Angina pectoris is a stronger indicator of diffuse vascular atherosclerosis than intermittent claudication: Framingham study.

OBJECTIVE: To compare implications of Angina Pectoris (AP) and Intermittent Claudication (IC) as indicators of clinical atherosclerosis in other vascular territories. STUDY DESIGN AND SETTING: Prospective cohort study of cardiovascular disease (CVD) in 5,209 men and women of Framingham, MA, aged 28-62 years at enrollment in 1948-1951, who received biennial examinations during the first 36 years of follow-up. Comparative 10-year incidence of subsequent atherosclerotic CVD in participants with IC and AP relative to a reference sample free of CVD was determined. RESULTS: On follow-up, 95 CVD events occurred in 186 participants with IC and 206 of 413 with AP. After age, sex, and risk-factor adjustment, the proportion acquiring other CVD was 34.0% for IC and 43.4% for AP. Relative to the reference sample, those with IC had a 2.73-fold higher age and sex-adjusted 10-year hazard of CVD (95% CI 2.21, 3.38) and for AP was 3.17 (95% CI 2.73, 3.69). CVD hazard ratios remained more elevated for AP and statistically significant after standard risk factor adjustment. Risk factors accounted for more of the excess CVD risk associated with IC (34.8%) than AP (9.5%). CONCLUSION: AP is as useful as IC as a hallmark of diffuse atherosclerotic CVD and an indication for comprehensive preventive measures.

Body fat distribution and breast cancer in the Framingham Study.

We examined the relation between central body fat distribution and breast cancer in a prospective cohort of women who participated in the Framingham Study. At the baseline examination in 1948, a total of 2,201 women aged 30-62 years were analyzed. An index of central to peripheral body fat (the central adiposity ratio) was calculated from the sum of the trunkal skinfolds (chest, subscapular, and abdominal) divided by the sum of the extremity skinfolds (triceps and thigh). These skinfolds were measured at the fourth examination in 1954. The cohort was followed for up to 28 years and yielded 106 cases of breast cancer. When divided into quartiles based on the central adiposity ratio, only women in the fourth quartile (those with the highest central to peripheral body fat distribution) demonstrated an increased risk for breast cancer. The age- and adiposity-adjusted relative risk estimate for having an increased central adiposity ratio (fourth quartile) compared to lower central adiposity ratios was 1.8 (95% confidence interval, 1.2-2.6). Adjustment for potential confounders of height, parity, and education did not appreciably alter this estimate (1.7, 1.1-2.5). There was no association between degree of adiposity, as measured by the sum of the five skinfolds or by body mass index (weight in kg divided by height in m2), and subsequent breast cancer. The results of this study suggest that increased central to peripheral body fat distribution predicts breast cancer risk independently of the degree of adiposity and may be a more specific marker of a premalignant hormonal pattern than degree of adiposity.

Tumor-associated antigen levels (carcinoembryonic antigen, human chorionic gonadotropin, and alpha-fetoprotein) antedating the diagnosis of cancer in the Framingham study.

Determinations of carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), and alpha-fetoprotein (AFP) were done by use of frozen serum samples antedating the diagnosis of cancer for 9 pancreatic and 8 gastric carcinoma patients from the Framingham Heart Study. The longest intervals for elevated antigens before cancer diagnosis were 10 months for CEA and 26 months for HCG. (The single elevated AFP was found in a sample 10 days before clinical diagnosis.) Samples from 31 controls matched with the cancer subjects by age, sex, vital capacity, and smoking status showed over 20% "false" positive CEA elevations (all smokers with low vital capacities) and over 20% borderline false positive HCG elevations in postmenopausal females. Although 10-26 months' lead time could infer some potential for use of these tumor-associated antigens to help detect malignant neoplasms at an earlier stage, a serious problem of frequent false positives prevents CEA and HCG levels from being useful as cancer-screening tests at this time.

Is alcohol consumption related to breast cancer? Results from the Framingham Heart Study.

We studied the relation between alcohol consumption and breast cancer among women in the Framingham Heart Study cohort. A total of 2,636 women aged 31-64 years provided information on alcohol consumption at the second biennial examination. They were followed for up to 32 years; during this period, breast cancer was diagnosed in 143 of these women. Alcohol intake was also assessed at 10 and 20 years of follow-up and every 2 years thereafter. In analyses using only baseline alcohol intake, the multiple risk factor-adjusted relative risk (RR) estimate of breast cancer for any drinking, compared with nondrinking, was 0.8 [95% confidence interval (CI), 0.5-1.1]. For three levels of alcohol intake (0.1-1.4 g/day, 1.5-4.9 g/day, and greater than or equal to 5.0 g/day), the baseline analyses yielded RRs (vs. nondrinking) of 1.0 (CI, 0.6-1.5), 0.7 (CI, 0.4-1.1), and 0.6 (CI, 0.4-1.0), respectively. In analyses incorporating repeated measures of alcohol, the comparable RRs were 0.9 (CI, 0.6-1.2) for any drinking (vs. nondrinking) and 0.7 (CI, 0.4-1.4), 1.1 (CI, 0.7-1.8), and 0.8 (CI, 0.5-1.2), respectively, for the three levels of intake (vs. nondrinking). Alcohol consumption was not associated with an increased risk of breast cancer in this cohort.

Physical activity and risk of large bowel cancer in the Framingham Study.

We examined the relation between self-reported physical activity and large bowel cancer in a prospective cohort of men and women who participated in the Framingham Study. Self-assessments of physical activity were available from the fourth biennial examination on a total of 1906 men and 2308 women aged 30 to 62 yr in 1954. The cohort was followed for up to 28 yr and yielded 152 cases (73 men, 79 women) of large bowel cancer. Inactivity was associated with an increased risk of large bowel cancer among men but not among women. The relative risk estimates for large bowel cancer among men in the middle and lowest tertiles of a physical activity index (compared with the highest tertile) were 1.4 (95% confidence intervals, 0.8-2.6) and 1.8 (1.0-3.2), respectively. Among women the comparable estimates were 1.2 (0.7-2.1) and 1.1 (0.6-1.8), respectively. These findings were unchanged after adjustment for body mass index, serum cholesterol, alcohol, and other potentially confounding variables. The narrow range of physical activity and the minimal heavy activity reported by women in this cohort may have limited our ability to detect an association between physical activity and large bowel cancer among women.

Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study.

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.

Diabetes, intermittent claudication, and risk of cardiovascular events. The Framingham Study.

The impact of diabetes on intermittent claudication was examined in 1813 men and 2504 women with 34-yr follow-up data in the Framingham study. For both sexes, diabetes was associated with a two- to threefold excess risk of intermittent claudication compared with its absence. A pronounced excess risk was also observed in subjects on oral hypoglycemic therapy and in women receiving insulin. Although diabetes was often associated with an atherogenic-risk profile, controlling for age and several concomitant risk factors failed to eliminate the association with intermittent claudication. Those who developed both intermittent claudication and diabetes were at an especially high risk of incident cardiovascular events. In women, the risk of coronary heart disease, stroke, and cardiac failure was increased 3-4 times when diabetes and intermittent claudication occurred together compared with when either condition existed alone. In diabetic men, the presence of intermittent claudication doubled the risk of stroke, and cardiac failure was approximately 3 times more likely in subjects with both conditions compared with either alone. We conclude that diabetes is an important risk factor for intermittent claudication, which in turn confers a serious prognosis for subsequent cardiovascular outcomes in the patient with diabetes.

Sudden death: lessons from subsets in population studies.

Sudden coronary death is an important feature of clinical coronary disease, the incidence doubling with each decade of age after age 45 and with women lagging behind men in incidence by 20 years. Fifty percent of the sudden deaths in men and 64% in women occur in persons without prior coronary heart disease, and 18% of coronary attacks in men and 24% in women present as sudden death. More than half of coronary mortality is in the form of sudden death. Persons with overt established coronary heart disease are at 3-fold to 12-fold increased risk depending on age, the risk ratio diminishing with advancing age. When overt coronary disease is established, the major coronary risk factors have little discernible effect on the risk of sudden death. Risk appears related chiefly to the degree of myocardial damage as indicated by electrocardiographic abnormality and evidence of cardiac failure. In subjects free of overt coronary heart disease, the risk of sudden death varies widely in relation to risk factors, including systolic pressure, serum cholesterol, vital capacity, cigarette smoking, relative weight, heart rate and electrocardiographic abnormality. Multivariate combination of these risk factors allows an efficient prediction of sudden death in both sexes. The key to the prevention of sudden death in the general population is to prevent coronary attacks by avoidance or correction of the aforementioned risk factors. No risk factors thus far identified are clearly specific for sudden death.(ABSTRACT TRUNCATED AT 250 WORDS)

The epidemiology of heart failure: the Framingham Study.

Congestive heart failure has become an increasingly frequent reason for hospital admission during the last 2 decades and clearly represents a major health problem. Data from the Framingham Heart Study indicate that the incidence of congestive heart failure increases with age and is higher in men than in women. Hypertension and coronary heart disease are the two most common conditions predating its onset. Diabetes mellitus and electrocardiographic left ventricular hypertrophy are also associated with an increased risk of heart failure. During the 1980s, the annual age-adjusted incidence of congestive heart failure among persons aged > or = 45 years was 7.2 cases/1,000 in men and 4.7 cases/1,000 in women, whereas the age-adjusted prevalence of overt heart failure was 24/1,000 in men and 25/1,000 in women. Despite improved treatments for ischemic heart disease and hypertension, the age-adjusted incidence of heart failure has declined by only 11%/calendar decade in men and by 17%/calendar decade in women during a 40-year period of observation. In addition, congestive heart failure remains highly lethal, with a median survival time of 1.7 years in men and 3.2 years in women and a 5-year survival rate of 25% in men and 38% in women.

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.

Risk stratification of dyslipidemia: insights from the Framingham Study.

Dyslipidemia, fundamental to the atherosclerotic process, is now a readily correctable risk factor with established efficacy of treatment for reducing risk of CHD and strokes. The current focus on LDL-cholesterol for risk assessment needs to be broadened to accommodate the two-way traffic of cholesterol entering and leaving the arterial intima reflected by the LDL/HDL ratio or the Total/HDL ratio. The choice of lipid therapy should be individualized to take into account the presence of the metabolic syndrome and the lipid profile of the patient. The intensity of therapy and goals should be linked to multivariable risk, particularly in those with modest lipid values. Cardiovascular risk factor clustering is pronounced for each lipid, is promoted by adiposity and greatly influences its CHD hazard. Global risk assessment taking clustering into account is essential for efficient preventive management of lipids. More attention needs to be afforded the absolute risk reduction attainable and must recognize that the number needed to treat to prevent one event increases the lower the lipid value, the lower global risk and the healthier the subject.

Drinking and its relation to smoking, BP, blood lipids, and uric acid. The Framingham study.

Drinking habits and other characteristics were observed for 20 years in a cohort of 5,209 Framingham, Mass, men and women. During this period the average amount of alcohol consumed rose 63%. The percent increase was greater for women than men and greater for younger persons than older. Serum uric acid and phospholipid concentrations were higher at higher levels of alcohol consumption. Lipoprotein levels of 0 to 12 and 100 to 400 Svedberg units were positively associated with alcohol consumption in men but negatively associated with alcohol consumption in women. Blood pressure was higher in nondrinkers than light drinkers, but among drinkers BPs were higher at higher consumption levels. While cigarette smokers had lower BPs than nonsmokers, this seemed to be due to their lower weight. Persons who increased their alcohol consumption during follow-up had a small mean increase in serum phospholipid and uric acid levels, BP, and weight relative to the average changes for these variables.

Risk factors that attenuate the female coronary disease advantage.

OBJECTIVE: To compare the coronary disease experience of men and women in a community setting. DESIGN AND SETTING: Prospective cohort study. PATIENTS: Long-term follow-up of a population-based sample of 5209 men and women. RESULTS: Women outlive men and experience fewer cardiovascular events. By middle age, women lag 20 years behind men in the incidence of myocardial infarction, but the gap closes in the elderly, when cardiovascular disease becomes the leading cause of death in women as well as in men. Menopause promptly escalates coronary disease risk threefold and greatly erodes the advantage over men. Women and men share the same major risk factors for coronary disease, although women experience a lower absolute risk. However, high ratios of total/high-density lipoprotein cholesterol level ratios, left ventricular hypertrophy, and diabetes tend to eliminate the female advantage. CONCLUSION: Coronary disease is not a minor problem in women. Consequently, women should take vigorous preventive measures. There is a need for particular attention to glucose tolerance and blood lipid levels and a greater sense of urgency when hypertension progresses to left ventricular hypertrophy.

Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham Study.

Chronic atrial fibrillation without valvular disease has been associated with increased stroke incidence. The impact of atrial fibrillation on the risk of stroke with increasing age was examined in 5184 men and women in the Framingham Heart Study. After 30 years of follow-up, chronic atrial fibrillation appeared in 303 persons. Age-specific incidence rates steadily increased from 0.2 per 1000 for ages 30 to 39 years to 39.0 per 1000 for ages 80 to 89 years. The proportion of strokes associated with this arrhythmia was 14.7%, 68 of the total 462 initial strokes, increasing steadily with age from 6.7% for ages 50 to 59 years to 36.2% for ages 80 to 89 years. In contrast to the impact of cardiac failure, coronary heart disease, and hypertension, which declined with age, atrial fibrillation was a significant contributor to stroke at all ages.

Lipoproteins, cardiovascular disease, and death. The Framingham study.

Based on six years of follow-up evaluations of the Framingham, Mass, men and women aged 49 to 82 years, it was found that a low-density lipoprotein (LDL) cholesterol concentration was associated with a low incidence of coronary heart disease (CHD) risk but with a statistically significant excess of stroke incidence in women and of deaths from non-CHD causes in both sexes. There was no suggestion that an elevated HDL cholesterol level was associated with an excess incidence of any of the cardiovascular end points considered or of death. An inverse relation of high-density lipoprotein (HDL) cholesterol level with CHD and its major consequences, CHD death and congestive heart failure, was observed. Triglyceride determinations seem to add little information respecting cardiovascular risk to that elicited from HDL and LDL cholesterol and other known cardiovascular risk factors. While the relation of HDL and LDL cholesterol with CHD is paralleled by findings from a variety of sources, the inverse relation of LDL cholesterol with stroke in women and with death from non-CHD causes requires additional confirmation and exploration.

Clustering of metabolic factors and coronary heart disease.

BACKGROUND: The degree of clustering for common metabolic coronary disease risk factors is not well known, the antecedents of clustering are not well studied, and the impact of such clusters on coronary risk has not been assessed systematically. METHODS: Prospective community sample of 2406 men and 2569 women aged 18 to 74 years at baseline. The 6 metabolically linked risk factors considered were the lowest sex-specific quintile of high-density lipoprotein cholesterol and the highest quintiles of body mass index, systolic blood pressure, triglycerides, glucose, and serum total cholesterol. RESULTS: At baseline the risk factor sum, represented as integer values, ranged from 0 to 6, and clusters of 3 or more risk factors occurred at twice the rate predicted by chance. After adjustment for age and obesity level, a 2.25-kg (5-lb) weight increase over 16 years was associated with an increased risk factor sum in men (+20%; P=.002) and women (+37%; P<.001), and a 2.25-kg weight loss was associated with a decreased risk factor sum in men (-48%; P<.001) and women (-40%; P<.001). Clusters of 3 or more risk factors were associated with a 2.39 (95% confidence interval, 1.56-3.36) and 5.90 (95% confidence interval, 2.54-13.73) times greater risk of coronary heart disease in men and women, respectively (both P<.001). CONCLUSIONS: Atherogenic risk factor clustering is common in both sexes, worsens with weight gain, and is associated with greatly increased risk of coronary disease risk in both sexes.

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.

Impact of atrial fibrillation on mortality, stroke, and medical costs.

BACKGROUND: The impact of atrial fibrillation (AF) on mortality, stroke, and medical costs is unknown. METHODS: We conducted a prospective cohort study of hospitalized Medicare patients with AF and 1 other cardiovascular diagnosis (CVD) compared with a matched group without AF (n = 26,753), randomly selected in 6 age-sex strata from 1989 MedPAR files of more than 1 million patients diagnosed as having AF. Stroke rates were also determined in another cohort free of CVD (n = 14,267). Total medical costs after hospitalization were available from a 1991 cohort. Cumulative mortality, stroke rates, and costs following index admission were adjusted by multivariate and proportional hazard regression analyses. RESULTS: Mortality rates were high in individuals with CVD, ranging from 19.0% to 52.1% in 1 year. Adjusted relative mortality risk was approximately 20% higher in patients with AF in all age-sex strata during each of the 3 years studied (P < .05). Incidence of stroke was high in individuals with CVD, 6.2% to 15.4% in 1 year, with and without AF, and was at least 5-fold higher than in individuals without CVD. In those with CVD, stroke rates were approximately 25% higher in women with AF (P < .05) but only 10% higher in men. Adjusted total Medicare spending in 1 year was 8.6- to 22.6-fold greater in men, and 9.8- to 11.2-fold greater in women with AF (P < .05). Second- and third-year costs were increased as well. CONCLUSION: Prevention of AF and treatment of patients with AF and associated CVD may yield benefits in reduced mortality and stroke as well as reducing health care costs.

Elevated midlife blood pressure increases stroke risk in elderly persons: the Framingham Study.

BACKGROUND: Stroke risk predictions are traditionally based on current blood pressure (BP). The potential impact of a subject's past BP experience (antecedent BP) is unknown. We assessed the incremental impact of antecedent BP on the risk of ischemic stroke. METHODS: A total of 5197 stroke-free subjects (2330 men) in the community-based Framingham Study cohort were enrolled from September 29, 1948, to April 25, 1953, and followed up to December 31, 1998. We determined the 10-year risk of completed initial ischemic stroke for 60-, 70-, and 80-year-old subjects as a function of their current BP (at baseline), recent antecedent BP (average of readings at biennial examinations 1-9 years before baseline), and remote antecedent BP (average at biennial examinations 10-19 years earlier), with adjustment for smoking and diabetes mellitus. Models incorporating antecedent BP were also adjusted for baseline BP. The effect of each BP component (systolic BP, diastolic BP, and pulse pressure) was assessed separately. RESULTS: Four hundred ninety-one ischemic strokes (209 in men) were observed in eligible subjects. The antecedent BP influenced the 10-year stroke risk at the age of 60 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.68 [95% confidence interval, 1.25-2.25]; and men, 1.92 [95% confidence interval, 1.39-2.66]) and at the age of 70 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.66 [95% confidence interval, 1.28-2.14]; and men, 1.30 [95% confidence interval, 0.97-1.75]). This effect was evident for recent and remote antecedent BP, consistent in hypertensive and nonhypertensive subjects, and demonstrable for all BP components. CONCLUSIONS: Antecedent BP contributes to the future risk of ischemic stroke. Optimal prevention of late-life stroke will likely require control of midlife BP.

Profile for estimating risk of heart failure.

CONTEXT: We devised a risk appraisal function to assess the hazard of heart failure in persons who are predisposed by coronary disease, hypertension, or valvular heart disease. OBJECTIVE: To provide general practitioners and internists with a cost-effective method to select people at high risk who are likely to have impaired left ventricular systolic function and may therefore require further evaluation and aggressive preventive measures. METHODS: The routinely measured risk factors used in constructing the heart failure profile include age, electrocardiographic left ventricular hypertrophy, cardiomegaly on chest x-ray film, heart rate, systolic blood pressure, vital capacity, diabetes mellitus, evidence of myocardial infarction, and valvular disease or hypertension. Based on 486 heart failure cases during 38 years of follow-up, 4-year probabilities of failure were computed using the pooled logistic regression model for each sex; a simple point score system was employed. A multivariate profile was also produced without the vital capacity or chest x-ray film because these may not be readily available in some clinical settings. RESULTS: Using the risk factors that make up the multivariate risk formulation-derived from ordinary office procedures-the probability of developing heart failure can be estimated and compared with the average risk for persons of the same age and sex. Using this risk profile, 60% of events in men and 73% in women occurred in subjects in the top quintile of multivariate risk. CONCLUSIONS: Using this multivariate risk formulation, it is possible to identify high-risk candidates for heart failure who are likely to have a substantial yield of positive findings when tested for objective evidence of presymptomatic left ventricular dysfunction. The risk profile may also identify candidates who are at high risk for heart failure because of multiple, marginal risk factor abnormalities that might otherwise be overlooked.