Past, Present and Future of Cardiovascular Epidemiology and Prevention in the U.S.a.

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Journal of Epidemiology Vol. 6, No. 4 (Supplement) December

Past, Present and Future of Cardiovascular Epidemiology and Prevention in the U.S.A.

Millicent Higgins

Concern about rising coronary heart disease (CHD) death rates and awareness of internationaldifferences in CHD and stroke mortality led to early epidemiological studies includingFramingham Heart, Seven Countries and NI-HON-SAN studies. Elevated blood cholesterol andblood pressure, cigarette smoking and diet were identified as risk factors, predominantly in men.Clinical trials demonstrated the feasibility and efficacy of lowering risk factors throughpharmacologic and behavioral interventions. The continuing decline in CHD mortality began inthe late 1960's and is attributable to healthier lifestyles and improved medical management.Current epidemiological studies include more women and diverse populations and expandpotential risk factors and outcomes to include obesity, diabetes, hemostatic and psychosocialfactors, physical inactivity and genes, as well as markers of pre-clinical atherosclerosis, ischemia,and cardiac dysfunction.VD prevention encompasses national education programs, community interventions and highrisk approaches. In the future new insights are expected on the interplay of genetic susceptibilityand non-genetic risk and protective factors and on precipitants of clinical events. Advances intreatment and wider use of preventive measures should reduce or delay CVD especially amonglow socio-economic groups, the elderly and survivors of an event. National goals for lower ratesof CHD, stroke and risk factors have been set for the year 2000.J Epidemiol,1996 ; 6 : S203-S207.cardiovascular risk, epidemiology, prevention, trends

There have been remarkable developments in the epidemiol-ogy and prevention of cardiovascular diseases over the lastfifty years as there have been in basic science, diagnosis, andmanagement related to these conditions. I will discuss selectedexamples from past and present studies and approaches andcomment on some of the likely future directions for cardiovas-cular epidemiology and prevention in the United States.

HE PAST. 1950'S TO 1980'S.oncern about the "epidemic" of coronary heart disease

manifest in the rising death rate and frequency of sudden deathin middle aged men following the second world war stimulatedefforts to find the causes, describe the natural history anddevelop preventive approaches for CHD. Clinicians knew thathypercholesterolemia, hypertension, diabetes and hypothy-

roidism were associated with CHD in their patients, but it wasnot until 1948 when the National Heart Institute was foundedand the Framingham Heart Study was initiated that longitudi-nal population-based investigations were designed to test spe-cific hypotheses related to potential causes, to measure inci-dence, estimate risk, and describe the course of CVD.

he initial hypotheses addressed by the Framingham HeartStudy were that incidence of CHD was related to age, malesex, elevated levels of blood pressure, cholesterol and bodyweight, to tobacco smoking, diabetes mellitus, and gout 1).Physical activity and increased thyroid function were postulat-ed to be protective. Early results demonstrated associationsbetween CHD and blood pressure, cholesterol and smokingand showed that incidence rates increased as levels of theserisk factors increased throughout the range, from the lowest tothe highest levels. Early epidemiologic studies in the United

Department of Epidemiology, University of Michigan School of Public Health, Michigan, U.S.A.Address for correspondence :Millicent Higgins, Department of Epidemiology, University of Michigan School of Public Health, 109S. Observatory Street Ann Arbor Michigan, 48109 U.S.A.

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States collaborating in the Pooling project were in Albany,Chicago Western Electric Company, Chicago Peoples GasCompany, Framingham, Tecumseh, Los Angeles andMinnesota. The Pooling Project established the importance ofcholesterol, blood pressure and smoking as risk factors forwhite middle aged men 2). Since the mid 1960's multipleregression analyses have provided estimates of the probabilityof developing CHD and stroke based on composite risk factorprofiles which use information on sex, age, blood pressure,cholesterol, cigarette smoking, glucose intolerance, left ventric-ular hypertrophy, family history and prevalent heart disease.An important lesson was that several moderately elevated riskfactors increase risk as much or more than a single high riskfactor does.

nternational differences in death rates from heart diseaseand stroke had a major influence on the design and implemen-tation of epidemiological studies in the 1950's and 1960's 3).The Seven Countries Study pioneered international compar-isons of lifestyles, especially diet, and showed that fat contentof diets and serum cholesterol levels were correlated with heartdisease rates in men in ecologic analyses. Several other studiesenrolled cohorts in countries with substantially different CVDdeath rates. The NI-HON-SAN study used the opportunity pro-vided by migrants from Japan to Honolulu or San Francisco toexplore behavioral and environmental factors related to heartdisease and stroke in more genetically homogeneous popula-tions. Details of this study are presented in this volume.Comparisons with the Japanese population and with theFramingham cohort were envisaged when the Honolulu HeartProgram, the Puerto Rico and Yugoslavia studies were imple-mented, however, the latter two are no longer active.International comparisons showed that although the major riskfactors were the same, they did not account completely for thedifferences in CVD morbidity and mortality among these pop-ulations.

While it was known by the late 1960's that incidence ofCVD could be predicted for groups of people, it was not cer-tain that incidence could be reduced by lowering risk factorsthat were amenable to change. Primary prevention trials toanswer this question included the High Blood PressureDetection and Follow-up Program (HDFP) 4),The MultipleRisk Factor Intervention Trial (MRFIT) 5) and the LipidResearch Clinics Coronary Primary Prevention Trial (LRC-CPPT) 6).These randomized controlled trials enrolled thou-sands of middle-aged subjects; men and women in HDFP, menonly in MRFIT and LRC-CPPT. Endpoints were total mortali-ty, CVD and CHD deaths and nonfatal myocardial infarction.Follow-up over periods of 5 or more years showed that levelsof blood pressure, cholesterol and rates of cigarette smokingcould be reduced by hygienic measures or drug treatment, andthat end points could be reduced. The positive results of thesetrials published in the 1970's and 1980's have been major and

continuing influences on medical practice and on the behaviorof individuals. Clinical guidelines for treating high blood pres-sure and elevated levels of cholesterol through hygienic andpharmacologic means have been disseminated and accompa-nied by national education programs 7,8).he Conference on the Decline in Coronary DiseaseMortality in 1978, established the reality of the downwardtrend which began in the mid 1960's, and concluded that rea-sons for the decline were unclear though both primary preven-tion and better medical care had contributed. The conferencealso pointed out the need for new knowledge and for monitor-ing trends in mortality, morbidity and risk factors. A workinggroup on heart disease epidemiology subsequently set thedirection for the next generation of studies which were imple-mented beginning in 1984.

HE PRESENT 1984 -1996eeds and opportunities for research identified by the work-

ing group included; community surveillance to monitor trendsin incidence of fatal and nonfatal CHD and their relation tochanging risk factors; longitudinal studies of the developmentof and trends in risk factors over the entire age range; and clini-cal trials of reduced salt intake and weight reduction. Theycommented on the need for better measurements or moreinformation on physical activity, psychosocial characteristics,cigarette smoking, occupational exposures and water hardness.They also recommended studies of the quality of medical care,evaluation of interventions for CVD, as well as training pro-grams for epidemiologistsand biostatisticians.ndividual investigators initiated and continued epidemiolog-ical and prevention studies throughout the period and wereresponsible for many innovative approaches. A few examplesin addition to those mentioned above and below are the NursesHealth Study, the Minnesota Heart Survey, the Bogalusa andMuscatine Studies, the Charleston, Evans County, Worcester,and San-Antonio Heart Studies, the College Alumni and thePhysicians Health Studies.

he major new epidemiologic investigations initiated by theNational Heart Lung and Blood Institute were; CoronaryArtery Risk Development in Young Adults (CARDIA),Atherosclerosis Risk in Communities (ARIC), theCardiovascular Health Study (CHS) in people over 65 years ofage, the National Growth and Health Study, the Strong HeartStudy in American Indians, the Insulin ResistanceAtherosclerosis Study (IRAS) and most recently the FamilyHeart Study and the Family Blood Pressure Program s) Thesestudies extend studies predominantly of middle aged whitemen, to include young adults, the elderly, minority populationsand women. They, as well as studies continuing from the past,have broken new ground in detecting and confirming risk fac-tors such as lipids and lipoproteins, clotting and fibrinolytic


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factors, and the amount and distribution of body fat. Evidenceon the role of low birth weight, insulin, hyperhomocysteinemiais accruing as is information on potential protective factorsincluding vitamin E, flavonoids, other antioxidants, hormonereplacement therapy and moderate alcohol consumption. Theefficacy of aspirin for primary and secondary prevention hasbeen demonstrated for men and is under investigation inwomen.

Current or recent primary prevention trials include SystolicHypertension in the Elderly Program (SHEP), Antihyperten-sive and Lipid Lowering Treatment to Prevent Heart AttackTrial (ALLHAT), Postmenopausal Estrogen/ProgestinInterventions (PEPI), Trials of Hypertension Prevention(TOHP), Dietary Intervention Study in Children (DISC), Childand Adolescent Trial for Cardiovascular Health (CATCH),Obesity Prevention in American Indians (PATHWAYS),Dietary Approaches to Stop Hypertension (DASH), and theWomens Health Initiative (WHI)9). Information from theseand other ongoing clinical trials and epidemiologic studies hasbeen or soon will be published in the medical literature. Threecommunity-based prevention research demonstration studieswere completed recently. In the Stanford Five City Project, theMinnesota and the Pawtucket Heart Health Programs, educa-tional interventions were conducted using mass media, com-munity organizations and environmental strategies. Changes inknowledge, risk factors, morbidity and mortality were thegoals and evaluation of processes and results were essentialcomponents of these studies. Short-term benefits on CVD riskwere detected in treatment compared with control communitiesand were in addition to those experienced by the US popula-tion in general.

he earliest of the national education programs, Detection,Evaluation and Treatment of High Blood Pressure and theNational Cholesterol Education Program were initiated in 1972and 1985respectively7,8). heir countinuing success guided thenewer programs on Smoking, Obesity and Physical Activity,and the Heart Attack Alert Program which were inititatedrecently.

Major advances resulting from research in epidemiology andprevention in the present period include; increased understand-ing and recognitiuon of new CVD risk factors in general, andin previously understudied populations; use of new non-inva-sive technologies to detect and measure pre-clinical atheroscle-rosis, silent ischemia, and cardiac dysfunction; development ofcommunity surveillance and intervention strategies; anddemonstration of the efficacy of primary and secondary pre-vention approaches.

THE FUTUREecommendations for future research made in 1994 by the

Epidemiology and Prevention Task Force include for epidemi-

ology: clarifying relationships among subclinical atherosclero-sis, CVD risk factors and clinical CVD; identifying precipi-tants of acute events; and monitoring and increasing knowl-edge of etiology and prevention of heart failure, cardiomy-opathies and vascular disease of the kidney 10). he Task Forcealso recommended comparisons of CVD morbidity, disabilityand mortality in the U.S. and other countries, with assessmentof lifestyles, geographic, socioeconomic, racial and ethniccharacteristics as determinants of differences in CVD. Thereport states environmental and genetic factors influencing keyrisk factors should be identified; the interaction of gentic sus-ceptibility and environmental determinants of CVD should beinvestigated; interrelationships of lifestyles, hormone metabo-lism and psychosocial factors should be studied in women, asshould relationships of socio-economic status to CVD risk inmen and women. Observations on blood pressure, amount anddistribution of body fat are needed from childhood throughadult ages to identify determinants and effects on CVD of lev-els and changes over the life span. Research is recommendedon the determinants and precursors of CVD at older ages. Riskfactors considered in need of further study include nutritionalcomponents, physical activity, diabetes, insulin, glucosemetabolism, weight gain, obesity, thrombosis, platelet func-tion, inflammation and psychosocial factors; relationshipsbetween these and other risk factors, atherosclerosis and CVDrequire elucidation.

ecommendations for research on prevention of CVDinclude research on methods for translating knowledge aboutmodifying lifestyles and management of risk factors into pub-lic awareness, policy and practice. Specifically the Task Forcerecommended developing more effective methods for modify-ing blood lipids, preventing high blood pressure, obesity anddiabetes mellitus and eliminating smoking. Ways should befound to reduce CVD - related limitations on function andquality of life by influencing social settings and psychologicalvariables. Approaches to secondary prevention that were sug-gested involve physician education, clinical research and dis-semination of information about effective strategies againstdisease progression and death. The Task Force recommendedevaluation of interventions in older people, in women, minori-ties, groups with low socio-economic status, children and ado-lescents. They also cited needs for better understanding of eti-ology and prevention of congenital heart disease, for moreeffective methods for preventing rheumatic heart disease andfor treating Kawasaki disease.

any of these investigations are underway in ongoingobservational and intervention studies which will be presentingresults in the next several years 11).Longitudinal populationbased research studies continue to be necessary along with sur-veillance to monitor trends in prevalence, incidence and riskfactors, as well as mortality, case fatality and medical care. Thedramatic changes over time in death rates for CHD in the U.S.


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* White Male ...... Black Male*Age-adjusted Rate/100,000 Population *hi te Female - - - - Black Female*

*Nonwhite from 1950 -1959.

Figure 1. Death rates for CHD by race and sex.U.S. 1950-1994.

Reduce coronary heart disease deaths to no more than 100 per 100,000 people.Reduce stroke deaths to no more than 20 per 100,000 people.Increase to at least 50 percent the proportion of people with high blood pressure whose blood pressureis under control.Increase to at least 90 percent the proportion of people with high blood pressure who are taking actionto help control their blood pressure.Reduce the mean serum cholesterol level among adults to no more than 200 mg/dL.Reduce the prevalence of blood cholesterol levels of 240 mg/dL or greater to no more than 20 percentamong adults.Increase to at least 60 percent the proportion of adults with high blood cholesterol who are aware oftheir condition and are taking action to reduce their blood cholesterol to recommended levels.Reduce dietary fat intake to an average of 30 percent of calories or less and average saturated fatintake to less than 10 percent of calories among people aged 2 and older.Reduce overweight to a prevalence of no more than 20 percent among people aged 20 and older andno more than 15 percent among adolescents aged 12 through 19.Increase to at least 30 percent the proportion of people aged 6 and older who engage regularly,preferably daily, in light to moderate physical activity for at least 30 minutes per day.Reduce cigarette smoking to a prevalence of no more than 15 percent among people aged 20 andolder.Source: Healthy People 2000.

Figure 2. National Health Promotion and Disease Prevention Objectives.


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are shown in Figure 1. Comparable information on morbidityand a wider range of CVD is needed for the future. Studies ofeconomic costs, quality and availability of care are relativelynew directions in epidemiology and ones requiring develop-ment and testing of methods.

andomised clinical trials are needed to provide definitiveanswers about promising new preventive and therapeuticapproaches such as preventing hypertension, raising HDL-cho-lesterol and lowering homocysteine levels, and also to identifyany adverse effects of interventions which may otherwiseescape detection. Populations participating in clinical trials andcommunity interventions will be more diverse and research isneeded to enhance participation and retention of those who arehard to recruit.

n the national level, specific goals have been set in"Healthy People 2000" National Health Promotion andDiseasePrevention Objectives 12). he challenge for CHD is toreduce the death rate to no more than 100 per 100,000 people,and for stroke to reduce the death rate to no more than 20 per100,000people. Assuming recent rates of decline continue, thegoal for CHD should be attainable but the decline in strokemortality appears to be slowing down. Approaches to reachingthe objectives for CVD are indicated by the goals for reducingcholesterol, controlling high blood pressure, reducing theprevalence and initiation of cigarette smoking and reducing theprevalence of overweight by reducing dietary fat intake andincreasing physical activity. The targets for these risk factorsare shown in Figure 2. Although trends are generally encour-aging, obesity is increasing. Improvements in other risk factorshave been less in some subgroups than in others 13).his brief overview of accomplishments, opportunities andchallenges for epidemiology and prevention of CVD in theU.S.A. indicates that future improvements in cardiovascularand general health are necessary and possible if current knowl-edge and proven strategies are combined with unprecedentedopportunities to develop and apply new knowledge for thebenefit of individual patients, families and populations.

EFERENCES. Dawber T.R. The Framingham Study. 1980 Harvard

niversity Press. Cambridge, MA.. The Pooling Project Research Group. Relationship of

Blood Pressure, Serum Cholesterol, Smoking Habit,elative Weight and ECG Abnormalities to Incidence ofajor Coronary Events: Final Report of the Pooling

roject J Chron Dis 1978; 31: 201-306.3. Trends and Determinants of Coronary Heart Disease

ortality: International Comparisons. Higgins Millicent. and Luepker R.V. eds. International Journal ofpidemiology 1989: 18 (Supplement 1).

4. Hypertension Detection and Follow-up Program Co-perative Group. Five-year findings. JAMA 1979;

42:2562-2571.5. Multiple Risk Factor Intervention Trial Research Group.

ortality Rates after 10.5 Years for Participants in theultiple Risk Factor Intervention Trial. JAMA 1990;

63:1795-1801.6. The Lipid Research Clinics Program. The Lipid Research

linics Coronary Primary Prevention Trial Results.AMA 1984; 251:351-364.7. National Institutes of Health, National Heart, Lung, andlood Institute: The Fifth Report of the Joint Nationalommittee on Detection, Evaluation and Treatment ofigh Blood Pressure. NIH Publ 1993: 93-1088. 1993.

8. Expert Panel on Detection, Evaluation, and Treatment ofigh Blood Cholesterol in Adults: Summary of the sec-

nd report of the Adult Treatment Panel. JAMA 1993;69(23):3015-3023.

9. National Heart Lung and Blood Institute. Fact Book.iscal Year 1994. U.S. Department of Health and Humanervices. National Heart, Lung, and Blood Institute.ethesda, Maryland, U.S.A.10. Lenfant Claude.Task Force on Research in Epidemiologynd Prevention of Cardiovascular Diseases. Circulation994; 90 (6) : 2609-2617.

11. Lenfant Claude. Task Force on Research inpidemiology and Prevention of Caridovasculariseases. A Revisit Circulation 1996; 93: 1605-1607.

12. Healthy People 2000. Midcourse Review and 1995evisions. U.S. Department of Health and Humanervices. Public Health Service.Washington DC. USA.

13. Health United States 1995. U.S. Department of Healthnd Human Services. Public Health Service. WashingtonC. USA.

Past, Present and Future of Cardiovascular Epidemiology and Prevention in the U.S.a.

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