MY NAME'S ELIZABETH MURPHY AND
I'M THE HOST FOR DR. NOEL MERZ
TALK TODAY AND THERE ARE 2
I HAVE 2 HOUSEKEEPING ISSUES I AM
SUPPOSED TO DOLE WITH, 1 IS FOR
CME CREDIT, IF YOU WANT CME
CREDIT YOU HAVE TO TEXT THE
NUMBER 50122 AND THE SECOND
HOUSEKEEPING ISSUE I'M SUPPOSED
TO DEAL WITH IS FOR THOSE OF YOU
WHO ARE ONLINE, IF YOU HAVE
QUESTIONS FOR THE SPEAKER PLEASE
USE THE SEND LIVE FEEDBACK
BUTTON ON THE VIDEOCAST PAGE.
ALL RIGHT SO NOW THAT WE HAVE
THE HOUSEKEEPING ISSUES DONE
WITH, I WILL GO AHEAD AND
INTRODUCE TODAY'S SPEAKER.
IT'S MY TBRAIT PLEASURE TO
INTRODUCE TODAY'S WALS LECTURE
SPEAKER DR. NOEL MERZ, IS THE
PROFESSOR OF CARDIOLOGY AND
MOUNT CEDAR SINAI MEDICAL CENTER
IN LOS ANGELES, AT CEDAR SINAI
SHE HEADS UP THE BARBARA
STREISANDROGEN WOMEN'S HEALTH
CENTER AND I THINK SHE'S THE
BARBARA STREISAND OF WOMEN'S
MEDICAL INFORMATION.
SHE'S CHAIR OF THE NHLBI
SPONSORED WOMEN'S ISOTOPE KEEMIC
SYNDROME KNOWN AS Y-STUDY AND
THIS INVESTIGATES METHODS OF
DIAGNOSIS AND MEDICATION FOR
HEART DEC IN WOMEN, SHE'S
PUBLISHED OVER 150 PAPERS AND
CHAPTERS AND NUMEROUS AWARDS AND
HONORS TO GIVE HER TIME TO GIVE
HER LECTURE, I WON'T MENTION ALL
OF THEM BUT I WILL MENTION A
FEW, 1 IS SHE'S THE AMERICAN
COLLEGE BERNEA DEAN HEALY
LEADERSHIP AWARD IN WOMEN'S
CARDIOVASCULAR DISEASE IN 2016,
SHE ALSO RECEIVED THE RED DRESS
AWARD FOR LEADERSHIP IN
CARDIOVASCULAR RESEARCH IN
WOMEN, IN ADDITION TO HER
EXCEPTIONAL SCIENTIFIC
ACCOMPLISHMENTS, SHE WAS ALSO
AHEAD OF HER TIME AND A PIE O
NEAR IN RAISING PUBLIC AWARENESS
OF THE NEED FOR MORE STUDY IN
WOMEN'S HEALTH ISSUES AND
ESPECIALLY WOMEN'S
CARDIOVASCULAR DISEASE.
ON THE MANY THINGS SHE'S DONE TO
GET THE MESSAGE OUT AND RAISE
AWARENESS, SHE MODERATED A RED
DRESS AWARENESS PANEL DISCUSSION
AT THE RONALD REAGAN
PRESIDENTIAL LIBRARY WITH FIRST
LADIES LAURA BUSH AND NANCY
REAGAN AND THIS WAS IN 2007.
SHE ALSO HAS FREQUENT
APPEARANCES IN THE MEDIA AND
SHE'S APPEARED IN MANY DEFINITE
APPEARANCES SUCH IS ON 60
MINUTES, THE TODAY SHOW, GOOD
MORNING AMERICA, NBC, DATELINE
AND TWEBT 20.
SO WE'RE IN FOR A TREAT WITH HER
LECTURE TODAY EMPLOY SO IF YOU
COULD JOIN ME IN WELCOMING
DR. BAIRY MERZ, WITH A TALK
ENTITLED NOT YOUR FATHER'S HEART
DISEASE EMPLOY.
THE HERSTORY AND THE NHLBI WISE.
[ APPLAUSE ]
>> SO THANK YOU SO MUCH
DR. MURPHY AND YES, I AM
DELIGHTED TO BE HERE.
THE NATIONAL INSTITUTES OF
HEALTH IS JUST REALLY THE MOTHER
OF ALL OF THE BIOMEDICAL
DISCOVERY AND NOT TO SAY THAT
IT'S ALWAYS DONE IN THE UNITED
STATES BUT IT'S JUST AN HONOR TO
BE HERE AND SUCH WIDE RANGING
IMPACT OF THIS INSTITUTE, SO,
DR. MURPHY HAD IT RIGHT, I'M
GOING TO TALK ABOUT NOT YOUR
FATHER'S HEART DEC AND THIS IS
THE HERSTORY, I DID NOT COME UP
WITH THIS, A MALE COLLEAGUE DID
AND THE NATIONAL HEART LUNG AND
BLOOD SPONSORED WISE STUDY.
THESE ARE MY DISCLOSURES OF
COURSE, WE ALWAYS DISCLOSE
THESE, DO NOT HAVE ANYTHING TO
DO WITH WHAT WE'RE DOING TODAY
BUT THOSE ARE MY DISCLOSURES.
SO WHY WAS THE WISE THE WOMEN'S
ISCHEMIA SIS DROAM EVALUATION
FUNDED?
IT WAS INITIATED BY NHLBI, I
WILL TALK ABOUT THOSE PROGEC
OFFICERS IN A SUBSEQUENT SLIDE
BUT THEY WERE RESPONDING TO THIS
SLIDE WHERE FOR THE FIRST TIME,
EVER, IN THE 1970S, AS A
COUNTRY, WE STARTED SEX
STRATIFYING DISEASES AND IN
PARTICULAR CARDIOVASCULAR
DISEASE AND WHAT YOU CAN SEE
HERE IS THE RED LINES ARE THE
FEMALE CBT MORTALITY AND THESE
WERE AJUSTED FOR AGE, ADJUSTED
FOR ALL OF THE THINGS THAT MIGHT
CONTRIBUTE TO THIS, SO THESE ARE
TRUE SEX DIFFERENCES, COMPARED
TO THE MALE LINE, CBT MORTALITY
IN THE BLUE AND WHAT WE SEE WAS
FOR THE FIRST TIME IN 1984,
CARDIOVASCULAR DISEASE BECAME
THE MAJORITY OF VICTIMS WERE
FEMALE IN OUR COUNTRY, AND THIS
WAS QUITE SURPRISING, THIS
HASN'T HAPPEN INDEED RECORDED
HISTORY, I WILL TELL YOU A BIT
ABOUT THE YENTIL, AND THE YENTIL
SYNDROME WHICH DR. BERNEA DEAN
HEALY, A PRIOR DIRECTOR OF OUR
NIH COINED IN THE NEW ENGLAND
JOURNAL, IT TOOK ABOUT 12 YEARS
DOES IT TOOK A WHILE FOR THE
NATIONAL ACRONYM, AND THE
NATIONAL HEART ASSOCIATION AS WE
HEARD STARTED THEIR WOMEN'S
AWARENESS CAM WARENESS--CAMPAIGF
COURSE WAS IF IT WOULD HAVE HAD
SOMETHING TO DO WITH ERECTILE
DYSFUNCTION OR PROSTATE IT WOULD
HAVE BEEN GOING SOONER BUT OF
COURSE IT DID GET GOING.
WE HAVE STUDIES OF FRUIT, FLIES,
HAMSTERS, MICE, FROG, MONKEYS
AND MEN, WITH THIS MEDICAL
CONDITION, BUT MEDICAL RESEARCH
OF USING WOMEN AS MEDICAL
RESEARCH SUBRECYCLINGS NEVER
OCCURRED TO ANYBODY AND THAT
REALLY WAS TRUE AT THE TIME.
SO HERE ARE 2 WISE PROJECT
OFFICERS, THE DR. NICKENS ON THE
LEFT DR. GEORGE SABCO ON THE
RIGHT AND WHAT YOU CAN SEE IS
WHAT WAS INITIATED AS A CONTRACT
AND THESE ORIGINAL SITES WERE
CONTRACTED SO WORKING HAND IN
HAND WITH NATIONAL HEART LUNG
AND BLOOD WE DESIGNED--THERE WAS
AN IDEA ABOUT WHAT WE WERE
SUPPOSED TO STUDY, WE WERE
SUPPOSED TO RESPOND TO THIS
EPIDEMIC OF DEATH IN WOMEN THAT
WAS NOT UNDERSTOOD AT ALL AND
WHAT YOU CAN SEE, SUBSEQUENTLY,
IS A TREMENDOUS NUMBER OF
ADDITIONAL NIH FUNDING AS WELL
AS INDUSTRY PARTNERSHIPS AND I
WILL SHOW YOU ALL THE WAY TO
TRANSLATIONAL WHAT WE CONSIDER
BENCH TO COMMUNITY, RANDOMIZED
CONTROL TRIALS OF STRATEGIES TO
AGAIN, ADDRESS THIS EPIDEMIC OF
DEATH IN WOMEN.
AT THE GET-GO AND REMEMBER THIS
WAS IN THE 1980S, DIVERSITY
EQUITY AND INCLUSION WHICH WAS
NOT CALLED THAT THEN BUT BY
DESIGN AND FROM INCEPTION,
1996-THE CURRENT, THE WISE
STUDIES OVERSAMPLED ETHNIC
MINORITY DPROWPS, WOO DID THAT
BY CHOOSING OUR SITES CAREFULLY,
WOE EEEVER SAMPLED LOW SES,
AGAIN TO BE REPRESENTATIVE TO
THE AMERICAN PUBLIC, AND WE
INCLUDED DETAILED QUALITY OF
LIFE AND WHAT WE WOULD NOW CALL
PROMs, PATIENT REPORTED
OUTCOMES, BECAUSE BEING ALIVE
AND BEING DEAD IS NOT ALWAYS THE
END OF THE GAME AND SO WE'RE
PRETTY PROUD OF THAT, OF OUR
DIVERSITY, AND OUR
REPRESENTATION TO AMERICAN
WOMEN.
SO I'M GOING TO START NOW AND
JUST TELL YOU SORT OF HOW THIS
STUDY PROGRESSED BECAUSE AS YOU
CAN SEE, IT'S A PRETTY OLD STUDY
ALTHOUGH IT KEEPS RENEWING WITH
NEW AIMS, WE INITIALLY ADDRESSED
A PARADOX, DEMON TRAITING THAT
WOMEN HAVE A 2 FOLD INCREASE IN
WHAT'S CONSIDERED AT THAT TIME
NORMAL CORONARY ARTERIES IN THE
SETTING OF ACUTE CORONARY
SYNDROME, STEM NSTEMI, AND
STEMI, OUR WORST HEART TACKS,
ELEVATION AND MI, AND WE SIMPLY
LOOKED AT THE DATA AVAILABLE,
AND THESE OF COURSE WERE ALL
DATA SETS THAT HAD CORE LABS SO
WE DIDN'T HAVE TO GUESS ABOUT
WHETHER OR NOT THOSE ARTERIES
WERE OPEN OR CLOSED, WHETHER
THEY HAD OBSTRUCTED CORONARY
DISEASE OR NOT AND WHAT IT
DEMONSTRATED WAS PICK A STUDY OR
A CATEGORY OF ACUTE CORONARY
SYNDROME ALL OF WHICH ARE
THREATENED MIs OR MIs AND
YOU CAN SEE THAT WOMEN HAD 2-3
TIMES THE NUMBER OF OPEN
CORONARY ARTERIES COMPARED TO
THE MEN.
NOW REMEMBER, IN THE 1980S, 90S,
WE WERE--WE KNEW WHAT CAUSED
HEART ATTACKS, IT WAS PLUGGED UP
ARTERIES, RIGHT?
AND MORE SO, TO THE POINT WHERE
WE HAD THIS WHOLE SYSTEM OF
BYPASS SURGERY AND TINTS AND
DRUG ALLUDING STINTS AND DRUG
ABSORBING STINTS AND YET IT
DIDN'T LOOK LIKE THAT WOULD BE
RELEVANT IN UP TO A THIRD OF
WOMEN.
SO THIS WAS NOT A RELATIVELY
SMALL PROBLEM.
SO WITH THAT OBSERVATION AND WE
DESIGNED THE ORIGINAL AND 102
WISE TRIALS TO LOOK AT HERSTORY,
NOT HISTORY, AND OUR TEAM DEFINE
ITS AS A SYSTEMATIC APPROACH TOO
AN IDENTIFIED PROBLEM.
T1 IS BENCH TO BEDSIDE BUT NOTE,
I HAVE THE ARROWS GOING BOTH
DIRECTION, WE WILL MAKE
OBSERVATIONS AT THE BEDSIDE, OH
LOOK AT THAT, A WOMAN HAD A
HEART ATTACK WITH NO OBSTRUCTIVE
CORONARY DEC, I WONDER HOW THAT
HAPPENED?
SO THEN WE WILL GO BACK TO THE
BENCH AND WORK WITH OUR BASIC
COLLEAGUES.
T2 OF COURSE IS BEDSIDE TO
CLINIC SO WOE START TO DO
RANDOMIZED CONTROL TRIALS IN
HUMANS THAT HAVE THE CONDITION
AND THEN T3 IS THAT WE DO
STRATEGY TRIALS, WE DEMON TRAIT
THAT IT DOES OR DOES NOT WORK IN
A REAL WORLD SITUATION AND AGAIN
WE CAN MAKE OBSERVATIONS AT THE
COMMUNITY AND GO BACK AND REFINE
SOME'VE OUR CLINICAL TRIALS TO
MAKE THEM MORE ADAPTABLE.
SO 4 STEPS, OBSERVATION,
MECHANISMS, INTERVENTION AND
TRANSLATION, SO LET'S GO FORWARD
WITH FURTHER OBSERVATION.
SO WE WERE CURIOUS ABOUT THIS
PARADOX, HOW COULD WOMEN HAVE
HEART ATTACKS AND ACUTE CORONARY
SYNDROMES WITH NO CORONARY
DISEASE, I HAD THE GREAT BENEFIT
OF WORKING WITH DR. KARL
[INDISCERNIBLE] AND HE'S
REMAINED A CO-PI WITH ME
THROUGHOUT.
WE DESCRIBED A PHENOTYPE WHERE
YOU CAN SEE THE PATIENT IN PANEL
A HAS EXTERNAL AGINA WHERE THE
PHYSICIAN ORDERED A MYOCARDIAL
SPECT, THAT IS I LITTLE HEART
AND A CARDIOLOGIST WOULD TELL
YOU THAT IS WHERE THE ABNORMAL
BLOOD FLOW TO THE HEART IS AND
THAT'S WHAT'S CAUSING THE AN
GUINA AND THEREFORE BECAUSE IT'S
IN THE LEFT CORONARY DESCENDING
ARTERY, LET'S DO AN ANGIO GRAM
AND OPEN UP THE ARTERY BUT IT
TURNS OUT THE ARTERY IS OPEN,
WIDE OPEN.
DR. KARL PEPINE WAS A CORONARY
PHYSIOLOGIST, HAD GROWN UP AT
THE TIME WHERE MEASURING FLOW
AND UNDERSTANDING FLOW IN THE
ABSENCE OF OBLIGATIONS YECTIVE
CORONARY DEC WAS IMPORTANT AND
RELEVANT AND DR. PEPINE SAID
LET'S PUT DOWN WIRES.
WE USED TO BE ABLE DO THIS
BEFORE WE BECAME ANATOMISTS AND
WHAT LOW AND BEHOLD, AS WE DID
MORE AND MORE OF THIS, THESE
PATIENTS HAD AN ABNORMAL FLOW
RESERVE.
THEIR EPICARDIAL LARGE ARTERIES
WERE OPEN SO IT IS A SMALL
VESSEL PROBLEM AND THESE ARE THE
SMALL VESSELS YOU CAN'T SEE, YOU
CAN MEASURE FLOW BUT YOU
COOPERATE SEE THEM WITH THE
EXCEPTION OF SOME ADVANCED
IMAGING.
WE ALSO DID, WHICH WAS HIGHLY
NOVEL AT THE TIME INTRA VASCULAR
CORONARY ULTRASOUND, LITTLE TINY
ULTRASOUND PROBES GOING DOWN
INTO HUMAN CORONARY ARTERIES AND
WHAT WE DEMON TRAITED WAS
DIFFUSED ABNORMAL GLUCOSE
TOLERANCELER O SCLEROSIS DESPITE
ARTERIES AGAIN TYPICALLY IN
WOMEN, WITH A HEALTH ECONOMIST
AND LARGE DATA SET, NCDR, WE
ESTIMATED 3 MILLION PEOPLE IN
THE U.S. HAD THIS, A MUCH LARGER
PROBLEM THAN BREAST CANCER AND
IT WAS A LETHAL PROBLEM AND IT'S
NOW CALLED ISCHEMIA WITH NO
OBSTRUCTIVE CORONARY DEC, SO FOR
THOSE WHAT ARE IN THE CORONARY
AREA, OR GENERAL MEDICINE FOR
AREA, THIS IS NOW ACRONYMS AND
BILLING CODES FOR INOKA AT THIS
TIME.
WORKING WITH ANOTHER COLLEAGUE,
DR. MARTHA GILOTTI, WHO AT THE
TIME WAS AT CHICAGO IN
NORTHWESTERN, WE NEEDED A REFOR
INSTANCE CONTROL GROUP.
WE HAD WOMEN THAT WE HAD
FOLLOWED NOW FOR 5-7 YEARS AND
WE HAD ASKED ACTUALLY NHLBI IF
WE COULD INCLUDE MEN AS A
CONTROL GROUP AND THEY SAID NO.
SO WE FOUND A CONTROL GROUP
WORKING WITH DR. MARTHA GILOTTI,
WHO HAD REFERENCE TO A LARGE
CHICAGO ASYMPTOMATIC WOMEN PAIK
HEART STUDY WHERE THESE WOMEN
WERE ALL STUDIED INCLUDING
EXERCISE TREADMILL TESTING WHICH
WAS NEGATIVE AND WHAT WE DEMON
TRAITED WAS THESE WOMEN HAD 12
TIMES HIGHER, 12% 5 YEAR
COMBINED MACE RATE, MI,
CARDIOVASCULAR, DEATH, THIS WAS
NOT A BENIGN PROGNOSIS WHICH ALL
OF THE PREVIOUS STUDIES HAD
FOLLOWED LESS THAN A HUNDRED
WOMEN AND THEY HAD FOLLOWED THEM
FOR LESS THAN 3 YEARS.
SO THIS WAS A BIT EYE OPENING.
NOW WE'VE MADE SOME OTHER
OBSERVATIONS, I'M GOING TO JUST
SORT OF SPIN THROUGH THESE.
WORKING WITH DR. VERMONI, WHO
WAS AT THE UNIFORMED HEALTH
SERVICES HOSPITAL AND SHE HAD A
FREEZER FULL OF SUDDEN CARDIAC
DEATH VICTIMS WHO HAD ALL ALL
ABOUT NECROPSYSED TO SEE IF THEY
HAD HEART ATTACK OR SOME OTHER
PROBLEM.
BASICALLY IN COMPARING WOMEN ON
THE TOP, THIS CROSS SECTIONAL OF
THE CORONARY ARTERY COMPARED TO
MEN, BOTH HAD HAD HEART ATTACKS,
BOTH HAD SUDDEN DEATH, IT WAS
CLEAR THAT WOMEN WERE ERODING
THE FIBROUS CAP OF THE PLAQUE
WHERE MEN WERE EXPLODING AND THE
EROSION WILL CALLS MICROTHROMBI
AND WE WERE SUBSEQUENTLY ABLE TO
DEMONSTRATE SMALL, SMALL
NONSEGMENTAL INFARCs IN THESE
WOMEN COMPARED TO MEN WHO WOULD
HAVE A VERY LARGE THROMBUS, THEY
WOULD INCLUDE THE ARTERY AND I
HAVE MUCH MORE DEFINITIVE HEART
ATTACK, THESE SYMPTOMS OFTEN
WOULD COME AND GO, MIGHT BE
CALLED ATYPICAL, WHERE THIS
WOULD BE THE CLASSIC HOLLYWOOD
HEART ATTACK, AND THESE WERE
IMPORTANT DIFFERENCES, NOT ONLY
IN THE PLAQUE AND COMPOSITION
BUT THEY CONTRIBUTED TO THIS
UNDERSTANDING THAT WOMEN HAD
MORE QUOTE-ATYPICAL SYMPTOMS,
WHAT WE NOW RECOGNIZE IS THAT
WOMEN JUST HAVE DIFFERENT
SYMPTOMS.
THEY'RE NOT ATYPICAL, IN THE
INITANCE 51% OF THE POPULATION
IS FEMALE, WE MIGHT SAY THEY'RE
THE CLASSIC SYMPTOMS, SO WE ALSO
DID THIS INTRA VASCULAR CORONARY
ULTRA SOUND CALLED IBIS, IT WAS
NEW AT THE TIME AND WHAT WE WERE
ABLE TO DEMONSTRATE AND THIS IS
A CARTOON THAT CAPITULATES WHAT
WE FOUND WITH THE CLEVELAND
CLINIC BECAUSE AGAIN TO GET
CONTROL MALE PATTERN WE HAD TO
COLLABORATE WITH PEOPLE, SO
PANEL A IS A REP --REPRESENTATIE
MALE, AND THE LUMENNOGRAM WHEN
WE DO ANGIO APPLYINGS DEPICTED
BY THE RED, THE PRESSURE MEANING
THE FLOW HERE IS DEPICTED IN
THIS LINE AND THE PLAQUE IS THE
YELLOW.
THE YELLOW ABNORMAL --ABNORMAL E
TOLERANCELER O SCLERRIC ATTACK,
WHERE WOULD YOU BYPASS?
WHERE WOULD YOU STINT?
THAT'S THE SORT OF CLASSIC MALE
PATTERN TIMES WE CALL IT LUMPY
BUMPY, OR SIMILAR TO HOW MANY
WHEN THEY BECOME OVERWEIGHT OR
OBESE, THEY TYPICALLY PUT IT IN
1 SPOT IN THEIR VISCERA,
SOMETIMES CALLED THE BEER BELLY.
THE REPRESENTATIVE WOMAN AT THIS
POINT, SHE DIDN'T REALLY HAVE
ANY OBSTRUCTION, DID SHE BUT
SHE'S GOT PLENTY OF PLAQUE.
SHE HAS REMODELED HER ARTERY, TO
BE THE LUMEN OFTEN WILL BE
SMOOTH, SO A DIAGNOSTIC
LUMENNOGRAM, ANKIO GRAPH WILL
NOT SHOW YOU THAT AND YET HER
FLOW IS JUST AS BAD AS HIS FLOW
AT THE END OF THE ARTERY SO
MYOCARDIUM IS NOT GETTING
THEOXIEN IT NEEDS AND AGAIN, WE
NEED--ANALOGIZE THIS TO HOW DO
WOMAN WHEN THEY BECOME
OVERWEIGHT AND OBESE.
WELL IT'S THAT LOVELY CELLUE
LIE, IT'S NOT VISCERAL, IT'S
SMOOTH, AND MAYBE LESS HARMFUL,
WE DON'T KNOW ABOUT THE
DIFFERENCES IN PLAQUE HERE, BUT
IT WAS VERY CLEAR THAT WOMEN AND
MEN WERE LAYING DOWN THEIR
PLAQUE DIFFERENTLY IN RESPONSE
TO CORONONARY ABNORMAL GLUCOSE
TOLERANCELER O SCLEROSIS, SO
WITH THOSE OBSERVATIONS OF THESE
IMPORTANT PHENOTYPES THAT WERE
CHARACTERIZING ISOTOPE KEEMIC
HEART DEC IN WOMEN, WE MOVED ON
TO UNDERSTANDING MECHANISMS, AND
WORKING WITH MY PARTNER IN CRIME
DR. LESRY SHAH, SHE'S A HEALTH
OUTCOMES EXPERT AND AN ECONOMIC
ANALYSIS, WE SAID, OKAY, WHAT
WOULD BE SORT OF SOME TESTABLE
MECHANISTIC HYPOTHESIS, AND WE
DEVELOPED THIS HYPOTHE--THISICAL
NEW UNDERSTANDING OF ISOTOPE
KEEMIC HEART DEC IN WOMEN.
WE OF COURSE, WERE INTERESTED IN
A SEQUENCE AND WE HAVE FOLLOWED
SOME OF THESE WOMEN NOW FOR OVER
20 YEARS.
THE END GAME, RIGHT, IS
OBSTRUCTIVE CORONARY DISEASE,
AND WE HYPOTHESIZED THAT BY THE
TIME WOMEN DEVELOP THEIR
SUBCLINICAL ABNORMAL GLUCOSE
TOLERANCELER O SCLEROSIS THAT
THEY HAVE TRANSITIONED FROM A
NORMAL ARTERY AND A NORMAL
CORONARY FLOW RESERVE, THAT'S
WHAT CFR STANDS FOR TO BEGINNING
OF AN ABNORMAL FLOW RESERVE.
AND FOR REASONS POTENTIALLY
RELATED TO DIFFERENCES IN
HORMONES, DIFFERENCES IN FAT
DEPOSITION, HYPERTENSION AND
LIPIDS.
WE KNOW THAT WOMEN ARE MUCH MORE
LIKELY TO HAVE AUTOIMMUNE
DISEASES THAT MAY BE
CONTRIBUTING, THERE ARE LINKS TO
CARDIOVASCULAR DISEASE, AND WE
KNOW THAT WOMEN MORE LIKELY HAVE
ABNORMAL FUNCTION, WOMEN HAVE
MORE MIGRAINES WOMEN HAVE MORE
RENODES, SO THERE WERE MANY
MECHANISTIC PATHWAYS THAT WE
PROPOSE THAT MIGHT
PREVENTIVEIENTERALLY HAVE WOMEN
PRESENT WITH ISOTOPE KEEMIC
HEART DEC AS ABNORMAL SMALL
VESSEL DYSFUNCTION AS OPPOSE TO
WAITING UNTIL THEY BECOME
OBSTRUCTIVE PLAQUE.
SO WE'VE GONE FORWARD TESTING
THESE MECHANISMS, WE AGAIN
BROUGHT BACK WITH DR. PEPINE'S
HELP AND GOT YOUNG INVESTIGATORS
TO BE TESTING CORONARY FUNCTION
IN OUR CATH LABS, THIS IS
INVASIVE AND REQUIRES AN
INTERVENTIONAL CARDIOLOGIST, IT
IS A PCI OR PTCA SET UP AND THEN
WE BROUGHT IN THESE DOPPLER FLOW
PROBES THAT HAD BEEN SITTING IN
CLOSETS AND YOU KNOW THE
INTERVENTIONAL CARDIOLOGISTS ALL
THOUGHT WE WERE CRAZY BUT WE
DEVELOPED A SEQUENTIAL
INTERCORONARY TESTING WHERE WE
CAN TEST FOR PATHWAYS, THE
CORONARY MICROVASCULATURE
AUTOREGULATES ITSELF LIKE YOUR
COMPUTER IN YOUR CAR NOW, AND SO
WE COULD TEST EACH OF THESE
PATHWAYS AND PEOPLE WILL BE MORE
OR LESS DYSFUNCTIONAL DEPENDING
ON HOW MANY OF THESE PATHWAYS
ARE FUNCTIONING ABNORMALITIES
NORMALLY.
WITH THESE LONG-TERM FOLLOW UPS,
AS I'VE DESCRIBED, WE'VE BEEN
ABLE TO DEMON TRAIT, THAT WOMEN
MOST OFTEN, 2/3RDS OF THE TIME,
HAVE NONOBSTRUCTIVE ABNORMAL
GLUCOSE TOLERANCELER O SCLEROTIC
PLAQUE, THEY ALMOST ALWAYS HAVE
ENDOTHELIAL DYSFUNCTION, WE
DEMONSTRATE THAD THE IMPAIRED
VESSEL DILATION, THIS IS THE
MOST SERIOUS ADVERSE BECAUSE IT
PREDICTS, THE MACE AS WELL AS
ALL CAUSAL MORTALITY.
THE RESTRICTION CAUSES A LOT OF
AN GUINA THAT RESULTS IN COST
UTILIZATION AS WELL AS MORBIDITY
AND THIS IS WORKING WITH YOUNG
INVESTIGATORS, FELLOWS AND POST
DOCS WHO THEN GO ON, TO THEIR
OWN CAREERS, SO MOVING FROM
MECHANISMS, THEN OF COURSE, WE
NOW CAN TEST INTERVENTIONS IF WE
REPURPOSE DRUGS OR DEVICES THAT
WE ALREADY KNOW WORKS FOR SOME
COMPONENT OF THAT MECHANISM OR
EVEN A NEW DRUGS, SO WE OF
COURSE WANTED TO UNDERSTAND AND
THIS SLIDE DEMONSTRATES HOW WE
GOT STARTED.
THE GAL ON THE RIGHT IS BARBARA
STREISAND AND SHE IS DRESSED UP
LIKE A MAN, AND THOSE OF YOU
REMEMBER THE MOVIE IN 1991
YENTEL, SHE PORTRAYS A YOUNG
WOMEN WHO TURN OF THE CENTURY
EASTERN EUROPE WANTS TO BE
LITERATE, SHE WANTS TO LEARN HOW
TO READ AND WRITE AND AT THAT
TIME THE ONLY PEOPLE WHO COULD
LEARN THAT WERE MEN.
SO SHE DRESSES UP AS A MAN.
DR. HEALY OUR PRIOR BUT NOW
PASSED UNFORTUNATELY NIH
DIRECTOR AND A CLINICAL
INVESTIGATIVE CARDIOLOGIST
HERSELF OPINED IN THE NEW
ENGLAND JOURNAL, I THINK THE
REASON WE'RE MISSING THESE
WOMEN, WHY WE'RE SEEING THIS
INCREASE IN DEATH AND BECAUSE
THEY DON'T LOOK LIKE MEN.
AND SO AGAIN, WE STARTED WORKING
TO NOW TRANSLATE THESE FINDINGS
INTO SOMETHING THAT WOULD BE
RELEVANT.
THIS IS AN OPED THAT WE WROTE IN
RESPONSE TO EEVERL SUPER AN
STUDIES THAT WERE NOW
REPLICATING WHAT WE HAD FOUND IN
THE WISE AND AGAIN, A PATIENTS
IN THE CLINICCORRAL OR CENTRAL
FIGURE DEMON TRAITING THAT WHEN
WOMEN LOOK LIKE MEN, WHEN
THEY'RE ANGIOGRAMS LOOK LIKE MEN
IN AN OBSTRUCTIVE CORONARY
DISEASE MALE PATTERN, MORE MEN
RECEIVE TREATMENT.
WHEN WOMEN LOOK LIKE WOMEN, MALE
OR FEMALE PATTERN MICROVASCULAR
CAD, MORE WOMEN DIE.
AND THIS IS BECAUSE OF A LACK OF
TREATMENT, WE TESTED THAT
HYPOTHESIS AS WE WENT FORWARD
WITH THESE PHARMAICOLOGGIC PROBE
TRIALS.
GUIDELINES THERAPY, IF IT LOOKS
LIKE YOU HAVE ISOTOPE KEEMIC
HEART DISEASE IS ASSPRIN, BETA
BLOCKER, ACE AND STATIN, THESE 4
PILLS IF YOU WILL CONTINUE TO
TAKE THEM, YOU WILL SEE YOUR
CARDIOLOGIST A YEAR LATER, YOU
WILL NOT HAVE DIED FROM YOUR
CARDIOVASCULAR DISEASE, THIS IS
STRONG EVIDENCE BUT IT HAD NOT
BEEN TESTED IN FEMALE PATTERN.
WE HAD INCORPORATED IPT GREATER
CREASINGLY, THIS INTO CLINICAL
PRACTICE GUIDELINES, WHERE IF IT
MATTERED, IF IT LOOKED LIKE
THERE WAS A FEMALE PATTERN THAT
SHOULD BE ON A DIFFERENT
DECISION TREE IN CLINICAL
PRACTICE GUIDE LINES WE WORKED
HARD TO GET THESE INTO
GUIDELINES.
THE GUIDELINE IMPLEMENTATION
WHICH WAS OCCURRING AROUND THE
TIME THAT WE WERE DOING THESE
MECHANISTIC TRIALS, BUT THIS WAS
SORT OF A GOOD START, AND WORK
DONE BY ANOTHER GROUP, AND IT
JUST SHOWS YOU PREAND POST
TRANSITION OF THE GUIDELINE
IMPLEMENTATION, MUCH OF THIS CO
INSIDED WITH OUR AMERICAN
COLLEGE OF CARDIOLOGY GUIDELINE
CAMPAIGN, AND BASICALLY IF YOU
HAD AN ACS, OR AN ACUTE
MYOCARDIAL INFARCTION, YOU
NEEDED TO LEAVE THE HOSPITAL ON
THOSE 4 DRUGS, UNLESS THERE WAS
A STRONG CONTRA INDICATION THIS
FIGURE IS NOT PARTICULARLY
UNDERSTANDABLE, SO I COLOR
COATED IT, SO FOLLOWING
GUIDELINE IMPLEMENTATION, THE
MORTALITY FOR WOMEN IMPROVED,
AND THE SEX GAP NARROWS.
THE MALE HERE PRE AND POST
DIDN'T REALLY CHANGE.
WELL WHY?
THERE ANGIOGRAMS WERE SOMETHING
THE DOCTOR COULD DIAGNOSE AND
SAY I KNOW HOW TO TREAT THAT AND
THEY GOT TREATED.
THE PERSISTENT SEX GAP, SMALL,
BUT REAL AND WE'RE TALKING ABOUT
HUNDREDS OF THOUSANDS OF LIVES
EVERY YEAR IN OUR COUNTRY, THE
PERSISTENT SEX GAP SUGGESTS THAT
MORE WORK IS NEEDED TO
UNDERSTAND SEX SPECIFIC
PATHOPHYSIOLOGY TO IMPROVE THESE
OUTCOMES IN WOMEN AND MEN.
SO JUST WITH GUIDE LINE
CAMPAIGNS ALONE BEFORE WE REALLY
NEW HOW TO TREAT THOSE, WE SAW A
PRETTY DRAMATIC IMPROVEMENT IN
CARDIOVASCULAR DEC DEATH RATES,
IN WOMEN, IT WAS ALSO GOING DOWN
IN MEN, SO, MIGHT HAVE BEEN
SOMETHING IN THE WATER BUT WE
LIKE TO THINK THAT THESE
GUIDELINE CAMPAIGNS REALLY HAVE
BEEN DEMONSTRATED TO SAVE LIVES
AND WHAT WE SAW CLEARLY IN THE
WOMEN WHICH HAD BEEN PREVIOUSLY
HERETOFORE STILL GOING UP,
RIGHT, THAT A 43% IN
CARDIOVASCULAR DEC MORTALITY.
MORTAL--DISEASE MORETALLITY.
SO CONCURRENT WITH THESE
CAMPAIGN WE LAUNCHED THESE
INTERVENTION AND WE CALLED THESE
PHARMAICOLOGGIC PROBE TRIALS,
WHY?
BECAUSE WE HAD DRUGS, TIMES
DEVICES BUT DOMINANTLY DRUGS WE
HAD KNOWN PATHWAY EFFECT EMPLOY
SO USING PHARMACOLOGY TO THEN
TEASE OUT MECHANISTIC PATHWAYS.
AND WHAT WE DEMON TRAITED EARLY
ON IS ACE INHIBITORS, QUINIPRIL
IS AN ANGIO TENSEIN INHIBITOR,
NOT ONLY IMPROVED CORONARY FLOW
IN THE SMALL VESSELS BUT WAS
ANTIANGINNAL, AT 16 WEEKS OF
TREATMENT, NOBODY THOUGHT THAT
THIS WOULD DRUG WOULD IMPROVE
ANG INA, OTHERS WERE NOT SO
SUCCESSFUL, WE TRIED LOW DOSE
HORMONE REPLACEMENT THERAPY.
I'LL ALWAYS HAPPY TO TAKE
QUESTIONS ABOUT HRT BUT I WILL
JUST TELL YOU WOMEN ARE NOT JUST
HORMONES AND WE LEARNED THAT
LESSON.
WE DIDN'T HAVE ANY ADVERSE
EFFECTS, AND WE THINK THAT THEY
THOUGHT THEIR AN GUINA WAS
BETTER BECAUSE THEIR HOT FLASHES
WERE BETTER.
WISE, ETHIN ILLEGALS A PD5
INHIBITOR DID NOT APPEAR TO HELP
AND AN EARLY USE OF A DRUG
RANOLAZINE, ONLY 1 IN ITS CLASS,
NOBODY REALLY KNOWS HOW IT, WOS,
DIDN'T SEEM TO WORK.
SO WE HAD OUR WORK CUT OUT FOR
US THEN TO TRY TO TRANSLATE
THIS, SO NOW THAT WE KNEW AND
PREVIOUS WORK DONE AT MAYO AND
THE BRIGHAM DEMON TRAITED HIGH
INSTENSITY STATINS AND WE WORKED
THEN TO TRANSLATE THIS.
O THIS IS THE WARRIOR TRIAL
WHICH IS ONGOING, WOMEN'S
ISCHEMIA TREATMENT REDUCES
EVENTS IN NONOBSTRUCTIVE C,A D,
THE INVESTIGATORS AS CAN YOU SEE
ARE LISTED THERE, AS DESIGNED
AND FUNDED BY OUR CONGRESSALLY
DIRECTED RESEARCH PROGRAM OF THE
D.O.D., 4422 SUBRECYCLINGS WITH
AN BEGINNA AND NO OBSTRUCTIVE
CORONARY DISEASE RANDOMIZE 2
INDENSIVE MEDICAL THERAPY WHICH
IS, YOU KNOW HIGH INTENSITY
STATIN, MACK MALLY TOLERATED ACE
OR ARB, AND THAT WAS FOR THE
REDUCTION OF MACE,
HOSPITALIZATION, STROKE,
NONFATAL MI OR HEART FAILURE.
THIS IS OPEN CARE RANDOMIZATION,
OPEN LABEL DONE IN THE CLINIC
USING REPURPOSES FDA APPROVED
DRUGS THAT ARE EASY AND VERY
ECONOMICAL NOW IN CARDIOLOGY AND
USED EVERY DAY IN CARDIOLOGY AND
INTERNAL MEDICINE OFFICES AND
USUAL CARE WE DID NOT INTERRUPT
ANY CARE, BUT WE HEIGHTENED CARE
IN THE VAST MAJORITY OF
PATIENTS.
THIS HAS RELEVANCE TO ANOTHER
EPIDEMIC CALLED 22 MI, WE TALKED
ABOUT NSTEM I AND STEMI, BUT
WE'RE HAVING A CHANGE OF HEART
ATTACKS PROBABLY BECAUSE OF THE
WIDE SPREAD USE OF STATINS AND
OVER THE COUNTER ASPIRIN, TO
TYPE 2 MYOCARDIAL INFARCTION,
RISE AND FALL OF BIOMARKERS,
EVIDENCE OF ISCHEMIA BUT IT IS
TUE TO A MISMATCH IN THE
MYOCARDIAL OXYGEN SUPPLY AND
DEMAND AND TYPICALLY OPEN
ARTERIES, VAST MAIORITY MAIOR-Y
OF THE TIME, IT IS DOMINATED BY
WOMEN BUT NOT ALL WOMEN BECAUSE
TYPE 1 M. I. THE GOOD OLD BAD
STEMIs, PLAQUE, RUPTURE, MILD
OR NO PLAQUE OR FIXED BUT NOT A
PLAQUE RUPTURE AND THIS IS
DOMINATED BY WOMEN.
BECAUSE WE HAD DONE ALL THE
STUDY IN THE WISE, WE DO THINK
THAT THIS IS HELPFUL, MEANING,
WE ARE NOW INFORMING BECAUSE WE
DID THIS DEEP PHENOTYPING, WE
HAVE MUCH BETTER MECHANISTIC
UNDERSTANDING THAT WE NOW ARE
ABLE TO FOR EXAMPLE, HELP WITH
THESE USE IN PRACTICE, LOW TYPE
2 MI RISK, HIGH TYPE 2 MI RISK,
AND ONGOING AND STARTING TRIALS
NOW ARE TESTING NOW SHOULD THESE
PATIENTS BE TREATED?
THESE PATIENTS APPEAR TO HAVE
MINIMAL RISK SO BETTER
PHENOTYPES, BETTER PRECISION
CARE AND HOPEFULLY BETTER HEALTH
AS A RESULT OF RANDOMIZED
CONTROLLED TRIALS.
THE TYPE 2 MI ALSO THANKS THE
STUDY OF WOMEN AND HERSTORY
BECAUSE WE HAVE NEW CHEST PAIN
GUIDELINES THAT JUST CAME OUT A
YEAR AND A HALF AGO AND WE HAVE
AS A MENTIONED PREVIOUSLY NEW
ICD10 CODES SO NOW, PHYSICIANS
CAN ACTUALLY BILL WHEN THEY
TREAT THESE CONDITIONS, WHICH
PREVIOUSLY WE DIDN'T THINK THEY
WERE REAL.
SO FACED WITH A PATIENT WITH
NONOBSTRUCTIVE STENOSIS, IT IS
VERY CLEAR NOW THEY SHOULD BE
TREATED, THEY SHOULD BE GIVEN
MEDICATIONS BECAUSE THEY'VE HAD
A HEART ATTACK, UNLIKE OUR
WARRIOR TRIAL AND THAT THE
PHYSICIANS NOW CAN USE THESE
CODES AND THEY UNDERSTAND ALSO
HOW THEY WOULD DIAGNOSE THIS
PATIENT.
THIS WAS A CENTRAL FIGURE WITH
MY COLLEAGUE DR. MARTHA GULATI,
ANOTHER EXAMPLE OF GUIDELINES,
IMPACT AND RETURN ON INVESTMENT,
ECONOMISTS AT THE CONGRESSIONAL
BUDGET OFFICE DESCRIBED A HIEWM
REDUCTION IN ITS MEDICARE
FORECAST BETWEEN 2010 AND 2020.
MOST OF THESE REDUCTIONS CAME
FROM CHANGES TO PUBLIC HEALTH
AND THE PRACTICE OF MEDICINE
ITSELF AND SPECIFICALLY OLDER
AMERICANS ARE HAVING FEWER HEART
ATTACKS AND STROKES, AND THE
LIKELY RESULT OF EFFECTIVE
CHOLESTEROL AND BLOOD PRESSURE
MEDICINES.
AND SO THIS IS AN EXAMPLE AGAIN
OF NIH AND RETURN ON INVESTMENT.
AND WE NEED TO JUST POUND THAT
DRUM ALL THE TIME.
EVERY TIME WE ARE ASKING FOR
BUNLETS, WE'RE ASKING FOR
RESOLUTIONS, IT'S CRITICALLY
IMPORTANT.
SO HERE'S WHERE WE WERE THEN AS
WE DID THESE PROBE TRIALS AS WE
GOT INTO THE NIGHER GUIDELINES
AND NEWER CODING, ONCE AGAIN WE
SAW A DROP TO THE POINT WHERE
WOMEN NOW WERE AT PARITY WITH
MEN SHOWN IN THE RED LINE
COMPARED TO THE BLUE LINE ASKING
IS THIS OPTIMAL FOR WOMEN?
BECAUSE WOMEN USED TO DO BETTER
THAN MEN AND WOMEN CONTINUE TO
HAVE A LONGER LIFE SPAN ON
AVERAGE THAN MEN, SORT OF BUILT
TO LAST MIGHT BE 1 OF THE
PHYSIOLOGIC DIFFERENCES AND SO
THAT IS THE QUESTION.
SHOULD IT BE DOWN HERE IN IS
THERE MORE WORK TO BE DONE?
AND INDEED EVEN BEFORE THE
PANDEMIC AN ASSOCIATED AS WE
READ ON DEATHS OF DESPAIR AND
ERODING LIFESTYLE PRACTICES,
BOTH WOMEN AND MENS
CARDIOVASCULAR DEC IS ON THE
RISE AND WAS AIDED AND ABETTED
BY THE PANDEMIC, SO FOR THOSE OF
YOU IN CARDIOLOGY,
CARDIOVASCULAR DISEASE AND ALL
OF ITS RELATED DISCIPLINES WE
ARE ASSURED OF A JOB
UNFORTUNATELY.
YEAH, MORE WORK AHEAD.
ALL RIGHT, SO NOT YOUR FATHER'S
HEART DISEASE, THE HERSTORY AND
THE NHLBI'S SPONSOREDS WITH,
OBSERVINGAL STUDIES CONTINUE TO
DEMONSTRATE THAT INOCA IS COMMON
IN WOMEN, I DIDN'T SHOW THE DATA
IN THE INTEREST OF TIME BUT IT'S
COMING IN YOUNG MIDLIFE WOMEN,
PREMENOPAUSAL WOMEN MEANING
BETWEEN THE AGES OF 45 AND 55,
MECHANISMS INCLUDE TRADITIONAL
CARDIAC RISK FACTORS,A
LOS ANGELES AS --AS WELL AS NOVL
SPECIFIC RISK FACTORS, AND
INTERVENTIONAL TRIALS SUPPORT
TRADITIONAL AND NOVEL
INTERVENTIONS AND TRANSLATIONAL
WORK IS ONGOING TO PROMOTE
INVESTIGATIVE FINDINGS INTO
GUIDELINES AND CLINICAL PRACTICE
RESEARCH TOYS IMPROVE HUMAN
HEALTH AS WELL AS ELIMINATE
THESE SEX-RELATED CARDIOVASCULAR
DISPARITIES.
THIS IS WHERE WE ARE IN TERMS OF
IMETTING UP AND TO A MORE
CONTEMPORARY AREA.
AND IT IS A PARALLELLING THE
DECLINE, THE RED LINE FROM
CARDIOVASCULAR DEC, THIS IS
TRYING TO HELP US UNDERSTAND THE
RETURN ON INVESTMENT AND WHY
INVESTING IN WOMEN'S HEALTH IN
PARTICULAR RECENTLY ACKNOWLEDGED
BY THE WHITE HOUSE, IS
CRITICALLY IMPORTANT NOT ONLY
BECAUSE IT'S THE RIGHT THING TO
DO BUT IT TURNS OUT TO BE PRETTY
GOOD ECONOMIC INVESTMENT, WE ARE
CONTINUING IN OUR WISE STUDIES,
ON THE BASIS OF THE HEART
FAILURE PROGNOSIS, IF YOU RECALL
1 OF THOSE EARLY SLIDES IN THE
OBSERVATION SECTION, THAT THE
MAJORITY OF ADVERSE EVENTS IN
WOMEN ARE NOT HEART ATTACKS
ALTHOUGH WE MAY HAVE MISSED THEM
BECAUSE OF THE LACK OF THE TIME
OF HIGH SENSITIVITY, TNI, TRIP
OWNIN, BUT THEY CLEARLY GO INTO
HEART FAILURE, AND SO THIS IS
PROBABLY THE FODDER FOR HEART
FAILURE WITH PRESERVED EJECTION
FRACTION WHICH IS A NEW EPIDEMIC
OF THE LAST 20 YEAR ANDS THESE
ARE INVESTIGATORS WORKING WITH
US COLLABORATIVELY AND ON OUR
TEAM TO UNDERSTAND PATHWAYS TO
HEART FAILURE WITH PRESERVED
EJECTION FRACTION, FONDLY TERMED
HEFP A TH, AND WE ARE WORKING
VERY HARD AT UNDERSTANDING NOT
ONLY SUBENDOCARDIAL ISCHEMIA BUT
IN DOCUMENTING THAT THE TISSUES
ARE ACTUALLY ISOTOPE KEEMIC
USING MR SPECTROSCOPY BUT ALSO
LOOKING AT WHY DOES THE HEART
GET STIFF, AND IT APPEARS TO BE
INFILTRATED IN MANY OF THESE
CASES WITH TRIGLYCERIDE,
ACTUALLY FAT IN THE HEART
MUSCLE, POTENTIALLY DUE TO
METABOLIC DISREGULATION AND A
SHIFT FROM 3 FATTY ACIDS TO
FLUICOSE IN THE HIBERNATING
MYOCARDIUM THAT IS OXYGEN
STARVED.
WE ARE ALSO LOOKING AT ADVERSE
REMODELS AND DIFFUSE FIBROSIS IN
ADDITION TO FOCAL FIBROSIS, HAD
AND THEN LOOKING AT VERY
CAREFULLY AT NOT ONLY STRAIN HOW
MUCH THE HEART QUEEZS AND
TWISTS, IT IS PUMPING BUT ALSO
HOW THE VENTRICLES ARE WORKING
SYNCHRONOUSLY AND HOW THE ATRIA
AND THE VENTRICLES ARE WORKING
TOGETHER AND ALL OF THESE ARE
POTENTIAL MECHANISTIC TREATMENT
TARGETS AGAIN FOR NOVEL OR
EXISTING INTERVENTIONS.
THIS IS OUR BENEFACTOR WHO
RAISED THE MONEY BY GETTING HER
NETWORK TO ENDOW OUR CENTER FOR
RESEARCH AND POLICY, EDUCATION
AND POLICY AND RESEARCH THAT WE
WILL NEED SEED MONIES FOR AND
THEN THE EDUCATION AND POLICY
BECAUSE WE CANNOT WRITE GRANTS
FOR THAT.
SO, THAT MIGHT BE MY LAST SLIDE,
HERE'S MY LAST SLIDE, SO I
ALWAYS WANT TO THANK OUR
PARTICIPANTS AND I'M ALWAYS
HAPPY TO TALK TO INVESTIGATORS
BECAUSE THE MANTRA IS THAT YOU
CANNOT GET WOMEN TO VOLUNTEER
FOR RESEARCH STUDIES AND WOO
HAVE NOT FOUND THAT TO BE TRUE
AT ALL.
SO I'M ALWAYS HAPPY TO GIVE YOU
TIPS, STARTING WITH SOME FEMALE
INVESTIGATORS AS A GOOD FIRST
START, I WANT TO THANK MY
CLINICAL TEAM WHO DOES THIS
IMPORTANT WORK WITH OUR PATIENT
PARTICIPANTS, MY ADMIN TRAITIVE
TEAM AND MY COLLABORATORS AS
WELL AS MY CLINICIANS IN OUR
CENTER.
OKAY, SO, I'M ENDING ON TIME.
HAPPY TO TAKE QUESTIONS.
>> THANK YOU.
[ APPLAUSE ]
>> WE CERTAINLY WELCOME
QUESTIONS FROM THE AUDIENCE TO,
GET US GOING, I WASN'T ABLE TO
TYPE IT IN YET BUT THERE WAS A
QUESTION ABOUT PARTICIPATION IN
CLINICAL TRIALS SO MAYBE YOU CAN
EXPAND ON THAT LAST TIP YOU
SAID.
>> EXCELLENT.
NOW IF IT WAS A SPECIFIC
QUESTION TO THE WARRIOR
ENROLLMENT, DID END IN DECEMBER
AND WILL CLOSE FOLLOW UP OUT BY
UNI.
WE HAD--BECAUSE OF THE PANDEMIC,
AS YOU MIGHT IMAGINE, WE WERE
LIMPING ALONG BUT WE DID NOT
STOP AND SO WE'RE SOMEWHAT
UNDERENROLLED, WE WENT THROUGH
THANK YOU D.O.D. 3 COST
EXTENSIONS BUT WE ARE FINISHING
AND WE WILL HAVE RESULTS AT THE
AHA THIS COMING FALL.
SO UNFORTUNATELY THE QUESTION IS
YOU CANNOT ENROLL IN THAT
PARTICULAR STUDY, AND THEN ALL
OF OUR OTHER STUDIES PLEASE
SHOOT ME AN E-MAIL AND I'M HAPPY
TO TAKE REFERRALS OF PATIENTS OR
EVEN YOURSELF.
WE HAVE HISTORICALLY DONE WELL
FOR ENROLLMENT, I THINK THE
TRICKS ARE NUMBER 1, YOU CAN SEE
ON THIS PAGE A FAIR AMOUNT OF
FEMALE LEADERSHIP AND JUST LIKE
THAT PNAS STUDY THAT DEMON TRAIT
THAD FEMALE EMERGENCY DEPARTMENT
PHYSICIANS WERE BETTER AT TAKING
CARE IN TERMS OF OUTCOMES,
MORBIDITY AND MORTALITY OF HEART
ATTACK IF IT WAS CONGRUENT IF A
WOMAN DOCTOR WAS TAKING CARE OF
A WOMAN PATIENT, I THINK FOR
REASONS THAT ARE PROBABLY
RELATED TO THAT, OUR WOMEN FEEL
PRETTY CONFIDENT ABOUT, YOU KNOW
ENROLLING IN OUR CLINICAL TRIALS
AS WELL AS OUR OBSERVATIONAL
STUDIES SO HAVING FEMALE
INVESTIGATORS AND STAFF ON YOUR
TEAM, NOT EXCLUSIVELY, AS YOU
CAN SEE, WE HAVE MEN AS WELL,
NUMBER 2, THE PROTOCOL NEEDS TO
BE FEMALE FRIENDLY.
WE OFFER STIPENDS FOR TRAVEL.
WE HAVE STIPENDS FOR DAYS AWAY
FROM WORK OR FOR ELDER CARE OR
CHILDCARE AND YOU CAN'T HAVE
THESE ENROLLMENT CRITERIA WHERE
NO 1 OVER 75 CAN--A LOT OF OVER
75 WOMEN WOULD LIKE TO
PARTICIPATE IN A HEART FAILURE
TRIAL.
SO THE PROTOCOLS NEED TO BE
FEMALE FRIENDLY.
AND YOU KNOW THESE ARE NOT THAT
HARD TO DO AND YET WHEN YOU LOOK
AROUND THEY'RE NOT DONE VERY
OFTEN.
SO I HOPE THAT'S HELPFUL NVERY
EXCITING, YEAH.
NTHANK YOU FOR A WONDERFUL TALK,
I AM ALAN [INDISCERNIBLE] FROM
HEART LUNG BLOOD INSTITUTE, I
WAS CURIOUS THAT THE LAST SLIDE
THAT YOU MENTIONEDS ARE THE TRI
DPLIS RIDE INFILTRATION AND
CARDIAC ISSUE AND PATIENTS WITH
HEART FAILURE, IS THERE ANY
ASSOCIATION WITH [INDISCERNIBLE]
RICH PROTEINS THEMSELVES WITH
THAT FINDING?
>> YEAH, THAT'S A GREAT
QUESTION.
WELL, SO, THE OTHER OBVIOUS
QUESTION IS, THOSE ARE THE
DIABETICS, RIGHT?
THAT THEY'RE THE 1S THAT HAVE
THE HIGH CIRCULATING BLOOD
GLUCOSE AND THAT DOESN'T APPEAR
TO BE TRUE, EITHER, WE GOT THE
IDEA, WELL WE HAD A
SPECTROSCOPIST AND SHE WAS VERY
INTERESTED IN THIS AND WE WENT
TO THE LITERATURE AND THERE ARE
YOU KNOW 1-OFF UNUSUAL GENETIC
DISORDERS, OFTEN CHILDREN, WHERE
THEY CANNOT USE FREE FATTY
ACIDS, THEY USE FLUICOSE AS THE
PRIMARY METABOLIC FUEL, AND IT'S
TURNING OUT TO BE TRUE.
WE ARE HALFWAY THROUGH HER R,
DR. JANET WAYS R, AND WE WILL
SEE HOW MUCH IT TURNS OUT TO BE
TRUE, BUT SO FAR, NO, DOESN'T
APPEAR TO BE RELATED TO THAT.
>> IT WOULD BE INTERESTING TO
LOOK AT GOLDBERGARY WORK WHERE
HE DID PET SCANS IN PATIENTS
WITH GRIEK O PROTEIN LIPASE
DEFICIENCIES AND SHOWED
SWITCHING FROM FATTY ARK SID TO
GLUCOSE MAY CHANGE GENE
TRANSCRIPTION OF CARDIAC CELLS
AND MAYBE THAT'S A LINK THERE.
>> AND MAYBE THAT WAS 1 OF THE
THINGS THAT WE LOOKEDDA THE THAT
WE SAW SPRMS OF NATURE, RIGHT?
, THAT WE WONDERED AND AGAIN,
THESE PATIENTS CLINICALLY, OFTEN
HAVE CHEST PAIN AT ALL RHYME OR
REASON, NOT EXERTIONAL CHEST
PAIN AND WITH OUR CURRENT COHORT
WE'RE FINISHING, WE ALSO
DEMONSTRATED BY SOMETHING SIMPLE
AS HAND GRIP, THEY LEAK
TRIPONIN, SO THE IDEA IS IF YOU
DO THIS LONG ENOUGH, THEY MAY
REALLY GENUINELY HAVE A FORM FOR
US TO WHAT WE WOULD CALL
HIBERNATING MYOCARDIUM, THERE
ARE CELLS THAT ARE JUST HANGING
ON BY THEIR FINGERNAILS AND THE
LEAST AMOUNT OF EFFORT CAN CAUSE
DAMAGE, AND THEN, SHIFT IN
METABOLISM, RIGHT, WE THINK, YOU
CAN TELL US IF THAT'S A KNOWN
MECHANISM BUT MORE IMPORTANTLY
THE SMALL LATE GATTA LIDIUM
SCARSY THINK AND THE FIBROSIS,
YEAH.
>> THANK YOU.
>> THANK YOU NOEL, THAT WAS A
GREAT TALK.
I'M INTERESTED IN THE TYPE 2 MI.
SO IS FLOW REDUCED IN IS THERE
ANY--IS FLOW REDUCED IN THAT?
>> TYPE 2 MI, AGAIN, DEFINED AT
A ROUGH PHENOTYPE IS YOU KNOW
THEY HAVE A RISE AND FALL OF THE
TRIPONIN SO IT'S NOT A CONSTANT
AND THAT, YOU KNOW THE
MECHANISTIC UNDERSTANDING IS
THAT THE DEMAND OUTSTRIPS THE
FLOW AND SO IT'S AN IMBALANCE SO
WHAT WOULD BE A COMMON TYPE 2
MI,EUR O ACCEPTIS, SO EXTREME
OXYGEN DEMAND, RIGHT?
YOU'RE IN SHOCK, EVERYBODY'S
STARVING NOBODY'S GETTING ENOUGH
OXYGEN SO AS MUCH AS THEY CAN
VASE O DILATE AND DELIVER THAT
OXYGEN, IT OUTSTRIPS SO THAT
WOULD BE 1 MECHANISM BUT WE ALSO
SEE TYPE 2 MIs WHERE THE
DEMAND DOESN'T LOOK THAT
STRESSFUL, RIGHT?
AND SO THEN WE WOULD HYPOTHESIZE
AND THIS IS WORK THAT NEEDS TO
BE DONE BECAUSE THE TYPE 2 MI
HAS ONLY RECENTLY BEEN TARTED.
YOU KNOW IT'S ANOTHER 1 OF
THESE, WE HAVE TO WAIT 10 YEARS
FOR THE EPIDEMIOLOGIST TO SAY,
WHOA THIS IS AN EPIDEMIC.
[LAUGHTER]
WE'RE HAVING AN EPIDIMMIC OF
TYPE 2 MIs, GO STUDY IT SM AND
SO HOW MANY OF THEM ARE GOING TO
BE IN THOSE DIFFERENT CAMPS,
SORRY, THEY TEND TO BE OLDER BUT
AGAIN, WE MAY BE MISSING TYPE 2
MIs IN WOMEN BECAUSE OF THE
MALE PATTERN TRIPONIN THRESHOLD.
>> AND I WONDER WHETHER THERE'S
A METABOLIC COMPONENT TO IS.
THAT'S PART OF THE REASON.
IT WOULD BE INTERESTING TO LOOK
AT IT.
>> ABSOLUTELY COULD BE BECAUSE
YOU KNOW, YOU WILL SEE 55
YEAR-OLD WOMEN, YOU KNOW THEY
HAVE THE SAME AGE, SAME RISK
FACTORS, THEY HAVE THE SAME
MENOPAUSAL STATUS AND YET 1 GETS
INTO TROUBLE WITH THIS FLOW
RESERVE, AND HAS INOCA AND MIGHT
BE MINOCA AND THE OTHER 1'S JUST
FINE, HYPER TENSIVE, SAME ISSUES
BUT SHE'S--SO I THINK THAT'S
EXACTLY RIGHT AND THE OMICs
MAY HELP US UNDERSTAND THAT.
>> YES, SIR.
>> YES, VERY NICE TALK, QUESTION
IS HOW DOES LIPO TEEN DELAY
FACTOR IN YOUR POPULATION IN
WOMEN VERSUS MEN?
>> YEAH, GREAT QUESTION, IF MY
COLLEAGUE WAS HERE, SHE WOULD
SAY THIS IS SUCH A BIG PROBLEM
AND THANK GOODNESS THESE TRUGS
ARE COMING SO I HAVE TO TELL YOU
THERE'S CONTROVERSY IN THE
FIELD, NOEL WHO WORKED WHEN THE
CDC WAS WORKING WITH THE
NATIONAL CHOLESTEROL EDUCATION
PROGRAM TO CERTIFY THE NATION'S
LABS FOR THAT STANDARD LIPID
PANEL BECAUSE YOU KNOW YOU BEING
SEND SPLIT SAMPLES TO 2
DIFFERENT LABS AND YOU WOULD GET
TOTALLY DIFFERENT RESULTS, AT
THIS TIME WITH GEORGE MENSA THE
LP LITTLE ASSAYS WERE UP FOR
ALSO STANDARDIZATION, LIKE
EVERYBODY HAD TO DO IT THE SAME
WAY AND IT FELL OFF THE RADAR
AND WAS NOT IMPLEMENTED, DITTO
HOMOCYSTINE, SAME THING,
HOMOCYSTINE IS A REAL PROBLEM
FOR LAB VARIABILITY, NOW THAT
THIS IS COMING OUT, FUTURE DRUGS
ARE IN PHASE 2, PHASE 32, IT'S
ANYTHING TO BE AN ISSUE AGAIN,
AND SO FAR, OF THE PEOPLE THAT
I'VE TALKED TO THAT NOBODY IS
SUGGESTING THIS, OR NO WORK IS
BEING DONE AT AUTHORITATIVE
LEVELS SO I WOULD BE A LITTLE
SKEPTICAL ABOUT WHOSE REALLY
HIGH.
THE OTHER THING THAT INDUSTRY IS
GOING TO WANT TO TELL US THESE
DRUGS AND THEY'RE GOING TO SAY,
OKAY, WELL EVEN THOUGH IT'S ONLY
1 IN A HUNDRED OR 1 IN 250 THAT
HAS A HIGH ENOUGH LEVEL THAT WE
WOULD ENROLL THEM IN A CLINICAL
TRIAL, THEY'RE GOING TO SAY,
IT'S GOING TO BE A CONTINUOUS
SCALE.
THESE ARE GOING TO BE REALLY
EXPENSIVE DRUGS AND I--I WOULD
BE CAUTIOUS ABOUT HOW MUCH THIS
WILL PLAY OUT.
HAPPY TO BE WRONG.
BUT I THINK SO MANY OF THESE
OTHER TARGETS ARE GOING TO NEED
A PRECISION MEDICINE DIAGNOSTIC
TO REALLY UNDERSTAND WHOSE AT
RISK AND WHOSE NOT FOR THE SUPER
EXPENSIVE DRUGS.
>> THANK YOU.
>> AND SUPER EXPENSIVE, 200,000,
250,000 A YEAR LIKE SOME OF
THESE ONCOLOGY DRUGS.
YEAH, THAT'S MY TAKE.
>> DOCTOR, THANK YOU SO MUCH FOR
A WONDERFUL TALK, WE KNOW THAT
HDL VARIES WHAT'S DIFFERENT
BETWEEN MEN AND WOMEN AND EVEN
IN WOMEN AT THE SAME TIME PREAND
POST MENOPAUSAL DUE TO ALSO
HORMONES, BUT HERE, MY QUESTION
IS, IN ANY OF YOUR STUDIES WAS
THERE ANY ASSOCIATION BETWEEN--I
KNOW THERE MAY NOT BE LIKE ANY
HDL FUNCTIONALITY TESTS BUT ON
THE HDL, IT'S HDL-C LEVELS IN
DEVELOPING IN OCA OR STEMI.
>> ANOTHER GOOD QUESTION AND
ANOTHER AREA WHERE WE HAVE HDL
DRUGS THAT ARE NOT EXPENSIVE.
NIACIN IS A GREAT DRUG, HARD TO
TAKE BUT IT'S A GREAT DRUG AND
IT'S CHEAP.
IF YOU WERE A DESERT IESHES LAND
AND YOU COULD ONLY HAVE 1 DRUG,
YOU MIGHT WISH IT WAS NIACIN, SO
THERE'S BEEN A LOT OF WORK IN
HDECKER L, AND IT'S PRETTY MUCH
A BIG FAT NOTHING.
ALL OF THE HDL RAISING DRUGS
DON'T DO ANYTHING GOOD.
HDL FUNCTION IS VERY HARD TO
TEST SO THAT HAS NOT BEEN SCALED
UP TO CLINICAL TRIALS, IT HAS TO
BE DONE ON LIVE BLOOD, LIKE
PLATELET FUNCTION, SAME THING,
WE DON'T HAVE A LOT OF PLATELET
FUNCTION TESTS IN BIG CLINICAL
TRIALS, AND THEN, THE WORK THAT
WE HAVE DONE IN INOCA, MINOCA IS
A VERY WELL REPRODUCED J-SHAPED
CURVE.
SO THERE IS INCREASED
CARDIOVASCULAR MACE, MORBIDITY
AND DEATH AND VERY LOW HDL AND
VERY HIGH HDL.
AND THE THRESHOLDS FOR WOMEN ARE
UNDER 50 THAT WOULD BE
CONSIDERED LOW HDL, AND OVER 70
WHICH IS CONSIDERED HIGH HDL.
BUT IN DEVELOPING OBSTRUCTIVE OR
NONOBSTRUCTIVE MIs IS THERE A
DIFFERENCE IN HDLC LEVELS?
NTHAT WOULD BE A GOOD QUESTION.
WE COULD LOOK AT THAT BECAUSE WE
HAVE IN THE ORIGINAL WISE
COHORT, AGAIN BY DESIGN, BECAUSE
THEY WOULDN'T LET US HAVE MEN AS
CONTROLS, WE INCLUDED ABOUT A
THIRD OF THAT ORIGINAL COHORT
THAT DID HAVE OBLIGATIONS
TRUCTIVE CORONARY DEC, AND WE
HAVE THE LONG-TERM FOLLOW UP ON
THEM, SO I WILL HAVE MY FELLOW,
THAT'S DR. RON SINGA 1 OF OUR
CURRENT FELLOWS JUST PUBLISHED
IN THE AMERICAN JOURNAL
RJ-SHAPED CURVE, SOMETHING
THAT'S BEEN SEEN IN EPIDEMIOLOGY
IN GENERAL COHORTS ABOUT YOU
AGAIN WE HAVE THE INOCA, MINOCA
COHORT.
>> GOOD, THANK YOU.
NGREAT TALK EMPLOY I--
>> GREAT TALK.
I WAS WONDERING WITH OZEMPIC,
AND HAVE HAS AFFECTED YOUR
PATIENT COHORT AND INOCA AND
DEVELOPMENT OF ABNORMAL GLUCOSE
TOLERANCELER O SCLEROSIS IN
THESE PATIENTS?
>> GREAT QUESTION.
AND THERE'S 4 ON THE MARKET NOW
AND MORE TO COME, THERE'S
TREMENDOUS INTEREST AND
EXCITEMENT AND THEY'RE
ORIGINALLY DEVELOPED FOR
DIABETES, BUT BECAUSE THE FDA,
BECAUSE OF THE UREA PROBLEMS OF
CONTROLLING BLOOD SUGAR BUT OH
BY THE WAY KILLING THE PATIENT,
THEY REQUIRED THAT INDUSTRY
DEVELOP THESE DRUGS WITH VERY
CAREFUL CARDIOVASCULAR
MONITORING TO SHOW THAT IT WAS
SAFE AND LOW AND BEHOLD THESE
DRUGS AS WELL AS THE SGLT
INHIBITORS HAVE BEEN SHOWN TO BE
EFFECTIVE FOR REDUCING
CARDIOVASCULAR MORBIDITY AND
MORTALITY, NOT ONLY SAFE,
EFFECTIVE, AND THEY'RE
INCREASINGLY GETTING APPROVED
FOR THAT INDICATION.
SO THESE DIABETES DRUGS AND IT
WAS KNOWN, I MEAN IT'S A KNOWN
MECHANISM RIGHT OF INTERFERING
WITH THE GHASTIC HORMONE PROCESS
THAT PEOPLE LITE LESS, THERE'S
NOTHING MAGIC ABOUT THESE DRUGS
THEY JUST GET PEOPLE TO EAT LESS
SO I'VE HAD THESE ARGUE AMS WITH
PATIENTS, IT'S JUST THE SAME AS
EATING LESS, NO IT'S NOT, IT'S A
MIRACLE.
I'VE STRUGGLED MY WHOLE LIFE AND
I EAT NOTHING SO THAT'S THE
CLASS OF DRUGS THAT HE'S ASKING
ABOUT AND WHEN WE LOOK AT OUR
INOCA, MINOCA POPULATION, THEY
LOOK JUST LIKE AMERICA SO HALF
OF THEM ARE OVERWEIGHT AND A
SMALLER PERCENT ARE OBESE, SO
ABOUT 60% OF OUR PATIENTS JUST
LIKE AMERICANS ARE EITHER
OVERWEIGHT OR OBESE AND THEY
WANT THESE DRUGS, DR. MATHA
GULATI IS OUR PREVENTIVE
SPECIALIST, I'M MORE LIKE SHOW
ME THE DATA.
SO HERE'S THE DATA SO FAR, THESE
WERE APPROVED AND BEEN AVAILABLE
FOR ABOUT 2 YEARS.
AT THE END OF 1 YEAR, 26% OF
PATIENTS ARE STILL TAKING IT.
WHEN YOU STOP TAKING IT, THE
VAST MAIORITY OF PATIENTS REGAIN
THE WEIGHT, WE'VE HAD A LOT OF
PROBLEMS WITH WORSENING
INSURANCE COVERAGE AS THIS
MARKET HAS JUST EXPLODED.
AND SO FOR EXAMPLE, MEDICARE IF
YOU TALK ABOUT CARDIOVASCULAR
DEC, THE MAIORITY OF PATIENTS
WILL BE MEDICARE AGE, YOU HAVE
TO MEET CRITERIA BUT THEN YOU
GET FUNDED AND THAT MIGHT BE THE
26% THAT ACTUALLY GET IT
COVERED, A LOT OF THE INDEMNITY
INSURANCE, YOU KNOW, I HAD 1
PATIENT, DIABETIC, A1C
STABILIZED, LOST WEIGHT AND THE
DRUG COMPANY SAYS WE WON'T PAY
FOR IT ANYMORE BECAUSE YOU'RE
DIABETIC.
AND THE LAST REASON THAT I'M
MORE LIKE SHOW ME THE LONG-TERM
DATA BECAUSE OVERWEIGHT AND
OBESITY IS A CHRONIC ILLNESS,
WHAT HAPPENS WHEN YOU LOSE
WEIGHT, LET'S SAY YOU LOST
10-POUNDS, YOU LOST 6-POUNDS OF
FAT BUT YOU LOST 4-POUNDS OF
MUSCLE AND BONE AND WHAT DOES
THE AVERAGE ADULT DO WHEN THEY
REGAIN WEIGHT, DO THEY GO TO THE
GYM AND EXERCISE AND DO WEIGHT
TRAINING AND AEROBIC?
NO.
SO WHEN THEY REGAIN THE WEIGHT,
THIS AGAIN IS WELL DOCUMENTED,
IT'S ALMOST ALL FAT, SO, THIS
WEIGHT CYCLING POTENTIALLY WILL
CONTRIBUTE TO FRAILTY AND
INCREASED AGING SO,--AND THERE
ARE NO GUIDELINES YET, THERE'S
NO DATA ABOUT THE RUNWAY.
LIKE, HOW LONG CAN YOU TAKE
THESE DRUGS, WHAT HAPPENS WHEN
YOU WEIGHT CYCLE, WHAT HAPPENS
WHEN YOU HIT YOUR GOAL WEIGHT?
THEY'RE TRYING TO--THEY'RE
WORKING RIGHT NOW TO GET THE
SEMIGLUE TIDE ORAL AND THAT
MIGHT BE AN OFFRAMP, MIGHT, SO
I'M--I'M EXPRESSING SOME CONCERN
EXCEPT FOR MY HIGH RISK PATIENTS
AND THEN I SEND THEM TO
DR. GULATI, BECAUSE SHE LIKES
BATTLING WITH THE INNERSURANCE
COMPANIES.
>> THANK YOU.
>> WONDERFUL TALK, SO DVT IS A
WELL KNOWN SIDE EFFECT OF ORAL
CONTRACEPTIVES AND I WAS
WONDERING IF IN PREMENOPAUSAL
WOMEN IN YOUR STUDY IF YOU FOUND
ASSOCIATIONS BETWEEN INCREASED
MICROVASCULAR COMPLICATIONS AND
THEIR AT THAT TIMEUS ON ORAL
CONTRACEPTIVES.
>> GOOD QUESTION.
SO, WE DID A WHOLE LINE AGAIN
OBSERVATION BUT LOOKING FOR
MECHANISMS TO TRY TO UNDERSTAND
HOW MUCH ENDOGENOUS HORMONES AS
WELL AS EXOGENOUS WHICH WOULD BE
THE BIRTH CONTROL PILLS AND WE
BASICALLY DIDN'T FIND VERY MUCH
IN TERMS OF EXOGENOUS HORMONES
RISK OR BENEFIT, THESE ARE CROSS
SECTIONAL AND PERSPECTIVE
ANALYSIS, THEY'RE NOT THE SAME
AS RANDOMIZED CONTROLLED TRIALS
BUT, I WOULD--MY TAKE HOME WOULD
BE, IT LOOKED LIKE THE BIRTH
CONTROL PILLS WERE PROBABLY
RELATIVELY SAFE IN THESE INOCA,
AND MINOCA PATIENTS, I'M NOT
SAYING I WOULD PRESCRIBE THEM
BUT WE DID SEE EVIDENCE OF
SERIOUS HARM IN A THOUSAND
PATIENTS FOLLOWED NOW FOR 20
YEARS BUT ONLY PROBABLY 30%, 40%
WERE PREMENOPAUSAL AND HOW MANY
WERE TAKING THE BIRTH CONTROL
PILLS, I WOULD HAVE TO LOOK IT
UP.
SO I'M NOT SURE THAT WOULD BE
ENOUGH TO SAY THESE ARE SUPER
SAFE TO USE, WHAT WE DID FIND IN
ENDOGENOUS HORMONES IS VERY HIGH
PREVALENCE OF WHAT WE NOW CALL
HYPOTHALAMIC, HYPOESTRO
GENERATEDEMMIA AND THESE ARE
YOUNGER WOMEN, PREMOAN O PAUSAL
WOMEN UNDER THE AGE OF 50, AND
THEY TYPICALLY WILL SAY THEY
HAVE MENSTRUAL CYCLES BUT IF YOU
ACTUALLY HAVE THEM TRACK THEM,
WITH AN APP, THEY HAVE A LOT OF
MISSED PERIODS, THEY
PROBABLY--THEY ARE HAVING BREAK
THROUGH PLEADING, RATHER THAN
NICE REGULAR OVULEATORY CYCLES
AND THIS WAS ASSOCIATE WIDE
ACCELERATED ABNORMAL GLUCOSE
TOLERANCELER O SCLEROSIS.
WHO WAS HYPOTHALAMIC OR HYPO,
SOME OF THEM ARE AMENERRYIC, I
CAN'T TALK TODAY, THEY ARE MORE
LIKELY TO BE STRESSED, MORE
LIKELY TO DIABETIC, ATHLETES,
HIGH INTENSITY ATHLETES, VERY
LEAN, SOME EATING DISORDERS, AND
WE DID FIEND THAT IN OUR
ESTIMATION, THIS IS WORKING WITH
DR. SANDERS WHO IS NOW AT MAYO,
THIS IS PROBABLY BIGGER THAN PC
OS THIS HYPOTHALAMIC AMENERRIA.
DID I ANSWER YOUR QUESTION
EMPLOY.
>> THAT WAS PERFECT.
THANK YOU SO MUCH.
>> OKAY OKAY, THANK YOU EMPLOY.
>> OKAY, HI, THANK YOU SO UPON
FOR YOUR TALK.
SOMETHING I WAS WONDERING IS
WOULD YOU EXPECT SOMEONE WHO'S
TRANSGENDER WOMAN, SOMEONE WHO'S
BEEN TAKING ESTRO GENERATED
THERAPY FOR A LONG TIME AT LEAST
5 YEARS TO HAVE THE SAME I GUESS
PROPENSITY TOWARDS THE
NONOBSTRUCTIVE MIS, OR DO YOU
THINK THAT THERE'S MORE TO IT
THAN JUST LIKE ESTROIEN SORE
TESTOSTERONE BEING IN THE BLOOD
STREAM.
>> THIS IS A GOOD QUESTION AND I
ACTUALLY HAVE DATA TO ANSWER
THAT.
WE WERE INTERESTED AGAIN EARLY
ON TO TRY TO UNDERSTAND THESE
REPRODUCTIVE HORMONES, RIGHT
BECAUSE THAT--IT MAKES INTUITIVE
SENSE, WHAT ARE BASIC SEX
DIFFERENCES IF YOU WERE GOING TO
STUDY WOMEN, YOU WOULD STUDY
THESE REPRODUCTIVE HORMONES SO
WE HAD AN EXPERIMENT, SORT OF
NATURE BECAUSE I HAD WORKED A
BIT WITH ERIC [INDISCERNIBLE] AT
UCLA AND HE HAD A COHORT OF
TRANSGENDER WOMEN, MEN WHO HAD
TRANSITIONED TO BEING WOMEN AND
THEY HAD ALL AGREED TO RESEARCH
AND HE ALREADY HAD THEM IN A
COHORT STUDY, AND WE WANTED TO
UNDERSTAND THE DATA FROM DENMARK
THAT BECAUSE THEY HAD BEEN DOING
TRANSGENDER HEALTHCARE, HELPING
ALLOWING PEOPLE TO TRANSITION
FOR OVER 50 YEARS AND THEY HAD
LONG-TERM FOLLOW UP STUDIES
WHERE THE TRANSGENDER WOMEN HAD
ACCELERATED CARDIOVASCULAR
DISEASE WERE DYING PREMATURELY
WHERE THE TRANSGENDER MEN WERE
NOT, SO THAT WAS AN IMPORTANT
SEX DIFFERENCE, RIGHT AND THE
RECORDS WERE PRETTY GOOD, IT
SEEMED REASONABLY BELIEVABLE.
AND SO, WE INVITED ERIC'S COHORT
TO COME AND DO--YOU KNOW WE DID
DEEP FINE O TYPING AND WE DID
CARDIAC MRI AND AGAIN WE WERE
PRETTY INTERESTED IN THIS
MYOCARDIAL TRIGLYCERIDE AS WELL
AS ALL THE OTHER THINGS WE DO
WITH MRIs AND THE THEN THE
LAST THING WE DID WAS WE KEPT
GOING TO JUST ABOVE THE KNEE CAP
SO WE COULD SAY THAT THEY
DID--THEY HAD OR HAD NOT
RETAINED THEIR TESTICLES, RIGHT?
AND WE ALSO DID COMPLETE
HORMONAL PROFILES.
AND THE VAST MAJORITY OF THEM
HAD NOT ONLY FATTY LIVER WHICH
WAS KNOWN, THEY HAD FATTY HEART,
THEY HAD PREMATURE CORONARY
ABNORMAL GLUCOSE TOLERANCELER O
SCLEROSIS AND THEY WERE INSULIN
RESISTANT AND THEN WHAT RELATED
ON IT A LOT OF THIS WAS THE
CROSS TALK BETWEEN THEIR
ESTROIEN AND THEIR ANDROGENS AND
THOSE THAT HAD RETAINED THEIR
TESTICLES HAD A LOT MORE OF THIS
DISMETABOLICKISM, RIGHT?
SO WE PUBLISHED THAT.
WE TRIED TO GET AN RO-1 FUNDED
AT THE TIME WAS IN THE BUSH
ADMINITRATION, WASN'T
POLITICALLY CORRECT.
DOES THAT HELP?
>> YEAH, THANK YOU SO MUCH.
>> OKAY, VERY GOOD.
>> LOTS OF QUESTIONS ONLINE BUT
YOU COVERED A LOT YOU MAYBE 1
TOPIC WE HAVEN'T TOUCHED ON, HOW
DOES PREGNANCY AFFECT LONG-TERM
HEALTH IN YOUR STUDY, WERE YOU
ABLE TO COMPARE WOMEN WITH
PREGNANCIES AND WOMEN WITHOUT
PREGNANCIES?
>> YES, WE HAVE LOOKEDDA THE
THAT AS WELL AND WE REPLICATED
WHAT'S PRETTY WELL OBSERVED IS
WOMEN THAT HAVE NO CHILDREN AND
I'M NOT SAYING THIS IS YOU KNOW
A POLITICAL STATEMENT BUT THEY
TEND TO HAVE NOT AS GOOD HEALTH
AS WOMEN THAT HAVE AT LEAST 1
CHILD, THAT J-SHIP CURVE HAS
ALWAYS BEEN TRUE AND THEN AFTER
ABOUT 4 OR 5 CHILDREN HEALTH
BECOMES PREMATURE HEALTH IS A
PROBLEM.
WE DON'T KNOW BECAUSE OUR WISE
WOMEN, AGAIN RECRUITED INTO--BY
THE 1980S AND EARLY 90S, THEY
WERE JUST AT THE TIP OF THE
1960S ORAL CONTRACEPTION AND
WOMEN FINALLY BEING ABLE TO
SELF-MANAGE THEIR OWN FERTILITY
RATE, SO, IT'S A CHALLENGE TO
THE NEXT GENERATION TO STUDY
COHORTS AND NOT THE WOMEN'S
HEALTH BECAUSE THEY'RE THE SAME
AS OURS, AND NOT THE WOMEN'S
STUDY, THE JOANNE MANSON,
SOMEBODY'S GOT TO DO A BIG
STUDY, WE ARE SORT OF DOING THIS
WITH THE NEW MOM TO BE, ANOTHER
BIG NHLBI SPONSORED STUDY, BUT
THE POINT IS WHEN WOMEN CHOOSE
NOT TO HAVE CHILDREN, THAT'S
PROBABLY DIFFERENT FROM WOMEN
THAT ARE INFERTILE.
AND BECAUSE FERTILITY ONCE AGAIN
IS A WHOLISTIC HELT PREDICTER
AND THEN YOU MIGHT ASK WHY WHEN
YOU GET MORE THAN 4.5 CHILDREN
PER WOMAN AND THAT WAS THE
ELIZABETH CONNOR THE PIZZA
HYPOTHESIS.
THAT AS SOON AS YOU HAVE MORE
THAN 4 CHILDREN, YOU JUST EAT
PIZZA ALL THE TIME.
[LAUGHTER]
ALL RIGHT, YEAH.
THANK YOU.
[ APPLAUSE ]
>> THANK YOU VERY MUCH FOR THAT
WONDERFUL TALK AND THERE ARE
SOME REFRESHMENTS OUTSIDE SO WE
SHOULD JOIN THEM AND ALSO WANT
TO--WE'RE FOCUS ON THE
PRESENTING THE PLAQUE BUT I WANT
TO ACKNOWLEDGE THIS NICE PLAQUE
THAT WE WILL BE SENT TO YOU.
AND THANK YOU ALL FOR COME
NOTHING PERSON, THIS IS
WONDERFUL AND ENJOY, ENJOY
COOKIES OR FRUIT OR SOMETHING
OUTSIDE.