Robert J. Garrison

Prognostic Implications of Echocardiographically Determined Left Ventricular Mass in the Framingham Heart Study

A pattern of left ventricular hypertrophy evident on the electrocardiogram is a harbinger of morbidity and mortality from cardiovascular disease. Echocardiography permits the noninvasive determination of left ventricular mass and the examination of its role as a precursor of morbidity and mortality. We examined the relation of left ventricular mass to the incidence of cardiovascular disease, mortality from cardiovascular disease, and mortality from all causes in 3220 subjects enrolled in the Framingham Heart Study who were 40 years of age or older and free of clinically apparent cardiovascular disease, in whom left ventricular mass was determined echocardiographically. During a four-year follow-up period, there were 208 incident cardiovascular events, 37 deaths from cardiovascular disease, and 124 deaths from all causes. Left ventricular mass, determined echocardiographically, was associated with all outcome events. This relation persisted after we adjusted for age, diastolic blood pressure, pulse pressure, treatment for hypertension, cigarette smoking, diabetes, obesity, the ratio of total cholesterol to high-density lipoprotein cholesterol, and electrocardiographic evidence of left ventricular hypertrophy. In men, the risk factor-adjusted relative risk of cardiovascular disease was 1.49 for each increment of 50 g per meter in left ventricular mass corrected for the subjects height (95 percent confidence interval, 1.20 to 1.85); in women, it was 1.57 (95 percent confidence interval, 1.20 to 2.04). Left ventricular mass (corrected for height) was also associated with the incidence of death from cardiovascular disease (relative risk, 1.73 [95 percent confidence interval, 1.19 to 2.52] in men and 2.12 [95 percent confidence interval, 1.28 to 3.49] in women). Left ventricular mass (corrected for height) was associated with death from all causes (relative risk, 1.49 [95 percent confidence interval, 1.14 to 1.94] in men and 2.01 [95 percent confidence interval, 1.44 to 2.81] in women). We conclude that the estimation of left ventricular mass by echocardiography offers prognostic information beyond that provided by the evaluation of traditional cardiovascular risk factors. An increase in left ventricular mass predicts a higher incidence of clinical events, including death, attributable to cardiovascular disease.

High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.

The British Regional Heart Study (BRHS) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol (HDLC) and incidence of coronary heart disease was eliminated by covariance adjustment. Using the proportional hazards model and adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol, we analyzed this relation separately in the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF) and Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT). In CPPT and MRFIT (both randomized trials in middle-age high-risk men), only the control groups were analyzed. A 1-mg/dl (0.026 mM) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2% in men (FHS, CPPT, and MRFIT) and 3% in women (FHS). In LRCF, where only fatal outcomes were documented, a 1-mg/dl increment in HDLC was associated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality rates. The 95% confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably, and all contained the range 1.9-2.9%. HDLC levels were essentially unrelated to non-cardiovascular disease mortality. When differences in analytic methodology were eliminated, a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.

Echocardiographic criteria for left ventricular hypertrophy: The Framingham heart study

Of 6,148 original cohort and offspring subjects of the Framingham Heart Study who underwent routine evaluation, a healthy group of 347 men (aged 42 +/- 12 years) and 517 women (aged 43 +/- 12 years) was identified to develop echocardiographic criteria for left ventricular (LV) hypertrophy. Healthy subjects were defined as normotensive, receiving no cardiac or antihypertensive medications, nonobese and free of cardiopulmonary disease. Echocardiographic criteria (in accordance with the American Society of Echocardiography convention) for LV hypertrophy, based on mean plus 2 standard deviations for LV mass, LV mass corrected for body surface area and LV mass corrected for height in this healthy sample are, respectively: 294 g, 150 g/m2 and 163 g/m in men and 198 g, 120 g/m2 and 121 g/m in women. Criteria based on LV mass/height result in higher prevalence rates of LV hypertrophy than LV mass/body surface area while still correcting for body size. The prevalence of LV hypertrophy in the entire study population (using LV mass/height criteria) is 16% in men and 19% in women. Until outcome guided criteria for LV hypertrophy are developed, application of sex-specific criteria based on a healthy population distribution of LV mass offer the best approach to echocardiographic diagnosis of LV hypertrophy.

Left ventricular mass and incidence of coronary heart disease in an elderly cohort. The Framingham Heart Study.

OBJECTIVE To examine the association of echocardiographically determined left ventricular mass with incidence of coronary heart disease in an elderly cohort. DESIGN Cohort study with a follow-up period of 4 years. SETTING Population-based. SUBJECTS Elderly original volunteer subjects of the Framingham Heart Study who were free of clinically apparent coronary heart disease. This group included 406 men (mean age, 68 years: range, 60 to 90) and 735 women (mean age, 69 years: range, 59 to 90). MEASUREMENTS AND MAIN RESULTS During 4 years of follow-up, coronary heart disease events occurred in 37 men and 33 women. Baseline echocardiographically determined left ventricular mass was associated with incidence of coronary disease in both sexes (P less than 0.01). After adjusting for age, systolic blood pressure, smoking, and the ratio of total/high density lipoprotein cholesterol, the relative risk for a coronary event, per 50 g/m increment in left ventricular mass/height, was 1.67 in men (95% CI, 1.24 to 2.23) and 1.60 in women (95% CI, 1.10 to 2.32). CONCLUSIONS Echocardiographic assessment of left ventricular mass offers prognostic information beyond that provided by traditional risk factors, which can improve our ability to identify individuals at high risk for coronary heart disease. These findings may have widespread implications regarding the applications of echocardiography in clinical practice.

The framingham offspring study. Design and preliminary data

Abstract The Framingham Heart Study included 1644 spouse pairs as part of the original cohort. The new Framingham Offspring Study consists of examination of the offspring of these matings. Over 5000 offspring and their spouses have been identified and invited to an examination at the Framingham Heart Study facilities. Approximately 82% of the offspring still live in the New England area. Response rates for those living in New England are currently about 80%. Due to vigorous efforts to contact offspring who have moved from New England, it is estimated that over 20% of this group will also be examined. Comparison of age-specific means for the original cohort in 1950 and the offspring in 1972 show apparent reductions in blood pressure, serum cholesterol, and cigarette smoking in the offspring. In contrast, height in men and women and relative weight in men show significant increases in the offspring. Methodologic differences may account for certain of these changes, but it is possible that the observed reduction in the major CHD risk factors may result from generally increased health awareness in this sample or the institution of primary prevention measures.

Incidence and precursors of hypertension in young adults: The Framingham offspring study☆

The occurrence of hypertension and its precursors is examined in the Framingham Offspring Study of 2,027 men and 2,267 women ages 20-49 years followed for 8 years. The age-specific prevalence of hypertension was similar at both the first (1971-1975) and the second (1979-1983) examination for both men and women. Prevalence rates were higher among men than among women, and there was a higher rate of hypertension treatment at the second exam, particularly among women, 75% of whom reported being treated for hypertension. The incidence of hypertension in participants free from hypertension at the first examination increased threefold from the second to the fifth age decades in men and eight-fold in women. Under age 40, men were twice as likely as women to develop hypertension, but after age 40, 8-year incidence rates were similar in men (14.2%) and women (12.9%). Adiposity, relative weight, heart rate, alcohol intake, hematocrit, blood sugar, serum protein, triglyceride, and phosphorous were all related to hypertension occurrence in one or both sexes, controlling for age. In multivariate analysis, adiposity (P less than 0.01), heart rate (P less than 0.01), and triglyceride (P less than 0.05) were all significant independent predictors of hypertension in men. In women, adiposity (P less than 0.001), heart rate (P less than 0.01), hematocrit (P less than 0.05), and alcohol consumption (P less than 0.05) were independent contributors. When controlling for blood pressure measured at the first examination, the best single predictor of hypertension incidence, the multivariate assessment changed very little. Adiposity stands out as a major controllable contributor to hypertension. Changes in body fat over 8 years were related to changes in both systolic and diastolic blood pressure. Markedly obese women in their fourth decade were seven times more likely to develop hypertension than were lean women of the same age. Weight control deserves a high priority in efforts to prevent hypertension in the general population.

Postmenopausal estrogen use, cigarette smoking, and cardiovascular morbidity in women over 50. The Framingham Study.

Abstract We studied the effect of estrogen use on morbidity from cardiovascular disease in 1234 postmenopausal women, aged 50 to 83 years, participating in the Framingham Heart Studys 12th biennial examination (index examination). The medication history recorded at biennial examinations 8 through 12 was used to classify the degree of estrogen exposure before eight years of observation for cardiovascular morbidity and mortality. Despite a favorable cardiovascular risk profile and control for the major known risk factors for heart disease, women reporting postmenopausal estrogen use at one or more examinations had over a 50 per cent elevated risk of cardiovascular morbidity (P<0.01 ) and more than a twofold risk for cerebrovascular disease (P<0.01 ) after the index examination. Increased rates for myocardial infarction (P<0.05) were observed particularly among the estrogen users who smoked cigarettes. Conversely, among nonsmokers estrogen use was associated only with an increased incidence of stroke (P<0.0...

Cigarette smoking and HDL cholesterol the Framingham offspring study

High density lipoproteins were measured on fasting blood samples from 4107 men and women. Control for reported alcohol consumption and subscapular skinfold thickness using multiple regression analysis allowed an examination of the relationship between cigarette smoking and HDL cholesterol. Cigarette smoking was found to be associated with an average difference in HDL cholesterol of about 4 mg/dl in men and 6 mg/dl in women. Furthermore, when heavy alcohol drinkers were eliminated a significant negative association between number of cigarettes smoked and HDL cholesterol was demonstrable in both men and women. There was no evidence that former cigarette smokers, with the exception of those who switched to cigars or pipes or had quit less than one year, had lower HDL levels. Cigar or pipe smokers who had never smoked cigarettes had alcohol- and skinfold-adjusted HDL cholesterol comparable to the non-smoker. These observations indicate another possible link between inhaled tobacco smoke and the atherosclerotic process and suggest the need for further studies and experiments that might clarify the mutual relationship of HDL cholesterol, cigarette smoking and the atherosclerotic process.

Prevalence of coronary heart disease in the Framingham Offspring Study: Role of lipoprotein cholesterols

Forth-three of 1,312 men aged 35 to 54 years in the Framingham Offspring Study had clinically recognized coronary heart disease at the initial examination. Twenty-six men in this group had previously had a myocardial infarction. Of 1,296 women in the same age range, only 11 had coronary disease and 3 a prior myocardial infarction. The prevalence of coronary heart disease in men was strongly associated with age, smoking, high density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol using univariate analyses. When multivariate logistic regression analysis was used, age, smoking and HDL and LDL cholesterol retained their significant associatin with coronary heart disease. The total cholesterol/HDL cholesterol ratio was also strongly associated with coronary heart disease in the multivariate analysis. It is concluded that both HDL and LDL cholesterol are strongly and independently associated with the prevalence of coronary heart disease, whereas the level of very low density lipoprotein cholesterol makes no statistically significant independent contribution.

Risk factors for pulmonary embolism: The Framingham study

To assess potential long-term risk factors for major pulmonary embolism, 46 subjects from the Framingham Heart Study with autopsy-confirmed and clinically significant pulmonary embolism were identified in whom age, systolic blood pressure, cholesterol level, cigarette use, glucose level, Metropolitan relative weight, and varicose veins were ascertained at entry into the Study. These variables were compared among these 46 subjects, all 3,470 subjects in whom these variables were measured at the inception of the Study, and the 998 of these subjects who died within 26 years of follow-up. In multivariate analysis of subjects with autopsy-confirmed major pulmonary embolism and all subjects who died, only Metropolitan relative weight was significantly and independently associated with pulmonary embolism and only among women (p less than 0.001). These findings indicate that, in this cohort, increased adiposity in women is an important long-term factor for significant pulmonary embolism at autopsy. This raises the possibility that weight reduction in obese women may decrease the chances of pulmonary embolism.