Collaborative Prospective Studies of Cardiovascular Disease Nathan D. Wong, PhD Professor and...

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Transcript of Collaborative Prospective Studies of Cardiovascular Disease Nathan D. Wong, PhD Professor and...

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  • Collaborative Prospective Studies of Cardiovascular Disease Nathan D. Wong, PhD Professor and Director Heart Disease Prevention Program, Division of Cardiology
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  • Objectives Understand the design and structure of the major ongoing NIH and CDC-supported prospective epidemiologic studies of cardiovascular disease Understand opportunities for research projects and collaboration for residents, cardiology fellows, and faculty.
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  • Framingham Heart Study Longest running study of cardiovascular disease in the world Began in 1948 with original cohort of 5,209 subjects aged 30-62 at baseline Biennial examinations, still ongoing, most of original cohort deceased Offspring cohort of 5,124 of children of original cohort enrolled in 1971, and more recently and still being enrolled to better understand genetic components of CVD risk are up to 3,500 grandchildren of the original cohort. Routine surveillance of cardiovascular disease events adjudicated by panel of physicians
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  • Measurements Standard risk factors since inception of study, except HDL-C began around 1970. Serial ECGs (first to document high rate of unrecognized MIs) M-mode echocardiograms in 1980s, first large study to show prognostic importance of increased LV mass Newer measures done in subsets include: Carotid ultrasound, bone denistometry, coronary artery calcium, and other novel risk factors and biomarkers (e.g. natriuretic peptides)
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  • Framingham Most Significant Milestones 1960 Cigarette smoking found to increase the risk of heart disease 1961 Cholesterol level, blood pressure, and electrocardiogram abnormalities found to increase the risk of heart disease 1967 Physical activity found to reduce the risk of heart disease and obesity to increase the risk of heart disease 1970 High blood pressure found to increase the risk of stroke 1976 Menopause found to increase the risk of heart disease 1978 Psychosocial factors found to affect heart disease 1988 High levels of HDL cholesterol found to reduce risk of death 1994 Enlarged left ventricle (one of two lower chambers of the heart) shown to increase the risk of stroke 1996 Progression from hypertension to heart failure described
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  • Smoking Statement Issued in 1956 by American Heart Association It is the belief of the committee that much greater knowledge is needed before any conclusions can be drawn concerning relationships between smoking and death rates from coronary heart disease. The acquisition of such knowledge may well require the use of techniques and research methods that have not hitherto been applied to this problem. Circulation 1960; vol. 23 ___________________________________________________________ ____________________________________________________________ ___________________________________________________________
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  • CHD Risk by Cigarette Smoking. Filter Vs. Non-filter. Framingham Study. Men
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  • 9 Doubts about cholesterol as late as 1989
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  • 4-Year Follow-up, The Framingham Study LDL-Cholesterol Morbidity Ratio: 25 mg/dl 55 mg/dl 85 mg/dl WB Kannel Am Heart J. 1985;110:1100-1107. Relative Risk of CHD by HDL and LDL- Cholesterol Men 50-70 Years of Age Framingham Study
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  • Risk factors for long-term coronary prognosis after initial myocardial infarction: the Framingham Study. Wong ND, Cupples LA, Ostfeld AM, Levy D, Kannel WB. Am J Epidemiol. 1989 Sep;130(3):469-80. Links Wong NDCupples LAOstfeld AMLevy DKannel WB Age-adjusted analyses showed the risk of reinfarction to be positively associated with blood pressure and serum cholesterol. Risk of coronary death was strongly associated with blood sugar level, systolic blood pressure, serum cholesterol, heart rate, diabetes, and interim reinfarction. In multivariable analyses, systolic pressure, serum cholesterol, and diabetes were predictive of reinfarction; relative weight was inversely associated with reinfarction. Systolic pressure, serum cholesterol, and the prevalence of diabetes persisted as independent predictors of coronary death. When adjustments were made for the effects of these variables, women were at only half the risk of coronary death compared with men.
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  • Lifetime Risk of CHD Increases with Serum Cholesterol Framingham Study: Subjects age 40 years DM Lloyd-Jones et al Arch Intern Med 2003; 1966-1972 34 44 57 19 29 33 Cholesterol ___________________________________________________________________________ _______________________________________________________________________________
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  • CK Friedberg on Hypertension: Diseases of the Heart 1996 There is a lack of correlation in most cases between the severity and duration of hypertension and development of cardiac complications. ___________________________________________________________ ________________________________________________________ _______________________________________________________________
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  • Relation of Non-Hypertensive Blood Pressure to Cardiovascular Disease Vasan R, et al. N Engl J Med 2001; 345:1291-1297 10-year Age- Adjusted Cumulative Incidence Hazard Ratio* SBPWomenMen
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  • Risk of Myocardial Infarction with Isolated Systolic Hypertension Framingham Study 24 Yr. Follow-Up Annual Incidence Per 10,000 WB Kannel Prev Cardiol 1998; 1:32-39 Men ages 45-54 yrs.
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  • Joint Influences of SBP and Pulse Pressure on CHD Risk Franklin SS et al. Circulation. 1999;100:354-360. Franklin SS.Wong ND et al, Circulation 1999
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  • Franklin SS, Lopez VA, Wong ND, et al. Single Versus Combined Blood Pressure Components and Risk for Cardiovascular Disease. The Framingham Heart Study. Circulation Jan 2009 BACKGROUND: -The utility of single versus combined blood pressure (BP) components in predicting cardiovascular disease (CVD) events is not established. We compared systolic BP (SBP) and diastolic BP (DBP) versus pulse pressure (PP) and mean arterial pressure (MAP) combined and each of these 4 BP components alone in predicting CVD events. Methods and Results-In participants in the original (n=4760) and offspring (n=4897) Framingham Heart Study who were free of CVD events and BP-lowering therapy, 1439 CVD events occurred over serial 4-year intervals from 1952 to 2001. In pooled logistic regression with the use of BP categories, combining SBP with DBP and PP with MAP improved model fit compared with individual BP components (P
  • Incidence and Progression of Coronary Calcium (mean 2.4 years between scans): Multiethnic Study of Atherosclerosis (n=5570) (Wong et al., AHA 2006) P
  • Prevalence of AAC (>0), CAC (>0), ABI ( 1mm) by Age in Men (Wong et al., AHA 2006) P
  • Prevalence of AAC (>0), CAC (>0), ABI ( 1mm) by Age in Women (Wong et al., AHA 2006) P
  • Prevalence of CAC, Increased CIMT, and Low ABI by Presence of AAC Men (Wong et al., AHA 2006) Prevalence of CAC >0, CCA-IMT or ICA-IMT >1mm, or ABI
  • Prevalence of CAC, Increased CIMT, and Low ABI by Presence of AAC Women (Wong et al., AHA 2006) Prevalence of CAC >0, CCA-IMT or ICA-IMT >1mm, or ABI