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Subclinical Disease and Precipitation of Acute Events

• Clarify further the relationships of measures of subclinical atherosclerosis with cardiovascular disease risk factors and CVD.

• Expand population studies and epidemiological techniques to identify factors associated with the precipitation of acute events.

• Elucidate the relationships among thrombosis, platelet function, inflammation, and CVD risk.

Non-invasive imaging techniques, including carotid and aortic ultrasound, echocardiography, electrocardiography (ECG), magnetic resonance imaging, retinal photography and computed tomographic measurement of coronary calcium are incorporated into several large cohort studies of individuals and families of different geographic, age, sex, and racial groups. Results from these measurements provide increased ability to evaluate the status of subclinical cardiovascular disease, its association with CVD risk factors, and precipitating factors for development of overt disease. A variety of investigator-initiated studies are using many of these techniques, including endothelial function measures in the existing Framingham and CHS cohorts (Benjamin, Crouse) and ongoing studies in the Muscatine cohort (Lauer, Mahoney, Davis). Institute-initiated studies including ARIC, CHS, Framingham, Jackson, and MESA measure a variety of risk factors such as smoking, blood pressure, inflammation (CRP, WBC, fibrinogen, Factor VIII) and other precipitants of acute events. MESA is specifically designed to study precipitation of acute events and includes a range of measures of subclinical disease and its progression to overt heart disease and stroke endpoints. Relationships among thrombosis, platelet function, inflammation and CVD risk factors are being evaluated in ARIC, CHS, Framingham and other studies.

Investigator-Initiated Studies

Arterial Endothelial Function - An Epidemiologic Study (Ronald Lauer, PI)
Brachial Artery Vasoreactivity and Incident CHD (John Crouse, PI)
Carotid Artery Follow-up Study (John Crouse, PI)
Coronary Artery Calcium, Exercise Tests, and CHD Outcome (Ming Wei, PI)
Coronary Screening in a High Risk Subset (Robert Detrano, PI)
CT Vascular Calcium - An Epidemiology Study in the Young (Larry Mahoney, PI)
CVD Risk Factors and Brain Morphology in NHLBI Twins (Dorit Carmelli,PI)
Determinants of Coronary Heart Disease in High Risk Families (Lewis Becker, PI)
Early Natural History of Arteriosclerosis: Bogalusa Heart Study (Gerald Berenson, PI)
Endothelial Vasomotor Function in Framingham Study (Emilia Benjamin, PI)
Epidemiology of Carotid Artery Atherosclerosis in Youth (Patricia Davis, PI)
Epidemiology of Carotid Artery Disease in Older Adults (Kim Sutton-Tyrrell, PI)
Epidemiology of Coronary Calcification in the Elderly (Anne Newman, PI)
Epidemiology of Impaired Coagulant Balance in Diabetes (Russell Tracy, PI)
Genetic Epidemiology of Coronary Artery Disease (Charles Sing, PI)
Inflammation Markers over Time in Cardiovascular Disease (Russell Tracy, PI)
Inter-associations of Vascular Disease: Structure and Function (John Crouse, PI)
Intimal Thickening and Antioxidants in Hispanics and Anglos (James Dwyer, PI)
Modifiable Risk Factors for Sudden Death in Women (Christine Albert, PI)
Novel Hemostatic Risk Factors in Framingham (Murray Mittleman, PI)
Polyunsaturated Fats and Risk of Primary Cardiac Arrest (David Siscovick, PI)
Proarrhythmic Medicines and Primary Cardiac Arrest (David Siscovick, PI)
Subclinical Heart Disease in Insulin-Dependent Diabetes (Marian Rewers, PI)
Thrombosis Markers over Time in Cardiovascular Disease (Mary Cushman, PI)
Thrombogenic Factors and Recurrent Coronary Events (Arthur Moss, PI)

Institute-Initiated Studies

Atherosclerosis Risk in Communities Study (ARIC)
Cardiovascular Health Study (CHS)
Family Heart Study
Framingham Heart Study
Jackson Heart Study
Multi-Ethnic Study of Atherosclerosis (MESA)
Strong Heart Study

Distributions and Trends in Cardiovascular Disease

• Expand population studies to monitor heart failure, cardiomyopathies, and vascular disease of the kidney, and enhance knowledge on their etiology and prevention.

• Measure morbidity, disability, and mortality to major CVD in the US and compare with data from other countries, giving special emphasis to lifestyle, geographic, socioeconomic and racial and ethnic differences.

• Enhance knowledge concerning the distributions, trends, and determinants of CVD risk factors in populations.

Several investigator-initiated studies of coronary disease, congestive heart failure and renal disease will add to the body or research in terms of secular trends, morbidity, mortality, and health care utilization (Barker, Luepker, Roger, Shahar). Others investigate trends, distribution and determinants of CVD risk factors in a variety of populations and age groups (Austin, Carmelli, Stern). Investigator-initiated studies of hypertension (Bunker, Cooper, Rotimi) provide comparisons of hypertension incidence and prevalence among blacks living in rural West Africa, the Caribbean and the United States. A variety of Institute-initiated studies, including the Jackson Heart Study and CHS, are conducting research on etiology and prevention of heart failure, cardiomyopathies, and vascular diseases of the kidney. The ARIC Study includes community surveillance of morbidity and mortality in addition to the study of CVD risk factors. The National Longitudinal Mortality Study has analyzed socioeconomic, demographic and occupational differences in mortality within the United States and has compared mortality from ischemic heart disease and stroke among several European countries and the United States based on type of occupation. The WHO MONICA Project (monitoring trends and determinants in cardiovascular diseases) measured trends in survival and coronary event rates to changes in coronary heart disease mortality in across 37 populations in 21 countries. The Strong Heart Study has collected CVD morbidity and mortality data in geographically diverse groups of American Indians.

Investigator-Initiated Studies

Antihypertensive Medications, MI and Stroke (Bruce Psaty, PI)
Clinical Course of Coronary Heart Disease in Blacks (Richard Cooper, PI)
Community Surveillance of Congestive Heart Failure (Eyal Shahar, PI)
Community Surveillance of Cardiovascular Disease (Russell Luepker, PI)
Congestive Heart Failure Trends in the Elderly 1970-1994 (William Barker, PI)
Coronary Disease Morbidity and Mortality in a Population (Veronique Roger, PI)
CVD Risk Factors and Brain Morphology in Twins (Dorit Carmelli, PI)
Diabetes and Cardiovascular Risk in Mexico City (Michael Stern, PI)
Epidemic Hypertension in Nigerian Workers (Clareann Bunker, PI)
Gene-Diet Interactions and Heart Disease (Costa Rica) (Hannia Campos, PI)
Genetic Epidemiology of Coronary Artery Disease (Charles Sing, PI)
Genetics of Hypertension in Blacks (Richard Cooper, PI)
Genetics of CHD Factors in Japanese Americans (Melissa Austin, PI)
Glucose Tolerance and Risk for CVD in the Elderly (J. David Curb, PI)
HERITAGE Study: Genetics, Exercise and Risk Factors (Claude Bouchard, Arthur Leon, D.C. Rao, James Skinner, Jack Wilmore, PIs)
Hypertension in Populations of West African Origin (Richard Cooper, PI)
Hypertension in Families of African Origin (Charles Rotimi, PI)
Incidence of Diabetes and CVD in Mexican Americans (Michael Stern, PI)
Lp(a), Homocysteine and CVD Risk in End Stage Renal Disease (Joseph Longnecker, PI)
Molecular Epidemiology of Essential Hypertension (Eric Boerwinkle, PI)
Prevalence of Asymptomatic Ventricular Dysfunction (Joel Simon, PI)
Risk Factors for Congestive Heart Failure in Women (Claudia Chae, PI)
Serum Ascorbate and Coronary Risk in NHANES II (Joel Simon, PI)
Statistical Methods for Longitudinal Data (Margaret Pepe, PI)
The Prevalence of Asymptomatic Ventricular Dysfunction (Richard Rodeheffer, PI)
Variability in Outcomes for Congenital Heart Disease (Kathy Jenkins, PI)

Institute-Initiated Studies

Atherosclerosis Risk in Communities Study (ARIC)
Cardiovascular Health Study (CHS)
Framingham Heart Study
Insulin Resistance and Atherosclerosis Study (IRAS)
Jacksort Heart Study
Multi-Ethnic Study of Atherosclerosis (MESA)
National Longitudinal Mortality Study (NLMS)
Strong Heart Study
WHO MONICA Project

Environmental and Genetic Factors

• Enhance knowledge of environmental and genetic factors that account for differences in key risk factors among US racial and ethnic groups.

• Further examine genetic influences on host susceptibility to CVD and interactions of genetic factors with environmental determinants of CVD.

• Clarify the role of environmental and genetic factors in the development of CVD risk in young adults.

Investigator-initiated genetic studies of CVD risk factors cover a range of molecular, and family-based investigations of CVD and its risk factors (Becker, Bouchard, Moss). Gene-environment interactions are examined in several studies of diet and physical activity in relation to genetic factors (Bouchard, Campos, Kamboh). Determination of the extent and mechanisms by which cardiovascular diseases cluster in families are important goals of the Family Heart Study, the Framingham Heart Study and Jackson Heart Study. The Iron Overload and Hemochromatosis Study will evaluate the ethical, legal and social implications of genetic screening for this disorder in approximately 100,000 individuals, and will search for new genetic variants contributing to hemochromatosis. The Bogalusa and CARDIA studies of children and young adults address a host of environmental, lifestyle, and genetic contributors to the development of cardiovascular disease risk factors. The Bogalusa cohort is currently being used in a genome-wide scan to identify genes influencing the development of cardiovascular disease in young people and to develop statistical methods for examining genetic influences on longitudinal changes in CVD risk factors.

Investigator-Initiated Studies

Adolescent Risk Factors and Young Adult Cardiac Risk (Julia Steinberger, PI)
CVD Risk Factors and Brain Morphology in Twins (Dorit Carmelli, PI)
Determinants of Coronary Disease in High Risk Families (Lewis Becker, PI)
Diabetes and Cardiovascular Risk in Mexico City (Michael Stern, PI)
Early Natural History of Arteriosclerosis - Bogalusa Heart Study (Gerald Berenson, PI)
Epidemiology of Vitamin E and Carotenoids in Young Adults (David Jacobs, PI)
Epidemiology of Cardiac Development in Youth (Darwin Labarthe, PI)
Gene Mapping for Quantitative Traits (George Vogler, PI)
Gene-Diet Interactions and Heart Disease (Hannia Campos, PI)
Genetic Epidemiology of Blood Lipids and Obesity (Sue Kimm, PI)
Genetic Epidemiology of Hypertriglyceridemia (Melissa Austin, PI)
Genetic Epidemiology of Elevated Apo B Levels (Gail Jarvik, PI)
Genetic Epidemiology: Development of Cardiovascular Risk (Hermine Maes, PI)
Genetic Epidemiology of Lipoprotein-Lipid Levels (Mohammad Kamboh, PI)
Genetics of CHD Factors in Japanese Americans (Melissa Austin, PI)
Genetics of CVD Risk Factors in Samoans (Mohammad Kamboh, PI)
Genetics of Hypertension in Blacks (Richard Cooper, PI)
HERITAGE Study - Genetics, Exercise, and Risk Factors (Claude Bouchard, Arthur Leon, James Skinner, D.C. Rao, Jack Wilmore, PIs)
Hypertension in Families of African Origin (Charles Rotimi, PI)
Incidence of Diabetes and CVD in Mexican Americans (Michael Stern, PI)
Insulin and Blood Pressure Change during Adolescence (Alan Sinaiko, PI)
IRAS Family Study: Genetics of Insulin Resistance (Richard Bergman, Donald Bowden, Steven Haffner, Marian Rewers, Mohammed Saad, Lynne Wagenknecht, PIs)
Long QT Syndrome: Genetic Studies (Arthur Moss, PI)
Long QT Syndrome: Population, Genetic, and Cardiac Studies (Arthur Moss, PI)
Molecular Epidemiology of Essential Hypertension (Eric Boerwinkle, PI)
Mutations, HRT, and Venous Thromboembolism (Bruce Psaty, PI)
Plasma Homocysteine Distribution in the US (Jacob Selhub, PI)
Risk of Vascular Disease in CBS Heterozygotes (Warren Kruger, PI)
Visceral Fat, Metabolic Rate and CHD Risk in Young Adults (Stephen Sidney, PI)

Institute-Initiated Studies

Atherosclerosis Risk in Communities Study (ARIC)
Cardiovascular Health Study (CHS)
Coronary Artery Disease Risk Development in Young Adults (CARDIA)
Framingham Heart Study
Family Heart Study
Insulin Resistance and Atherosclerosis Study (IRAS)
Iron Overload and Hemochromatosis Study
Jackson Heart Study
Multi-Ethnic Study of Atherosclerosis (MESA)
Strong Heart Study

Development of CVD Risk Factors Throughout the Lifespan

• Clarify the determinants of blood pressure increases and other risk factors changes from childhood through adult ages for both sexes.

• Clarify the determinants of obesity and body fat distribution in childhood and their effects on cardiovascular risk factors and CVD throughout life.

• Clarify determinants of increases in blood pressure, especially systolic blood pressure with age and the relationship of blood pressure to vascular disease.

• Expand understanding of determinants of weight gain and obesity from childhood through the adult life-span.

Obesity is a major determinant of several other cardiovascular risk factors, but the relationships among obesity and other risk factors appear to differ by age and ethnic group. Investigator-initiated studies of childhood precursors to CHD (Berenson, Davis, Lauer), and studies of intra- abdominal fat and its relationship to the development of CHD provide a range of approaches to studying CVD risk factors in the young (Sidney). The interrelationships of obesity, blood pressure, and other risk factors have been examined in numerous studies that have focused on different life stages, from pre-adolescence (for example, in the NGHS) to old age (for example, in CHS), and among different ethnic groups, including Japanese Americans (Honolulu Heart Program) and African-Americans (CARDIA, ARIC, and the Jackson Heart Study). Aging-related trends in obesity and other risk factors have also been studied in longitudinal studies, clarifying how early risk factor status may influence risk factors and disease later in life.

Investigator-Initiated Studies

Adolescent Risk Factors and Young Adult Cardiac Disease (Julia Steinberger, PI)
Ambulatory Blood Pressure and Job Stress in Nurses (Iris Goldstein, PI)
Antecedents of Hypertension: Role of Race and Stress (Frank Treiber, PI)
Antecedents of Type A Behavior Pattern (Karen Matthews, PI)
Arterial Endothelial Function - An Epidemiologic Study (Ronald Lauer, PI)
Biobehavioral Determinants of Obesity in Black Women (Robert Klesges, PI)
Blood Pressure Control in Juveniles - Longitudinal Study (John Pratt, PI)
Central Obesity and Disease Risk in Japanese Americans (Wilfred Fujimoto, PI)
CT Vascular Calcium - An Epidemiology Study in the Young (Larry Mahoney, PI)
Early Natural History of Arteriosclerosis: Bogalusa Heart Study (Gerald Berenson, PI)
Energy Balance in Young Black and White NGHS Women (Sue Kimm, PI)
Epidemiology of Vitamin E and Carotenoids in Young Adults (David Jacobs, PI)
Epidemiology of Carotid Artery Atherosclerosis in Youth (Patricia Davis, PI)
Food and Exercise Habits in Framingham Offspring (Curt Ellison, PI)
Genetic Epidemiology of Blood Lipids and Obesity (Sue Kimm, PI)
Insulin and Blood Pressure Change During Adolescence (Alan Sinaiko, PI)
Intersalt - International Study (Jeremiah Stamler, PI)
Lifestyle and Chronic Disease in College Alumni (Ralph Paffenbarger, PI)
Meta-Analysis of Post-Smoking Cessation Weight Gain (Leslie Robinson, PI)
NHLBI Growth and Health Study (Stephen Daniels, George Schreiber, Bruce Barton, Zi Sabry, PIs)
Plasma Homocysteine Distribution in the US (Jacob Selhub, PI)
Psychosocial Factors and Cardiovascular Disease (Thomas Pickering, PI)
Risk Factors in Early Human Atherogenesis (Frederick Cornhill, Alex McMahan, Jack Strong, Renu Virmani, Robert Wissler, PIs)
Visceral Fat, Metabolic Rate and CHD Risk in Young Adults (Stephen Sidney, PI)

Institute-Initiated Studies

Atherosclerosis Risk in Communities Study (ARIC)
Cardiovascular Health Study (CHS)
Coronary Artery Disease Risk Development in Young Adults (CARDIA)
Family Heart Study
Jackson Heart Study
National Health and Nutrition Examination Survey (NHANES)
Strong Heart Study

CVD in Women

• Clarify further the interrelationships of lifestyles, hormone metabolism, and psychosocial factors in the development of CVD among women.

Major findings on the development of coronary heart disease in women, its progression and the effect of a variety of hormone replacement regimens come from investigator-initiated studies such as the Healthy Women's Study (Kuller, Matthews), a study of coronary heart disease risk factors in women as they progress through menopause, and from the Nurse's Health Study (Manson), which followed over 120,000 nurses for over 20 years to evaluate the effects of a variety of lifestyle and behavioral factors associated with development of coronary heart disease risk factors and disease endpoints. The Women's Pooling Project combines data collected over the past 40 years from long term, community-based studies in the United States in order to examine health issues in women that cannot be adequately addressed in a single study. Institute-initiated studies including ARIC, Framingham, CHS, Strong Heart have analyzed data on a variety of risk factors and hormone therapies in women. In middle-aged groups, the ARIC study has found that the established CHD risk factors are more predictive of coronary heart disease in women than in men.

Investigator-Initiated Studies

Biobehavioral Determinants of Obesity in Black Women (Robert Klesges, PI)
CVD Risk, Behavioral Stress and Reproductive Hormones (Karen Matthews, PI)
CVD Risk and Health in Postmenopausal Phytoestrogen Users (Donna Kritz-Silverstein, PI)
DHEAS and CVD Risk in Middle-Aged Men and Women (John McKinlay, PI)
Drug Therapy Effect on Reinfarction Risk in Women (Susan Heckbert, PI)
Epidemiology of Cardiovascular Risk Factors in Women (Lewis Kuller, PI)
Estrogen Replacement and CVD Outcomes in Diabetic Women (Katherine Newton, PI)
Modifiable Risk Factors for Sudden Death in Men and Women (Christine Albert, PI)
Mutations, HRT, and Venous Thromboembolism (Bruce Psaty, PI)
Myocardial Infarction and Current Oral Contraceptive Use (Lynn Rosenberg, PI)
Postmenopausal Progestins, MI and Stroke (Bruce Psaty, PI)
Risk Factors for Congestive Heart Failure in Women (Claudia Chae, PI)
Risk Factors for CVD in Women (Nurses' Health Study) (JoAnne Manson, PI)
The Women's Pooling Project (Lori Mosca, PI)

Institute-Initiated Studies

Atherosclerosis Risk in Communities Study (ARIC)
Cardiovascular Health Study (CHS)
Coronary Artery Risk Development in Young Adults Study (CARDIA)
Framingham Heart Study
Insulin Resistance and Atherosclerosis Study (IRAS)
Jackson Heart Study
Multi-Ethnic Study of Atherosclerosis (MESA)
Strong Heart Study

CVD in Older Individuals

• Enhance understanding of the determinants and precursors of CVD in older individuals.

Investigator-initiated studies of elderly cohorts cover a range of subclinical assessments of clinical cardiovascular disease risk factors (Carmelli, Curb, Nelson). One study following a previously recruited cohort of the Systolic Hypertension in the Elderly Program examines the prevalence and prognostic value of subclinical atherosclerosis in this cohort and a cohort of normotensive controls (Sutton-Tyrrell). The Institute-sponsored Framingham cohort was established in 1948 and provides 50 years of follow-up on the development and progression of CVD risk factors. As cohorts of these major studies age, progression of subclinical to clinical CVD can be followed from middle age into old age. The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of risk factors for the development and progression of coronary heart disease and stroke in adults over the age of 65 years. CHS has shown that in persons without evidence of clinical disease at baseline, subclinical disease was frequent and increased the risk of incident cardiovascular disease death and non-fatal myocardial infarction.

Investigator-Initiated Studies

Brachial Artery Vasoreactivity and Incident CHD (John Crouse, PI)
Congestive Heart Failure Trends in the Elderly (William Barker, PI)
CVD Risk and Brain Morphology in Twins (Dorit Carmelli, PI)
Endothelial Vasomotor Function in the Framingham Study (Emilia Benjamin, PI)
Epidemiology of Carotid Artery Disease in Older Adults (Kim Sutton-Tyrrell, PI)
Epidemiology of Coronary Calcification in the Elderly (Anne Newman, PI)
Genetic Epidemiology of Coronary Artery Disease (Charles Sing, PI)
Genetics of CHD Factors in Japanese Americans (Melissa Austin, PI)
Glucose Tolerance and Risk for CVD in the Elderly (J. David Curb, PI)
Homocysteine, Vitamin Status, and CVD Risk (Stephen Schwartz, PI)
Honolulu Heart Program: Study of Stroke and Dementia (James Nelson, PI)
Lifestyle and Chronic Disease in College Alumni (Ralph Paffenbarger, PI)
Molecular Epidemiology of Essential Hypertension (Eric Boerwinkle, PI)
Sociodemographic Regulation of CV Function and Structure (Frank Treiber, PI)
Thrombosis Markers over Time in Cardiovascular Disease (Mary Cushman, PI)

Institute-Initiated Studies

Atherosclerosis Risk in Communities Study (ARIC)
Cardiovascular Health Study (CHS)
Family Heart Study
Framingham Heart Study
Insulin Resistance and Atherosclerosis Study (IRAS)
Jackson Heart Study
Multi-Ethnic Study of Atherosclerosis (MESA)
National Health and Nutrition Examination Survey (NHANES)
Strong Heart Study

Socioeconomic Status, Psychosocial Factors, and CVD Risk

• Further clarify the relation between socioeconomic status and CVD risk.

• Incorporate cultural assessment techniques into cardiovascular studies.

• Define the relationship of psychosocial factors to variations in CVD risk factors and development of atherosclerosis.

Investigator-initiated studies of hypertension among blacks in rural West Africa, the Caribbean and the United States incorporate assessment of cultural and lifestyle factors which may contribute to risk factors for hypertension (Cooper). Such measures are also included in the San Antonio Heart Study (Stern). Psychosocial factors are a major focus of several investigator-initiated studies of hypertension, CVD, and women (Klesges, Matthews, Pickering). The National Longitudinal Mortality Study examines the relationship of mortality to socioeconomic status within a wide range of demographic (regional, gender, racial, ethnic) subgroups. All major Institute-initiated studies incorporate measures of psychosocial factors and socioeconomic status, such as hostility, stress, depression, education, income, discrimination, and social support, which are examined in relation to cardiovascular disease outcomes.

Investigator-Initiated Studies

Ambulatory Blood Pressure and Job Stress in Nurses (Iris Goldstein, PI)
Antecedents of Type A Behavior Pattern (Karen Matthews, PI)
Biobehavioral Determinants of Obesity in Black Women (Robert Klesges, PI)
Clinical Course of Coronary Heart Disease in Blacks (Richard Cooper, PI)
CVD Risk, Behavioral Stress and Reproductive Hormones (Karen Matthews, PI)
Diabetes and Cardiovascular Risk in Mexican Americans (Michael Stern, PI)
Early Natural History of Arteriosclerosis - Bogalusa Heart Study (Gerald Berenson, PI)
Epidemiology of Vitamin E and Carotenoids in Young Adults (David Jacobs, PI)
Genetics of Hypertension in Blacks (Richard Cooper, PI)
Hypertension in Populations of West African Origin (Richard Cooper, PI)
Incidence of Diabetes and CVD in Mexican Americans (Michael Stern, PI)
Lifestyle and Chronic Disease in College Alumni (Ralph Paffenbarger, PI)
Psychosocial Factors and Cardiovascular Disease (Thomas Pickering, PI)
Sociodemographic Regulation of CV Function and Structure (Frank Treiber, PI)

Institute-Initiated Studies

Atherosclerosis Risk in Communities (ARIC)
Cardiovascular Health Study (CHS)
Coronary Artery Risk Development in Young Adults Study (CARDIA)
Family Heart Study
Framingham Heart Study
Jackson Heart Study
Multi-Ethnic Study of Atherosclerosis (MESA)
National Health and Nutrition Examination Survey (NHANES)
National Longitudinal Mortality Study (NLMS)
Strong Heart Study

Physical Activity and Nutrition

• Enhance knowledge of the role of physical activity in reducing CVD and its complications.

• Further evaluate nutritional components that influence CVD risk factors and the development of atherosclerosis.

The goal of the investigator-initiated HERITAGE Study is to document the role of the genotype in the cardiovascular and metabolic responses to aerobic exercise-training, and the contribution of inherited factors in the changes brought about by regular exercise for several diabetes and cardiovascular disease risk factors. A long-term study of over 57,000 alumni from Harvard and the University of Pennsylvania has shown that taking up moderate physical activity is associated with a lower risk of developing coronary heart disease. Investigator-initiated studies address a variety of dietary and nutritional factors which may play a role in the development of cardiovascular disease risk factors and atherosclerosis. These include evaluation of dietary patterns and nutrient intake and their relationship with CVD risk factors such as blood pressure, BMI, lipid levels, and homocysteine. (Avins, Longnecker, Millen, Selhub, Siscovick). All major Institute-initiated studies collect data on physical activity associated with both work and leisure and evaluate these data with relationship to CVD risk factors. In the ARIC study, white men in the highest quartile of physical activity had an approximately one-third lower risk of developing hypertension. Nutrition histories are incorporated in all of the Institute-initiated prospective studies on development of cardiovascular disease. The Framingham, ARIC and CARDIA studies have made significant contributions to understanding the relationship between folate status, homocysteine levels, and CVD risk.

Investigator-Initiated Studies

Children's Activities and Nutrition (Frank Treiber, PI)
Coronary Artery Calcium, Exercise Tests, and CHD Outcome (Ming Wei, PI)
Diet, Insulin Resistance and Cardiovascular Risk (Elizabeth Meyer-Davis)
Diet and Activity in Mexican American and Anglo Children (Philip Nader, PI)
Dietary Etiologies of Heart Disease and Cancer (Walter Willett, PI)
Dietary Patterns and Risk of CVD (Frank Hu, PI)
Energy Balance in Young Black and White Women (Sue Kimm, PI)
Epidemiologic Studies of Dietary Fiber and Blood Pressure (Jiang He, PI)
Food and Exercise Habits in Framingham Offspring (R. Curt Ellison, PI)
Framingham Nutrition Studies (Barbara Millen)
Gene-Diet Interaction and CHD (Hannia Campos)
HERITAGE Study: Genetics, Exercise and Risk Factors (Claude Bouchard, Arthur Leon, D.C. Rao, James Skinner, Jack Wilmore, PIs)
INTERMAP - Macronutrients and Blood Pressure (Jeremiah Stamler, PI)
Lifestyle and Chronic Disease in College Alumni (Ralph Paffenbarger, PI)
LP(a), Homocysteine and CVD Risk Factors in End Stage Renal Disease (Joseph Longnecker, PI)
Physical Activity and Cardiovascular Disease Prevention (Joan Dorn, PI)
Plasma Homocysteine Distribution in the U.S. (Jacob Selhub, PI)
Polyunsaturated Fats and the Risk of Primary Cardiac Arrest (David Siscovick, PI)
Prospective Study of Diet and CVD (Jiang He, PI)
Re-evaluating Triglycerides in CHD (Andrew Avins, PI)
Relationship Between Sodium Intake and BP Control (Mark Espeland, PI)
Risk Factors for CVD in Women (Nurse's Health Study) (Joanne Manson)

Institute-Initiated Studies

Atherosclerosis Risk in Communities (ARIC)
Cardiovascular Health Study (CHS)
Coronary Artery Risk Development in Young Adults Study (CARDIA)
Family Heart Study
Framingham Heart Study
Insulin Resistance and Atherosclerosis Study (IRAS)
Jackson Heart Study
National Health and Nutrition Examination Survey (NHANES)
Strong Heart Study

Diabetes, Insulin, Obesity and Glucose Metabolism

• Clarify relationships among diabetes, insulin, obesity and glucose metabolism and the related risks of CVD in different populations.

All of the current large population studies are investigating one or more aspects of the relationships of diabetes and glucose intolerance to the risk of cardiovascular diseases including CHD, stroke, peripheral vascular disease and congestive heart failure. Several investigator-initiated studies have examined this issue including the HERITAGE Study and the San Antonio Heart Study. The relationship of insulin, insulin resistance and obesity as both independent factors and as possible mediators of the glucose-CVD relationship has been investigated in IRAS, ARIC, Framingham and CHS. These studies have shown that diabetes is a powerful risk factor for incident events, particularly in women. In the absence of diabetes, fasting insulin and glucose levels appear to be associated with both subclinical atherosclerosis measured by ultrasound and incident. There are differences in the strength of these associations among racial and ethnic groups with the strongest associations found in non-Hispanic whites and the weakest associations among African Americans.

Investigator-Initiated Studies

Diabetes and Cardiovascular Risk in Mexican Americans (Michael Stern, PI)
Diet, Insulin Resistance and Cardiovascular Risk (Elizabeth Mayer-Davis, PI)
Epidemiological Study of CVD in People with Type I Diabetes (Ronald Klein, PI)
Epidemiology of Impaired Coagulant Balance in Diabetes (Russell Tracy, PI)
Estrogen Replacement and CVD Outcomes in Diabetic Women (Katherine Newton, PI)
Genetics of CHD Risk Factors in Japanese Americans (Melissa Austin, PI)
Glucose Tolerance and Risk for CVD in the Elderly ( J. David Curb, PI)
HERITAGE Study: Genetics, Exercise and Risk Factors (Claude Bouchard, Arthur Leon, D.C. Rao, James Skinner, Jack Wilmore, PIs)
Incidence of Diabetes and CVD in Mexican Americans (Michael Stern, PI)
IRAS Family Study: Genetics of Insulin Resistance (Richard Bergman, Donald Bowden, Steven Haffner, Marian Rewers, Mohammed Saad, Lynne Wagenknecht, PIs)
Subclinical Heart Disease in Insulin-Dependent Diabetes (Marian Rewers, PI)
Visceral Fat, Metabolic Rate and CVD in Young Adults (Stephen Sidney, PI)

Institute-Initiated Studies

Atherosclerosis Risk in Communities Study (ARIC)
Cardiovascular Health Study (CHS)
Coronary Artery Risk Development in Young Adults Study (CARDIA)
Family Heart Study
Framingham Heart Study
Insulin Resistance and Atherosclerosis Study (IRAS)
Jackson Heart Study
Multi-Ethnic Study of Atherosclerosis (MESA)
National Health and Nutrition Examination Survey (NHANES)
Strong Heart Study

Technical Resources

• Develop technical resources for continuing effective population studies of CVD epidemiology and prevention.

Several investigator-initiated studies promote the development of statistical, data collection, and research methodologies to extend and evaluate the use of innovative methods in longitudinal studies (Barnhart, Cai, Joffe, Pepe, Rosner). Phase I and II Small Business and Innovative Research (SBIR) grants support the development of software and surveys related to cardiovascular disease research (Goldstein, Smith). Institute-initiated studies adapt and refine a variety of data collection and management tools for use on a population basis including subclinical disease imaging, case-control methodology, and statistical genetic software. Computer-aided software is used to read and synthesize physiological measurements from such varied techniques as ultrasound, spirometry, ECGs; when developed with contract support, these methods become freely available. Study manuals and forms are also available from contract-supported studies and many are posted on Internet sites such as those for Framingham (http://www.nhlbi.nih.gov/about/framingham/index.htm).

Investigator-Initiated Studies

A Self-Scored CVD Risk Appraisal (Kevin Smith, PI)
Analysis of Longitudinal Cardiopulmonary Data (Bernard Rosner, PI)
Brachial Artery Vasoreactivity and Incident CHD (John Crouse, PI)
Methods for Estimating Casual Effects in Longitudinal Studies (Marshall Joffee, PI)
Quality Assurance System for Radiology Reporting (Peter Haug, PI)
Statistical Methods for Longitudinal Data (Margaret Pepe)
Statistical Problems in Multivariate Survival Analysis (Jianwen Cai, PI)
Statistical Methods for Randomly Repeated Measures (Huiman Barnhart, PI)
WINCATI Software Tool for Survey Research (Robert Goldstein, PI)

Institute-Initiated Studies

Atherosclerosis Risk in Communities Study (ARIC)
Cardiovascular Health Study (CHS)
Coronary Artery Risk Development in Young Adults Study (CARDIA)
Family Heart Study
Framingham Heart Study
Insulin Resistance and Atherosclerosis Study (IRAS)
Jackson Heart Study
Multi-Ethnic Study of Atherosclerosis (MESA)
Strong Heart Study

Research Training

• Overcome critical shortages in the training of individuals qualified to pursue needed research in epidemiology and prevention of CVD.

NHLBI funds Institutional training grant programs on cardiovascular disease epidemiology and biostatistics. Areas of emphasis include traditional cardiovascular disease epidemiology and methods, biostatistics and statistical genetics. There are also training opportunities within Institute-initiated programs. The Jackson Heart study addresses the shortage of minority investigators trained in epidemiology by providing training at the high school, undergraduate and graduate levels during the school year and through intensive summer training opportunities. The Framingham Study, Cardiovascular Health Study and MESA provide opportunities for fellows or graduate students be part of the study operations. In conjunction with the American Heart Association, the Institute sponsors a ten-day program which provides an intensive introduction to epidemiology, biometry and preventive cardiology for health professionals. Two Institute-sponsored meetings on training programs and an Institute committee have provided valuable input and recommendations on ways to improve the training programs, match training to current scientific needs and identify ways to provide cross-training among more than one discipline. Further information about these programs can be obtained from the following website: http://www.nhlbi.nih.gov/funding/training/epi-bio/index.htm.

Cardiovascular Epidemiology and Biostatistics Training Programs:

Brigham and Women's Hospital
Case Western Reserve University (Genetic Epidemiology)
Johns Hopkins University
Stanford University
University of Minnesota
University of North Carolina at Chapel Hill (Biostatistics)
University of North Carolina at Chapel Hill (Cardiovascular Epidemiology)
University of Pittsburgh
University of Washington (Biostatistics)
University of Washington (Cardiovascular Epidemiology)
Ten-day Training Workshop in Cardiovascular Epidemiology

Recent Career Development Awards:

Adolescent Risk Factors and Young Adult Cardiac Risk (Julia Steinberger, PI)
Clinical Index to Predict Survival in Heart Failure (Keith Aaronson, PI)
Is There Sex Bias in Use of Coronary Angiography? (Candice Wong, PI)
Lp(a) Homocysteine and Cardiovascular Risk in End Stage Renal Disease (Joseph Longnecker, PI)
Modifiable Risk Factors for Sudden Death in Men and Women (Christine Albert, PI)
Risk Factors for Congestive Heart Failure in Women (Claudia Chae, PI)
Thrombosis Markers Over Tim in Cardiovascular Disease (Mary Cushman)
Variability in Outcomes for Congenital Heart Disease (Kathy Jenkins, PI)
Women's Pooling Project (Lori Mosca, PI)

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