TODAY IS THE FIRST SEMINAR OF ROUNDTABLE 3, WHICH IS THE HEALTH DISPARITIES ON AGING POPULATION, WE HAVE THE PLEASURE TO HAVE DR. MICHELE EVANS. SHE'S THE SENIOR INVESTIGATOR, AN INTERNIST, MEDICAL ONCOLOGIST CURRENTLY SERVES AT NATIONAL INSTITUTE ON AGING DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH PROGRAM, RECEIVED HER MEDICAL DEGREE FROM RUTGERS, STATE UNIVERSITY OF NEW JERSEY, ROBERT WOOD JOHNSON MEDICAL SCHOOL IN PISCATAWAY, RECEIVED TRAINING AT EMORY, FELLOWSHIP IN MEDICAL ONCOLOGY WITHIN THE MEDICINE BRANCH OF THE CLINICAL ONCOLOGY PROGRAM AT THE NATIONAL CANCER INSTITUTE, SHE FOCUSES ON DNA REPAIR AND AGING DISPARITIES. PLEASE HELP ME WELCOME DR. MICHELE EVANS. [APPLAUSE] >> WE'LL DO IT WITHOUT A POINTER. GOOD AFTERNOON. THANK YOU FOR THE INVITATION. I GUESS I HAVE TO HAVE A LITTLE BIT OF A DISCLAIMER. IT'S BECAUSE I WORK IN THE AGING INSTITUTE, BUT I'M NOT REALLY TALKING TODAY ABOUT HEALTH DISPARITIES IN IT THE AGED. AS YOU KNOW, AGING IS A LIFE PROCESS AND ONE OF THE THEORIES OF AGING AND HEALTH DISPARITIES IS WE SEE PREMATURE AGING IN YOUNG POPULATIONS, SO I WILL TALK TO YOU TODAY ABOUT YOUNG POPULATIONS WHO ARE EXPERIENCING AGING RELATED TO MANY OF THE SOCIAL DETERMINANTS OF HEALTH. SO WHAT DO WE TALK ABOUT -- THIS IS AN EDUCATED GROUP, SO I'M SURE WE CAN SORT OF GO QUICKLY THROUGH THE EARLY PART OF THE SLIDES. WHEN WE'RE TALKING ABOUT PURSUING HEALTH DISPARITIES AND UNDERSTANDING WHAT HEALTH DISPARITIES ARE, THERE'S LOTS OF WAYS TO DEFINE HEALTH DISPARITIES. I THINK WE ALL COULD AGREE THAT THERE ARE DIFFERENCES IN HEALTH THAT OCCUR RELATED TO A NUMBER OF THE DIFFERENT TOPICS THAT ARE HIGHLIGHTED THERE IN THE SLIDE IN BLUE. AND AS YOU PROBABLY KNOW, THERE ARE NARROWING OF SELECTED HEALTH DISPARITIES IN THE UNITED STATES. BUT YOU SHOULD KNOW THAT HEALTH DISPARITIES THAT ARE RELATED TO RACE, ETHNICITY AND SOCIOECONOMIC STATUS ARE IN FACT PERSISTENT. THEY ARE NOT NARROWING. THIS IS MOST HIGHLIGHTED PERHAPS BY STATISTICS THAT DEAL WITH ALL CAUSE MORTALITY, CAUSE SPECIFIC MORTALITY, INCIDENTS AND PREVALENCE OF CHRONIC DISEASE AS WELL AS LIFE EXPECTANCY, AS IS ILLUSTRATED ON THIS SLIDE WHERE WE SEE A GREAT GAP BETWEEN LIFE EXPECTANCY AT BIRTH BETWEEN WHITE FEMALES AND AFRICAN-AMERICAN MALES. THIS IS ABOUT 10.7 YEARS. THAT IS PERSISTENT. IF THE YOU LOOK AT URBAN DWELLING AFRICAN-AMERICAN MALES, IN HOUSTON OR BALTIMORE OR WATTS AND COMPARE THEM TO REALLY THE BEST OFF IN AMERICAN SOCIETY WHO ARE ASIAN FEMALES, THAT LIFE EXPECTANCY GAP GROSS TO ABOUT 20 YEARS. SO WE'RE STILL TALKING ABOUT SIGNIFICANT DIFFERENCES IN HEALTH STATUS AMOPPING AMONG THE POOR, DISENFRANCHISE AND MINORITY GROUPS. YOU'VE HEARD A LOT ABOUT BALTIMORE. IT'S A VERY METROPOLITAN CITY, IF YOU LOOK AT THE METROPOLITAN STATISTICAL AREA WE HAVE TWO MILLION IN BALTIMORE CITY PROPER, MAYBE 630,000 PEOPLE, BUT DESPITE THE COSMOPOLITAN FEATURE OF BALTIMORE AND PRESENCE OF MANY ABSOLUTELY EXCELLENT MEDICAL RESEARCH COMMUNITIES AND FACILITIES, THERE ARE GLARING HEALTH DISPARITIES IN BALTIMORE. IF YOU LOOK AT BALTIMORE METROPOLITAN STATISTICAL AREA AND YOU COMPARE IT TO OTHERS IN THE UNITED STATES, BALTIMORE RANKS 19th OR 20th, BUT IF YOU LOOK AT AIDS CASE REPORT, IT'S USUALLY NUMBER 3 OR 4. SO IT'S RIGHT UP THERE WITH BIG CITIES, LIKE NEW YORK, MIAMI, ALTHOUGH BALTIMORE CERTAINLY IS MUCH SMALLER. SO ALTHOUGH I'M A BASIC SCIENTIST AND A MEDICAL ONCOLOGIST, THESE GLARING HEALTH STATISTICS WERE TROUBLING WHEN I LEFT BUILDING 37, WHICH IS WHERE I DID THE EARLY PART OF MY CAREER AT NIH, AND WENT TO BALTIMORE TO BE PART OF THE AGING INSTITUTE. AND SO I WAS INTERESTED IN BALTIMORE LIFE EXPECTANCY DISPARITIES. AND SO IF YOU LOOK AT BALTIMORE DISPARITIES, ALL RIGHT, THEY ARE A LITTLE LOWER THAN THE UNITED STATES HEALTH DISPARITIES. IF YOU LOOK AT LIFE EXPECTANCY IN THE UNITED STATES, IT'S ABOUT 78, BALTIMORE IS 72, LOWER THAN MARYLAND, BUT IF YOU START LOOKING AT BALTIMORE ON A NEIGHBORHOOD BASIS, ROWLAND PARK WHERE MANY HOPKINS PROFESSORS LIVE, YEAH, THEY ARE LIVING TO 83, 84, DOING GREAT. BUT THEN IF YOU GO TO SOME OF THE MORE POVERTY STRICKEN AREAS OF THE CITY, HIGHLANDS MARKET, NOT FAR FROM UNIVERSITY OF MARYLAND'S MEDICAL CAMPUS, IT'S 63. WOW! 63 VERSUS 83 IN ONE CITY. AND THEN IF YOU LOOK AT THAT 63-YEAR LIFE EXPECTANCY, IT'S KIND OF LIKE WHAT YOU WOULD BE GETTING IN THE UNITED STATES IN 1940. THIS IS THE DATA FROM 2008, BUT IT HASN'T CHANGED. THE DATA RLY HASN'T CHANGED. THE SAME IS WHAT PEOPLE IN BANGLADESH LIVING NOW HAVE, AND PEOPLE LIVING IN NEPAL HAVE. AND THIS IS IN THE GOOD OL' UA OF A. THIS WAS A STARTLING STATISTIC TO ME. WHEN YOU LOOK AT BALTIMORE'S NEIGHBORHOODS, THERE'S A GRADIENT OF SURVIVAL DEPENDING ON WHERE YOU LIVE. IT'S PRETTY REMARKABLE. AND IF YOU LOOK AT U.S. LIFE EXPECTANCY IN 2011 FOR EVERYBODY, ALL COMERS, 78.6 YEARS, THAT'S THIS LINE. AND YOU JUST SEE HOW FAR BELOW MANY OF THE NEIGHBORHOODS IN BALTIMORE ARE, YOU REALIZE THAT THERE IS SOMETHING WORTH STUDYING IN TERMS OF BEING ABLE TO LOOK IN COMMUNITIES OF HEALTH DISPARITIES TO TEASE OUT SOME CAUSES AND PERHAPS FIGURE OUT HOW DO WE ELIMINATE HEALTH DISPARITIES. ONE OF THE THINGS WE THOUGHT ABOUT WAS PERHAPS THESE HEALTH DISPARITIES OCCUR SORT OF IN THE CONTEXT OF BALTIMORE'S NEIGHBORHOODS, AND THAT CERTAINLY IS AN IMPORTANT THING TO KEEP IN MIND. IF YOU LOOK AT SEGREGATION, RESIDENTIAL SEGREGATION IN BALTIMORE, THAT'S OF THE GREEN-BLUE HERE, IN 2001, THIS IS ALL SEGREGATED SO IT'S ONE RACE OR THE OTHER. MODERATELY INTEGRATED IS THIS DARKER ORANGE. NOT TOO MUCH INTEGRATION. SO IT'S ALL WHITE OR ALL BLACK. AND THEN IN 2012 THE JOINT CENTER FOR POLITICAL AND ECONOMIC STUDIES, YOU KNOW, DID A STUDY ON PLACE IN HEALTH AND FOUND THAT UNFORTUNATELY THAT'S PRETTY MUCH STILL THE SAME, THE BLACK PEOPLE ARE THE PURPLE DOTS, CONCENTRATED, BLUE DOTS ARE THE WHITE PEOPLE. WE STILL HAD A FAIR AMOUNT OF RESIDENTIAL SEGREGATION, SOME INTEGRATION BUT QUITE A BIT OF SEGREGATION, AND THIS IS IN 2012. SO WHAT'S DIFFERENT ABOUT THESE NEIGHBORHOODS? WELL, NOT ALL OF THE HOUSING STOCK IS BAD. THIS IS PRETTY NICE. THIS IS NOT SO GOOD. THIS IS SKETCHY. THEN WE GO TO HIGHLAND BARK. I WANT TO LIVE HERE. WE GOT THE RANGE ROVER IN FRONT OF THE CLONAL. ROWLAND PARK, WE HAVE A PARK, IT'S NOT A MISNOMER, WITH A BOUTIQUEY SHOPPING CENTER. IT MUST BE NICE. WHAT ARE THE MECHANISMS, HOW DOES ENVIRONMENT, HOW DOES NEIGHBORHOOD, INFLUENCE HEALTH DISPARITIES AND HOW ARE THESE DIFFERENT SOCIAL DETERMINANTS OF HEALTH RELATED? AND WE COULD SIT HERE AND TALK ABOUT THIS SLIDE LIKE ALL NIGHT, BECAUSE NOBODY REALLY UNDERSTANDS. IS IT, YOU KNOW, THEY ARE DEPRESSED, IS IT RACISM, IS IT STRESS, IS IT EVERYBODY SMOKES, THEY HAVE POOR HEALTH BEHAVIOR, OR IS IT JUST THEY ARE JUST POOR? YOU KNOW, OR IS IT, YOU KNOW, POPULATION DISTRIBUTION OF HEALTH AS GENDER, WE COULD TALK ABOUT THIS, WE ALL WOULD SAY, YES, YES, YES, YES, YES, BUT HOW DO THEY INTERACT? AND THAT'S WHAT WE STILL DON'T KNOW. SO I'M INTERESTED IN HEALTH DISPARITIES BECAUSE THERE'S JUST SO MUCH THAT WE DON'T KNOW. YOU KNOW, HOW DO THESE SOCIAL AND BEHAVIORAL THINGS TURN INTO POOR HEALTH? SO IF YOU LOOK AT MODELS OF HEALTH DISPARITIES, I DON'T KNOW IF YOU GUYS HAVE DONE THIS, BUT AS WE WERE SORT OF PLOTTING AND PLANNING HOW WE WERE GOING TO BEGIN TO STUDY HEALTH DISPARITIES IN BALTIMORE, WE THOUGHT OF LOOKING AT WHAT ARE THE KNOWN MODELS OUT THERE, AND HOW MAYBE DO THEY TURN INTO A WAY TO GROUP SOME OF THESE SOCIAL DETERMINANTS OF HEALTH FROM THE PREVIOUS SLIDE? THERE'S THE RACIAL GENETIC MODEL, THE HEALTH BEHAVIOR MODEL, YOU SMOKE, YOU EAT KENTUCKY FRIED CHICKEN EVERY NIGHT, THAT'S WHAT'S CAUSING IT, OR IS IT YOU ARE JUST POOR AND HAVE A BAD JOB, OR IS IT THAT JUST THE STRESS OF LIFE ISING YOU SICK? SO WE SORT OF CAME UP WITH THE WAY WE WANTED TO WORK, AND TO BEGIN TO UNCOVER SOME OF THE IMPORTANT FACETS IN DRIVING HEALTH DISPARITIES, SORT OF A COMBINATION OF LOOKING AT THESE SOCIOENVIRONMENTAL CONDITIONS, INCLUDING STRESS, AND THEN CULTURALLY GENERATED BEHAVIOR, AND HOW THEY PLAYED INTO THE DEVELOPMENT OF HEALTH DISPARITIES. BUT ALSO TO CONSIDER UNDERSTANDING THE BIOLOGY OF HEALTH DISPARITIES, SORT OF A COMBINATION OF A RACIAL, GENETIC AND BIOLOGIC METHOD OF TRYING TO UNDERSTAND AND TEASE APART IMPORTANT FACETS OF HEALTH DISPARITY THAT PERHAPS IN THE FUTURE COULD BE TARGETED TOWARDS THE AMEALORRATION OF THESE HEALTH DIFFERENCES. SO WE CAME UP WITH HANDLES, WHICH IS AN INTERDISCIPLINARY COMMUNITY BASED LONGITUDINAL EPIDEMIOLOGIC STUDY THAT EXAMINED ARE THE DEVELOPMENT OF AGE-ASSOCIATEELED HEALTH DISPARITIES AMONG AFRICAN-AMERICANS AND WHITES, ALL OF WHOM RESIDE IN THE CITY OF BALTIMORE, AND AT THE START OF THE STUDY BETWEEN THE AGES OF 30, NOT JUST OLD PEOPLE, WE STARTED STUDYING PEOPLE AT 30 YEARS OLD BECAUSE WE FEEL THEY ARE AT RISK FOR DEVELOPING DISEASE MUCH EARLIER THAN THEIR WHITE COUNTER PARTS, AND WE ENDED IT AT 64, IN HOPES OF STUDYING THEM FOR 20 YEARS, SO WE WOULD BE STUDYING SOME PEOPLE AS THEY TRANSITION INTO MIDDLE AGE, OTHERS WHO WOULD BE THEN LEAPING INTO THE OLDER YEARS, 65, 70, WHERE THEY ARE AT RISK OF CERTAIN DISEASES. THE CRUX WAS TO DISSEN TANGLE RACE AND SOCIOECONOMIC STATUS. MUCH OF THE WORK IN HEALTH DISPARITIES, IT'S DIFFICULT TO SEPARATE THAT BECAUSE THEY STUDY POOR BLACK PEOPLE AND WHITE PEOPLE WHO MOST OF THEM ARE NOT POOR. SO POOR AND BLACK EQUAL THE SAME THING. REALLY NOT ALWAYS. SO WE HAVE TO FIND A WAY TO TEASE THAT APART. AND SO THAT WAS, YOU KNOW, SORT OF THE NIDUS IN OUR MIND AS WE WERE DEVELOPING THE STUDY. WE WANTED TO KNOW HOW DID RACE AND SOCIOECONOMIC STATUS INFLUENCE THE DEVELOPMENT OF AGE-ASSOCIATED DISEASE, HOW FAST YU AGE, AND THIS ISSUE OF FUNCTIONAL DECLINE, AND ULTIMATELY DISABILITY, AND THEN WHAT'S THE BIOLOGY BEHIND ALL OF THAT? SO THE STUDY IS COMPOSED OF A NUMBER OF DIFFERENT DOMAINS, SO WE HAVE LOTS OF COLLABORATORS FROM ACROSS THE COUNTRY, BECAUSE WE FELT THAT EACH OF THE THINGS LISTED HERE ON THE SLIDE WAS IMPORTANT TO UNDERSTANDING WHAT WERE THE DRIVERS THAT WE COULD SEPARATE OUT IN BALTIMORE, MAYBE IT WOULD BE APPLICABLE TO OTHER PARTS OF THE COUNTRY, MAYBE NOT. WE STILL DON'T KNOW BECAUSE, YOU KNOW, WE'RE ONLY IN YEAR TEN OF THE STUDY. IT'S A TWENTY-YEAR STUDY. EACH OF THESE ARE IMPORTANT BECAUSE WE KNOW THEY ARE RELATED TO AGING. WE KNOW THEY ARE RELATED TO HEALTH DISPARITIES. AND WE KNOW THAT MANY OTHER STUDIES ACROSS THE COUNTRY ARE LOOKING AT ONE OR TWO OF THESE, AND WHY IS THAT IMPORTANT? THIS IS CALLED LEVERAGING POPULATION AND LEVERAGING DOLLARS. ONE OF THE BIGGEST STUMBLING BLOCKS TO DOING HEALTH DISPARITIES RESEARCH IS ENROLLING ENOUGH MINORITIES AND LOW SES POPULATIONS SO THAT YOU CAN COLLECT ENOUGH DATA AND HAVE ENOUGH POWER TO DRAW CONCLUSIONS. AND SO WE WANTED TO MAKE SURE THAT WHOEVER WE COULD RECRUIT INTO OUR STUDY WOULD IN SOME WAY BE COMPARABLE TO OTHER NATIONALLY REPRESENTATIVE COHORTS SO WE COULD WORK TOGETHER BECAUSE MANY OF US HAD VERY SIMILAR AIMS AND INTERESTS. SO WHAT WE WOUND UP DOING IS WE DEVELOPED AN AREA OF PROBABILITY SAMPLE OF THE CITY OF BALTIMORE. 13 CENSUS SEGMENTS WERE SELECTED, BASED ON THE 2000 CENSUS DATA BECAUSE IT WAS BELIEVED THAT THESE SEGMENTS WOULD YIELD SUFFICIENT INDIVIDUALS TO BE REPRESENTATIVE OF THE CITY OF BALTIMORE AND FIT WITHIN OUR SAMPLING FRAME, WHICH IS WHITES AND AFRICAN-AMERICANS, MEN AND WOMEN, WHO WERE BETWEEN 30 AND 64, AND WHO WERE EITHER ABOVE OR BELOW THE POVERTY LINE, AND THE POVERTY LINE WE SELECTED WAS 125% OF POVERTY BASED ON THE 2004 HHS GUIDELINES. SO THIS WAY, WE WOULD BE STUDYING BLACKS AND WHITES, WHO WERE BOTH ABOVE AND BELOW THE POVERTY LINE. THAT 125% POVERTY LINE, ABOVE THAT MOST OF THE TIME YOU'RE NOT ELIGIBLE FOR MANY OF THE BENEFITS THAT THE HEALTH AND HUMAN SERVICES DEPARTMENT GIVES. AND SO THE GOAL WAS AT THE END OF 20 YEARS, TO SORT OF WIND UP WITH 1600 PARTICIPANTS IN THE STUDY. SO THAT SORT OF WAS OUR THOUGHT, SO WE WOUND UP SELECTING 13 NEIGHBORHOODS IN BALTIMORE, AND THIS IS THE BASE OF HOW WE DEVELOPED OUR COHORT. SO WE WOUND UP HAVING TO GO AROUND THE CITY. ONE OF THE ISSUES WITH RECRUITING MINORITY AND POOR PARTICIPANTS IS THEY DON'T NECESSARILY WANT TO COME TO YOU FOR WHATEVER REASON. SO WE DECIDED WE WOULD GO TO THEM. AND WE WOULDN'T SET UP A BRICK AND MORTAR FRONT. WE DEVELOPED TRUCKS AND WE JUST GO TO THE DIFFERENT NEIGHBORHOODS SO THAT WE FREQUENTLY ARE IN WALKING DISTANCE TO THEIR HOMES, AND IF NOT WE HAVE A VEHICLE WE DRIVE OUT AND BRING THEM TO US. AND THAT IS SORT OF THE METHODOLOGY WE USE. SIMILAR TO WHAT THEY HAVE DONE IN THE NHANES NATIONAL EXAMINATION SURVEY. SO WHAT DID WE ASK THEM? WELL, FIRST WE WENT INTO THEIR HOMES AND ASKED THEM A NUMBER OF SORT OF DEMOGRAPHIC INFORMATION. S, RELIGIOUSIITY, INCOME, WE LOOKED AT PSYCHOSOCIAL EDUCATION, INITIALLY IN A HOUSEHOLD VISIT, AND -- THIS THING HAS A LIFE OF ITS OWN. THEY CAME TO THE MEDICAL RESEARCH VEHICLE, WHERE WE DID A NUMBER OF PROCEDURES, LOOKING AT CAROTID AND ARTERIAL STIFFNESS, BODY COMPOSITION AND BONE DENSITY, PHYSICAL FUNCTION AND PERFORMANCE, NUTRITION, NEUROPSYCHOLOGICAL TESTING, A WASH OF EXAMINATIONS ON THEM. WE WERE CONCERNED THIS WOULD BE A LITTLE BIT TOO MUCH IN TERMS OF PARTICIPANT BURDEN, BUT AT THAT TIME WHEN WE STARTED THE STUDY IN 2004, REMEMBER THIS IS BEFORE OBAMACARE, SO A LOT OF THESE PEOPLE HADN'T SEEN A DOCTOR IN 10 OR 15 YEARS AND WERE HAPPY TO PARTICTE BECAUSE THEY HAD A DOCTOR ALL TO THEMSELVES FOR A WHOLE DAY TO GET THEIR EXAMS DONE AND WE ALSO GAVE THEM FEEDBACK ON THEIR HEALTH AND THEN TRIED TO GET THEM TO APPROPRIATE PROVIDERS. SO HOW DID WE DO? WE WERE ABLE TO ACCRUE OVER 3700 INDIVIDUALS, AND WHAT IS INTERESTING IS THE DEMOGRAPHICS OF THE STUDY, EXACTLY MIRRORED THE CENSUS DATA FOR 2000. WE FELT WE WERE, YOU KNOW, VERY FORTUNATE TO HAVE BEEN ABLE TO GET A TRULY REPRESENTATIVE SAMPLE OF BALTIMORE. IT'S NOT NATIONALLY REPRESENTATIVE BUT IT IS REPRESENTATIVE OF THE CITY OF BALTIMORE. WHAT DID WE FIND OUT ABOUT THE HEALTH OF THESE 3700 INDIVIDUALS? EVEN IF THEY WERE YOUNG, THEIR HEALTH MAY NOT BE VERY GOOD. LOTS OF DIABETES, LOTS OF OBESITY, LOTS OF SMOKING, LOTS 6 OTHER NEGATIVE HEALTH INDICATORS. SO IT CERTAINLY PUT US IN THE POSITION OF BEING ABLE TO DO SORT OF AN EXAMINATION OF TRYING TO UNDERSTAND THIS TRANSDUCTION PROCESS OF SOCIAL DETERMINANTS OF HEALTH INTO DISEASE, AND TO REALLY ADDRESS THE ISSUE, IS THERE A BIOLOGY OF DISADVANTAGE, AND BECAUSE OF THE EARLY ONSET OF SOMETIMES VERY SIGNIFICANT CARDIOVASCULAR DISEASE, VERY EARLY IN THE COHORT, LOOKING AT THIS QUESTION OF IS HEALTH DISPARITIES A PHENOTYPE THAT IS REALLY ACCELERATED AGING, AND THEN WHAT'S THE MOLECULAR BASIS OF THIS. SO WE STARTED LOOKING FOR COMMON PATHWAYS RELATED TO AGING AND HEALTH DISPARITIES, AND SO THIS ISSUE OF THE PREMATURE ACCELERATED AGING PHENOTYPE IS IMPORTANT AS A DNA REPAIR SCIENTIST, I SPENT MY EARLY CAREER WHEN I WAS ON THIS CAMPUS STUDYING HUTCHINSON GILFORD, PROGEROID SYNDROME, FEATURES CONCORDANT WITH HUMAN AGING. AGAIN, THOSE ARE GENETICALLY HER ITABLE SYNDROMES, THEY EACH HAVE SOMETHING THAT IS SIMILAR TO WHAT WE SEE IN NORMAL HUMAN AGING, BUT THIS IS SORT OF A DIFFERENT PREMATURE AGING BECAUSE IT'S COMING FROM SOMETHING THAT'S MAYBE NOT HERITABLE BUT IS ENVIRONMENTAL. AND SO THAT ALSO GOT US THINKING ABOUT BIOLOGIC PROCESSES THAT COULD BE ASSOCIATED WITH THIS, YOU KNOW, SUCH AS THE HARMON FREE RADICAL THEORY OF AGING, ONE OF THE REASONS IS THAT WE ACCUMULATE OXIDATIVE STRESS, DAMAGE TO DNA THAT DOES NOT GET REPAIRED AND THAT WE GET DAMAGE TO TISSUES AND CELLS OVER THE LIFESPAN THAT LEADS TO CELLULAR SINESENCE, IS THAT RELATED TO WHAT WE'RE SEEING IN OUR COHORT, THESE ARE THE QUESTIONS THAT WE HAD IN THE BACK OF OUR MINDS. POVERTY, CRIME, INCOME, DIET, EDUCATION, PSYCHOSOCIAL STRESS THAT GOES THROUGH THE LIFESPAN, WHAT'S THE BIOLOGIC TRANSDUCER THAT LEADS TO THIS ACCELERATED AGNG PHENOTYPE HEALTH DISPARITIES AND ULTIMATELY A SHORTENED LIFESPAN BECAUSE THESE PEOPLE ARE DYING HERE. MANY ARE NOT GETTING TO THE 80 YEARS OR SO THAT MANY IN THE U.S. POPULATION ENJOY IN TERMS OF LIFESPAN. SO WE DECIDED WE WANTED TO BE ABLE TO LOOK AT OUR DATA AND OUR COHORT PARTICIPANTS IN TERMS OF A BIOPSYCHOSOCIAL MODEL OF HEALTH OUTCOME BECAUSE WE HAD DATA ON ALL OF THESE DEMOGRAPHIC FACTORS, SOCIOECONOMIC STATUS, AS INDICATED BY EDUCATION, COME, WEALTH, OCCUPATION, HEALTH BEHAVIORS, WE HAD ALL OF THIS. HOW DID THESE BECOME BIOLOGIC RISKS AND ULTIMATELY NEGATIVE HEALTH OUTCOMES? ONE THING THAT WAS NOT IN THIS MODEL AS PUT FORTH BY CRIMMINS AND SEEMEN IS THE ISSUE OF PSYCHOLOGICAL STRESS WHICH WE THOUGHT WAS PERHAPS AN IMPORTANT COMPONENT OF THIS, AS WELL AS GENETICS AND ENVIRONMENT. SO ONE OF THE FIRST THINGS WE DID WAS TO LOOK AT SOCIOECONOMIC STATUS, RACE, AND HEALTH OUTCOMES, TRYING TO UNDERSTAND POVERTY PARTICULARLY, AND WE KNOW POVERTY IS ASSOCIATED WITH MANY NEGATIVE HEALTH OUTCOMES, AND THAT ALMOST 30% OF AFRICAN-AMERICANS IN 2012 LIVED IN POVERTY. SO WE WANTED TO BE ABLE TO ESTABLISH SOME SPECIFIC LINKS ABOUT SPECIFIC DISEASE OUTCOMES, AND SO WE FIRST LOOKED AT RENAL DISEASE. CHRONIC KIDNEY DISEASE, AS YOU KNOW, IS A VERY IMPORTANT DISEASE ENTITY IN AFRICAN-AMERICANS. THEY HAVE DISPROPORTIONATE RISK OF DEVELOPING END STAGE RENAL DISEASE REQUIRING DIALYSIS OR ACTUALLY NEEDING RENAL TRANSPLANT. NOW, THERE WAS INFORMATION IN THE LITERATURE THAT LOW SES AND AMERICAN RACE WERE ASSOCIATED WITH END STAGE RENAL DISEASE AND MAYBE EVEN PROGRESSIVE CHRONIC KIDNEY DISEASE BUT IT WASN'T INDEPENDENT EFFECT OF POVERTY IN TRIED TO LOOK IN THE POPULATION TO DETERMINE THIS. WHAT WE SAW WAS ABOUT 6.2% OF OUR PARTICIPANTS HAD CHRONIC KIDNEY DISEASE, AND THIS IS VERY EARLY IN THE STUDY. HOWEVER, RACE WAS NOT SIGNIFICANTLY ASSOCIATED WITH CKD, AFRICAN-AMERICANS AND WHITES HAD THE SAME PERCENTAGE. THAT'S NOT STATISTICALLY SIGNIFICANT. NOW, WHEN WE LOOKED AT ADVANCED LEVEL ALSO OF CHRONIC KIDNEY DISEASE WE FOUND AFRICAN-AMERICANS HAD MUCH MORE OF A RISK OF HAVING SIGNIFICANT KIDNEY DISEASE THAN WHITES, BUT IT WASN'T UNTIL WE LOOKED AT POVERTY SPECIFICALLY WHERE WE FOUND THAT LOWER SES WAS ASSOCIATED WITH A GREATER PREVALENCE OF CHRONIC KIDNEY DISEASE IN AFRICAN-AMERICANS BUT NOT IN WHITES. POVERTY DID NOT SEEM TO INFLUENCE RISK OF KIDNEY DISEASE IN WHITES, ONLY IN AFRICAN-AMERICANS. SO WHAT'S THE CONNECTION BETWEEN POVERTY IN AFRICAN-AMERICANS? IS POVERTY DIFFERNT FOR AFRICAN-AMERICANS THAN FOR WHITES? WE DON'T KNOW. THAT'S A QUESTION THAT WE'RE LOOKING AT. WE WANT TO UNDERSTAND THIS INTERACTION OR EFFECT MODIFICATION OF POVERTY SO WE'RE LOOKING FROM GENETIC AND BIOLOGIC PERSPECTIVE, ALSO EXAMINING EFFECT OF EDUCATION AS WELL AS DIET, AND PSYCHOLOGICAL STRESS. SOME OF OUR RECENT DATA SUGGESTS HAT PERCEIVED RACIAL DISCRIMINATION IS ASSOCIATED WITH A GREATER CHANCE OF PROGRESSIVE CHRONIC KIDNEY DISEASE IN AFRICAN-AMERICAN FEMALES, SO THAT'S PRELIMINARY DATA BECAUSE WE HAVE ASKED PEOPLE ABOUT THE EFFECT OF DISCRIMINATION IN THEIR LIFE, YOU KNOW, WE TALKED WITH THEM ABOUT THAT AND WE ACTUALLY HAVE MEASURES THAT LOOK AT THAT. AND SO PSYCHOLOGICAL STRESS HERE MAY ALSO PLAY A ROLE IN THE PROGRESSION AND DEVELOPMENT OF THE DISEASE. SO WHEN YOU LOOK AT THESE NEIGHBORHOODS, WHERE I GREW UP AND WHERE MOST OF YOU ARE RIGHT NOW, WE WANTED TO KNOW CAN NEIGHBORHOOD FACTORS REALLY BE STUDIED TO UNRAVEL HEALTH DISPARITIES IN THE LABORATORY, SO WE TOOK SOME OF THE QUESTIONS THAT WERE IMPORTANT AND TRIED TO KIND OF GO INTO THE LAB AND SEE WHAT COULD WE FIND OUT ABOUT THE IMPORTANCE OF IT. SO ONE OF THE OTHER WAYS THAT WE EVALUATE AGING AND TRIED TO LOOK AT WHAT ARE SOME OF THE CAUSES OR THE SCIENTIFIC COMPLEX OF AGING IS THIS ISSUE OF INFLAMMATION. WE KNOW THAT THIS CHRONIC LOW GRADE INFLAMMATORY STATE COMES ON AS YOU AGE, WHERE YOU HAVE INCREASED IN LEVELS OF VERY IMPORTANT INFLAMMATORY MEDIATORS SUCH AS CYTOKINES, AND ACUTE PHASE PROTEINS. AND WE KNOW THAT INFLAMMATION IS AN IMPORTANT DRIVER OF MANY AGE-RELATED DISEASES, INCLUDING ALZHEIMER'S DISEASE, DIABETES, CORONARY ARTERY DISEASE, OSTEOARTHRITIS, CANCER, HYPERTENSION. AS YOU KNOW, THAT'S ONE OF THE IMPORTANT INITIATIVES THAT NIH IS NOW PUTTING TO THE FOREFRONT TRYING TO UNDERSTAND THE ROLE OF INFLAMMATION IN DISEASE. NOT JUST THE ONES WE THINK ABOUT LIKE AUTOIMMUNE DISEASES THAT WE OW INFLAMMATION IS IMPORTANT THERE, BUT INFLAMMATION LIKELY PLAYS A ROLE IN CHRONIC DISEASE IN GENERAL. SO IN OUR SETTING, AGAIN USING THAT THOUGHT ABOUT, WELL, WHAT'S THE TRANSDUCER, SO HOW IS IT POSSIBLE THAT THESE SOCIAL DETERMINANTS OF HEALTH GUY TO PREMATURE DEATH AND ACCELERATING AGING AND ALL OF THESE DISEASES, IS IT THROUGH INFLAMMATION? THAT'S THE QUESTION. IT'S NOT JUST THESE SOCIAL DETERMINANTS OF HEALTH, THERE'S ALSO BEHAVIOR, BMI, SMOKING, POOR DIET, PHYSICAL DIET AND ECONOMIC STRAIN. WITH THE CHANGE IN ECONOMY 2007-2008 WE SAW CHANGES IN PARTICIPANT HELD AND STARTED MEASURING THAT AS A STRESSOR THAT COULD BE RELATED TO INFLAMMATION THAT THEN COULD RESULT IN NEGATIVE OUTCOMES. SO WE DECIDED OF ALL OF THESE THINGS THAT ARE IMPORTANT IN INFLAMMATION, TO LOOK AT WHAT WE CALL ACUTE PHASE REACTANTS, AND PROBABLY THE MOST WELL KNOWN ACUTE FACE REACTIVE IS C REACTIVE PROTEIN, WHICH IS AN INFLAMMATORY BIOMARKER, YOU'RE PROBABLY TOO YOUNG, BUT IN MY AGE GROUP WHEN I GO TO GET MY BLOOD DRAWN THEY DO MEASURE C-REACTIVE PROTEIN BECAUSE IT CONVEYS A CERTAIN RISK FOR CARDIOVASCULAR DISEASE. SO IT'S A CLINICAL MARKER OF INFLAMMATION, BUT WE DON'T REALLY UNDERSTAND A LOT ABOUT THE PATHOPHYSIOLOGIC ROLE OF IT. AND WE KNOW THAT CRP GENE VARIANTS ARE ALSO IMPORTANT AND HAVE AN INFLUENCE ON THE MAGNITUDE OF THE CRP RESPONSE LOTS OF AREAS TO EXPLORE IN TERMS OF THE IMPORTANCE OF C-REACTIVE PROTEIN IN INFLAMMATION AND DEVELOPMENT OF DISEASE. IT'S MADE IN THE LIVER. AND IL-6, IL-1 BETA AND TUMOR NECROSIS FACTOR ARE RELATED TO THE EXPRESSION OF CRP, SO CERTAINLY IT'S PART OF THE INITIALLY ACUTE RESPONSE BUT THEN IT GOES ON TO BE PRESENT AS PART MUCH CHRONIC INFLAMMATION. BUT UNDERSTANDING THAT Y WHAT CRP IS DOING IN THE TRANSITION AND UNDERSTANDING BODY THAT SUSTAINS INFLAMMATION IS UNKNOWN. IN TERMS OF THE CLINICAL MEASURE, AS I MENTIONED, IF YOU HAVE A LOW C-REACTIVE PROTEIN, LESS THAN ONE, THEN YOUR RISK OF CARDIOVASCULAR DISEASE IS VERY LOW. IF YOUR CRP LEVEL IS GREATER THAN 3, YOUR RISK IS HIGH. SO WHERE DO YOU THINK THE HANDLS PARTICIPANTS WERE? MOST WERE WELL OVER 3. WE ARE CRPs INTO THE 20s IN THE COHORT. SO WE DECIDED THIS MAY BE A GOOD MARKER TO STUDY TO UNDERSTAND WHAT CRP WAS DOING IN THEIR BLOODSTREAM. AND WE WERE PARTICULARLY INTERESTED IN WOMEN, IN CARDIOVASCULAR DISEASE, BECAUSE AS MANY OF YOU KNOW, CARDIOVASCULAR DISEASE IN WOMEN IN MIDDLE AGE IS OFTEN OVERLOOKED AND IT'S PARTICULARLY OVERLOOKED IN AFRICAN-AMERICAN WOMEN WHO HAVE A VERY HIGH RISK OF DEATH FROM CARDIOVASCULAR DISEASE IN THEIR LATE 40s THROUGH THEIR 60s. SO WE WERE VERY INTERESTED IN LOOKING AT WOMEN'S CRP BECAUSE WHEN YOU LOOK AT AFRICAN-AMERICAN WOMEN WHO ARE AGES 20 AND OLDER, 46% OF THEM, AT LEAST, HAVE SOME KIND OF CARDIOVASCULAR DISEASE. AND SO, AGAIN, WE TRY TO NARROW IT DOWN TO ASK SPECIFIC QUESTIONS ABOUT SPECIFIC SUBCOHORTS WITHIN THE POPULATION. SO THE OTHER THING TO BE AWARE OF IS THAT REMEMBER WE TALKED ABOUT THAT THEORY OF AGING WHERE OXIDATIVE STRESS, DNA DAMAGE IS ALSO IMPORTANT IN THE DEVELOPMENT OF AGING. WELL, WE WANTED ALSO TO SEE IS THERE AN ASSOCIATION BETWEEN INFLAMMATION AND OXIDATIVE STRESS, AND ONE WAY WE COULD DO THAT IS TO LOOK AT C-REACTIVE PROTEIN AND WHAT REACTION IT HAD IN A VASCULAR CELL MODEL SO WE WOULD BE ABLE TO EVALUATE THE PERHAPS CONNECTION BETWEEN INFLAMMATION AND OXIDATIVE STRESS. SO WHAT WE DID WAS TAKE OUR COHORT OF MIDDLE AGE WOMEN WHO HAD LOW, MIDDLE AND HIGH CRP VALUES, AND AS I TOLD YOU A LOT OF PEOPLE ARE CRP LEVELS GREATER THAN 3. ONE OF THE CAVEATS WHEN I TELL PEOPLE, OH, WE LOOKED AT PEOPLE WHO ARE CRPs GREATER THAN 10, THEY SAID THAT'S DUE TO INFECTION. WELL, NO, IT'S NOT. IF YOU LOOK IN THE WOMEN'S HEALTH STUDY, WOMEN HERE, VALUES GREATER THAN 10 WERE CONSIDERED A VERY HIGH RISK GROUP, GREATER THAN 20 ARE EXCEPTIONALLY ELEVATED RISK FOR VASCULAR DISEASE SO THAT LETS YOU KNOW THAT SOME PEOPLE THINK, WELL, MAYBE IT'S IN MEN THAT GREATER THAN 10 IS ASSOCIATED WITH INFECTION. BUT IN WOMEN, THAT'S NOT THE CASE. I POINT THAT OUT TO YOU BECAUSE IT IS VERY IMPORTANT FOR YOU TO FOCUS ON THE POPULATION, AND BE SPECIFIC ABOUT THE POPULATION THAT YOU'RE STUDYING. IN THIS AGE OF PERSONALIZED MEDICINE, THAT'S ONE OF THE THINGS THAT I LEARNED BECAUSE I HAD I LISTENED TO PEOPLE WHO SAID, OH, NO, THOSE PEOPLE IN YOUR STUDY WHO HAVE GREATER THAN 10, NONE HAVE CARDIOVASCULAR DISEASE AND YOU SHOULDN'T BE STUDYING THEM BECAUSE THEY HAVE INFECTION. I SAID I COULD NOT FIND INFECTION IN THEM. WELL, WE'RE TELLING WHAT YOU THE LITERATURE SAYS. WELL, YEAH, THAT'S NOT ALWAYS THE CASE. SO WE WANTED TO EXAMINE SORT OF THIS OVERLAY OF OXIDATIVE DAMAGE AND STRESS AND INFLAMMATION WITH RISK FOR THE DEVELOPMENT OF CHRONIC DISEASE. WHAT WE DID WAS WE TOOK PURE C-REACTIVE PROTEIN AND WE TREATED HUMAN UMBILICAL ENDOTHELIAL CELLS WITH C-REACTIVE PROTEIN AND STAINED THE CELLS TO SEE IF WE COULD SEE OXIDATIVE LESIONS. ONE OF THE THEORIES OF CARDIOVASCULAR DISEASE IS AS THE VESSEL WALL -- AT THE VESSEL WALL THERE'S OXIDATIVE DAMAGE SO THERE'S A LOT OF THEORIES ABOUT WHERE THAT OXIDATIVE DAMAGE COMES FROM. WE KNOW C-REACTIVE PROTEIN IS A RISK FACTOR FOR SUDDEN DEATH AND CARDIOVASCULAR DISEASE BUT WHAT IS IT DOING AT THE VESSEL WALL? THAT'S THE QUESTION WE WANTED TO KNOW IF OUR PARTICIPANTS. SO DOES CRP CAUSE OXIDATIVE DAMAGE? AND WHAT WE FOUND WAS IN FACT THAT CRP DID CAUSE THE INDUCTION OF 8-OXO-G LESIONS. WHEN WE TREATED WITH C-REACTIVE PROTEIN, WE ARE ABLE TO VISUALIZE WITH THESE DARKER RED CELLS THE PRESENCE OF 8-OXO-DG. WHEN WE TREATED WITH N-ACETYL-L-CYSTEINE WE WERE ABLE TO PREVENT, IF WE TOOK THE CELLS AND TREATED WITH MENADIONE, AGAIN, WE SEE EXACTLY THE SAME THING SO CRP CAUSES A SIMILAR PRESENCE OF 8-OXO-DG AS MENADIONE AND WHAT ABROGATES IS PRE-TREATMENT WITH NAC THAT WE KNOW IS ABLE TO PREVENT OXIDATIVE DAMAGE. AND SO THIS IS THE FIRST TIME THAT ANYBODY WAS ABLE TO PROVE IN FACT THAT C-REACTIVE PROTEIN CAUSES DAMAGE AT THE VESSEL WALL. AND NOW WE WANTED TO BE SPECIFIC, IS THAT IT THE ONLY KIND OF DAMAGE THAT C-REACTIVE PROTEIN CAUSES? IT SEEMS AS THOUGH IT IS. IT DOESN'T INDUCE SINGLE STRAND BREAKS, AT ALL, WE DID THIS DOING A COMET EXPERIMENT WHERE WE WERE ABLE TO MEASURE HOW MUCH STRAND BREAKAGE HAPPENS IN DNA BY TREATING IT WITH HYDROGEN PEROXIDE WHICH CHEWS DNA UP AND MAKES LOTS OF VERY SMALL FRAGMENTS THAT WE'RE ABLE TO MEASURE AS THE OLIVE TAIL MOMENT. HOWEVER, WHEN YOU TREATED THE CELLS WITH CRP OR MENADIONE OR CRP FOR LONGER WE DIDN'T GENERATE ANY SINGLE STRAND BREAKS, THIS IS SPECIFIC AT THE VESSEL WALL. 8-OXO-DG. 9/ WE WANTED TO SEE ARE SUPEROXIDES INDUCED IN THE HUMAN UMBILICAL CELLS, AND WHEN WE MEASURED FOR SUPEROXIDE WE WERE ABLE TO SEE, HERE WE DID NO TREATMENT, HERE WE TREATED WITH CRP AND WE WERE ABLE TO PICK UP SUPEROUCH DLKS OXIDE, WHEN WE TREATED WE FOUND THE SAME THING. CRP DOES NOT CAUSE DAMAGE IN MITOCHONDRIA, AND THIS CAUSES DAMAGE BUT NOT CRP, IT'S A SPECIFIC LESION THAT INTRACELLULAR BUT DOES NOT INVOLVE MITOCHONDRIA. SO HERE WE FOUND THAT 8-XODDY LEVELS INCREASED, IN WOMEN OBESITY, A RISK FACTOR FOR CARDIOVASCULAR DISEASE AND OTHER CARDIOVASCULAR VARIABLES WERE RELATED TO 8-OXODG LEVELS AND THEY INCREASE WITH CRP SO THE HIGHER YOUR CRP IS, THE HIGHER YOUR LEVELS OF 8-OXODG ARE IN YOUR SERUM, BUT ALSO IN THE EXPERIMENTAL SENSE IN THE VASCULATURE. WE THINK THE GENERATION IN THE ENDOTHELIUM IN WOMEN AT LEAST MAY BE A VERY IMPORTANT FACTOR AND THAT SORT OF IS ONE AREA OF RESEARCH THAT'S NOW OPENING UP TO UNDERSTAND WHY WOMEN PARTICULARLY AFRICAN-AMERICAN WOMEN IN THE YOUNGER AGE GROUP WITH A DISPROPORTIONATE RISK OF CARDIOVASCULAR DISEASE. IN LOOKING AT THE BIOPSYCHOSOCIAL MODEL WE WERE INTERESTED IN THE INTERACTION BETWEEN RACE AND VITAMIN D STATUS. AND GENETICS. NOW, WHY VITAMIN D STATUS? WHY GENETICS? I'M VERY INTERESTED IN ALSO UNDERSTANDING AGING FROM THE POINT OF VIEW OF GENETICS AND EPIGENETICS BECAUSE WE KNOW GENE ACTION COULD MODULATE THE PROCESS OF AGING. ARE THERE AGING GENES OR ARE THERE CLOCK GENES THAT ONCE THAT GENE TURNS ON, ALL THE CELLS SAY, OH, TIME TO GO ON VACATION, THEY ARE OLD NOW, I DON'T HAVE TO FUNCTION ANYMORE? OR IS IT SOME OTHER PROCESS THAT CAUSES AGING THAT'S DRIVEN BY GENES? SO THIS GOT US TO THINKING ABOUT HOW COULD WE STUDY THAT. ONE OF THE OTHER PARADOXES THAT WAS IN HUMAN HEALTH THAT WAS RELATED TO AFRICAN-AMERICANS IS THIS ISSUE OF VITAMIN D AND HEALTH. WE KNOW VITAMIN D IS IMPORTANT IN METABOLIC BONE DISEASE AND RELATED TO INCREASE IN ALL-CAUSE MORE MORTALITY, INCREASE IN ALL-CAUSE MORTALITY, VITAMIN D DEFICIENCY HAS A NEGATIVE ASSOCIATION WITH SURVIVAL AND IS ALSO ASSOCIATED WITH A NUMBER OF CHRONIC DISEASES. NOW, ONE OF THE THINGS ABOUT DIAGNOSING SOMETHING WITH VITAMIN D DEFICIENCY IS THAT EVERYBODY'S GOT A DIFFERENT NUMBER, INSTITUTE OF MEDICINE, ENDOCRINE SOCIETY, WHAT'S SUFFICIENT, LESS THAN 12 OR LESS THAN 20, THERE'S A LOT OF CONTROVERSY. I LIKE TO PURSUE CONTROVERSY. AND MOST IMPORTANTLY, IT'S BECAUSE -- I DON'T KNOW HOW MANY AFRICAN-AMERICANS IN THE ROOM HAD A VITAMIN D TEST DONE BUT AFRICAN-AMERICANS CONSISTENTLY HAVE LOWER TOTAL VITAMIN D THAN WHITES, AND IT MEETS THE STD FOR VITAMIN D DEFICIENCY BY A NUMBER OF THESE DIFFERENT MEASURES, BUT AFRICAN-AMERICANS SEEM TO HAVE HIGHER BONE MINERAL DENSITY AND LOWER RISK OF FRACTURES AND OSTEOPOROSIS. VITAMIN D IS CRITICAL IN BONE HELD. WHAT THE HECK? IF VITAMIN D IS ASSOCIATED WITH POOR SURVIVAL, WELL, MAYBE THAT'S THE KEY TO HEALTH DISPARITIES? THE PROBLEM IS ALL THESE POOR PEOPLE AND BLACK PEOPLE WHO HAVE HEALTH DISPARITIES HAVE LOW VITAMIN D, IF WE SUPPLEMENT EVERYBODY ALL THIS WILL GO AWAY. SO MY THOUGHT WAS THAT THERE COULD BE SOMETHING GENETIC IN THIS. SO WE DECIDED TO SORT OF THINK ABOUT IT IN TERMS OF WHAT ARE THE OTHER THINGS THAT ARE CENTRAL TO VITAMIN D PROCESSING IN THE BODY, ONE OF THE THINGS IS VITAMIN D BINDING PROTEIN THAT BINDS ABOUT 90% ALMOST OF THE VITAMIN D THAT'S CIRCULATING IN YOUR BODY. ANOTHER 8 TO 9% IS BOUND TO ALBUMIN AND THE REST IS SORT OF FREELY FLOATING AROUND. THE CLINICAL ASSAY THAT YOU GET WHEN YOU GO TO THE DOCTOR ONLY BOUND TO VITAMIN D BINDING PROTEINS. THAT'S THE ONLY THING THAT YOU GET FROM THAT TEST. SO VITAMIN D BINDING PROTEIN IS ABOUT THE SIZE OF ALBUMIN, AND IT HAS THE HIGHEST BINDING AFFINITY FOR VITAMIN D. BUT, THIS IS WHERE THE GENETICS COMES IN, THERE ARE THREE MAJOR POLY MORPHIC VARIANTS, GC1F, AND GC1S IN EUROPEAN-BASED POPULATIONS, AND THE POLYMORPHIC VARIANTS HAVE DIFFERENT ABUNDANCES BUT HAVE DIFFERENT BINDING CONSTANTS FOR VITAMIN D. SO THAT MANY GOT US TO THINKING, WELL, IF THERE ARE DIFFERENCES IN THESE VITAMIN D BINDING PROTEIN PERCENTAGES, THEN MAYBE THAT HAS SOMETHING TO DO WITH WHY THESE VITAMIN D LEVELS FOR AFRICAN-AMERICANS ARE CONSISTENTLY SO LOW. SO TWO QUESTIONS, YOU KNOW, DO THESE VITAMIN D BINDIN PROTEIN GENOTYPES AND THE CONCENTRATION OF VITAMIN D BINDING PROTEIN DELIVER BETWEEN AFRICAN-AMERICANS AND WHITES AND DOES THAT ACCOUNT FOR OBSERVED RACIAL DIFFERENCES? WE WENT TO THE HANDLS PARTICIPANTS, MEASURED TOTAL VITAMIN D, PARATHYROID, BONE MINERAL DENSITY AND GENOTYPED FOR THE TWO MOST PREVALENT, REDS7041 AND RS4588 AND ESTIMATED BIOAVAILABLE VITAMIN D, WHAT ELSE IS FLOATING AROUND AND ARE THERE DIFFERENCES IN THAT? SO AS AS EXPECTED, THE BLACK HERE IS THIS DARKER COPPER, THE VITAMIN D LEVELS IN OUR HANDLS PARTICIPANTS WERE LOWER THAN WHITES. WE ALSO FOUND THAT VITAMIN D BINDING PROTEIN AGAIN HERE LOWER THAN WHITES. AND THIS DIFFERENCE PERSISTED NO MATTER WHICH WE DID THE MULTI-VARIANT ADJUSTMENT. WE SAW AS EXPECTED THE BONE MINERAL DENSITY WAS HIGHER IN AFRICAN-AMERICANS THAN WHITES SO THE SAME THING THAT'S BEEN PUBLISHED, WE REPLICATED IN OUR COHORT. HOWEVER, WHEN WE LOOKED AT THE GENETIC POLYMORPHISMS OF VITAMIN D BINDING PROTEIN, WHEN WE LOOKED AT THE LOCUS RS 7041 WE FOUND AFRICAN-AMERICANS WERE MORE LIKELY THAN WHITES TO HAVE A T AT RS 70 HAD 1 AND T WAS ASSOCIATED WITH DECREASED LEVELS OF VITAMIN D BINDING PROTEIN IN AFRICAN-AMERICANS AND IN THE FEW WHITES THAT ALSO HAD A T AT THIS LOCUS. WHITES WERE MORE LIKELY TO HAVE A G AT THIS LOCATION. THE T ALLELE WAS ALSO ASSOCIATED WITH LOW LEVELS OF VITAMIN D IN THE BLOOD AMONG AFRICAN-AMERICANS. NOW, WHEN WE LOOKED 4588, THE A ALLELE WAS ASSOCIATED. AFRICAN-AMERICANS WERE LESS LIKELY TO HAVE THE A AT 4588. AND IN WHITES, THAT A ALLELE WAS ASSOCIATED WITH LOWER LEVELS OF TOTAL VITAMIN D. SO WHEN WE BEGAN TO LOOK AT THE POLYMORPHISMS AND OTHER FACTORS THAT CONTRIBUTE TO WHAT YOUR VITAMIN D LEVEL IS, WE FOUND THAT THESE POLYMORPHISMS EXPLAINED ALMOST 10% OF THE VARIATION OF VITAMIN D, AND WHEN YOUR VITAMIN D LEVEL CHANGES DEPENDING ON HOW MUCH SUNLIGHT YOU GET AND RACE, THAT'S ANOTHER 10 TO 7.3%. HOWEVER, THINGS LIKE POVERTY, BMI, CALCIUM INTAKE, THAT DIDN'T ACCOUNT FOR A LOT OF VARIATION. OVERALL ABOUT 31% WAS EXPLAINED BY ALL OF THIS TOGETHER. AND SO THE CONCENTRATION OF VITAMIN D BINDING PROTEIN AND GENOTYPE TOGETHER EXPLAINED A FAIR AMOUNT OF THE VARIATION AS WELL. AND THIS BECOMES CLEAR WHEN YOU LOOK AT THE ACTUAL PHENOTYPE OF THE VITAMIN D BINDING PROTEIN. WHEN WE LOOK AT HOMOZYGOTES GC 1F, AFRICAN-AMERICANS LARGELY HERE, WHITE HOMOZYGOTES MOST ARE GC1F. WHEN WE LOOK AT BINDING PROTEIN WE SEE THE AFRICAN-AMERICANS HAVE MUCH LESS BINDING PROTEIN THAN THE WHITES WHO WERE HERE FURTHER OUT IN THE CURVE. BUT WHEN WE LOOKED AT HOW MUCH FREE VITAMIN D WAS PRESENT, IT'S ESSENTIALLY THE SAME. 2.9 VERSUS 3.1. SO WHEN YOU LOOK AT THE AMOUNT OF FREE VITAMIN D BETWEEN BLACKS AND WHITES IT'S EXACTLY THE SAME. WHAT'S DIFFERENT IS THE BOUND AMOUNT. SO IN SOMEONE WHO HAS NO SYMPTOMS OF VITAMIN D DEFICIENCY, AND WHOSE FREE AMOUNT OF VITAMIN D IS THE SAME AS THE WHILE POPULATION CAN YOU REALLY CALL THEM VITAMIN D DEFICIENT? THAT'S THE QUESTION THIS PAPER RAISED. IS THE TEST THAT WE USE TO MEASURE VITAMIN D PERSONALIZED AND SPECIFIC TO THE QUESTION L THAT TEST IS MEASURING IS THAT'S BEING TOTALLED, BECAUSE HOW MUCH IS BOUND TO YOUR BINDING PROTEIN. IT IS NOT MEASURING WHAT'S BIOAVAILABLE, AND WHAT'S BIOAVAILABLE WE THINK IS WHAT'S IMPORTANT. AND SO OUR THOUGHT IS THAT THAT'S REALLY A MISNOMER TO TELL EVERY AFRICAN-AMERICAN WITHOUT EITHER DOING A GENETIC EVALUATION OR MEASURING FREE VITAMIN D AND FORCING THEM TO TAKE SUPPLEMENTATION THAT'S NOT NECESSARY. AND SO WE ALSO LOOKED AT IT FROM THE POINT OF VIEW OF PARATHYROID HORMONE, AND ALTHOUGH AFRICAN-AMERICANS HAD LOWER LEVELS OF TOTAL VITAMIN D PER LEVEL OF PARATHYROID HORMONE, PARATHYROID HORMONE IS AN IMNT INDICATOR OF VITAMIN D SUFFICIENCY IN THE SYSTEM, WHEN WE LOOKED AT THIS BIOAVAILABILITY OF VITAMIN D WE FOUND THAT THERE WAS ABSOLUTELY NO DIFFERENCE BETWEEN AFRICAN-AMERICANS AND WHITES, EVEN WHEN YOU TOOK INTO ACCOUNT THE LEVEL OF PARATHYROID HORMONE. SO THAT PARATHYROID HORMONE REALLY DID NOT HAVE AN INFLUENCE ONE WAY OR ANOTHER IN THE DIFFERENCE BETWEEN AFRICAN-AMERICANS AND WHITES IN LEVELS OF VITAMIN D. SO WE FOUND THAT THESE 25-HYDROXY VITAMIN D LEVELS ARE IN PART GENETICALLY DETERMINED, AND THAT THESE POLYMORPHISMS ACCOUNT FOR A GREATER PROPORTION OF TOTAL VITAMIN D THAN MANY OF THE OTHER FACTORS THAT ARE KNOWN TO EFFECT VITAMIN D LEVELS, SO THAT WE NEEDED TO TAKE INTO ACCOUNT THE ISSUE OF THE POLYMORPHISM, WHEN WE'RE TRYING TO ACCOUNT FOR THE DIFFERENCES BETWEEN BLACKS AND WHITES. AND MAYBE THE MOST IMPORTANT THING IS COULD BIOAVAILABLE VITAMIN D MEASUREMENT BE A MORE APPROPRIATE CROSS RACIAL MARKER OF VITAMIN D DEFICIENCY, AND IS IT REALLY NECESSARY TO PROVIDE ROUTINE SUPPLEMENTATION FOR PEOPLE WHO HAVE LOW TOTAL VITAMIN D AND LOW VITAMIN D BINDING PROTEIN, BECAUSE IF YOU HAVE LOW VITAMIN D BINDING PROTEIN THE TEST WILL MEASURE HOW MUCH IS THERE THAT'S BOUND TO YOUR LOW VITAMIN D, NOT TAKING INTO ACCOUNT THAT OTHER VITAMIN D THAT WE THINK IS THE MORE BIOACTIVE. THIS IS AN AREA OF HUGE CONTROVERSY IN THE FIELD NOW, WE'RE WORKING TO DEVELOP AN ASSAY THAT IS MORE REPEATABLE TO BE ABLE TO MEASURE ONLY VITAMIN D BIOAVAILABILITY RATHER THAN MEASURE VITAMIN D THAT'S BOUND TO THE BINDING PROTEIN. SO HANDLS IS A STUDY OF HEALTH DISPARITIES, IT'S MUCH LIKE HEALTH DISPARITIES ITSELF IN THAT THERE ARE SO MANY DIFFERENT FACTORS WE THINK IMPINGE ON DIFFERENCES IN HEALTH THAT WE SEE IN THE POPULATION THAT IT'S GOT TO BE AN INTERDISCIPLINARY, A MULTI-DISCIPLINARY APPROACH WITH INVESTIGATORS FROM A BROAD RANGE OF EXPERTISE, NOT PEOPLE WHO ARE BEHAVIORAL SCIENTISTS NOR PEOPLE WHO ARE JUST BASIC SCIENTISTS, IT HAS TO BE A WORK FORCE COMPOSED OF PEOPLE WITH MULTIPLE LEVELS OF EXPERTISE AND THAT'S PROBABLY THE MOST IMPORTANT MESSAGE TO CONVEY. SO DON'T THINK IF YOU'RE A BASIC SCIENTIST HEALTH DISPARITIES ARE NOT FOR ME. NO, THERE ARE SOME QUESTIONS THAT ARE RELEVANT TO DISSECTION AT THE BENCH AS WELL AS PSYCHOSOCIAL FACTORS THAT NEED TO BE EVALUATED BY PSYCHOSOCIAL AND BEHAVIORAL SCIENTISTS. I THANK YOU FOR YOUR ATTENTION AND WANT TO SHOW YOU OUR HANDLS STAFF, AND LAB-BASED STAFF AND FIELD-BASED STAFF AND HANDLS PROGENY. ONE OF THE OPERATIONAL GOALS OF THE STUDY HAS BEEN TO PREPARE MINORITY INVESTIGATORS AND OTHERS INTERESTED IN HEALTH DISPARITIES FOR THAT ARE NEXT STEP IN THEIR CAREER, AND I THINK WE'VE BEEN FAIRLY SUCCESSFUL THUS FAR IN GETTING PEOPLE ON THE TENURE TRACK AND MOVING UP INTO, YOU KNOW, FAIRLY GOOD POSITIONS AT MAJOR UNIVERSITIES. THEN AGAIN THE COLLABORATORS, MY MAIN CLAPPATOR ALAN ZONDERMAN, AND JOHN RUFFIN, FORMER DIRECTOR OF THE NATIONAL INSTITUTE OF MINORITY HEALTH AND HEALTH DISPARITIES WHO GAVE US THE INITIAL FUNDING, AND OUR ASSOCIATE INVESTIGATORS AND COLLABORATORS. THANK YOU. [APPLAUSE] >> NOW IS THE OPPORTUNITY TO ASK QUESTIONS. >> A LOT OF THE RESEARCH TOWARDS THE END OF THE PRESENTATION WAS KIND OF RELATING TO RACE AS A BIOLOGICAL FACTOR, INFLUENCING HEALTH DISPARITIES. HOW CAN YOU CONFIDENTLY CONNECT THE HEALTH DISPARITIES TO RACE AS A BIOLOGICAL FACTOR AS OPPOSED TO SOCIAL FACTOR WHEN RACE IS A SOCIAL CONSTANT? >> YEAH, RACE IS A SOCIAL CONSTRUCT, THAT IS HOW WE APPROACH IT. HOWEVER, WHEN YOU LOOK BIOLOGICALLY AS IN THE VITAMIN D STUDY, WE LOOKED AT POLYMORPHISMS THAT ARE MORE PROMINENT IN AFRICAN-AMERICANS VERSUS WHITES, SO IN THAT SENSE RACE IS IMPORTANT. IT'S NOT IMPORTANT -- IN THAT SENSE, IT IS A BIOLOGIC CONSTRUCT. HOWEVER, IN GENERAL, WE LOOK AT IT AS A SOCIAL CONSTRUCT BECAUSE THAT'S WHAT IT IS. AND IT'S A SOCIAL CONSTRUCT THAT'S IMPORTANT BECAUSE IN OUR STUDY, IF YOU LOOK AT SOME OF THE WORST HEALTH PROFILES, THEY ARE FROM THE LOW SES INNER CITY WHITES, WHO UNFORTUNATELY HAVE RUN INTO A LOT OF THE SAME PROBLEMS AS OUR INNER CITY BLACKS, EXCEPT THEY WEREN'T ABLE TO FLEE WHEN THEIR COUSINS MOVED TO HOWARD COUNTIES AND HARTFORD COUNTY THEY DIDN'T HAVE IT TO GO THERE. THAT CERTAINLY SHOWS US THAT THE ENVIRONMENT HAS A LOT TO DO WITH IT. BUT YOU DO HAVE TO LOOK PARTICULARLY IN THE CASE OF VITAMIN D WHEN THE QUESTION IS POSED, WE PURSUED THE VITAMIN D QUESTION, BASED ON OUR -- WE HAVE A HANDLS MEDICAL REFERRAL NETWORK. I GET TOGETHER WITH LOCAL DOCS IN THE AIR WHO AGREE TO SEE HANDLS PATIENTS, BECAUSE WE'RE NOT ACTIVELY TREATING PEOPLE BUT WHEN WE DIAGNOSE SOMETHING I HAVE TO HAVE SOMEPLACE TO SEND THEM SO WE HAVE THIS LITTLE BRAIN TRUST AND THEY WERE CALLING ME SAYING ALL THESE PEOPLE I'M DOING THIS VITAMIN D TEST ON, ALL THE BLACK PEOPLE ARE COMING UP WITH LOW VITAMIN D, AM I SUPPOSED TO TREAT THEM ALL, WHAT DOES IT MEAN? THAT'S HOW THE VITAMIN D PROJECT KICKED OFF BECAUSE I WAS INTERESTED IN, YOU KNOW, STUDYING GENETICS, AND SO THERE WERE SOME THINGS THAT PRESENT THEMSELVES, THAT'S A FACT. THERE'S NOTHING WE CAN DO ABOUT IT. WE'RE NOT SAYING IT'S BAD OR GOOD. SO I DON'T WANT YOU TO TAKE IT IN THAT CONTEXT. BUT I THINK IT CERTAINLY SHOWS THAT THE NEED FOR PERSONALIZED MEDICINE, BECAUSE WE HAVE A MAJOR TEST THAT HAS A FINDING THAT MAY NOT BE 100% APPLICABLE TO ALL OF THE PEOPLE WHO ARE TAKING THAT TEST AND THEN BEING TREATED BASED ON THAT TEST. DO YOU UNDERSTAND WHAT I'M SAYING? >> YES. >> (INAUDIBLE). >> IT'S A RADIOLIGAND ASSAY, IT'S ABLE TO MEASURE VITAMIN D BOUND TO ALBUMIN AND ALSO THE SMALL PERCENTAGE THAT'S FREE, BUT SINCE THEY ARE TRYING TO GO FOR A PATENT I CAN'T SAY ANYTHING MORE. >> SO THE VITAMIN D, THAT ASSAY IS MEASURING VITAMIN D BINDING PROTEIN, IS THAT WHAT YOU SAID? >> WHICH THE STANDARD MEDICAL TEST, STANDARD CLINICAL TEST MEASURES AMOUNT OF VITAMIN D THAT IS BOUND TO VITAMIN D PROTEIN, IT DOES NOT MEASURE ANYTHING ELSE. >> YOU SEDATIVE VITAMIN D IS MORE ASSOCIATED WITH THAT, PEOPLE WITH LOWER VITAMIN D BINDING PROTEIN DOES THAT HAVE EFFECT ON THEIR QUALITY OF LIFE? >> NO. AND THAT'S EXACTLY THE POINT. >> IT'S SOMETHING ELSE THAT HAS AN EFFECT ON THEIR QUALITY OF LIFE, OR IS THAT WHAT THEY ARE COMING IN FOR? >> NO. THIS IS -- WE DO THIS AS JUST PART OF THE PANEL OF TESTS THAT WE DO. SO THEY ARE NOT COMING IN WITH A CHIEF COMPLAINT. THERE ARE PEOPLE WHO DO HAVE VITAMIN D DEFICIENCY, THEY FREQUENTLY WILL HAVE BONE DISEASE. THEY WILL HAVE OSTEOPOROSIS, THEY WILL HAVE AN INCREASE INCIDENCE OF FRACTURE, SOME WILL HAVE RENAL DISEASE. YES, THERE IS AN ENTITY OF VITAMIN D DEFICIENCY. AND THOSE PEOPLE, IF YOU DO THAT TEST ON THEM, THEY MAY WELL HAVE VITAMIN D DEFICIENCY. THE PARADOX IN THE AFRICAN-AMERICAN POPULATION IS THEY GET THAT SAME TEST, IT COMES BACK DEFICIENT BUT THEY HAVE NONE OF THE CLINICAL STIGMATA OF THAT. THEY HAVE HIGHER BONE MINERAL DENSITY, A LOWER INCIDENCE OF FRACTURE, AND SO, YOU KNOW, IT'S TRYING TO SORT OF UNDERSTAND WHAT'S THE DIFFERENCE, AND AT LEAST IN OUR HANDS ONE OF THE DIFFERENCES IS THE PHENOTYPE IS GENETICALL Y DRIVEN BY A POLYMORPHISM OF THE VITAMIN D BINDING PROTEIN. >> A RELATED QUESTION, SO, YOU KNOW, FROM A CLINICAL PERSPECTIVE IF THERE'S EVIDENCE TO SUGGEST THAT THERE SHOULDN'T BE ONE TEST THAT'S A FIT-ALL, AND I'M WONDERING WHAT THE EFFECT SIZES ARE TO THE EXTENT IT SEEMS PROBLEMATIC IF YOU DETERMINE WHICH MEDICAL TEST TO PRESCRIBE BASED ON RACE, BECAUSE UNLESS IT'S LIKE 100% OF, YOU KNOW, X RACE, NEEDS TO BE EVALUATED AT THIS LEVEL, THEN YOU'RE GOING TO MISS PEOPLE, THAT ALSO SEEMS PROBLEMATIC FROM A CLINICAL PERSPECTIVE. >> RIGHT. SO IT MAY NEED TO BE SORT OF A TWO-STEP THOUGHT PROCESS FOR CLINICIANS. YOU DO THE STANDARD TEST, YOU HAVE SOMEBODY WHO HAS NORMAL BONE MINERAL DENSITY IN FRONT MUCH YOU, A LOW VITAMIN D LEVEL, MAYBE THAT PERSON NEEDS TO GO FOR A SECONDARY ANALYSIS, EITHER TO DO A POLY MORPHIC EVALUATION OF THEIR VITAMIN D BINDING PROTEIN MAYBE OR LET'S MEASURE THEIR FREE VITAMIN D TO SEE WHETHER OR NOT THAT FALLS WITHIN NORMAL LIMITS, AND THE PROBLEM WITH THAT IS FINDING OUT WHAT'S NORMAL LIMITS. AND THAT'S ONE OF THE THINGS THAT WE'RE CERTAINLY GOING TO TRY TO DO. BUT SOME OF THIS IS, YOU KNOW, I THINK IN MEDICINE WE'VE GOTTEN INTO WE TREAT THE TEST. OKAY? THE TEST SAYS THIS IS WRONG SO WE NEED TO TREAT THIS. WE DON'T PUT TOGETHER LISTENING TO THE PATIENT, LOOKING AT THE PATIENT, EXAMINING THE PATIENT, AND THINKING ABOUT THE DATA AS A CONCEPTUAL WHOLE. WE'RE TREATING THE PIECE OF PAPER. AND THAT'S ONE OF THE THINGS THAT I THINK HAPPENS WITH VITAMIN D. WE HAVE A KNEE JERK REACT TO TREAT AN ABNORMALITY BEFORE WE KNOW IT HAS A CLINICAL CONSEQUENCE OR NOT. >> FOR THE PREVIOUS STUDY, THE ONE WITH INFLAMMATION, YOU MENTIONED THE WOMAN WITH THE OBESITY -- SO I'M WONDERING FOR WOMEN WITH OBESITY, KNOW IF YOU LOOKED AT -- FOR THOSE WHO DO LOSE WEIGHT DO YOU SEE THAT THE 8-OXODG LEVELS DECREASE? >> THAT'S A GOOD QUESTION. WE HAVE NOT LOOKED AT THAT TO SEE, AND NOW WE ACTUALLY MAY BE ABLE TO DO THAT EXPERIMENT, BECAUSE, YOU KNOW, NOW WE FINALLY HAVE BEEN ABLE TO SEE THEM FOR THREE FULL VISITS, SO WE CAN CHART -- WE HAVE THREE POINTS TO SEE WHAT'S HAPPENED TO THEIR WEIGHT AND THAT WOULD BE AN INTERESTING QUESTION FOR US NOW TO BE ABLE TO ASK. THAT STUDY WAS DONE AT THE TIME. WE HAD FULL BASELINE DATA AND WE'RE INTO WAVE THREE. NOW WE'RE INTO WAVE FOUR AND PEOPLE ARE COMING BACK FOR THE FULL REVISIT WE CAN POSE QUESTIONS LIKE THAT. IS IT A MARKER, SHOWING AS YOU LOSE WEIGHT SOME OF YOUR INFLAMMATORY AND OXIDATIVESS PROFILE CHANG ES WITH THAT. WE'VE HAD CHANGES WITH WEIGHT LOSS, SO THAT'S GOOD. >> ANOTHER QUESTION, YOU MENTIONED THAT PEOPLE OF AFRICAN DESCENT TEND TO HAVE LOWER LEVELS OF THE 25 HYDRO VITAMIN D. IS THAT MOSTLY BASED ON LIKE RESEARCH IN THE AFRICAN-AMERICANS, ARE THERE ANY RESEARCH LIKE AFRICANS ON THE CONTINENT TO SEE IF THIS -- IF THEY ALSO EXHIBIT THE SAME LOW LEVELS OF BOUND VITAMIN D? >> NOW, I'VE NOT DONE THAT RESEARCH, BUT, YEAH, IT DOES SEEM AS THOUGH THERE ARE LOWER LEVELS OF VITAMIN D FOR OTHER MEMBERS OF THE AFRICAN-AMERICAN DIASPORA. >> OKAY. SORRY. SO CORRECT ME IF I'M WRONG, FOR T CELLS I THINK IT HAS BEEN SHOWN PEOPLE OF AFRICAN DESCENT TEND TO HAVE LOWER LEVELS, OR SOMETHING LIKE THAT, AS OPPOSED TO THEIR COUNTERPARTS, SINCE YOU'RE IN THE AREA OF INFLAMMATION I WONDER IF THAT'S SOMETHING YOU'RE LOOKING INTO, SIMILAR TO THE HYDRO? >> RIGHT NOW WE'RE NOT LOOKING SPECIFICALLY AT T CELLS AND T CELL FUNCTION OR T CELL NUMBER AS PART OF INFLAMMATION OR INFECTION. I MEAN, THAT'S SOMETHING, YOU KNOW, WE'VE DEBATED ABOUT DOING. WE'RE SORT OF HAMPERED IN THAT TO REALLY DO THOSE STUDIES WELL, YOU REALLY NEED TO HAVE LARGE QUANTITIES OF BLOOD AND LARGE NUMBERS OF CELLS WHICH YOU CAN GET IF YOU CYTOPHORESE, A LOT ARE HOOKED UP TO LABS WHERE YOU GET BIG PACKS OF CELLS. WE'RE MOBILE, WE CAN'T DO THAT AS A FIELD-BASED STUDY BUT IN OUR POPULATION, WE DO HAVE ACCESS FOR MANY, MANY DIFFERENT REASONS. SO IT'S REALLY NOT PRACTICAL. SO WE'VE SORT OF NOT GONE IN THAT DIRECTION, BECAUSE WE REALLY DIDN'T THINK THAT WE HAD THE OPTIMAL MATERIAL TO REALLY POSE THOSE KINDS OF QUESTIONS, WHICH I THINK ARE IMPORTANT, BUT IT'S SOMETHING WE'RE JUST NOT ABLE TO DO. >> I WAS WONDER IF YOU FOUND ANY LIKE SIGNIFICANT DIFFERENCES IN HEALTH BETWEEN THE PEOPLE OF DIFFERENT NEIGHBORHOODS, IF THERE WAS ANY CORRELATION BETWEEN DIFFERENCES IN HEALTH? >> WELL, INITIALLY WE HAD HOPED LONGITUDINALLY TO BE ABLE TO STUDY THAT, BUT AS YOU CAN IMAGINE, PEOPLE MOVE. SO IT IS -- IT'S A LITTLE DIFFICULT TO DO THAT OVER TIME. BUT I WILL SAY THAT IN SOME OF THE LOWEST OF THE ECONOMIC STRATA, WE DID FIND MORE COMORBIDITY SO THAT YOU NOT JUST HAD ONE CONDITION, YOU HAD MULTIPLE CONDITIONS. >> IS ANYONE LOOKING AT MECHANIC MECHANISTICKIC DIFFERENCE BETWEEN THE POLYMORPHISM TO EXPLAIN WHY YOU CAN HAVE SIMILAR OUTCOMES BETWEEN INDIVIDUALS WITH RADICALLY DIFFERENT LEVELS OF BINDING PROTEIN? >> NO, WE HAVEN'T WORKED ON THAT. >> I JUST HAD A FEW QUESTIONS. SO HOW OFTEN DID YOU SAY THAT LIKE THE SELF REPORT OR SUBJECTIVE MEASURES ARE COLLECTED? >> THEY ARE COLLECTED EVERY TIME THEY COME, SO IT'S ABOUT EVERY FIVE YEARS. >> EVERY FIVE YEARS, OKAY. BECAUSE I WAS KIND OF CURIOUS ABOUT SINCE YOU'RE USING SUCH A COMPREHENSIVE BIOPSYCHOSOCIAL MODEL, ABOUT MAYBE LIKE LOOKING AT CUMULATIVE STRESS, OVER TIME SINCE YOU HAVE SUBJECTIVE AND OBJECTIVE MEASURES, I THINK THAT'S PRETTY INTERESTING TO SEE WHETHER THERE WOULD BE, YOU KNOW, DIFFERENT TRENDS OVER TIME, WHETHER THERE WOULD BE DIFFERENCES BY RACE, AND IF THAT WOULD AFFECT ANY OUTCOMES YOU'RE LOOKING AT. >> YEAH, THAT'S ONE OF THE THINGS WE'RE HOPING TO DO, AND, AGAIN, DOING LONGITUDINAL RESEARCH IS LIKE DELAYED GRATIFICATION. OKAY, YOU CAN ONLY DO CROSS-SECTIONAL WORK AFTER YOU FINISH THE BASELINE AND THEN WHEN YOU HAVE ONE FOLLOW-UP, THAT'S GOOD, BUT YOU ONLY HAVE TWO MEASURES, NOW THAT WE'RE, YOU KNOW, GETTING INTO THE FULL SWING OF THE THIRD SET OF MEASURES WE'LL BE ABLE TO POSE SOME QUESTIONS LIKE THAT. WE ALREADY HAVE SOME COLLABORATORS WHO STARTED TO CONTACT US TO SORT OF ASK ABOUT, YOU KNOW, WHAT THEY MAY BE ABLE TO ASK WITH USING THE COHORT DATA. >> I WAS WONDERING AT THE BEGINNING OF THE PRESENTATION YOU SHOWED LIFE EXPECTANCIES OF BALTIMORE NEIGHBORHOODS, YOU SAID IT WAS MOSTLY STABLE SINCE 2008. NOW WITH OBAMACARE HAVE YOU SEEN OR DO YOU EXPECT TO SEE ANY MAJOR DIFFERENCES IN THOSE GAPS THAT MORE PEOPLE ELIGIBLE FOR HEALTH INSURANCE? >> THAT'S WHAT WE'RE HOPING TO SEE. WE VERY A NATURAL EXPERIMENT THAT'S BEEN CREATED BY THE AFFORDABLE CARE ACT, YOU KNOW, SO WE'LL BE ABLE TO DO BEFORE AND AFTER. WHAT I WILL TELL YOU THOUGH IS THERE ARE STILL GAPS IN OBAMACARE THAT ARE VERY HARD TO PLUG. I HAVE A SOCIAL WORKER WHO IS MY CLINICAL -- ACTUALLY OUR STUDY MANAGER IS A SOCIAL WORKER, AND WE HAVE A SOCIAL WORKER INTERN FROM THE UNIVERSITY OF MARYLAND, AND BETWEEN THE TWO OF THEM, WE CONTACTED EVERY PARTICIPANT AT THE BEGINNING OF OBAMACARE AND YOU KNOW THE MARYLAND ROLLOUT FOR OBAMACARE WAS A NIGHTMARE. A NIGHTMARE! AND WE COMPLAINED SO MUCH AND IF YOU THINK I'M DIFFICULT, MY CLINICAL STUDY MANAGER, WE COMPLAINED SO MUCH ABOUT THE TROUBLE WE HAD, WE HAD OUR OWN PERSONAL NAVIGATOR FROM MARYLAND THAT DID HANDLS PARTICIPANTS. WE GOT THEM IN CARE BUT THIS RE-ENROLL. RE-ENROLLMENT ISSUE IS A PROBLEM. IF THEY LOSE THEIR JOBS, IT'S A PROBLEM GETTING THEM ENROLLED INTO MEDICAID. PIECES THAT ARE NOT NAILED DOWN BECAUSE I THOUGHT, WELL, AFTER OBAMACARE COMES IN, THE AFFORDABLE CARE ACT, I'M NOT GOING TO NEED MY MEDICAL REFERRAL NETWORK AT MUCH. BUT I'VE HAD TO USE MY MEDICAL REFERRAL NETWORK. WELL, NO, YOU KNOW, THEY SAID MY CARDS RAN OUT, I DIDN'T KNOW I HAD TO REUP. OH, THE PREMIUM WENT UP, IT'S TOO HIGH, I CAN'T AFFORD IT NOW. I'M STILL HAVING PROBLEMS. BUT, AGAIN, I THINK WE NEED T3 ADJUST THE AFFORDABLE CARE ACT TO SORT OF MEET SOME OF THESE EXOGENCIES, BUT I'M RUBBER TO THE ROAD SEEING IT WITH PEOPLE WITH DIASTOLIC BLOOD PRESSURE OF 120, WHAT DO YOU MEAN YOUR AFFORDABLE CARE ACT CARD DOESN'T WORK ANYMORE? I'M ON THE PHONE TO THE HYPERTENSION CLINIC TO MY BUDDY, SAYING I'M SENDING YOU A LIVE ONE. I'M FULL TODAY. NO, YOU'RE NOT. WE'RE BRINGING HER OVER. I'M STILL CALLING IN FAVORS TO GET PEOPLE THE CARE THEY NEED BECAUSE SOMEHOW THE PAPERWORK HASN'T ALL ROLLED IN THE RIGHT WAY. SO I STILL NEED SOCIAL WORKERS. I DIDN'T TAKE A SOCIAL WORK STUDENT BECAUSE I FIGURED, OH, I'M GOOD NOW. AND MARILYN SAID DON'T YOU WANT ANOTHER SOCIAL WORKER? NO, WE'RE FINE. NEXT SEMESTER I'LL HAVE ONE BECAUSE I HAVE TOO MUCH FOLLOW-UP TO DO. I NEED A SOCIAL WORK INTERN, IT'S GOOD, SHE GETS HER CLINICAL HOURS, WE GET OUR PEOPLE'S PAPEWORK STRAIGHTENED OUT, SO THAT WE DON'T HAVE THEM ROLLING IN WITH THE BLOOD SUGARS OF 600 THAT I SAW AT THE BEGINNING OF THE STUDY AND I HAD HOPED THAT WE WOULDN'T SEE AGAIN. BUT WE'RE STILL SEEING IT. NOT AS OFTEN, SO MAYBE THERE'S HOPE, BUT THERE'S STILL A LITTLE BIT OF TWEAKING AND, YOU KNOW, ADJUSTING THAT NEEDS TO OCCUR. >> (INAUDIBLE) AND YOU'RE NOT ASKING PEOPLE THESE QUESTIONS OR DOING TESTS AND STUFF LIKE THAT? >> YOU MEAN IF THEY WENT TO THEIR DOCTOR AND BROUGHT THE INFORMATION TO US? >> YEAH, IN A WAY LIKE THE DOCTORS CAN PARTICIPATE IN THE STUDIES OR -- YOU KNOW WHAT I'M SAYING? >> YEAH. WE HAD THOUGHT ABOUT THAT, TO HAVE IT MORE INTERACTIVE, AND, YOU KNOW, THE MEDICAL REFERRAL NETWORK AND I TALKED ABOUT THIS, YOU KNOW, BACK IN 2004. THE PROBLEM IS I NEED CONTROL OF THE DATA QUALITY. I KNOW HOW THE BLOOD PRESSURE IS TAKEN, IT'S TAKEN THE SAME WAY EVERY TIME. I KNOW HOW THE HEIGHT AND WEIGHT IS MEASURED EVERY TIME. IT'S A RESEARCH STUDY. SO I NEED TO ASSURE QUALITY OF DATA. AND I AM UNWILLING TO DELEGATE THAT TO SOMEONE WHO HAS NOT BEEN TRAINED TO DO THAT. NOW, IF WE -- EVERYTHING THAT WE DO, WE SEND TO THEIR DOCS, THEIR DOCS KNOW THE RESULTS OF EVERYTHING THAT WE DO, AND THEY HAVE THE -- THE PARTICIPANTS HAVE A COPY AS WELL, BUT I WAS NOT ABLE, I THINK, TO FORM A MODEL. SOME IS BECAUSE PRIVATE PRACTITIONERS OR EVEN THESE CLINICS THAT ARE SUPPORTED BY HUGE BLOCK GRANTS, THEY REALLY JUST DON'T HAVE THE TIME. THEY ARE UNDERSTAFFED AND OVERWORKED. SO THEY CAN BARELY GET THE PATIENTS IN, SEEN AND OUT. DOCTORS VISITS, YOU KNOW, YOU PEOPLE ARE YOUNG SO YOU DON'T REALLY HAVE A LOT OF PROBLEM.EY ARE SHORT. >> THEY ARE SHORT. OUR VISITS, WHEN THEY COME TO THE MRV, THEY GET THERE AT 8:30, THEY DON'T WALK OUT UNTIL ABOUT 3:30. IT'S A WHOLE DAY DEAL. BECAUSE WE WANT TO TALK TO THEM AND WE WANT TO HEAR WHAT THEY ARE SAYING. PARTICULARLY IN THE MEDICAL HISTORY, BECAUSE THAT'S HOW YOU LY FIGURE OUT WHAT'S GOING ON WITH THIS PERSON. AND THAT TAKES TIME, AND TIME UNFORTUNATELY THAT PRACTICING DOCS DON'T GET BECAUSE OF MEDICAL INSURANCE REQUIREMENTS AND ALL OTHER SORTS OF THINGS. YOU KNOW, THEY HAVE TO SEE A CERTAIN NUMBER OF PATIENTS TO STAY IN BUSINESS. >> DO YOU EVEN SEE THAT CHANGING THOUGH BECAUSE THAT'S A PROBLEM, IS THAT THEY HAVE SUCH A SMALL AMOUNT OF TIME, THEY CAN'T REALLY LIKE -- THAT'S WHY THEY HAVE TO LIKE TAKE THE PAPER AND DO THE TEST AND STUFF LIKE THAT? >> YEAH, I MEAN, I THINK IT'S HARD. WE'RE IN AN EVOLUTIONARY PROCESS HERE, AND HOPEFULLY WITH CHANGES IN OBAMACARE THAT REALLY BRING UP THE NEED FOR PREVENTIVE HEALTH, YOU CANNOT PROVIDE PREVENTIVE HEALTH IF YOU'RE NOT LISTENING TO THE PARTICIPANTS. WHY ARE THEY EATING? WHY ARE THEY SMOKING? YOU HAVE TO GET TO THAT. YOU HAVE TO SPEND TIME KIND OF GETTING TO KNOW THE PATIENT, AS WE GET TO KNOW OUR PARTICIPANTS. I MEAN, TEN YEARS OF DOING THAT I THINK ONE OF THE REASONS THE STUDY IS SUCCESSFUL IS THAT THE STAFF GETS TO KNOW THE PARTICIPANTS. WHO LIKES WHAT, WHO HAD A GRAND KID, WHOSE HUSBAND DIED, WE GET TO KNOW THEM AT THAT LEVEL. SO THEY ARE WILLING TO SHARE. BUT THAT'S NOT SOMETHING THAT THEY ARE GOING TO DO IF WE HAVE IT'S 11 MINUTES. IT COULD BE 5 MINUTES. WHEN WE ASK PEOPLE TO GET N I GO TO THE DOCTOR.T UNDRESSED THEY WERE LIKE, WHAT'S GOING ON HERE? FOR A PHYSICAL EXAM, YOU NEED TO HAVE YOUR CLOTHES OFF. HERE'S A GOWN. PUT IT ON WITH IT OPEN TO THE BACK. THAT WAS A WHOLE NEW CONCEPT TO THEM. BECAUSE THE DOCTOR JUST LISTENS THROUGH MY CLOTHING. YEAH, I DON'T KNOW WHEN I WENT TO MEDICAL SCHOOL WE DIDN'T DO IT LIKE THAT, BUT I'M OLD, SO THAT'S -- YOU KNOW, IT'S A NEW WAVE WITH YOU YOUNG PEOPLE. >> ANY OTHER QUESTIONS? >> I REALIZE THAT YOU'RE NOT GH YOUR STUDY BUT YOU DID MENTION ABOUT NEIGHBORHOODS CHANGING AND I WAS WONDERING IF YOU HAD ANY, I DON'T KNOW, IF YOU NOTICED ANY TRENDS IN THE HEALTH OF PEOPLE THAT DID STICK AROUND AFTER THEIR NEIGHBORHOOD WAS, YOU KNOW, CHANGED? >> YEAH, WE HAVE PROBABLY TWO NEIGHBORHOODS, AND I THINK WE DON'T HAVE ENOUGH DATA TO REALLY CALL THAT -- ONE OF THE NEIGHBORHOODS, RESERVOIR HILL, CHANGED DRAMATICALLY IN TERMS OF BEING REVITALIZED. WHEN WE WERE IN RESERVOIR HILL THERE WERE LOTS OF SORT OF BUILDINGS THAT WERE SORT OF HALF TORN DOWN AND LOTS OF BOARDED UP, I TOOK A LOT OF PICTURES IN THE NEIGHBORHOOD. BUT NOW WHEN YOU GO BACK TO THE RESERVOIR HILL AREA, WE CAN'T EVEN PARK IN RESERVOIR HILL BECAUSE THEY'VE GOT THESE BEAUTIFUL NEW REFURBISHED BUILDINGS, AND SO I'LL BE ANXIOUS WHEN WE HAVE RESERVOIR HILL COME BACK THIS TIME. WE HAVEN'T DONE THEM AGAIN FOR THIS WAVE OF THE STUDY. FOR THE PEOPLE WHO STILL ARE THERE, WHAT'S HAPPENED WITH THEIR HEALTH. THEY HAVE -- WE'VE GONE TO THEIR NEIGHBORHOOD ASSOCIATION MEETINGS, TO HEAR WHAT THE PLANS FROM THE CITY WERE AND PRIVATE DEVELOPERS, IT'S BEEN DRAMATICALLY CHANGED. AND THAT'S WONDERFUL TO SEE. AND PERHAPS IN RESERVOIR HILL WE WILL SEE SOME IMPROVEMENT IN HEALTH, IMPROVEMENT IN ACTIVITY LEVEL, ONE THING WE WOULD MEASURE, SMOKING, IN OUR COHORTS ALMOST 50% OF THE COHORTS SMOKE. IN THE UNITED STATES, ONLY ABOUT 19.9 TO 20% OF THE POPULATION SMOKES. SO WE HAVE A LOT OF BAD HEALTH BEHAVIORS AND SO THOSE ARE THE KINDS OF THINGS WE WOULD LIKE TO SEE, DOES THAT CHANGE WHEN YOUR NEIGHBORHOOD ENVIRONMENT IMPROVES. THE PROBLEM IN BALTIMORE THAT WE'RE FINDING NOW IS THAT ALTHOUGH THERE'S SOME IMPROVEMENT IN SOME PHYSICAL HOUSING STATUS, THE CRIME RATE IS SOARING. AND SO WE ARE ALSO LOOKING AT CRIME, AND THE ENVIRONMENT OF CRIME, AND WHAT THAT INFLUENCE IS ON HEALTH AS WELL. BECAUSE THE CRIME RATE CERTAINLY HAS IMPACTED US BECAUSE SOME OF THE PLACES THAT WE WOULD GO, THIS TIME OF YEAR WE SHOULD BE AT PIMLICO RACETRACK BUT WE COULDN'T GO BECAUSE THEY FOUND A FEW TOO MANY DEAD BODIES AT THE EDGE OF THE RACETRACK OF PIMLICO, MAYBE WE SHOULDN'T GO BECAUSE IT WAS IN THE MIDDLE OF A GANG TURF WAR. SO WE THEN ARE BUSING PARTICIPANTS FROM THAT NEIGHBORHOOD TO US, WE PARKED THERE EVERY TIME WE'VE BEEN IN THAT AREA OF THE CITY BUT IT'S JUST A LITTLE TOO DANGEROUS FOR US TO BE THERE. >> I REALLY FIND YOUR RESEARCH RATHER FASCINATING. SO TO THE LAST QUESTION, DO YOU FIND WITH THE PLACES THAT ARE BEING SORT OF REFURBISHED SO TO SPEAK, ARE THERE PRIMARY RESIDENCES, ARE THEY BEING ALLOWED TO LIVE THERE, CAN THEY AFFORD TO LIVE THERE? I DON'T KNOW IF THAT'S -- >> THAT'S A BIG FIGHT. NO, THAT'S ONE REASON WHY WE GO TO THE COMMUNITY MEETINGS, AND THIS HAPPENS TO BLACKS AND WHITES, WHEN SOME OF THE REFURBISHMENTS OF NEIGHBORHOODS WAS HAPPENING, PEOPLE WHO LIVED THERE FOR YEARS AND YEARS WERE BEING EDGED OUT. THAT ALSO HAS HAPPENED. THAT'S ONE THING THAT'S SORT OF DISPERSED OUR POPULATION. SOME HAVE LEFT BALTIMORE, SO WE ALSO THEN HAVE PEOPLE WHO NOW TRAVEL TO SEE PARTICIPANTS WHO HAVE LEFT BALTIMORE BECAUSE THEY FELT PUSHED OUT. SOME HAVE PUSHED OUT JUST TO SORT OF SURROUNDING NEIGHBORHOODS, BUT SOME HAVE JUST SAID, WELL, I'M JUST GETTING OUT OF HERE COMPLETELY. AND, YOU KNOW, LIVING IN NORTH CAROLINA, LIVING IN WASHINGTON STATE, AND SO, YEAH, THAT IS HAPPENING. THAT HAD BEEN A FOCAL DISCUSSION AT MANY OF THE VERY EARLY COMMUNITY MEETINGS THAT WE WENT TO, BECAUSE PEOPLE FELT AS THOUGH THEY WERE BEING PUSHED OUT OF THEIR OWN NEIGHBORHOODS. >> LASTLY IN TERMS OF CONCEPTUAL MODELS, IT'S GREAT BECAUSE THERE'S ALL THESE DIFFERENT COMPONENTS BUT WHEN IT COMES TO INTERVENTIONS, IT'S VERY FOCUSED ON ONE THING. ARE THERE LIKE ALSO MOVEMENTS WHERE IT'S IF WE WANT TO DO COLLABORATIVE RESEARCH IS INTEREST COLLABORATIVE INTERVENTIONS BECAUSE PEOPLE DON'T LIVE IN ISOLATED STATES, LIKE PEOPLE WHO ARE POOR, SICK AND POOR, NOT JUST POOR, AND SO LIKE IF YOU JUST FOCUS ON LIKE ONE OF THESE THINGS I DON'T KNOW IF YOU CAN SPEAK TO THAT, ARE THERE MOVEMENTS TOWARDS THIS OR -- >> WELL, YOU KNOW, I THINK THERE ARE LOTS OF GROUPS THAT ARE INTERESTED IN COMMUNITY-BASED PARTICIPATORY RESEARCH, THAT REALLY INVOLVE THE COMMUNITY MEMBERS DIRECTLY IN THE RESEARCH, AND THEN ALSO IN WAYS TO IMPROVE ON SOME OF THE FINDINGS. AND SO THAT'S SOMETHING THAT WE'RE CERTAINLY INTERESTED IN. WE'VE HAD A COMMUNITY ADVISORY BOARD. WE HAVE FOCUS GROUPS WITH PARTICIPANTS TO FIND OUT WHAT THEY LIKE ABOUT THE STUDY, WHAT THEY DON'T LIKE ABOUT THE STUDY. WE TRY TO COMMUNICATE OUR FINDINGS TO THEM SO THEY KNOW WHAT'S GOING ON. BUT THAT WOULD BE LIKE A WHOLE OTHER STUDY. YOU KNOW, I'M SORT OF NOT IN A POSITION TO THEN ALSO NOW LET'S HAVE A COMMUNITY-BASED PARTICIPATORY RESEARCH EFFORT ON X, MAYBE IT'S PHYSICAL ACTIVITY, MAYBE IT'S SMOKING INTERVENTION, THERE'S A NUMBER OF THINGS I COULD THINK OF, BUT, YES, THERE ARE SOME THINGS THAT PARTICULARLY IN TERMS OF BEHAVIOR WOULD BE RIGHT FOR THAT KIND OF RESEAR >> OKAY. WELL, LET'S THANK ONCE AGAIN DR. EVANS. [APPLAUSE]