Framingham Heart Study, Cardiovascular Health Study (CHS), Coronary Artery Risk Development in Young Adults (CARDIA), and Other Population Based Research Projects

Wong ND, Pio JR, Franklin SS, L'Italien GJ, Kamath TV, Williams GR. ; Larson MG; Levy D.
Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome.
Am J Cardiol. 2003 Jun 15;91(12):1421-6. Unique ID: 12804727.
Abstract: We estimated the coronary heart disease (CHD) events that are preventable by treatment of lipids and blood pressure in patients with metabolic syndrome (MetS), a contributor to coronary heart disease (CHD). Among patients aged 30 to 74 years (without diabetes or CHD) in the United States, MetS was defined by National Cholesterol Education Program criteria. CHD events over a period of 10 years were estimated by Framingham algorithms. Events that could be prevented by statistically "controlling" blood pressure, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol to either normal or optimal levels according to national guidelines were calculated. Of 7.5 million men and 9.0 million women aged 30 to 74 years with MetS, approximately 1.5 million men and 0.45 million women, if untreated, developed CHD events in 10 years. In men and women, blood pressure control to normal levels "prevented" 28.1% and 12.5% of CHD events, respectively (p <0.01); control to optimal levels resulted in preventing 28.2% and 45.2% of events, respectively (p <0.01). Control of HDL cholesterol to normal levels resulted in preventing 25.3% of events in men and 27.3% in women; optimal control prevented 51.2% and 50.6% of events, respectively. Control of LDL cholesterol to normal levels prevented 9.3% of events in men and 9.8% of events in women; control to optimal levels prevented 46.2% and 38.1% of events (p <0.05), respectively. Control of all 3 risk factors to normal levels resulted in preventing 51.3% of events for men and 42.6% for women; control to optimal levels resulted in preventing 80.5% and 82.1% of events, respectively. Thus, many CHD events in patients with MetS may be preventable by nominal or optimal control of lipids and/or blood pressure.
Wong ND, Thakral G, Franklin SS, L'Italien GJ, Jacobs MJ, Whyte JL, Lapuerta P.
Preventing heart disease by controlling hypertension: impact of hypertensive subtype, stage, age, and sex.
Am Heart J. 2003 May;145(5):888-95. Unique ID: 12766749.
Abstract: BACKGROUND: Hypertension is related to significant morbidity and mortality rates from coronary heart disease (CHD). This report examines the relative and absolute impact on risk for CHD by controlling hypertension to high normal and optimal levels. METHODS: Among all subjects with untreated or inadequately treated hypertension in the National Health and Nutrition Examination Survey (NHANES) III who were 30 to 74 years of age and without prior CHD, the 10-year risk of CHD was calculated. With the use of sampling weights, the number of CHD events by age group, hypertension subtype (isolated diastolic hypertension [IDH], systolic-diastolic hypertension [SDH], and isolated systolic hypertension [ISH]), and stage of hypertension was estimated. Risk was recalculated and the number of events reestimated, assuming a reduction in blood pressure (BP) to high normal and optimal levels. The number and proportion (population-attributable risk, or PAR%) of events that could be prevented were determined from the differences in events and risk between uncontrolled and controlled BP levels. Derived from this was the number of persons needing treatment per CHD event prevented. RESULTS: Control of hypertension to high normal levels could prevent approximately one fifth (PAR 19%) of CHD events in men and one third (PAR = 31%) of CHD events in women, whereas control to optimal levels may prevent 37% and 56% of CHD events, respectively (P <.01 for differences between men and women). Of CHD events that could be prevented, the greatest proportion occurred from controlling BP among older persons, men, and those with stage 1 hypertension (vs stages 2 and 3) or with ISH (vs IDH or SDH). The number of persons with hypertension needing treatment to prevent one CHD event ranged from 20.5 in men to 38.6 in women when controlled to high normal BP and 10.7 in men and 21.3 in women when controlled to optimal BP. CONCLUSIONS: The greatest impact from control of hypertension occurs in older persons, men, and those with ISH, whereas the greatest PAR% occurred in women. Optimal control of BP could prevent more than one third of CHD events in men and more than half of events in women. Greater efforts to control hypertension in these populations may have a substantial impact in preventing CHD events.

Wong ND, Pio J, Valencia R, Thakal G.
Distribution of C-reactive protein and its relation to risk factors and coronary heart disease risk estimation in the National Health and Nutrition Examination Survey (NHANES) III.
Prev Cardiol. 2001 Summer;4(3):109-114. Unique ID: 11828186.
Abstract: The authors examined the distribution of, and risk factors associated with, the inflammatory marker C-reactive protein (CRP) among a large sample of non-institutionalized American adults aged 30-74 years of age, and its relation to estimated 10-year coronary heart disease risk. The population studied comprised 4472 men and 5212 women aged 30-74 years, without coronary heart disease, who had CRP measurements in the Third National Health and Nutrition Examination Survey (NHANES III). The 10-year risk of coronary heart disease was estimated from Framingham risk factor algorithms among those with CRP levels of less-than-or-equal0.21 mg/dL, >0.21 to <0.5mg/dL, 0.5 to <1.0 mg/dL, and greater-than-or-equal1.0 mg/dL. Mean (SD) levels of CRP were 0.41 (0.64) mg/dL in men and 0.55 (0.91) mg/dL in women. Levels of at least 1 mg/dL were measured in 6.4% of men and 12.9% of women. CRP levels were highest among non-Hispanic black men and Mexican-American women. According to multiple logistic regression analysis, cigarette smoking and increased age, body mass index, and systolic blood pressure in men, and body mass index and diabetes in women, were strongly associated with a greater likelihood of CRP levels of greater-than-or-equal1.0 mg/dL (p<0.001). Among persons with CRP levels of less-than-or-equal0.21 mg/dL, >0.21 to <0.5 mg/dL, 0.5 to <1.0 mg/dL and greater-than-or-equal1.0 mg/dL, the 10-year estimated risk of coronary heart disease were 13.4%, 17.6%, 19.6%, and 21.1% among men, respectively, and 2.7%, 3.6%, 4.1% and 4.3% among women, respectively (both p<0.001 across CRP categories); higher risks across CRP groups were also found among ethnic/gender subgroups. CRP remained a significant predictor of coronary heart disease risk in unadjusted and age-adjusted analyses. Conclusion. Elevation of CRP is associated with several major coronary heart disease risk factors and with unadjusted and age-adjusted projections of 10-year coronary heart disease risk in both men and women. (c)2001 CHF, Inc. Presented at the Fifth International Conference on Preventive Cardiology, Osaka, Japan, May, 2001.

Franklin SS, Jacobs MJ, Wong ND, L'Italien GJ, Lapuerta P.
Predominance of isolated systolic hypertension among middle-aged and elderly US hypertensives: analysis based on National Health and Nutrition Examination Survey (NHANES) III.
Hypertension. 2001 Mar;37(3):869-74. Unique ID: 11244010.
Abstract: The purpose of the present study was to examine patterns of systolic and diastolic hypertension by age in the nationally representative National Health and Nutrition Examination Survey (NHANES) III and to determine when treatment and control efforts should be recommended. Percentage distribution of 3 blood pressure subtypes (isolated systolic hypertension, combined systolic/diastolic hypertension, and isolated diastolic hypertension) was categorized for uncontrolled hypertension (untreated and inadequately treated) in 2 age groups (ages <50 and >/=50 years). Overall, isolated systolic hypertension was the most frequent subtype of uncontrolled hypertension (65%). Most subjects with hypertension (74%) were >/=50 years of age, and of this untreated older group, nearly all (94%) were accurately staged by systolic blood pressure alone, in contrast to subjects in the untreated younger group, who were best staged by diastolic blood pressure. Furthermore, most subjects (80%) in the older untreated and the inadequately treated groups had isolated systolic hypertension and required a greater reduction in systolic blood pressure than in the younger groups (-13.3 and -16.5 mm Hg versus -6.8 and -6.1 mm Hg, respectively; P:=0.0001) to attain a systolic blood pressure treatment goal of <140 mm Hg. Contrary to previous perceptions, isolated systolic hypertension was the majority subtype of uncontrolled hypertension in subjects of ages 50 to 59 years, comprised 87% frequency for subjects in the sixth decade of life, and required greater reduction in systolic blood pressure in these subjects to reach treatment goal compared with subjects in the younger group. Better awareness of this middle-aged and older high-risk group and more aggressive antihypertensive therapy are necessary to address this treatment gap.

Franklin SS, Larson MG, Khan SA, Wong ND, Leip EP, Kannel WB, Levy D.
Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study.
Circulation. 2001 Mar 6;103(9):1188-90. Circulation. 2001 Nov 27;104(22):E128-9. Unique ID: 11238268.
Abstract:BACKGROUND: We examined the relative importance of diastolic (DBP), systolic (SBP) and pulse pressure (PP) as predictors of coronary heart disease (CHD) risk in different age groups of Framingham Heart Study participants. METHODS AND RESULTS: We studied 3060 men and 3479 women between 20 and 79 years of age who were free of CHD and were not on antihypertensive drug therapy at baseline. Cox regression adjusted for age, sex, and other risk factors was used to assess the relations of BP indexes to CHD risk over a 20-year follow-up. In the group <50 years of age, DBP was the strongest predictor of CHD risk (hazard ratio [HR] per 10 mm Hg increment, 1.34; 95% CI, 1.18 to 1.51) rather than SBP (HR, 1.14; 95% CI, 1.06 to 1.24) or PP (HR, 1.02; 95% CI, 0.89 to 1.17). In the group 50 to 59 years of age, risks were comparable for all 3 BP indexes. In the older age group, the strongest predictor of CHD risk was PP (HR, 1.24; 95% CI, 1.16 to 1.33). When both SBP and DBP were considered jointly, the former was directly and the latter was inversely related to CHD risk in the oldest age group CONCLUSIONS: With increasing age, there was a gradual shift from DBP to SBP and then to PP as predictors of CHD risk. In patients <50 years of age, DBP was the strongest predictor. Age 50 to 59 years was a transition period when all 3 BP indexes were comparable predictors, and from 60 years of age on, DBP was negatively related to CHD risk so that PP became superior to SBP.

Franklin SS; Khan SA; Wong ND; Larson MG; Levy D.
Is pulse pressure useful in predicting risk for coronary heart Disease? The Framingham heart study.
Circulation, 1999 Jul 27, 100(4):354-60. Unique ID: 99350763.
Abstract: BACKGROUND: Current definitions of hypertension are based on levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), but not on pulse pressure (PP). We examined whether PP adds useful information for predicting coronary heart disease (CHD) in the population-based Framingham Heart Study. METHODS AND RESULTS: We studied 1924 men and women between 50 and 79 years of age at baseline with no clinical evidence of CHD and not taking antihypertensive drug therapy. Cox regression, adjusted for age, sex, and other risk factors, was used to assess the relations between blood pressure components and CHD risk over a 20-year follow-up. The association with CHD risk was positive for SBP, DBP, and PP, considering each pressure individually; of the 3, PP yielded the largest chi(2) statistic. When SBP and DBP were jointly entered into the multivariable model, the association with CHD risk was positive for SBP (HR, 1.22; 95% CI, 1.15 to 1.30) and negative for DBP (HR, 0. 86; 95% CI, 0.75 to 0.98). Four subgroups were defined according to SBP levels (<120, 120 to 139, 140 to 159, and >/=160 mm Hg). Within each subgroup, the association with CHD risk was negative for DBP and positive for PP. A cross-classification of SBP-DBP levels confirmed these results. CONCLUSIONS: In the middle-aged and elderly, CHD risk increased with lower DBP at any level of SBP>/=120 mm Hg, suggesting that higher PP was an important component of risk. Neither SBP nor DBP was superior to PP in predicting CHD risk.
Franklin SS; Gustin W IV; Wong ND; Larson MG; Weber MA; Kannel WB; Levy D.
Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study.
Circulation, 1997 Jul 1, 96(1):308-15. (UI: 97379651)
Abstract: BACKGROUND: We attempted to characterize age-related changes in blood pressure in both normotensive and untreated hypertensive subjects in a population-based cohort from the original Framingham Heart Study and to infer underlying hemodynamic mechanisms. METHODS AND RESULTS: A total of 2036 participants were divided into four groups according to their systolic blood pressure (SBP) at biennial examination 10, 11, or 12. After excluding subjects receiving antihypertensive drug therapy, up to 30 years of data on normotensive and untreated hypertensive subjects from biennial examinations 2 through 16 were used. Regressions of blood pressure versus age within individual subjects produced slope and curvature estimates that were compared with the use of ANOVA among the four SBP groups. There was a linear rise in SBP from age 30 through 84 years and concurrent increases in diastolic blood pressure (DBP) and mean arterial pressure (MAP); after age 50 to 60 years, DBP declined, pulse pressure (PP) rose steeply, and MAP reached an asymptote. Neither the fall in DBP nor the rise in PP was influenced significantly by removal of subsequent deaths and subjects with nonfatal myocardial infarction or heart failure. Age-related linear increases in SBP, PP, and MAP, as well as the early rise and late fall in DBP, were greatest for subjects with the highest baseline SBP; this represents a divergent rather than parallel tracking pattern. CONCLUSIONS: The late fall in DBP after age 60 years, associated with a continual rise in SBP, cannot be explained by "burned out" diastolic hypertension or by "selective survivorship" but is consistent with increased large artery stiffness. Higher SBP, left untreated, may accelerate large artery stiffness and thus perpetuate a vicious cycle.
Wong ND; Gardin JM; Kurosaki T; Anton-Culver H; Sidney S; Roseman J; Gidding S.
Echocardiographic left ventricular systolic function and volumes in young adults: distribution and factors influencing variability.
American Heart Journal, 1995 Mar, 129(3):571-7. (UI: 95177026)
Pub type: Journal Article; Multicenter Study.
Abstract: Low left ventricular ejection fraction (LVEF), a measure of global systolic left ventricular dysfunction, is associated with an increased risk of recurrent coronary events or death in persons with cardiac disease. There are few data on the distribution of resting LVEF and component volumes in healthy young adults or on any association of LVEF with coronary risk factors. LVEF and left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV, respectively) were measured by two-dimensional echocardiography in 1782 men and women 23 to 35 years old without self-reported heart disease (other than mitral valve prolapse, n = 53) who were participants in the multicenter Coronary Artery Risk Development in Young Adults study. Factors analyzed as potential contributors to LVEF, LVEDV, and LVESV included age, gender, race, blood pressure, alcohol use, current smoking, family history of myocardial infarction, total and high-density lipoprotein cholesterol concentrations, obesity, reported physical activity, and fitness as assessed by treadmill exercise testing. LVEF was lower in men (mean 62.6% SD 5.7%) than in women (mean 63.9%, SD 5.7%) (p < 0.01) but did not differ significantly between black and white subjects. Ninety percent of subjects had an LVEF between 53% and 71%. LVEDV and LVESV were > 25% greater in men than in women. From multivariate analysis, male gender, history of hypertension, and current smoking were each positively and independently associated with an approximately 1% lower LVEF. Body surface area, a family history of premature myocardial infarction, and treadmill workload 150 time were positively related, whereas total skinfold thickness was negatively related to LVEDV and LVESV.(ABSTRACT TRUNCATED AT 250 WORDS)

Bild DE; Fitzpatrick A; Fried LP; Wong ND; Haan MN; Lyles M; Bovill E; Polak JF; Schulz R.
Age-related trends in cardiovascular morbidity and physical functioning in the elderly: the Cardiovascular Health Study.
Journal of the American Geriatrics Society, 1993 Oct, 41(10):1047-56.(UI: 94014054)
Abstract: OBJECTIVE: To describe relationships between age and sub-clinical cardiovascular disease, manifest chronic disease, and physical functioning and limitations among persons aged 65 years and older, with emphasis on the "oldest old," those 85 years and older. DESIGN: Observational population-based study. SETTING: Four U.S. communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. PARTICIPANTS: 5,201 men and women aged 65 years and older. MEASUREMENTS: Demographic data; histories of cardiovascular disease (CVD), chronic lung disease, arthritis, diabetes, and hypertension; measures of subclinical disease including arm and ankle blood pressures, internal carotid wall thickness and stenosis, ejection fraction, left ventricular mass, fractional shortening, and diastolic function, electrocardiographic left ventricular hypertrophy and cardiac injury score, forced expiratory flow and volume; functional status including self-reported physical functioning, hearing and sight limitations and health status, and performance-based measures of function. These variables were examined among men and women in three age groups: 65-74 years, 75-84 years, and 85 + years. Subgroups of participants with and without manifest CVD were also examined. MAIN RESULTS: In women, the prevalence of CVD and other chronic conditions increased with age, and the highest rates occurred among those 85 years and older. In men, prevalence rates increased between the two younger groups, but the oldest group had lower than expected rates for coronary heart disease, cerebrovascular disease, hypertension, and chronic lung disease. In contrast, there were strong age-related linear trends in most of the subclinical measures of blood pressure, atherosclerosis and pulmonary function and in virtually all measures of functional status in both gender groups across the age range. There was a particularly marked decline in functional status between the two older age groups. While subclinical disease was greater and functional status was poorer among those with manifest CVD, with few exceptions, age-related trends were not significantly different between the two groups. CONCLUSIONS: Lower than expected prevalence rates of CVD among those aged 85 years and older, particularly among men, in this study of community-dwelling elderly may represent selection bias or a real plateauing in disease prevalence with age. However, subclinical disease appears to increase and functional status to decline across the age range in both men and women regardless of the presence of CVD. The apparent increase in subclinical disease with age indicates potential for CVD prevention after age 65.

Cupples LA; Gagnon DR; Wong ND; Ostfeld AM; Kannel WB.
Preexisting cardiovascular conditions and long-term prognosis after initial myocardial infarction: the Framingham Study.
American Heart Journal, 1993 Mar, 125(3):863-72. (UI: 93175312)
Abstract: Preexisting cardiovascular conditions (angina pectoris, intermittent claudication, stroke or transient ischemic attack, and congestive heart failure) were evaluated in relation to long-term prognosis after an initial MI in 828 subjects from the Framingham Heart Study. Preexisting angina pectoris and intermittent claudication in men were associated with increased risk of coronary mortality and recurrent MI, whereas congestive heart failure increased coronary mortality. In women, prior angina pectoris increased the risk of recurrent MI and congestive heart failure increased the coronary mortality. Adjusting for the major cardiovascular risk factors measured before MI, these results held for men but no significant adverse effects persisted in women. Among subjects who survived to return for subsequent examinations, only prior congestive heart failure in men increased the risk after adjusting for post-MI risk factors. In women who returned, angina pectoris and intermittent claudication were associated with poor post-MI prognosis. These results suggest that atherosclerosis is a diffuse disease of the circulatory system, and one in which post-MI prognosis is influenced by the presence of other preexisting cardiovascular conditions. Hence a patient who has an MI after prior expression of cardiovascular disease requires more vigorous preventive management.

Ettinger WH; Wahl PW; Kuller LH; Bush TL; Tracy RP; Manolio TA; Borhani NO; Wong ND; O'Leary DH.
Lipoprotein lipids in older people. Results from the Cardiovascular Health Study. The CHS Collaborative Research Group [see comments].
Circulation, 1992 Sep, 86(3):858-69. (UI: 92386686)
Abstract: BACKGROUND. Cardiovascular disease is the leading cause of death and disability in older people. There is little information about the distributions of risk factors in older populations. This article describes the distribution and correlates of lipoprotein lipids in people greater than or equal to 65 years old. METHODS AND RESULTS. Lipoprotein lipid concentrations were measured in 2,106 men (M) and 2,732 women (F) who were participants in the Cardiovascular Health Study, a population-based epidemiological study. Distributions of lipids by age and sex and bivariate and multivariate relations among lipids and other variables were determined in cross-sectional analyses. Mean concentrations of lipids were cholesterol: M, 5.20 +/- 0.93 mmol/l (201 +/- 36 mg/dl) and F, 5.81 +/- 0.98 mmol/l (225 +/- 38 mg/dl); triglyceride (TG): M, 1.58 +/- 0.85 mmol/l (140 +/- 75 mg/dl) and F, 1.57 +/- 0.78 mmol/l (139 +/- 69 mg/dl); high density lipoprotein cholesterol (HDL-C): M, 1.23 +/- 0.33 mmol/l (48 +/- 16 mg/dl), and F, 1.53 +/- 0.41 mmol/l (59 +/- 16 mg/dl); low density lipoprotein cholesterol (LDL-C): M, 3.27 +/- 0.85 mmol/l (127 +/- 33 mg/dl) and F, 3.57 +/- 0.93 mmol/l (138 +/- 36 mg/dl). The total cholesterol to HDL-C ratios were M, 4.49 +/- 1.29 and F, 4.05 +/- 1.22. TG, total cholesterol, and LDL-C concentrations were lower with increasing age, the last more evident in men than in women. TG concentration was positively associated with obesity (in women), central fat patterning, glucose intolerance, use of beta-blockers (in men), and use of estrogens (in women) and negatively associated with age, renal function, alcohol use, and socioeconomic status. In general, HDL-C had opposite relations with these variables, except that estrogen use was associated with higher HDL-C concentrations. LDL-C concentration was associated with far fewer variables than the other lipids but was negatively associated with age in men and women and positively correlated with obesity and central fat patterning and negatively correlated with renal function and estrogen use in women. There were no differences in total cholesterol and LDL-C concentrations among participants with and without prevalent coronary heart disease and stroke, but TG concentration was higher and HDL-C lower in men with both coronary heart disease and stroke and in women with coronary heart disease. CONCLUSIONS. Cholesterol and cholesterol/HDL-C ratio were lower and HDL-C higher than previously reported values in older people, suggesting that lipid risk profiles may be improving in older Americans. TG and HDL-C concentrations, and to a lesser extent LDL-C, were associated with potentially important modifiable factors such as obesity, glucose intolerance, renal function, and medication use.

Gardin JM; Arnold A; Gottdiener JS; Wong ND; Fried LP; Klopfenstein HS; O'Leary DH; Tracy R; Kronmal R.
Left ventricular mass in the elderly. The Cardiovascular Health Study.
Hypertension, 1997 May, 29(5):1095-103.
Pub type: JOURNAL ARTICLE; MULTICENTER STUDY. (UI: 97293778)
Abstract: Left ventricular (LV) mass, as estimated from M-mode echocardiography (echo), has previously been shown to be an independent predictor of incident cardiovascular disease morbidity and mortality. We evaluated the relationship at baseline of echo LV mass to relevant cardiovascular disease risk factors and other potential covariates in the Cardiovascular Health Study, multicenter study sponsored by the National Heart, Lung, and Blood Institute of 5201 men and women aged 65 years or older (mean, 73). Two-dimensionally directed M-mode echo LV mass measurements could be obtained in 1357 men and 2053 women (66% of this elderly cohort). Stepwise linear regression analyses of the relationship of echo LV mass to demographic and risk factor, physical activity, electrocardiographic, and prevalent disease variables resulted in a model that explained 37% of the variance for the entire cohort. In order of decreasing importance, factors positively associated with echo LV mass were body weight, male sex, systolic pressure, presence of congestive heart failure, present smoking, major and minor electrocardiographic abnormalities, treatment for hypertension, valvular heart disease, aortic regurgitation by color Doppler, and mitral regurgitation by color Doppler (in men) whereas diastolic pressure, bioresistance (a measure of adiposity), and high-density lipoprotein cholesterol were inversely related to echo LV mass. Although height and weight were both related to LV mass, height added nothing once weight was entered in multiple linear regression analyses. Furthermore, in the multiple regression models, diastolic pressure was inversely and systolic BP positively related to LV mass, with similar magnitudes for their coefficients. In consonance with these findings, pulse pressure was positively related to LV mass in bivariate analyses. Multiple linear regression analyses explained less of the variance for ventricular septal thickness (R2 = .13) and LV posterior wall thickness (R2 = .14) than for LV mass (R2 = .37) and LV diastolic dimension (R2 = .27). Intriguing findings in the elderly Cardiovascular Health Study cohort included the presence of pulse pressure as a positive correlate, and high-density lipoprotein cholesterol as an inverse correlate, of LV mass. Longitudinal studies in the Cardiovascular Health Study cohort will help to clarify the importance of demographic, risk factor, and other variables, and changes in these variables, in predicting changes in echo LV mass and its components as well as the prognostic significance of LV mass in the elderly.
Gardin JM; Wong ND; Bommer W; Klopfenstein HS; Smith VE; Tabatznik B; Siscovick D; Lobodzinski S; Anton-Culver H; Manolio TA.
Echocardiographic design of a multicenter investigation of free-living elderly subjects: the Cardiovascular Health Study [published erratum appears in J Am Soc Echocardiogr 1992 Sep-Oct;5(5):550].
Journal of the American Society of Echocardiography, 1992 Jan-Feb, 5(1):63-72. (UI: 92153440) Pub type: Clinical Trial; Journal Article; Multicenter Study.
Abstract: The Framingham study has shown by M-mode echocardiography that left ventricular hypertrophy is a powerful, independent predictor for the development of coronary heart disease and that increased left atrial dimension has been associated with an increased risk of stroke. No previous population-based study has evaluated the risk factor correlates and predictive value for coronary heart disease and stroke of two-dimensional and Doppler, as well as M-mode, echocardiography. The Cardiovascular Health Study is a multi-year prospective epidemiologic study of 5201 men and women older than 65 recruited from four geographic sites in the United States. The main objectives of incorporating echocardiography were to determine whether echocardiographic indices, or changes in these indices, are (1) correlated with traditional risk factors for coronary heart disease and stroke; and (2) independent predictors of morbidity and mortality for coronary heart disease and stroke. Echocardiographic measurements of interest include those related to global and segmental left ventricular systolic and diastolic structure and function and left atrial size. For each subject, a baseline echocardiogram was recorded in super-VHS tape using a standard protocol and equipment. All studies were sent to a reading center where images were digitized and measurements were made using customized computer algorithms. Calculated data and images were stored on optical disks to facilitate retrieval and future comparisons in longitudinal studies. A second echocardiogram is scheduled in year 7, with a goal of determining whether changes in cardiac anatomy or function over a 5-year period are important predictors of morbidity or mortality from coronary heart disease and stroke. Quality control measures included standardized training of echocardiography technicians and readers, technician observation by a trained echocardiographer, periodic blind duplicate readings with reader review sessions, phantom studies, and quality control adults.

Wong ND; Wilson PW; Kannel WB.
Serum cholesterol as a prognostic factor after myocardial infarction: the Framingham Study [see comments].
Annals of Internal Medicine, 1991 Nov 1, 115(9):687-93. (UI: 92027249)
Abstract: OBJECTIVE: To determine the relation between serum cholesterol levels and the long-term risk for reinfarction, death from coronary heart disease, and all-cause mortality in persons who recover from myocardial infarction. DESIGN: Prospective, longitudinal study. SETTING: A geographically defined population-based cohort of adults participating in the Framingham Heart Study. PATIENTS: Men (n = 260) and women (n = 114), 33 to 88 years of age (mean age, 62 years), who had a history of myocardial infarction. MEASUREMENTS: A complete physical examination, including electrocardiographic evaluation, blood pressure measurement, height and weight measurements, determination of smoking habits, and casual determinations of blood glucose and serum cholesterol, was done approximately 1 year after recovery from initial myocardial infarction. Patients were followed after infarction for the occurrence of reinfarction or death (mean follow-up, 10.5 years; range, 0.8 to 31.6 years). MAIN RESULTS: The mean cholesterol level after infarction was 5.21 mmol/L (242.8 mg/dL); 20% of patients had levels below 5.17 mmol/L (200 mg/dL), and 22% had levels of 7.11 mmol/L (275 mg/dL) or more. Compared with patients who had cholesterol levels below 5.17 mmol/L, patients with levels of 7.11 mmol/L or more were at increased risk for reinfarction (relative risk, 3.8; 95% Cl, 1.6 to 8.7), death from coronary heart disease (relative risk, 2.6; Cl, 1.4 to 4.8), and all-cause mortality (relative risk, 1.9; Cl, 1.2 to 2.9) based on multivariate Cox regression analyses adjusted for other coronary risk factors. Intermediate cholesterol levels (5.17 mmol/L to 7.11 mmol/L) were generally not associated with increased risk. The association between elevated serum cholesterol and increased risk was strongest in men; however, elevated cholesterol levels were found to be most strongly related to death from coronary disease and to all-cause mortality in persons who were 65 years of age or more. CONCLUSIONS: Patients who have recovered from a myocardial infarction and who have high cholesterol levels are at an increased long-term risk for reinfarction, death from coronary heart disease, and all-cause mortality. Our results confirm the prognostic value of cholesterol levels measured after myocardial infarction and support the role of lipid management in this population.

Wong ND; Levy D; Kannel WB.
Prognostic significance of the electrocardiogram after Q wave myocardial infarction. The Framingham Study.
Circulation, 1990 Mar, 81(3):780-9. (UI: 90167989)
Abstract: The prognostic value of abnormalities on the electrocardiogram (ECG) present 1 year after initial myocardial infarction (MI) is examined in relation to reinfarction and coronary death throughout 32 years (mean, 10.1 years) of follow-up in the Framingham Heart Study. Resting 12-lead ECGs were available in 251 survivors (190 men and 61 women) of clinically recognized Q wave MI. The ECG reverted to normal in 31 (12.4%) cases and was abnormal but without Q waves in 37 (14.7%). Q waves persisted without other significant abnormalities in 108 (43.0%) and with other abnormalities in 75 (29.9%) cases. Electrocardiographic abnormalities at follow-up were more common in women and in those persons whose initial MI was anterior as compared with inferior. Nonspecific T wave, ST segment changes, and electrocardiographic left ventricular hypertrophy on the ECG before or after MI were powerful predictors (p less than 0.01) of coronary death. The relation of these residual post-MI electrocardiographic findings to reinfarction and coronary death was assessed by Cox regression analysis. The follow-up electrocardiographic status was unrelated to the risk of subsequent reinfarction. Subjects who lost Q wave evidence of MI but whose ECG continued to show evidence of repolarization abnormalities, left ventricular hypertrophy, or blocked intraventricular conduction were at a 3.5-fold increased risk (p less than 0.01) of coronary death as compared with those reverting to a normal ECG. Persons with a persistent Q wave MI accompanied by these abnormalities were at a 2.7-fold excess risk (p = subsequent reinfarction. Subjects who lost Q wave evidence of MI but whose ECG continued to show evidence of repolarization abnormalities, left ventricular hypertrophy, or blocked intraventricular conduction were at a 3.5-fold increased risk (p less than 0.01) of coronary death as compared with those reverting to a normal ECG. Persons with a persistent Q wave MI accompanied by these abnormalities were at a 2.7-fold excess risk (p = 0.01) of coronary death as compared with those with a normalized ECG. These findings remained significant when considering age and standard coronary risk factors. The presence of other electrocardiographic abnormalities without persistent Q waves yields a worse prognosis than a Q wave persisting alone. The prognostic value of a follow-up ECG with abnormalities other than a persistent Q wave MI also remained after considering the effects of left ventricular hypertrophy and cardiac enlargement on x-ray, functional classification, and diuretic usage. Specific electrocardiographic abnormalities present before infarction, however, were potent indicators of long-term prognosis prognosis and diminished the importance of the follow-up ECG. Although survival after initial MI is improved only if the ECG reverts to normal, information on electrocardiographic abnormalities before MI can be especially useful in evaluating long-term risk.

Last Updated Decemberb 18, 1998