Relation of alcohol intake to left ventricular mass: The Framingham Study.

Alcohol has direct toxic effects on the myocardium and is associated with elevated blood pressure, but its relation to left ventricular mass independent of blood pressure level has not been assessed. Reported alcohol intake and left ventricular mass measured by echocardiography were evaluated in 1,980 men and 2,511 women 17 to 90 years of age and free of cardiovascular disease in the Framingham offspring and cohort study. The relation of reported alcohol intake to left ventricular mass was assessed by gender-specific multivariate regression analysis adjusting for age, height, body mass index, systolic blood pressure, history of hypertension and cigarette smoking. Alcohol intake was positively associated with left ventricular mass in men (p less than 0.01) but not in women (p = 0.64). When stratified by beverage type, beer and wine in both men and women and liquor in men were positively related to left ventricular mass. The lack of association of total alcohol intake to left ventricular mass in women appeared to be due to a negative association (p less than 0.01) with liquor. The strongest positive associations were with wine in men (p less than 0.001) and beer in women (p less than 0.05). Alcohol use is independently associated with left ventricular mass; this association may vary by beverage type. In persons with unexplained left ventricular hypertrophy, excessive alcohol intake should be considered.

Is coffee consumption a contributor to cardiovascular disease? Insights from the Framingham Study.

Reported coffee consumption during 1954 to 1958 and 1971 to 1973 was used to test for association with cardiovascular disease (CVD) incidence and lipid values in the Framingham cohort. Multivariate analysis was employed, regressing CVD on age, systolic pressure, cigarette use, body mass index, total cholesterol, and coffee intake. In pooled analyses (2648 men with 549 CVD cases and 3566 women with 462 CVD cases) coffee intake was not associated with CVD incidence in either smokers or nonsmokers, irrespective of sex. Similarly, multivariate analyses for individuals with existing cardiovascular disease showed no association between coffee intake and subsequent cardiovascular disease. In men significant negative associations between coffee and total cholesterol, and very-low-density lipoprotein cholesterol were seen, whereas in women positive associations with low-density lipoprotein cholesterol were observed. Although inconsistent effects on the lipid profile were seen, no increase in primary or secondary CVD was seen with coffee drinking.

Emerging noninvasive biochemical measures to predict cardiovascular risk.

New predictors of cardiovascular events are needed to improve the accuracy of risk stratification. Such predictors should be easily measurable in the population and potentially modifiable. This review reports on new biomarkers that are closely linked to the pathogenic mechanisms underlying the progression of the atherosclerotic plaque leading to rupture and thrombosis that ultimately precipitate acute clinical events, such as stroke and myocardial infarction. These risk factors have been associated with subclinical or clinical cardiovascular disease in large populations and include markers of lipoprotein and lipid metabolism, vitamin B12 metabolism, fibrinolysis, coagulation, inflammation, infection, endothelial dysfunction, the angiotensin system, and oxidative stress. For other key processes of atherosclerosis and cardiac disease, such as apoptosis or programmed cell death, there are currently no markers that can be measured noninvasively. Atherosclerosis is a multifactorial condition and possibly only a subset of factors are the main determinants of disease in a given patient. A better definition of the cardiovascular risk profile will help to better target primary and secondary prevention. Further epidemiological studies are needed to characterize the actual predictive and clinical value of these new emerging cardiovascular biomarkers.

Considerations in the use of echocardiography in epidemiology. The Framingham Study.

To quantify potential biases in the use of echocardiography in epidemiologic studies, we assessed the relationship of sex, age, vital capacity, body fatness, and overt cardiovascular disease to prevalence of acceptable echocardiograms in 6148 Framingham men and women aged 17 to 90 years. Echocardiograms adequate to assess left ventricular chamber dimensions and wall thickness, aortic root, and left atrial dimensions as well as mitral and aortic valves were obtained in 4947 (80%) of the 6148 subjects. The prevalence of acceptable echocardiograms ranged from less than 50% for those more than 80 years of age to more than 96% for subjects under 30 years of age. A significant learning curve was apparent, particularly in the older subjects (more than 60 years of age) for whom prevalence of acceptable echocardiograms rose from a minimum of 28% during the first 5 months of studies to a maximum of 74 to 81% during studies 2 years later. The likelihood of unacceptable echocardiograms was slightly greater in men. Obesity (in subjects younger than 60 years of age), lower vital capacity, and overt cardiovascular disease were associated with unacceptable echocardiograms, independent of age. Consideration of these biases should aid in the interpretation and planning of epidemiologic and other studies using echocardiography.

Longitudinal and secular trends in lipoprotein cholesterol measurements in a general population sample. The Framingham Offspring Study.

Two fasting lipoprotein cholesterol measurements have been made on Framingham Offspring Study participants, first in 1971-75 and again in 1979-83. Longitudinal analysis (n = 2433, age 20-49 at first exam) using multivariate regression found aging, weight gain, vasectomy, menopause, and increased smoking are associated with worsening lipoprotein profiles, while increased alcohol consumption is associated with increased high density lipoprotein cholesterol (HDL-C). Average increases in low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) in women accelerate with age; in men the increases are similar or perhaps decelerate with age. Secular trends were measured using age-adjusted mean values for individuals aged 25-54. Averages of total cholesterol, LDL-C (men only), systolic and diastolic blood pressure, body mass index, number of cigarettes per day, and alcohol consumption were lower at the second examination. Two secular trends in women indicate a possible worsening of population lipoprotein profiles: mean VLDL-C was higher and mean HDL-C lower at the second exam.

The relation of antemortem characteristics to cardiovascular findings at necropsy--The Framingham Study.

The relation of premorbid cardiovascular risk attributes routinely measures at regular biennial examinations to cardiac necropsy findings using a special autopsy protocol was examined among 127 decedents of the Framingham cohort. Necropsy findings analyzed were: heart weight, left ventricular (LV) muscle thickness, percent luminal insufficiency of the coronary arteries, and percent intimal involvement with atherosclerosis. Clinical data analyzed included weight, height, blood pressure and serum cholesterol measured 1, 5, and 9 years prior to death. Systolic blood pressure, but not diastolic, correlated strongly with heart weight and LV muscle thickness in both sexes, and with atherosclerotic involvement in women, but not men. Serum cholesterol 1, 5, and 9 years antemortem all correlated positively with the degree of luminal insufficiency in men, while in women only cholesterol 9 years before death correlated significantly. In multivariate analysis only systolic pressure in women correlated independently with left ventricular muscle thickness and relative weight was the only independent correlate of heart weight. Only age was an independent significant correlate of the extent of coronary atherosclerosis in women. For men, coronary atherosclerotic involvement was independently correlated with only the serum cholesterol and measures of obesity were the major predictors of heart size. The degree of coronary pathology also correlated positively with heart weight in men and LV muscle thickness in women. In general clinical data measured just prior to death did not correlate as well with pathological findings as did earlier measurements.

ABO blood group and cardiovacular disease: the Framingham study.

Following determination of ABO blood type at the sixth biennial examination, the Framingham Heart Study cohort was followed for the occurrence of cardiovascular events for a period of 10 years. A significant association was found between blood type and intermittent claudication, with blood group O showing the lowest rates. Slight but non-significant excesses for certain other CHD events were also found in non-O individuals. Serum cholesterol showed marginally significant but consistent elevations in non-O subjects but the increased risk in non-O individuals was found to occur independently of the known intermittent claudication risk factors. Since the observed relationship between blood type and intermittent claudication occurs independently of the usual atherosclerotic risk factors, blood type, possibily through an effect on clotting, should be considered in the pathogenesis of intermittent claudication.

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.

Obesity and nutrition in elderly diabetic patients.

Obesity and lipid abnormalities are powerful independent predictors of both diabetes and cardiovascular disease. Nutrition affects the rate of atherogenesis in elderly patients with diabetes. Excess calories worsen glucose tolerance; recent studies relate dietary fats both to serum cholesterol levels within populations and to the development of coronary disease. Dietary and drug interventions for hypercholesterolemia have been found to reduce coronary disease rates. Some nutrients also elevate blood pressure, which further accelerates diabetic atherogenesis. For elderly diabetic patients who are at high risk of atherosclerotic cardiovascular disease, control of diabetes should include--in addition to normalization of blood sugar levels--correction of blood lipids and control of weight and blood pressure.

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.

Association of echocardiographic left ventricular mass with body size, blood pressure and physical activity (the Framingham Study).

Left ventricular (LV) hypertrophy has been found to predispose to increased cardiovascular morbidity and mortality. To assess the clinical correlates and potential determinants of LV mass, the relation of echocardiographically determined LV mass to a variety of clinical parameters was examined in a general population. From 1979 to 1983 Framingham Heart Study participants underwent routine evaluation including medical history, physical examination and M-mode echocardiography. LV mass was determined using an anatomically validated formula that incorporates measurements of LV wall thickness and LV internal diameter. The study population consisted of 2,226 men and 2,746 women (mean age 51 years, range 17 to 90). Age, height, systolic blood pressure and body mass index (a measure of obesity) were statistically significant and independent correlates of LV mass in both sexes (p less than 0.001). In men under age 50, leisure-time physical activity was associated with LV mass (p less than 0.05), but this was not observed in women. Results from multivariate analyses in which body mass index and subscapular skinfold thickness were included suggest that lean body mass is correlated with LV mass. Maintenance of ideal body weight and normal blood pressure, weight reduction in obese persons and blood pressure control in hypertensive patients may contribute to the primary and secondary prevention of LV hypertrophy and its sequelae. Clinical interpretation of echocardiograms should include consideration of the correlates of LV mass to gain better insight into the pathogenesis of LV hypertrophy.

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.

Cardiovascular risk factors and graded treadmill exercise endurance in healthy adults: The Framingham Offspring Study.

To help describe the association between exercise endurance and cardiovascular risk factor profiles, 2,606 young and middle-aged healthy adults in the Framingham Offspring Study were given submaximal treadmill tests. For both men and women, exercise endurance was inversely related to resting heart rate (p less than 0.001), body mass index (p less than 0.001), systolic blood pressure (p less than 0.001) and blood glucose (p less than 0.01), and positively related to high density lipoprotein (HDL) cholesterol (p less than 0.05). In men, cigarette smoking (p less than 0.05), high levels of total cholesterol (p less than 0.01) and very low density lipoprotein (VLDL) cholesterol (p less than 0.001) were also associated with poor exercise endurance. After adjusting for age, resting heart rate and body mass index, significant independent associations persisted for HDL cholesterol (p less than 0.05) in both sexes and for systolic blood pressure, VLDL cholesterol, blood glucose and cigarette smoking in men (p less than 0.05). Risk factors associated with overt cardiovascular disease in older individuals are also associated with poor exercise endurance in those who are younger and asymptomatic.

Prevalence and correlates of posterior extra echocardiographic spaces in a free-living population based sample (the Framingham study).

To obtain epidemiologic information on extra echocardiographic spaces immediately posterior to the left ventricular free wall, 2,028 subjects in the original Framingham cohort study (mean age 70 +/- 7 years) and 3,624 of the offspring of the cohort (and their spouses) (mean age 44 +/- 10 years) with adequate echocardiograms were evaluated. Extra echocardiographic spaces were detected in 370 (6.5%) of the 5,652 subjects. The prevalence ranged from less than 1% in subjects in the 20- to 30-year age decade to greater than 15% for those in their 80s. Extra echocardiographic spaces tended to be more common in subjects who were older, female, obese, more hypertensive, and who had higher blood sugar levels and higher low density lipoprotein cholesterol levels (measured 8 years earlier). The high prevalence of extra echocardiographic spaces and the independent association with age (cohort and offspring), obesity (cohort and male offspring), and ventricular septal hypertrophy (cohort and male offspring) is compatible with at least 2 hypotheses among others that should be tested: (1) Subepicardial fat may often masquerade as pericardial fluid producing a posterior extra echocardiographic space, especially in obese elderly subjects. (2) Small posterior extra echocardiographic spaces may often be early markers of subclinical hypertensive heart disease.

Prevalence of submitral (anular) calcium and its correlates in a general population-based sample (the Framingham Study).

To obtain epidemiologic information on submitral calcium, 2,069 subjects in the original Framingham Study cohort (mean age 70 +/- 7 years) and 3,625 of the offspring of the cohort and their spouses (mean age 44 +/- 10 years) with adequate echocardiograms were evaluated. Submitral calcium was detected in 162 (2.8%) of the 5,694 subjects; greater than 90% of the subjects with such calcium came from the 40% of the study group greater than 59 years of age. Women were more than twice as likely to have such calcium as men. Age in both sexes, systolic blood pressure in men, and obesity in women were significantly and independently associated with submitral calcium. There was a 12-fold excess of atrial fibrillation in subjects with (20 of 162, 12%) compared with those without (53 of 5,532, 1%) submitral calcium.

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.

Obesity and lipoprotein cholesterol in the Framingham offspring study.

This study examines the relationship between obesity and low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and very-low-density lipoprotein (VLDL) cholesterol in 4260 young adult men and women. The strongest association between obesity and LDL cholesterol was found in 20-29 yr-old males, the weakest in 40-49-yr-old males. Conversely, in women the relationship between LDL cholesterol and obesity was modest except in the oldest (40-49 yr) age group. An inverse relationship between obesity and HDL cholesterol was of similar shape and strength in all sex and age-specific groups. When the ratio of total cholesterol (TCHOL) to HDL cholesterol was compared in lean and grossly obese 20-29-yr-old males, substantial differences were found. Since other data show this index of the lipoprotein profile to be the single best indicator of CHD risk, it would appear that the atherogenic potential of obesity is greater than would be suggested by the relatively weak association between obesity and TCHOL or any single lipoprotein cholesterol. These data also suggest that the impact of obesity as a risk factor for CHD may have been underestimated. The paucity of lean males 40-49-yr-old prevents firm conclusions about the CHD risk in such a group. Indirect evidence indicates that lean 40-49-yr-old men would have a markedly more favorable lipoprotein profile and consequently a much lower risk of CHD.

HDL-cholesterol in a sample of black adults: the Framingham Minority Study.

A group of 100 adult black residents of Framingham, MA were examined and their plasma lipids were determined by the Framingham Heart Study Lipoprotein Laboratory. The age range of the participants was 20-69 yr, and the mean age was 42 yr for both sexes. The mean plasma total cholesterol, HDL-cholesterol (HDL-C), and triglyceride (TG) values for the 45 black men were 184,37.2, and 78 mg/dl, respectively. The corresponding levels for the 55 black women were 192,50.4, and 49. Even after adjusting for obesity, alcohol intake, and cigarette use, the HDL-C levels among the blacks were significantly lower (p less than 0.001) than the levels for Framingham white men and women. This black sample is more highly educated than black groups previously studied, and appears to be as active as the Framingham white sample. We conclude that this black population has quite low HDL-C levels, and the results suggest that the lipoprotein distributions in this group differ from those previously reported for blacks.

Acquired cupping of the optic nerve head in normotensive eyes.

Clinical measurements of a horizontal cup/disc ratio were obtained among a sample of 160 normal twin subjects by stereoscopic biomicroscopy. Measurements of horizontal cup/disc ratio were normally distributed and theere was no significant association with sex, laterally, race, or refractive error in the mid-range. However, there was a significant association between size of the cup/disc ratio and age as well as intraocular pressure. After taking into account the correlation between age an intraocular pressure in normal eyes, the association between cup/disc ratio and each of these variable remained statistically significant. It is not always recoginized that the size of the normal physiological cup increases with age, and it was not previously observed that "normal" cupping occurs with age apart from the effect of pressure. The average effect of age on cup/disc ratio, amounting to an icrease of 0-0026 per year for this sample, is small. But, allowing for individual variation, some persons could show a recognizable acquired increase in cup/disc ration with age, even in the absence of glaucoma. The possibility of "normal"cupping occurring in association with age, pressure, or high myopia, alone or in combination, merits cosideration in the clinical evaluation of glaucoma suspects and serves to re-emphasize the importance of an adequate central visual field examination in the diagnosis of glaucoma. Studies are needed on the differentiatin between "normal" and "morbid" moulding of the optic nerve head.