPARED TO MEN AND
HAVE A GREATER CARDIOVASCULAR
RISK ASSOCIATED WITH
INSUFFICIENT SLEEP THAN MEN.
THAT'S WHY WE FIRST DECIDED TO
STUDY WOMEN TO FIGURE OUT WHAT'S
GOING ON.
WE RANDOMIZED WOMEN WITHOUT
TAKING SUPPLEMENT AGE BETWEEN 20
AND 65.
PREDOMINANTLY EARLY MIDDLE AGE
AND RANDOMIZED THEM AND THEY HAD
TO HAVE BASELINE NORMAL SLEEP
DURATION AS DEFINED BY SEVEN TO
EIGHT HOURS AND CONFIRMED BY
SCREENING.
WE RANDOMIZED TO THEIR HABITUAL
SLEEP AND WE TOLD THEM TO GO TO
BED ONE AND A HALF HOURS LATER
THAN THEIR HABITUAL SLEEP TIME
WHICH WAS DETERMINED 37--
DETERMINED.
WE FOUND THAT IN THEIR
ENDOTHELIAL CELLS OXIDATIVE
STRESS WAS SIGNIFICANTLY
INCREASED OF THE SIX WEEKS OF
SLEEP RESTRICTION.
THE SLEEP DURATION WAS
OBJECTIVELY MONITORED
THROUGHOUT.
HOWEVER, TO OUR SURPRISE AND
HERE I'M PRESENTING AND THERE
WAS NO UPREGULATION DESPITE THE
INCREASE IN OX DATIVE STRESS.
AND THIS HIGHLIGHTS THE NEED TO
STUDY WHICH ORGANISMS WHICH ARE
USEFUL TO DELINEATE CERTAIN
PROCESSES.
WHAT IS HAPPENING HERE?
WE HAVE TO LOOK AT THE PATHWAYS
AFFECTED.
NOT MODEL ORGANISM ANTIOXIDANT
RESPONSES ARE REGULATED AFTER
SLEEP RESTRICTION ARE AND YOU
SEE IT HAS A TERRIBLY UNWIELDY
NAME AND THIS IS A RE-DUX
SENSITIVE TRANSCRIPTION FACTOR
KEPT IN THE LATE STATE THROUGH
THE INTERACTION WITH THE LIGASE
COMPLEX UNDERGOING DEGRADATION
AT ALL TIMES-THINK OF IT AS NF
KAPPA BETA 3 AND THIS LIGASE IS
INACTIVATED.
IT TRANS LOCATES BINDING TO
ELEMENTS AND ACTIVATED
ANTIOXIDANT GENES AND RESPONSES.
AND IT COUNTER ACTS INEFFICIENT
SLEEP.
CAN CLICK A FEW MORE TIMES.
AND THIS IS TRANS LOCATED INTO
THE NUCLEUS BUT WE LOOKED AT THE
ENDOTHELIAL CELLS AND THERE WAS
NONE IN THE NUCLEUS WHATSOEVER.
AT THE SAME TIME, THE mRNA AND
PROTEIN WAS SIMILAR.
THAT'S NOT THE CAUSE.
AND HERE ON THE RIGHT SIDE WE
LOOKED AT THE WHERE IT'S HIDING
IF IT'S NOT IN THE NUCLEUS.
IT'S RETAINED AS INDICATED BY
THE INCREASED CO-LOCALIZATION.
IT'S REPRESSOR.
THIS DOESN'T GO IN THE NUCLEUS
AND ACTIVATE THE GENES.
SO WE WONDER WHY IS THIS
HAPPENING?
WHAT DOES MILD SLEEP RESTRICTION
HAVE TO DO WITH THIS?
WE TOOK AN UNBIASSED APPROACH
AND LOOKED AT THE UNHARVESTED
ENDOTHELIAL CELLS AND FOUND THAT
13 GENES WERE DIFFERENTIALLY
EXPRESSED.
THOSE IN GREEN DOWN REGULATED
AND IN RED WERE UPREGULATED.
WE LOOKED AT PROTEIN PRODUCT FOR
EACH OF THE GENES USING
PREDICTED PROTEIN INTERACTION
ALGORITHM AND WE LOOKED
SPECIFICALLY WHETHER ANY OF
THESE 13 GENES BINDS TO ANY PART
OF THIS UBIQUINATION PROCESS AND
INTERESTI
INTERESTINGLY THE DOMAIN
CONTAINING 3 WAS A TOP HIT FOR
BINDING TO A MAJOR REPRESSOR OF
NRF2.
WE FOUND IN RNA SEQ IT WAS DOWN
REGULATED AND CONFIRMED THAT
WITH RTPCR.
IT'S DOWN AFTER SLEEP
RESTRICTION.
WHAT DOES THIS DO?
THERE'S A TOTAL OF SIX PAPERS
ABOUT IT AND IN THE
NON-ENDOTHELIAL CELLS IT BINDS
AND SUPPRESSES TOWARDS THE
PLASMA MEMBRANE AND
DISASSOCIATES WITH NRF2 COMPLEX
AND FACILITATES THE ACCUMULATION
AND STOPS BEING DEGRADED IN THE
PROTEASOME AND TRANS LOCATE AND
INITIATE ACTIVATION OF
ANTIOXIDANT RESPONSE.
THIS WAS DOWN REGULATING.
SUGGESTING THAT IT MAY PLAY A
ROLE IN THE PROCESS.
SO, FIRST WE FOUND THAT THIS IS
DOWN AND PULLING LESS TOWARDS
THE PLASMA MOMENT BRAIN.
THIS WAS PUBLISHED IN A CARTOON
IN THE INTEREST OF TIME AND THIS
ALLOWS FOR DEGRADATION AND
DOESN'T ANTIOXIDANT RESPONSE OR
BLOCK OXIDATIVE STRESS.
WE DIDN'T KNOW MUCH ABOUT IT AND
WE INVESTIGATED WHAT REGULATES
THIS AND IT TURNS OUT IT'S
CALLED SERUM RESPONSE FACTOR
WHICH IS IS NOT IN THE SERUM,
IT'S INTRACELLULAR TRANSCRIPTION
FACTOR WHICH BINDS TO THE
ELEMENT AND IN FACT THAT'S HOW
IT WAS FIRST DISCOVERED AS A
TARGET OF SERUM RESPONSE FACTOR.
SO WE INTERROGATED WHETHER IT
WAS UP REGULATED OR DOWN
REGULATED AFTER SLEEP
RESTRICTION COMPARED TO ADEQUATE
SLEEP.
SO WHAT IS THIS SERUM RESPONSE
FACTOR DOING ACTUALLY?
THIS IS VERY INTERESTING BECAUSE
RECENTLY THE TRANSCRIPTION
FACTOR THAT PRIMES CEREBRAL
CORTEX RESPONSE TO SLEEP
RESTRICTION IN MICE AND YOU MAY
KNOW IT BETTER UNDER ITS NAME
BLISTER AND IT BLAZE A KEY ROLE
IN ACTIVITY DEPENDENT MODULATION
OF SYNAPTIC STRENGTH AND
REQUIRED TO INCREASE SLEEP
DURATION OF THE SOCIAL ENRIPMENT
AND HAVE NORMAL RESPONSE.
AND THE EXPRESSION OF THIS SERUM
RESPONSE FACTOR FOLLOWS THE
CIRCADIAN PATTERN AND AFTER
SHORT-TERM SLEEP RESTRICTION IN
MICE THE DAYTIME ABUNDANCE IS
REDUCED AND THAT RESEARCHEDS
WITH THE HARVESTING OF
ENDOTHELIAL CELLS IN OUR
PARTICIPANTS.
THIS STILL DOESN'T EXPLAIN WHY
MILD SLEEP RESTRICTION WOULD
MOVE THIS.
IT'S INTERESTING THE ACTION OF
SERUM RESPONSE FACTOR UPON
BINDING TO SERUM RESPONSE
ELEMENT LIKE THIS REQUIRES
PRESENCE OF GROWTH MORE
HORMONE.
THIS IS INTERESTING BECAUSE
DELAYING BED TIME IN THE SHORT
TERM STUDIES OF SLEEP
DEPRIVATION WAS SHEN TO BLUNT
THIS RELEASE OF GROWTH HORMONE
IN MEN AND WOMEN THOUGH WOMEN
HAD MORE BLUNTED PEAKS BUT BOTH
SEXES HAVE HIGH SPEED BETWEEN
11:00 P.M. AND 2:00 A.M. AND WE
WORKED ON THIS IN A CARTOON FORM
IN THE INTEREST OF TIME YOU CAN
CLICK ON THE NEXT SLIDE, PLEASE.
>> YOU HAVE TWO MINUTES.
THIS IS A SUMMARY OF WHAT IS
DESCRIBED SO FAR.
IN SLEEP RESTRICTION IF YOU
DELAY BED TIME THERE'S A
REDUCTION IN THE RELEASE OF
GROWTH HORMONE WHICH REDUCES THE
REACTION OF SERUM RESPONSE
FACTOR AND DOWN STREAM IT
REDUCES THE EXPRESSION OF THIS
WHICH DOES NOT GO TOWARDS THE
PLASMA MEMBRANE.
IT LEAVES IT IN A COMPLEX
UNDERGOING DEGRADATION AND DOES
NOT TRANS LOCATE TO THE NUCLEUS
AND DOES NOT ACTIVATE ANTIOX
DISTANT RESPONSES AND OXIDATIVE
STRESS REMAINS.
MELATONIN PREVENTS AUTOSOMAL
DEGRADATION.
A
AND ENDOTHELIAL MOTOR TONE IS
REDUCED.
REMEMBER, THESE ARE COMPLETELY
HEALTHY WOMEN.
THEY JUST SLEPT A LITTLE LESS
AND WE LOOKED AT THE
INFLAMMATION BY THE NUCLEAR
TRANS LOCATION AND FOUND IT'S
INCREASED AFTER THE MILD SLEEP
RESTRICTION COMPARED IT ADEQUATE
SLEEP.
THERE'S ACTIVATORS INSISTENCE
AND THEY WERE TESTED IN PATIENTS
WITH DIABETES BECAUSE IT WAS
SHOWN IN THE DIABETIC MICE THE
ACTIVATOR ATTENUATES
ATHEROSCLEROSIS AND
ANTIINFLAMMATORY PROPERTIES
CORRELATES BUT IN THE TWO TRIALS
PUBLISHED IN THE NEW ENGLAND
JOURNAL IT DID IMPROVE
ATHEROSCLEROTIC BURDEN BUT HAD A
VERY POOR SAFETY PROFILE.
AND HAS TO BE USED AND ANOTHER
INTEREST THING IS GROWTH HORMONE
SHOWN TO UPREGULATE AND REVERSES
THE NEGATIVE PROCESS.
I'M NOT SUGGESTING TO START
USING GROWTH HORMONE BUT SOME
COMPONENTS THE AND MELATONIN
WITH A GOOD SAFETY PROFILE.
AND WE HAVE TO LOOK AT THE
MELATONIN PROFILE AND WHETHER IT
CAN RECTIFY THE CHANGES.
AND MILE SLEEP DISTURBANCE MAY
OVERTIME INCREASE CARDIOVASCULAR
RISK AND SHOULD NOT ONLY ASK
ABOUT SLEEP QUANTITY BUT QUALITY
AND CONSULT INDIVIDUALS IN THEIR
HEALTH CARE ENCOUNTER ABOUT THE
IMPORTANCE OF ADEQUATE SLEEP
DURATION FOR THE CARDIOVASCULAR
HEALTH NOW THAT WE HAVE ACTUALLY
THESE CAUSAL BIOLOGICAL
EVIDENCE.
I'LL ACKNOWLEDGE MY LAB AND MY
COLLABORATORS AND BROOKE AND
FUNDERS.
>> NOW DR. FILIF SWIRSKI TALKING
ABOUT THE INFLUENCE OF SLEEP ON
BRAIN-BODY COMMUNICATIONS.
>> THANK YOU, BROOKE.
GOOD AFTERNOON, EVERYONE.
I WOULD LIKE TO IN THE TO
MINUTES I HAVE INTRODUCE ANOTHER
PROCESS WE STUDY THE EFFECTS OF
VARIOUS EXPOSOMES ON THE
CARDIOVASCULAR SYSTEM IN GENERAL
AND SPECIFICALLY IN THE LAST
SEVERAL YEARS ON BRAIN BODY
COMMUNICATION.
HOW DO PERSONAL EXPOSOMES SUCH
AS EXERCISE, DIET, STRESS AND
MORE GENERAL EXPOSOMES OVER
WHICH WE HAVE LESS CONTROL LIKE
POLLUTION, CLIMATE CHANGE OR THE
ENVIRONMENT SHAPE BRAIN BODY
COMMUNICATION IN THE CONTEXT OF
CARDIOVASCULAR HEALTH AND
DISEASE.
THE PROCESS WE'VE BEEN
INTERESTED IN STUDYING OVER A
NUMBER OF YEARS AND IS RELEVANT
FOR CONVERSATIONS WE'RE HAVING
TODAY PERTAINING TO
CARDIOVASCULAR HEALTH,
RESILIENCE AND SLEEP IS
HEMATOPOIESIS.
THE PRODUCTION OF IMMUNE CELLS
WHICH OCCURS PREDOMINANTLY BUT
NOTE EXCLUSIVELY IN THE BONE
MARROW.
THE REASON IT'S IMPORTANT AND
INTERESTING TO US AND
ATHEROSCLEROSIS OR THE
COMPLICATIONS DEPENDS ON AND IS
DRIVEN BY ACCUMULATION OF
LEUKOCYTES AND DRIVEN BY THE
INFLAMMATORY DISEASE AND
MYELOPOIESIS IN THE BONE MARROW
IS THE OTHER -- ORIGINATION OF
WHAT WE CALL INFLAMMATION AND
THAT GOES BACK TO SOME OF THE
EARLIER DISCUSSIONS ABOUT
SCALES.
AND INVOLVES INFLAMMATORY CELLS.
MANY ARE NEUTROPHILS AND
PRODUCED IN THE BONE MARROW.
WE THINK STUDYING THE PROCESS IN
THE BONE MARROW AND
UNDERSTANDING HOW IT'S
CONTRIBUTING TO THE GROWTH OF
LESIONS IN CARDIOVASCULAR HEALTH
AND DISEASE IN GENERAL IS
IMPORTANT.
SO HERE ARE SOME OF THE SPECIFIC
LIFESTYLE FACTORS WE HAVE
STUDIED AND TO BETTER UNDERSTAND
THE PROCESS AND THE ONE OF
COURSE THAT IS A SUBJECT OF
TODAY.
AND WE'RE NOT GETTING ENOUGH
SLEEP.
AND WE SHOULD BE GETTING
FORESLEEP -- MORE SLEEP IN THE
CONTEXT OF SLEEP APNEA OR IN THE
CONTEXT OF SLEEP FRAGMENTATION
ELEVATES RISKS FOR THE
PROFESSORS OF MYOCARDY
INFARCTION AND CARDIOVASCULAR
DISEASE.
WE HEARD THIS FROM A NUMBER OF
TALKS TODAY THAT SLEEP ELEVATES
RISK FOR CARDIOVASCULAR DISEASE
IN THE NUMEROUS STUDY.
SOME LARGE AND SOME SMALL
OBSERVATIONAL STUDIES THAT HAVE
SHOWN THIS IS THE CASE AND
DEMONSTRATED FOR EXAMPLE THE
INTERRUPTION OR FRAGMENTATION
INCREASE THE SIZES OF
ATHEROSCLEROTIC PLAQUE.
WE RECOGNIZE THE UNDERLYING
BIOLOGY REMAINS POORLY
UNDERSTOOD AND THIS IS VERY MUCH
AND MANY OF WHAT WE DO IN THE
LAB IS USED AND WE UTILIZED
SLEEP FRAGMENTATION WHERE MICE
SLEEP IN A CAGE WITH A SLEEP BAR
THAT INTERRUPTS THEIR SLEEP AT
DEFINED INTERVALS.
WE CAN GO NEXT AGAIN AND THIS
ALLOWS US TO TRACK SLEEP
FRAGMENTATION AND LOOK AT AWAKE
BOUTS AND VARIOUS ELEMENTS OF
SLEEP ARCHITECTURE.
THE WORK WAS DONE BY A FORMER
POSTDOC A PROCESS IN THE LAB AT
THE CARDIOVASCULAR RESEARCH
INSTITUTE AT SINAI.
AND SLEEP MODULATE THE IMMUNE
SYSTEM WHEN WE PUT THIS TOGETHER
INVARIABLY WE NEED TO TAKE A
TRANS DISCIPLINARY APPROACH.
AND USE OPTO GGENETIC APPROACHE
TO MANIPULATE NEURONS.
UNDERSTAND WHAT IS HAPPENING IN
THE BRAIN AND AS WE DISRUPT
SLEEP MODULATES HEMATOPOIETIC
SYSTEMS AND AND LOOK AT
CARDIOVASCULAR DISEASE WHETHER
ATH
ATHEIR -- ATHEROSCLEROSIS AND
THIS IS A CHALLENGE WE'LL
DISCUSS AT SOME POINT IN TERMS
OF STRUCTURING MECHANISM TO
ALLOW FOR TRANS DISCIPLINARY
WORK WHERE THERE'S SUFFICIENT
EXPERTISE TO LOOK AT AND USE AND
EVALUATE THE APPROACH.
AND LOOKING AT THE ROLE OF SLEEP
ON CARDIOVASCULAR AND LOOKED AT
ATHERO SCLEROTIC LESIONS AND
OVER TIME AS MICE ARE SUBJECTED
TO SLEEP FRAGMENTATION THE
ATHEROSCL SCSCLEROTIC LESIONS G
ASSOCIATED WITH AGE INCREASED
NUMBER OF INFLAMMATORY MONOCYTES
WE CAN RETRIEVE FROM THE BLOOD
AND SEE THE NICE CIRCADIAN
RHYTHM OVER THE COURSE OF A DAY.
SOMETHING WE ALREADY DISCUSSED
DURING TODAY'S SESSION ABOUT THE
VARIOUS CIRCADIAN FLUCTUATIONS
AND MONOCYTES AND NEUTROPHILS
ARE SUBJECT TO THE CIRCADIAN
RHYTHMS AND THERE'S TIMES OF DAY
WHERE WE SEE MORE MONOSITESSS -
MONOSITESITE -- MONOCYTES IN TH
BLOOD AND FRAGMENTATION INCREASE
THE AMOUNT OF MONOCYTES IN THE
BLOOD AND THEY'RE REQUIRED FOR
THE GROWTH OF ATHEROSCLEROTIC
LESIONS.
THIS GOES TO INCREASED PROCESS I
SPOKE ABOUT EARLIER WE FIND
HEMATOPOIETIC CELLS GIVE RISE TO
MONOCYTES IN HIGHER RATES.
AND TO SUMMARIZE THIS PART OF
THE STORY.
AND THE LESIONS GROW IN THE
LESIONS IN THE BONE MARROW.
AND IT'S A NEURO PEPTIDE
PRODUCED IN THE HYPOTHALAMUS
THAT ACTS AS A MODULATOR OF
HEMATOPOIESIS AND AS A BREAK ON
THE PRODUCTION OF MONOCYTES
BECAUSE IT LIMITS THE
AVAILABILITY OF THE FACTOR 1.
.
IF WE INTERRUPT SLEEP WHAT WE DO
IS INTERRUPT THIS NATURAL RHYTHM
AND DECREASE THE PRODUCTION AND
WHAT THIS MEANS IS THAT THE
BREAKS AND CSF LEVELS RISE AND
LEADS TO THE GROWTH OF
ATHEROSCLEROTIC LESIONS.
ONE QUESTION THAT CAME OUT OF
THE STUDY WAS HOW LONG LONG
LASTING ARE THE EFFECTS?
WE START TO TOUCH ON THE CONCEPT
OF RESILIENCE.
YOU CAN SEE DURING SLEEP
FRAGMENTATION THE BOUTS ARE
HIGHER BUT TAKES A WHILE.
IN FACT SEVERAL WEEKS FOR THE
MICE TO GO BACK TO THEIR NORMAL
BOUTS.
THERE'S A PROCESS WHERE THEY
RETURN BACK TO HOMEOSTASIS.
WHAT YOU SEE CONTROL MICE, MICE
SUBJECTED TO SLEEP FRAGMENTATION
AND THOSE SUBJECTED TO
FRAGMENTATION AND ALLOWED TO
RECOVER WE STILL HAVE
MONOCYTOSIS IN THE BLOOD AND
HAVE PROGENITOR CELLS AND
HEIGHTENED PROLIFERATION.
BUT IF WE WAIT 10 WEEKS ALL OF A
SUDDEN NOW WE FIND THE PROCESS
RETURNED TO HOMEOSTASIS AND
THERE'S A PROTRACTED PERIOD
WHERE THE CELLS RESPOND STILL
SUBJECTED TO SLEEP FRAGMENTATION
AND AT 10 WEEKS WE SEE MONOCYTE
NUMBERS RETURNING TO NORMAL AND
PROLIFERATION RETURNING TO
NORMAL AND THERE'S A CATCH I'LL
RETURN TO IN A MOMENT.
AND THEY'RE TRANSFERRED TO
RECIPIENT MICE AND WE WANT TO
TRACK THE TRANSFERRED CELLS TO
AN ENVIRONMENT THAT NEVER
EXPERIENCE THE FRAGMENTATION AND
THEN CAN DISTINGUISH BETWEEN THE
FRAGMENTED AND NON-FRAGMENTED
EXPERIENCE CELLS AND WE FIND
CELLS THAT WERE SORTED FROM MICE
SUBJECTED TO SLEEP FRAGMENTATION
CONTINUED TO PROLIFERATE AT A
HIGHER RATE EVEN IN THE NEW
ENVIRONMENT.
THERE'S A LONG LASTING AFFECT.
WE LOOK AT 24 HOURS AFTER THE
TRANSFER, THESE CELLS OUTCOMPETE
THE ONES FROM CONTROL MICE.
THERE'S ELEMENTS THAT ENDOW THE
CELLS WITH THE CAPACITY TO
PROLIFERATE AT A HIGHER RATE.
SINCE WE'RE LOOKING AT CELLS
THAT GO TO A NEW ENVIRONMENT
THIS SUBJECTS THERE IS SOME E
EPIGENETIC MANIPULATION OF THIS
WHICH LEADS US TO THIS SLIDE.
THIS MAY HAVE DISCUSSION ABOUT
RESILIENCE AND SUSCEPTIBILITY.
HERE WE'RE LOOKING AND PREPARING
THREE GROUPS, CONTROL ANIMALS
AND SLEEP FRAGMENTED ANIMAL AND
THOSE THAT RECOVERED AND LOOKED
AT ENHANCER REGIONS.
IF YOU LOOK AT THE BLUE THAT
TURN RED AND THEN BLUE, THESE
ARE ENHANCER REGIONS THAT
QUICKLY RECOVER AND THOSE THAT
GO BACK TO RED AND BLUE AND
THERE'S PRESERVED SIGNATURES
THAT LINGER AND 10 WEEKS IS NOT
ENOUGH TO CHANGE THEM AND MANY
MAP ON TO TO GENES INVOLVED IN
MYELODIFFERENTIATION AND CYCLINE
AND WE CAN MEASURE THEM AT THE
mRNA LEVEL.
THIS SO AN EXAMPLE OF ELEMENTS
IN THE EPIGENOME BEING EASY TO
RECOVER AND OTHERS BEING FAIRLY
STUBBORN AFTER 10 WEEKS OF
RECOVERY MAINTAINING THE
SIGNATURE ACQUIRED DURING SLEEP
FRAGMENTATION.
WE NO LONGER HAD MONOCYTOSIS AND
YET IF WE BEGIN SLEEP
FRAGMENTATION AGAIN WHAT WE FIND
IS THAT BLOOD MONOCYTOSIS COMES
QUICKER AND IF WE SUBJECT THE
ANIMALS TO SEPSIS WE HAVE A
HEIGHTENED ABUNDANCE OF
MONOCYTES AND QUICKER RESPONSE
OF THE IMMUNE SYSTEM.
IT HAS CONSEQUENCES FOR
SURVIVAL.
AND ONE THAT'S BEEN HEAVILY
DISCUSSED IN CARDIOVASCULAR
FUNCTION AND THE IDEA THAT AS
THE HEMATOPOIETIC SYSTEM MAY
COME TO IN FER RISK AND USING
VIRUSES AND TRACKING CLUSTERS OF
TAGGED HEMATOPOIETIC CELLS IN
RESPONSE TO SLEEP
DEFRAGMENTATION WE'RE SEEING
REDUCED DIVERSITY AS A
CONSEQUENCE OF INCREASED NEUTRAL
DRIFT.
THIS IS A MATHEMATICALLY
MODELLED AND EXPERIMENTALLY
SHOWN.
THIS TELLS US THIS WAS NOT A
NEED IN THE DRIVER MUTATION THAT
SLEEP FRAGMENTATION ITSELF
REDUCES DIVERSITY AND WE CAN
THINK OF IT AS A MEASURE OF
ACCELERATED BIOLOGICAL AGING
SOMETHING WE TALKED ABOUT THIS
MORNING.
DOUGH ANY OF THESE PHENOMENA IN
THE MOUSE SEE SOMETHING LIKE
THIS IN HUMANS AND THE SLEEP
RESTRICTION STUDY WE DID AND THE
SAME STUDY SHOWED IN THE EARLIER
TALK AND HERE WE ASKED HOW TO
TRACK INDIVIDUALS WITH SLEEP AND
THE SLEEP WAS REDUCED WHETHER WE
SEE CHANGES IN THE MONOCYTES WE
CAN RETRIEVE FROM THE BLOOD.
HERE IT'S IMPORTANT TO DRAW YOUR
ATTENTION TO THE MONOCYTE WE CAN
RETRIEVE FROM THE BLOOD OF THESE
INDIVIDUALS.
IT ZIZ -- IT'S IMPORTANT WE
MONITOR THEM IN THE MORNING AND
EVENING AND MICE SLEEP DURING
THE DAY SO IN THE MORNING WE
DON'T SEE DIFFERENCES IN
MONOCYTES WE CAN RETRIEVE SO HAD
WE NOT DONE THE EVENING DRAW WE
WOUTH HAVE THOUGHT IT'S A NUL
EXPERIMENT AND THERE'S
ANTICIPATORY INFLAMMATION AS
THEY SHIFT BETWEEN VISCERAL
ORGANS IN THE BLOOD AND
ANTICIPATION OF INJURY AND WE
SEE THIS IS THE CASE IN TERMS OF
HSBCs.
IT'S EASIER TO RETRIEVE THEM IN
HUMAN BLOOD AND MICE NEXT.
AND THERE'S A CARTOON
REPRESENTATION OF THE MECHANISM
I SHOWED EARLIER THE MECHANISM
THAT HELPS US BETTER UNDERSTAND
HOW IS IT INTERRUPTING SLEEP
INCREASES INFLAMMATION AS IT
PERTAINS TO MONOCYTES THE
CARDINAL INFLAMMATORY CELLS AND
WHAT WE FIND IS THAT THIS
INVOLVES BRAIN BONE MARROW
ACCESS WHEREBY A SECRETED
NEUROPEPTIDE ACTS ON THE
SPECIFIC POPULATION LOCATED
STRATEGICALLY IN NICHES OF THE
BONE MARROW THAT MODULATE THE
RATE OF PRODUCTION OF MONOCYTES
WHICH ACCUMULATE.
THERE'S MORE THAT HAPPENS AND
MANY MORE MECHANISMS NOT SHOWN
HERE BY WHICH THE BONE MARROW
AND THE IMMUNE SYSTEM AND
VASCULATURE COMMUNICATE WITH
EACH OTHER BUT THIS IS ONE
EXAMPLE AND ON THE RIGHT SIDE
WHAT I'M DESCRIBING AND SHOWING
IS THIS IDEA THAT INCREASED
PROLIFERATION AND PRODUCTION OF
HEMATOPOIETIC CELLS THAT OCCURS
WHEN SLEEP IS INTERRUPTED SERVES
TO DECREASE THE HETEROGENEITY OF
HEMATOPOIETIC CELLS AND THE
CLONALITY OF THAT POOL AND
ACCELERATING AGING.
SO THAT'S MY LAST SLIDE.
THESE WILL SOME OF THE PEOPLE
WHO CONTRIBUTED TO THIS WORK.
THANK YOU.
>> THANK YOU.
THAT WAS A FASCINATING TOPIC AND
DATA.
THANK YOU.
NOW OUR LAST SPEAKER FOR TODAY
DR. DAYNA JOHNSON FROM EMORY
UNIVERSITY.
SHE'LL BE TALKING ABOUT
MULTI-LEVEL DETERMINATES OF
SLEEP IN CARDIOVASCULAR
DISPARITY THE ROLE OF RISK AND
RESILIENCE.
SO WELCOME DR. JOHNSON.
OVER TO YOU.
>> THANK YOU.
THERE'S BEEN GREAT CONVERSATIONS
TODAY AND I THINK THIS TALK WILL
ALSO CONTRIBUTE TO THAT.
SO I'M TALKING ABOUT BOTH RISK
AND RESILIENCE BECAUSE WITHIN
THE WORK THAT I'M CONDUCTED
WE'RE THINKING ABOUT RESILIENCE
AS THIS WAY TO MODIFY THE RISK
FACTORS ON SLEEP HEALTH AMONG
MINORITIZED POPULATIONS.
SO FIRST I WANT TO DEFINE SLEEP
HEALTH DISPARITY.
WHEN WE'RE TALKING ABOUT
DISPARITIES WE'RE TALKING ABOUT
DIFFERENCES IN SLEEP HEALTH AND
DEFINING SLEEP HEALTH ACCORDING
TO THE CONSTRUCT THAT WAS PUT
FORTH AS SLEEP AS THE CONSTRUCT
OF REGULARITY, ALERTNESS AND
EFFICIENCY AND DURATION BUT
WE'RE THESE DIFFERENCES THAT
OCCUR ON A CONSISTENT BASIS THAT
ADVERSE AFFECT DISADVANTAGED
POPULATIONS.
THESE ARE DUE TO UNFAIR AND
UNJUST CIRCUMSTANCES AND BY THE
NIH DEFINITION THESE ARE THE
GROUPS THAT ARE CONSIDERED
DISADVANTAGED.
THERE ARE STRIKING DISPARITIES
IN SLEEP DISORDERS.
HISTORICALLY MINORITIZED
INDIVIDUALS HAVE SHORTER SLEEP
DURATION.
WHEN WE THINK OF THE
INTERSECTIONALITY FRAMEWORK
DISCUSSED EARLIER BY DR. COOK,
WE LOOK AT THE INTERSECTION OF
GENDER AND SOCIO ECONOMIC STATUS
AS WELL AS SEX WE SEE THAT OR TO
FOCUS ON THE RACE AND SEX FIRST,
BLACK MEN HAVE THE SHORTEST
SLEEP DURATION AND WHITE WOMEN
HAVE THE LONGEST SLEEP DURATION.
LOOKING AT THOSE TWO GROUPS
THERE'S A DIFFERENCE OF ABOUT
TWO HOURS.
ON AVERAGE WE SEA HISTORICALLY
MINORITIZED INDIVIDUALS HAVE AN
HOUR SHORTER SLEEP DURATION IN
COMPARE TO NON-HISPANIC WHITE
INDIVIDUALS.
SO ADDITIONALLY WE SEE THE
GROUPS HAVE A HIGHER PREVALENCE
OF SLEEP APNEA AND VARIES
DEPENDING ON THE RACIAL GROUP
AND STUDIES HAVE SHOWN BETWEEN
ED ODDS OF SLEEP APNEA.
ALSO WE SEE THESE GROUPS HAVE A
TWOFOLD HIGHER CHRONIC APNEA FOR
ASIAN AND BLACK INDIVIDUALS AND
THEN THERE'S A STUDY THAT HAS
SHOWN BLACK INDIVIDUALS HAVE A
67% INCREASED RISK OF INSOMNIA
DISORDER WITH SHORT SLEEP WHICH
IS A SEVERE PHENOTYPE AND
THERE'S DATA THAT SHOWS INSOMNIA
WITH SHORT SLEEP IS ASSOCIATED
WITH HYPERTENSION AND
ASSOCIATION IS STRONGER THAN IF
WE LOOK AT INSOMNIA OR SHORT
SLEEP ALONE.
WE SEE BLACK INDIVIDUALS ARE
MORE VULNERABLE TO THE FACT OF
THAT ASSOCIATION BETWEEN
INSOMNIA AND CARDIOVASCULAR
HEALTH OUTCOMES.
WHILE IT'S LIMITED THERE ARE
SOME DATA THAT SHOW MINORITIZED
INDIVIDUAL HAVE A TWOFOLD ODDS
OF DELAYED SLEEP AND SEE
DIFFERENCES IN CIRCADIAN FACTORS
AS WELL.
IT'S IMPORTANT TO THINK ABOUT
WHAT'S DRIVING THESE
DISPARITIES.
WHAT ARE THE FACTORS THAT ARE
CONTRIBUTING.
BASED ON THE SOCIAL DETERMINATES
OF HEALTH YOU POINT TO ZRIPG
DISCRIMINATION AND INCOME.
HOWEVER WE'RE NOT SEEING
EDUCATION AND INCOME ARE
AFFORDING THE SAME ADVANTAGES BY
RACE ACROSS THE DIFFERENT
GROUPS.
SO HERE'S SOME DATA FROM A
NATIONALLY REPRESENTATIVE SAMPLE
WHICH SHOWS THE PREVALENCE OF
SHORT SLEEP DURATION FOR MEN AND
WOMEN AND BY OCCUPATION OR
OCCUPATION CATEGORIES WHICH WE
CAN THINK ABOUT AS A PROCESS FOR
SOCIO ECONOMIC STATUS.
SO PROFESSIONAL COULD BE
CONSIDERED THE HIGHER SUPPORT AS
MIDDLE AND LABORERS AS LOWER
INCOME.
HERE WE SEE THE LOWEST
PREVALENCE OF SHORT SLEEP
DURATION IS FOR PROFESSIONAL
WHITES WHILE THE HIGHEST
PREVALENCE OF SHORT SLEEP
DURATION IS AMONG PROFESSIONAL
BLACK MEN AND WOMEN.
SO IN TERMS OF LABORERS FOR MEN
IT'S A MORE NARROW DIFFERENCE IN
THE PREVALENCE OF SHORT SLEEP
DUR AND FOR WOMEN IT'S ALMOST
NON EXISTENT AND THE HIGHER
DISPARITY IS OF THOSE OF HIGHER
SOCIO ECONOMIC STATUS.
THAT WAS AN OLDER STUDY AND THIS
WAS PUBLISHED RECENTLY WHICH
SHOWS THE SAME THING BUT USING
USING A DIFFERENT MEASURE SUCH
AS EDUCATION.
THE HIGHEST PREDICTIVE
PROBABILITY OF SHORT SLEEP IS
AMONG LOWER OR THOSE WITH LESS
THAN A HIGH SCHOOL DIPLOMA AND
THE SHORTEST, LOWEST PREDICTED
PROBABILITY FOR WHITE
INDIVIDUALS ARE THOSE WITH
GREATER THAN A COLLEGE DEGREE.
WE SEE THE SAME FOR BLACK
INDIVIDUALS AS WELL AS FOR
HISPANIC INDIVIDUALS.
IN THINK ABOUT FACTORS THAT
AFFORD AN AVERAGE FOR SLEEP
HEALTH, INCOME, OCCUPATION IS
NOT AFFORDING THE SAME
ADVANTAGES FOR BLACK AND
HISPANIC INDIVIDUALS AS FOR
WHITE INDIVIDUALS.
WE ARE SEEING WORSE SLEEP HEALTH
AMONG BLACK AND HISPANIC
INDIVIDUALS OF HIGHER AND SOCIO
ECONOMIC STATUS.
WE'RE CONSIDERING FACTORS THAT
CAN DIRECTLY OR INDIRECTLY SHAPE
SLEEP HEALTH AND SO WHEN WE
THINK ABOUT ADDRESSING THESE
HEALTH INEQUITIES IT'S MORE
UPSTREAM FACTORS THAT SHOULD BE
CONSIDERED SUCH AS ECONOMIC AND
SOCIAL OPPORTUNITIES AND
RESOURCES WHICH SHAPE MORE DOWN
STREAM FACTORS SUCH AS PERSONAL
BEHAVIOR.
SO THERE ARE MULTI-FACTORS OR
SEVERAL DETERMINATES OF SLEEP
AND CIRCADIAN DISPARITIES THAT
OCCUR ACROSS THE LIFE SPAN THAT
ARE TRULY MULTI-FACTORIAL.
SOME OF THOSE SOCIAL
DETERMINATES WHICH ARE LIKELY
EXPLAINING SOME DISPARITY WE'RE
SEEING AMONG THE HIGHER
INDIVIDUALS, BLACK AND HISPANIC
ACCORDING TO EXPERIENCES OF
DISCRIMINATION AND STRESS.
THESE INDIVIDUALS THEY'RE
EXPOSED TO MORE EXPERIENCES OF
DISCRIMINATION AND
MICROAGGRESSIONS AND
ADDITIONALLY ENVIRONMENTAL
FACTOR A DETERMINANT OF SLEEP
DISPARITIES.
WE KNOW INDIVIDUALS THAT LIVE IN
AREAS OF LOWER INCOME ARE MORE
LIKELY TO BE EXPOSED TO AIR
POLLUTION AND OTHER ADVERSE
ENVIRONMENTAL FACTORS THAT
AFFECT SLEEP HEALTH AND THEN
ADETERMINELY DESPITE INDIVIDUAL
LEVEL INCOME WE SEE HISTORICALLY
MINORITIZED INDIVIDUALS ARE MORE
LIKELY TO LIVE IN DISADVANTAGED
NEIGHBORHOODS STEM FROM AFFECTS
OF RED LINING AND OTHER
DISCRIMINATORY LAWS AND POLICIES
THAT PROHIBITED UPWARD MOBILITY.
AND THEN THERE'S SLEEP RELATED
BEHAVIORS WHICH ARE RARELY A
DOWN STREAM FACTOR OF EXPOSURE.
LAWS AND POLICIES THAT PROMOTE
CERTAIN BEHAVIORS.
SO MINIMUM WAGE WE KNOW IS NOT A
LIVING WAGE AND INDIVIDUALS WHO
HAVE A MINIMUM WAGE JOB ARE MORE
LIKELY TO NOT BE HOME TO
IMPLEMENT CONSISTENT BED TIMES
FOR THEMSELVES OR THEIR
CHILDREN.
IT'S A GOOD EXAMPLE OF THINKING
HOW THE MORE UPSTREAM FACTORS OR
POLICIES DETERMINE UPSTREAM
BEHAVIORS.
WE JUST FOCUS ON THE DOWN
STREAM, WE'RE MISSING THE
CONTEXT IN WHICH INDIVIDUALS
LIVE IN ORDER FOR US TO BE ABLE
TO TARGET INTERVENTIONS.
THESE CAN CONTRIBUTE TO SLEEP
HEALTH DISPARITIES.
HERE'S A FIGURE THAT MY DOCTOR
STUDENT AND I PUT TOGETHER WHICH
SHOWS HOW STRUCTURAL RACISM AND
THESE DIFFERENT INTERSECTING
IDENTITIES WILL DETERMINE
EXPOSURES TO DIFFERENT
INSTITUTIONAL AND SYSTEMATIC
STRUCTURES WHICH SHAPE THE
ENVIRONMENTS IN WHICH WE LIVE
AND HOW THESE GET UNDER THE SKIN
FOR US TO EMBODY THE STRESSFUL
EXPERIENCES WHICH COULD BE
MEASURES VIA ALLO STATIC LOAD
AND LEAD TO MORTALITY.
HERE'S A FIGURE PUBLISHED BY THE
AMERICAN HEAR THE ASSOCIATION
WHICH SHOWS THE ROOT CAUSES OF
HEALTH DISPARITIES OVER ALL.
HERE WE SEE POLICIES AND LAWS
AND JIM CROW LAWS AND RED LINING
CONTRIBUTED TO CONCENTRATED
POVERTY AND SOCIAL DETERMINATES
AND POOR ACCESS TO HEALTH CARE
AND HOUSING CONDITIONS AND
POORLY FUNDED SCHOOLS AND ACCESS
TO CAPITAL WHICH CAN DETERMINE
SOMEONE'S UPWARD MOBILITY.
THE FIGURE THAT WAS PUBLISHED BY
THE AMERICAN HEART ASSOCIATION
WE ARE HYPOTHESIZING THE FACTORS
CONTRIBUTE TO ADVERSE SLEEP
HEALTH AND SLEEP DISORDERS WHICH
THEN LIKELY CONTRIBUTES TO
INCREASED HEART DISEASE AND
STROKE RISK FACTORS WHICH IS
ASSOCIATED WITH WORSE
CARDIOVASCULAR AND STROKE
OUTCOMES.
SO AGAIN, WITHIN THE WORK WE'RE
DOING, IT'S FOCUSSED ON HOW
SLEEP MAY BE ON THE PATHWAY
BETWEEN SOCIAL DETERMINATES OF
HEALTH AND CARDIOVASCULAR HEALTH
OUTCOMES.
EYE
HERE SHOWS THE PATH OF SOCIO
ENVIRONMENTAL FACTORS TO SLEEP
IN CARDIOVASCULAR HEALTH
DISPARITY.
AGAIN, IN THINKING ABOUT THE
MULTI-LEVEL FACTORS HOW
INDIVIDUALS ARE IN BROADER
ENVIRONMENTS TO DETERMINE THEIR
EXPERIENCE WITH DISCRIMINATION
AND STRESS AND ALSO FACTORS
WITHIN THE NEIGHBORHOOD
ENVIRONMENT AND HOW THAT CAN
SHAPE THE ENVIRONMENT IN TERMS
OF EXPOSURES OF AIR POLLUTION
AND OPPORTUNE LIGHT EXPOSURES
LEADING TO DISTURBANCES IN SLEEP
AND CARDIOVASCULAR HEALTH
OUTCOMES.
HERE I WANT TO SHOW FACTORS THAT
CAN PROMOTE RESILIENCE.
WE'RE THINKING ABOUT PROTECTIVE
AND RISK FACTORS.
HERE WE USED DATA FROM THE
MULTI-ETHNIC STUDY OF ATH
ATHEROSCLEROSIS AND HEALTHY
OUTCOMES USING AC TIG GRAPHY AND
WE FOUND THATTIGRAPHY AND WE
FOUND THAT AND THOSE WITH BETTER
ENVIRONMENTS AS LOWER ODDS OF
SHORT SLEEP DURATION AT
POPULATION LEVEL THESE ARE
STRIKING AND COULD MOVE THE
POPULATION CURVE.
I THINK THERE WERE SOME
MODIFICATIONS WHEN THE SLIDE
DECK WAS PUT TOGETHER.
HERE WE'RE ALSO SHOWING SO AREAS
THAT TYPICALLY ARE ASSOCIATED
WITH PROTECTIVE FACTORS FOR
OBESITY IS ASSOCIATED WITH WORSE
SLEEP HEALTH.
LIVING IN ENVIRONMENTS WITH
HIGHER DENSITY, WALKING
DESTINATIONS, ALSO WITH MORE
PROPORTIONED DETAIL AND LIVING
IN THE MORE BUILT ENVIRONMENTS
WERE ASSOCIATED WITH SLEEPING
LESS ON AVERAGE AND ALSO WITH
HIGHER ODDS OF SHORT SLEEP
DURATION.
AND IT'S LIKELY THAT THESE
ASSOCIATIONS ARE EXPLAINED BY
NOISE AND INOPPORTUNE SLIGHT
EXPOSURE.
-- LIGHT EXPOSURE.
HERE WE'RE INTERESTED IN
UNDERSTANDING AGAIN AS THE
POTENTIAL INTERVENTION POINT
WHAT IS EXPLAINING THESE RATIO
DISPARITIES AND USING THE SAME
DATA SET THE MULTI-ETHNIC STUDY
OF ATHEROSCLEROSIS THE PHYSICAL
ENVIRONMENT EXPLAINED THE
HISPANIC-WHITE DIFFERENCE IN
SLEEP DUR ATION OR PARTIALLY
EXPLAINED.
IT EXPLAINED 40% TO 38% OF THE
HISPANIC-WHITE DIFFERENCE IN
SLEEP DURATION.
IF WE COULD MODIFY THE PHYSICAL
ENVIRONMENT WE CAN POTENTIALLY
REDUCE THE HISPANIC-WHITE
DISPARITY IN SLEEP DURATION.
WE USED DATA FROM THE NHANES
STUDY WHICH HAS OBJECTIVE
MEASURES OF SLEEP AND WE LOOKED
AT LIGHT AT NIGHT AND LIGHT IS
GOOD BUT WE WANT LIGHT DURING
THE DAY AND SO HERE WE WERE
LOOKING AT INOPPORTUNE LIGHT
EXPOSURE MEASURED TO LIGHT AT
NIGHT AND THEY HAD AN 80% HIGHER
ODDS OF SHORT SLEEP DURATION IN
COMPARISON TO THOSE WHO HAD NO
EXPOSURE TO LIGHT AT NIGHT.
WE FOUND NO ASSOCIATIONS WITH
LONG SLEEP DURATION BUT WE CAN
SEE THIS GRADIENT AS LIGHT AT
NICE INCREASES THE ODDS OF SHORT
SLEEP ALSO INCREASES.
SO WE WERE ALSO INTERESTED IN
INFORMATION HOW THESE
ASSOCIATIONS MAY VARY BY RACE
AND BY SEX.
>> EXCUSE ME, SPEAKER,
TWO-MINUTE WARNING.
>> THANK YOU.
WE SEE THE DISASSOCIATION IS
FOUND AMONG FEMALES SHOWN ON THE
RIGHT SIDE OF THE FIGURE AND SO
REGARDLESS OF RACE, WE SAW
WHITE, MEXICAN AND BLACK FEMALES
WERE PARTICULARLY VULNERABLE TO
THE AFFECT OF LIGHT AT NIGHT ON
SLEEP DURATION.
BOTH THE SOCIAL AND THE
ENVIRONMENT MAY BE RELATED TO
THINGS SUCH AS SAFETY AND SO WE
SEE THAT FROM SOME OF OUR
STUDIES WITHIN THE HOUSEHOLD
THAT CERTAIN POPULATIONS UTILIZE
THE TELEVISION AS A SOURCE OF
PROMOTING NOISE AND LIGHT AS A
SOURCE OF SAFETY.
SO THE PROBLEM WITH THAT IS THAT
LIGHT AT NIGHT CAN ALTER
ENDOCRINE SIGNALLING, IMPAIR
SLEEP, OF COURSE DISRUPT
CIRCADIAN RHYTHMS ASSOCIATED
WITH WEIGHT GAIN.
AND SO THEN MOVING ON TO
THINKING ABOUT THE FACTORS THAT
ARE PROMOTING HEALTHY SLEEP WE
LOOKED AT SOCIAL COHESION AND
SAFETY AND FOUND THAT
INDIVIDUALS THAT LIVE IN
NEIGHBORHOODS WITH HIGHER SOCIAL
COHESION AND KNOW AND TRUST
THEIR NEIGHBORS AND FEEL SAFER
IS ASSOCIATED WITH SLEEPING
LONGER EIGHT TO NINE MINUTES
LONGER ON AVERAGE.
AND THEN WHEN WE LOOKED AT THESE
ASSOCIATIONS BY RACE, ETHNICITY,
WE FOUND THESE ASSOCIATIONS WERE
PARTICULARLY PRONOUNCED AMONG
THE BLACK AND HISPANIC
PARTICIPANTS.
SO BLACK INDIVIDUALS THAT LIVED
IN THESE AREAS WITH HIGHER
SOCIAL COHESION AND SAFETY,
SLEPT ON AVERAGE ABOUT 15
MINUTES LONGER WHICH IS MORE
CLINICALLY MEANINGFUL IF WE
THINK ABOUT WHAT DURATION OF
SLEEP MATTERS IN TERMS OF HEALTH
OUTCOMES.
SO IN LOOKING AT THE PATHWAY
THAT MAY BE CONNECTING
NEIGHBORHOOD SOCIAL COHESION AS
A PROTECTIVE OR RESILIENT FACTOR
IS PERCEIVED STRESS THAT
EXPLAINS A SMALL BIT SO THERE'S
LIKELY SOMETHING ELSE AFFORDING
AN ADVANTAGE ON SLEEP-HEALTH
DURATION.
SOMETHING ABOUT THE SOCIAL
CONNECTION IS MEANINGFUL FOR
BLACK INDIVIDUALS AND SOMETHING
THAT SHOULD BE LEVERAGED AND
UNDERSTANDING THESE CON CAN
ECSES.
-- CONNECTIONS.
SO WE FOUND THAT RUMINATION IS
PART OF THIS PATHWAY.
SO THE SAME DISPARITIES WE'RE
SEEING IN SLEEP WE ALSO SEE IN
CARDIOVASCULAR HEALTH THAT
RACIAL AND ETHNIC MINORITIZED
INDIVIDUAL HAVE SOCIO RISK
FACTORS.
AND SO SOME OF THE RESEARCH HAS
SHOWN SLEEP DISPARITIES
CONTRIBUTE TO CARDIOVASCULAR
DISPAR
DISPARITIES.
SO HERE IS A STUDY THAT SHOWED
THE RACIAL DIFFERENCE IN CARDIO
METABOLIC HEALTH WAS EXPLAINED
BY SLEEP DURATION AND
EFFICIENCY.
IT EXPLAINS BETWEEN 41% AND 51%.
SLEEP IS LIKELY AN AVENUE WHERE
WE CAN MODIFY AND INTERVENE ON
TO REDUCE CARDIOVASCULAR
INEQUITIES.
SO HERE'S DATA FROM A STUDY IN
ATLANTA CALLED AND HERE IT WAS
INTERESTED AT LOOKING AT
INDIVIDUALS ENROLLED IN
RESILIENT AND ADD RISK
NEIGHBORHOODS.
THOSE THAT LIVED IN
NEIGHBORHOODS WITH LOWER
CARDIOVASCULAR RISK AND THIS IS
AMONG BLACK ADULTS THEY HAD
BETTER AESTHETIC QUALITY AND
WERE SAFER AND HAD ACCESS TO
HEALTHY FOOD, HIGHER SOCIO
COHESION AND PURPOSE AND LIFE
AND OPTIMISM.
THESE ARE SPECIFIC MEASURES OF
RESILIENCE THAT WERE ASSOCIATED
WITH REDUCED CARDIOVASCULAR
RISK.
THE SAME FACTORS ARE ALSO
ASSOCIATED WITH BETTER SLEEP
HEALTH OUTCOMES.
HERE'S SOME DATA FROM A STUDY
WITH DID USING THE NATIONAL
REPRESENTATIVE SAMPLE INTERESTED
IN UNDERSTANDING HEALTH
PROMOTING FACTORS.
HERE WE LOOKED AT SOCIAL SUPPORT
IN RELATION TO SLEEP AND FOUND
THAT INDIVIDUALS WITH HIGHER OR
MORE SOURCES OF SOCIAL SUPPORT
WHICH INCLUDED FINANCIAL
SUPPORT, EMOTIONAL ATTENDANCE.
WE SAW AS THOSE DIFFERENT
SOURCES INCREASED, WE SAW AN
INCREASE IN SLEEP DURATION.
WE THINK FOR BLACK INDIVIDUALS
THERE'S A MORE STARK INCREASE
THAT OCCURS CAN WITH THIS
ADVANTAGE OR HAVING SOCIAL
SUPPORT.
WE SEE MULTI-LEVEL FACTORS ARE
CONTRIBUTING TO ADVERSE HEALTH
AND CAN LEVERAGE RESILIENCE
FACTORS SUCH AS SOCIAL COHESION
AND SOCIAL SUPPORT WHICH ARE
PARTICULARLY BENEFICIAL FOR
BLACK AND HISPANIC INDIVIDUALS.
SO SINCE THE DISPARITY
CONTRIBUTING TO CARDIOVASCULAR
DISPARITIES WE CAN LIKELY REDUCE
CARDIOVASCULAR INEQUITIES.
HERE'S A LIST OF THE RESEARCH
GAPS.
IT'S IMPORTANT TO THINK HOW
RESILIENCE CAN BE USED TO
MITIGATE HARMFUL AFFECTS OF
THESE DIFFERENT RISK FACTORS ON
SLEEP AND LOOK AT SPECIFIC
MEASURES SUCH AS MASTERY AND
COPING AND ALSO UNDERSTANDING
THE DIFFERENCE LINKS.
LEVERAGING DIFFERENT
LONGITUDINAL AND POPULATION
LEVEL DATA TO UNDERSTAND THE
SPECIFIC MECHANISMS.
I'LL END WITH THE TWO QUESTION.
WHAT ARE EFFECTIVE STRATEGIES
FOR PROMOTING INDIVIDUAL AND
NEIGHBORHOOD RESILIENCE.
ALSO, DO RESILIENCE FACTORS
MODIFY THE ASSOCIATIONS BETWEEN
RISK FACTORS AND SLEEP AND/OR
CARDIOVASCULAR HEALTH.
FOR FUTURE DIRECTION IT'S
IMPORTANT TO THINK ABOUT AND
UTILIZE AND HELP EQUITY
FRAMEWORK TO EXPLORE THE ROLE OF
RESILIENCE IN ADDRESSING SLEEP
AND CARDIOVASCULAR INEQUITIES
AND LEVERAGING RESILIENCE AT THE
INTERVENTION STRATEGY.
THANK YOU AGAIN FOR LISTENING
AND YOUR TIME.
>> THANK YOU, DR. JOHNSON.
THAT WAS A TERRIFIC TALK AND
INTRIGUING DATA.
>> WE HAVE ABOUT 20 MINUTES TO
DO A DISCUSSION AND QUESTION AND
ANSWER SESSION BEFORE WE WRAP UP
THE DAY.
LIKED TO THANK THE SPEAKERS FOR
THE AFTERNOON SESSION AND
WELCOME THEM BACK TO HAVE A
PANEL DISCUSSION WHILE WE'RE
GATHERING QUESTIONS FEEL FREE TO
PUT THEM IN THE CHAT OR UNMUTE
TO ASK.
I'LL GIVE A BRIEF SUMMARY.
WE HEARD ABOUT CARDIOVASCULAR
RISK WITH INEFFICIENT SLEEP AND
MOST THE EVIDENCE WE HAVE ABOUT
SLEEP IN CARDIOVASCULAR RISK WAS
ORIGINALLY DERIVED FROM EXTREME
SHORT EXPERIMENTAL STUDIES BUT
HAS RECENTLY SHOWN EVIDENCE THAT
MILD SLEEP CURTAILMENT
CONTRIBUTE TO OXIDATIVE STRESS
AND INFLAMMATION AND THERAPEUTIC
TARGETS INCLUDING ACTIVATORS AND
GROWTH HORMONE WHICH IS VERY
EXCITING AND DR. SWIRSKI
PRESENTED EVERYDAY ABOUT MICE
AND SLEEP FRAGMENTATION AND
INCREASES HEMATOPOIESIS IN THE
BONE MARROW AND WHEN WE
INTERRUPT SLEEP IT KICKS A
PROCESS THAT LEADS TO
ATHEROSCLEROTIC GROWTH AND IT'S
INTERESTING THE MICE RETURNING
BACK TO HOMEOSTASIS TOOK A LONG
TIME AND THERE WERE EPIGENETIC
CHANGES ON THE HEMATOPOIETIC
STEM CELLS AND DR. JOHNSON
TALKED ABOUT SLEEP DISPARITIES
AND NON-HISPANIC WHITES.
IING OUT THE WAS INTERESTING
WHAT YOU TALKED ABOUT HIGHER SES
WAS NOT PROTECTIVE AMONG THE
GROUPS.
THE REASONS MAY BE DUE TO THE
BUILT ENVIRONMENT WHICH IS GOOD
FOR PREVENTING OBESITY BUT NOT
NECESSARILY GOOD FOR SLEEP
HEALTH POTENTIALLY DUE TO NOISE
AND LIGHT.
SLEEP MAY BE A PROMISING AREA TO
INTERVENE ON RACIAL DISPARITIES
IN CARDIOVASCULAR HEALTH.
THANK YOU AGAIN TO OUR SPEAKERS
AND THERE'S QUESTIONS IN THE
CHAT.
I SEE A QUESTION ABOUT
ENDOTHELIAL CELL DYSFUNCTION AND
YOU'RE WELCOME TO ASK IT LIVE.
OR IF YOU WANT ME TO READ IT I'M
HAPPY TO AS WELL.
>> I WAS JUST CURIOUS IF YOU
COULD SPECULATE ABOUT THE SEX
DIFFERENCES IN GROWTH HORMONE
SECRETION AND WHETHER THAT MAY
HOW IT INDICATES INSUFFICIENT
SLEEP AND RISK.
>> I HAVE NO IDEA.
MEN HAVE A SHARP SPIKE AND THE
STUDY WAS A SIX-WEEK OUT PATIENT
STUDY FOR GROWTH HORMONE YOU
NEED A SAMPLING EVERY HALF AN
HOUR TO BALANCE THE FUNDS OF
EVERYTHING.
I THINK YOU NEED TO PROFILE
CONSTRUCT THE CURVES AND I DO
THINK IT NEEDS TO BE LOOKED AT.
>> THANK YOU SO MUCH.
I DIDN'T KNOW.
>> SINCE SUCH LIGHT EXPOSURE CAN
PROMOTE AROUSAL WAS THE ONSET OF
SLEEP TIME ALTERED FOR THE BOUTS
OF WAKEFULNESS LONGER?
>> THAT'S A GREAT QUESTION.
SO, WE USED DATA FROM NHANES A
POPULATION-LEVEL DATA SET.
WE AND WE MEASURED SLEEP BUT THE
WAY THE DATA ARE SHARED YOU CAN
ONLY CAPTURE SLEEP ACROSS 24
HOURS IN TERMS OF DURATION.
WE'RE WORKING NOW TO TRY TO
SEPARATE OUT SOME OF THE DATA TO
LOOK AT OTHER DIMENSIONS OF
SLEEP.
AND SO THE SHORT ANSWER IS WE
HAVE NOT LOOKED AT THAT YET
HOWEVER, WE DO PLAN ON IT AS
SOON AS WE FIGURE OUT HOW TO
MANIPULATE THE DATA SET THAT WAS
SENT.
WE HAVE OTHER STUDIES SO FOR MY
RO1 WE HAVE INDIVIDUALS WEAR A
LIGHT SENSOR FOR 24 HOURS AND 14
DAYS AND COLLECTING ACTIGRAPHY
AND WE'RE STILL IN THE DATA
COLLECTION PHASE.
>> WONDERFUL, THANKS.
QUICK FOLLOW-UP ALSO IN THE
CHAT, IN TERMS OF THE HEALTH
DISPARITY FRAMEWORK IF THERE'S A
FRAMEWORK YOU SUGGEST COULD BE
USED FOR RESEARCH.
>> GREAT QUESTION.
I OFTEN USE THE SOCIAL
ECOLOGICAL MODEL.
THE MODEL IS DISPLAYED ON THE
NIMHD WEBSITE.
THERE'S ALSO SEVERAL PAPERS ON
SLEEP DISPARITIES THAT UTILIZE
THIS AND CONSIDERS THE
CONTEXTUAL FACTORS IN HOW
INDIVIDUALS ARE NESTED WITHIN
THE BROADER FRAMEWORKS AND IT'S
THOSE BROADER ENVIRONMENTS THAT
ARE ACTUAL LY LEAD TO THE POORE
OUTCOMES AND BEHAVIORS.
I GAVE AN EXAMPLE THAT
INDIVIDUALS THAT LIVE IN
NEIGHBORHOODS THAT HAVE MORE
CRIME OR VIOLENCE OFTEN USE THE
TELEVISION TO PROMOTE NOISE AND
LIGHT AS A PROXY FOR SAFETY BUT
AT THE INDIVIDUAL LEVEL YOU SEE
SOMEONE AND TELL THEM TO TURN
OFF THE TELEVISION AT NIGHT AND
IGNORES THE BROADER CONTEXT AND
THEY'RE PROBABLY NOT ABLE TO DO
THAT.
YOU'RE PUSHING THE TRADE-OFF FOR
SLEEP FOR SAFETY IN THE CONTEXT.
USING THAT FRAMEWORK WILL HELP
THINK WITH THE HOUSEHOLD AND
NEIGHBORHOOD AS WELL AS THE
WORKPLACE ENVIRONMENT IN THERE
AND ALSO SOCIETAL FACTORS SUCH
AS LAWS THAT PROMOTE CERTAIN
BEHAVIORS.
>> GREAT POINT.
I THOUGHT IT WAS A COMPELLING
FINDING ABOUT THE TV BEING USED
FOR SAFETY AND IMPORTANT IN
LOOKING AT SLEEP BEHAVIORS.
THANK YOU.
>> WE KNOW ABOUT THE MICE AND
THE SLEEPING BAR AND THE
LINGERING EFFECTS AND KNOW YOU
STARTED TO WORK WITH HUMANS IN A
SLEEP RESTRICTION TRIAL AND
LOOKING AT HEMATOPOIESIS AND I
THINK ABOUT NEW MOTHERS WHO MAY
BE WOKEN UP SEVEN OR EIGHT TIMES
A NIGHT FOR A YEAR OR LONGER AS
A NEW MOTHER AND HAVE YOU
STARTED TO LOOK AT SLEEP
DISTURBANCES AMONG HUMANS OR
JUST SLEEP RESTRICTION SO FAR?
>> THOSE ARE GREAT QUESTIONS.
IT'S TRUE WE'RE COMPARING MICE
TO PEOPLE AND THERE'S MANY
DIFFEREN
DIFFERENCES IN TERMS MUCH WHEN
MICE AND HUMANS SLEEP.
A FEW THINGS TO SAY TO THIS.
THE SLEEP FRAGMENTATION INDUCING
IN MICE IS NOT THE SAME AS SLEEP
DEPRIVATION.
IT'S INTERRUPTING SLEEP AND THE
MICE DO CATCH UP ON SLEEP SO THE
ARCHITECTURE IS VERY MUCH
DIFFERENT AND IT'S AKIN TO WHAT
HAPPENS IN THE CONTEXT OF
NARCOLEPSY AND IN THE CONTEXT OF
SLEEP APNEA ELIMINATING THE
HYPOXIC ELEMENT TO IT MAY BE
SOMETHING THAT VERY MUCH HAPPENS
WHEN THERE IS WORK SHOWING
WHETHER IT'S FRAGMENTATION OR
DEPRIVATION, ATHEIR SCLEROTIC
LESIONS INCREASE AND THE MICE
EXPOSED TO SLEEP DEFRAGMENTATION
AND PEOPLE JUST SLEEPING AN HOUR
AND A HALF LESS SAY WE STILL SAW
A SIMILAR EFFECT ON THE
CIRCULATING MONOCYTES THAT LINE
WITH THEIR CIRCADIAN RHYTHM
WHICH SPEAKS TO FUNDAMENTAL
BIOLOGY WITH SLEEP ARCHITECTURE
AND THE LAST QUESTION THAT YOU
ASKED THERE'S QUITE A BIT TO
UNPACK.
WE HAVE STUDIES ONGOING ON THE
ONE HAND WE'RE INTERRUPTING
SLEEP IN PREGNANT MOMS OR
SUBJECTING THEM TO STRESSORS AND
THERE'S A BIT TO EXPLORE WHETHER
THE STRESSORS ARE SLEEP OR
PSYCHOLOGICAL STRESS FASTING IS
AN ELEMENT TO THIS AND HOW IT
AFFECTS BIOLOGY EVEN IN THE NEXT
GENERATION.
>> WOW, OKAY.
THAT'S INTERESTING.
THANK YOU.
SOUNDS LIKE THE EFFECTS COULD BE
FAR REACHING.
WHERE HE -- WE LOOK FORWARD TO
THAT.
I HAVE A QUESTION FOR DR. JELIC.
YOU PRESENTED RESEARCH ON HOW
INEFFICIENT SLEEP INCREASES
CARDIOVASCULAR RISK AND WHEN WE
WERE PLANNING THE WORKSHOP WE
STARTED TO THINK AND TALK ABOUT
HOW SLEEP COULD POTENTIALLY
IMPROVE CARDIOVASCULAR
RESILIENCE AND THAT'S NOT REALLY
WHERE THE FIELD IS YET.
I WAS THINK OF IMPROVING
CARDIOVASCULAR RESILIENCE OR
RISK FACTORS.
>> I THINK THE BIOLOGICAL
EFFECTS OF THE SO-CALLED
POSITIVE BEHAVIOR LIKE POSITIVE
SLEEP BEHAVIOR WOULD BE A THING
LIKE SLEEPING EIGHT HOURS IS
GREAT AND WE KNOW THIS FROM
NEGATIVE STUDIES WE DON'T KNOW
WHETHER REVERSING SOMEBODY WHO
SLEEPS POORLY OR SHORTLY OR
INSUFFICIENTLY WHETHER THAT
WOULD IMPROVE THEIR RESILIENCE
THAT WOULD TRANSLATE TO
RESILIENCE.
I WANT TO MAKE CLEAR WE'RE JUST
LOOKING AT SURROGATE MARKERS OF
CARDIOVASCULAR HEALTH BECAUSE
DESIGNING THE PREVENTION STUDIES
IS NOT POSSIBLE INCLUDING THIS.
WE HAVE TO BE HAPPY WITH THE
ASSOCIATIONS AND SOMEONE WITH C
PAP HAVING A DISCUSSION WITH
SEVERAL PEOPLE WHO LIKE C PAP
IT'S VERY DIFFICULT WE WILL NEED
TO PROFILE AND PHENOTYPE IN
DETAIL WHAT TYPE OF SLEEP
PROBLEM THEY HAVE BECAUSE IT'S
NOT ONLY SLEEP DURATION BUT
SLEEP QUALITY EVEN IF YOU HAVE
ENOUGH SLEEP DURATION MAYBE POOR
QUALITY IS PLAYING A ROLE OR
HAVE A VARIABLE SLEEP TIME AND I
I'LL USE THE FEW MINUTES IN THE
STUDY I PRESENTED WE ADVISED
WOMEN TO KEEP A CONSTANT BED
TIME AND WEIGHT YOU WOULD THINK
THAT'S EASY TO FOLLOW BUT
TWO-THIRDS FOLLOWED THE DEVICE
AND ONE-THIRD DID NOT.
THOSE WHO FOLLOWED THE
GUIDELINES REDUCED INFLAMMATION
SYSTEMIC INFLAMMATION AND LOOKED
AT THE PLATELET AGGREGATES AND
MIRACULOUSLY REDUCED ADIPOSE AND
VISCERAL BODY COMPOSITION AFTER
SIX WEEKS OF ADJUSTING THE
SLEEP.
I FIND THE POSITIVE BEHAVIORS
EVEN IF YOU THINK YOU'RE DOING
GREAT, PERHAPS THERE'S ALWAYS
SOME ROOM FOR SLIGHT
IMPROVEMENT.
YES, DEFINITELY I THINK WE APPLY
FOR GRANTS ABOUT SLEEP
DEPRIVATION IS BAD BUT MAYBE
SOMETHING POSITIVE I THINK IS
NEEDED.
>> GREAT POINT AND IT'S AMAZING
AFTER SIX WEEKS OF ADJUSTING
SLEEP THEY LOST A SIGNIFICANT
AMOUNT OF VISCERAL FAT.
I SEE A QUESTION IN THE CHAT FOR
DR. JOHNSON AND IF YOU WANT TO
ANSWER IT LIVE IT MAY BE EASIER
INSTEAD OF TYPING YOUR ANSWER.
THE QUESTION WAS THINK ABOUT
RESILIENCE IN THE FACE OF
ADVERSITY.
THERE MAY BE AN ARGUMENT
MINORITIZED PEOPLE THAT LIVE
WITH STRUCTURAL RACISM HAVE HAD
NO CHOICE BUT TO BE RESILIENT
AND DO WE THINK OF THIS IN TERMS
OF CARDIOVASCULAR DISEASE AND IF
SO, HOW?
>> THAT'S A GREAT QUESTION AND
ONE WE'RE REGULARLY PONDERING IN
MY RESEARCH GROUP.
FIRST IT'S IMPORTANT TO NOT
ASSUME RESILIENCE IS ALWAYS A
GOOD THING.
AS BRIEFLY MENTIONED IN THE
RESPONSE FROM DR. COOK EARLIER,
IT ALSO CAN BE ASSOCIATED WITH
NEGATIVE HEALTH OUTCOMES AND CAN
HAVE A NEGATIVE OUTCOME AND
BEING RESILIENT CAN BE
ASSOCIATED WITH THE SENSE OF
BEING TOLERANT OF ADVERSITY
WHICH IS NOT NECESSARILY A GOOD
THING AND ALSO CAN ALSO
ENCOURAGE FALSE EXPECTATIONS AND
WE'VE LOOKED AT THINGS LIKE LOW
STRIVING STRESS IN RELATION TO
SLEEP AND FOUND IT WAS
ASSOCIATED WITH POOR SLEEP
HEALTH AMONG BLACK ADULTS IN THE
SOUTH.
I ENCOURAGE READING ABOUT IT AND
IT TALKS ABOUT INDIVIDUALS WHO
ARE FACED WITH HIGH ADVERSITY
AND HOW THEY'VE HAD COPING.
THERE'S DATA THAT SHOW THAT'S
ASSOCIATE WITH HIGHER BLOOD
PRESSURE AND HYPERTENSION
SPECIFICALLY AND THIS SIS MY
SUGGESTION IN THE FRAMEWORK OF
THE THE SECOND PART OF YOUR
QUESTION BECAUSE HIGH EFFORT
COPING IS ASSOCIATED WITH
HYPERTENSION BUT FACTORS THAT
MAY PROMOTE HEALTH OUTCOMES.
THINKING OF RESOURCES.
I SHOWED DATA ABOUT SOCIAL
SUPPORT.
THINKING OF OTHER FACTORS THAT
MAY MITIGATE SOME OF THE
STRESSORS MINORITIZED
INDIVIDUALS ARE FACED WITH AND
WE HAVE A STUDY CALLED MECCA AND
I'M HAPPY TO SHARE RESOURCES
WHICH EMPHASIZE SOME OTHER
CONCEPTS THAT ARE RESILIENCE BUT
MORE POSITIVE FOR COPING.
>> THAT'S AN IMPORTANT
DISTINCTION AND THERE'S TIME FOR
ONE MORE QUESTION IN THE Q&A
ABOUT HOW DO WE ASSESS SOCIO
ECONOMIC STATUS THAT'S NOT A
SIMPLISTIC MEASURE.
AS YOU SHOWED HIGHER SES DOES
THE NECESSARILY TRANSLATE TO
BETTER SLEEP AND THIS PERSON
MAKES A DID GOOD POINT THAT
ACADEMICS ARE USUALLY SLEEP
DEPRIVED.
IS THERE A BETTER WAY TO ASK
ABOUT EDUCATION LEVEL OR SES?
>> SO GREAT QUESTION.
AS AN EPIDEMIOLOGIST OFTEN TIMES
WE ADJUST FOR EDUCATION BUT WE
DON'T CONSIDER THE QUALITY.
IT'S GOING TO BE VERY DIFFERENT
BASED ON THE ENVIRONMENT IN
WHICH PEOPLE LIVE, GOING TO A
PRIVATE SCHOOL IS NOT THE SAME
AS GOING TO PERHAPS AN INTERCITY
PUBLIC SCHOOL.
SO ALSO HOW MUCH MONEY YOU MAKE
DOES NOT MEAN HOW MUCH MONEY YOU
HAVE.
SO I ENCOURAGE PEOPLE TO
CONSIDER OTHER MEASURES OF SOCIO
ECONOMIC STATUS SUCH AS DEBT.
MEASURING DEBT WHICH CAN BE
RECEIVED WITH CERTAIN QUESTIONS
LIKE AT THE END OF THE MONTH YOU
PAID ALL YOUR BILLS DO YOU HAVE
MONEY LEFT OVER?
DO YOU HAVE LESS MONEY OR IS IT
THE SAME.
CONSIDERING OTHER DIMENSIONS
THAT GET AT SOMEONE'S ECONOMIC
ADVANTAGE AND THEN I'LL CIRCLE
BACK TO CONSIDERING THE
ENVIRONMENT IN WHICH PEOPLE LIVE
AND SO THERE ARE MEASURES AT THE
CENSUS TRACK LEVEL THAT CAN BE
USED TO HELP UNDERSTAND THE
RESOURCES WITHIN THAT
ENVIRONMENT AND FEEL FREE TO
EMAIL ME.
I'M HAPPY TO OFFER OTHER
SUGGESTIONS AS WELL.
>> FANTASTIC.
THANK YOU SO MUCH.
I SEE WE'RE RIGHT AT TIME SO
I'LL WRAP UP.
I WANT TO THANK OUR SPEAKERS FOR
TODAY SO MUCH AND WONDERFUL
TALKED AND THANK YOU TO THE
WORKSHOP ORGANIZERS AND I'LL
TURN IT OVER TO OVER FOR ANY
LAST REMARKS.
>> SO I WANT TO GIVE A BIG
THANKS TO ALL OF TODAY'S
SPEAKERS FOR THEIR EXCELLENT
TALKS.
AND AGAIN I WANT TO ACKNOWLEDGES
DR. AGGARWAL AND JONES AS
BRILLIANT CO-CHAIR FOR DAY ONE
AND WE'LL CONVENE FOR DAY TWO OF
THIS WORKSHOP THIS COMING
FRIDAY.
APRIL 26 AT 10:00 A.M. EASTERN
TIME.
WITH THAT, I HOPE EVERYONE HAS A
WONDERFUL EVENING AND WE LOOK
FORWARD TO SEEING YOU ON FRIDAY.