Olfactory sensitivity in humans: genetic versus environmental control.

Olfactory sensitivity to acetic acid, isobutyric acid, and 2-sec-butyl-cyclohexanone was tested in 97 adult male twin pairs to determine the extent to which variation in odor perception was genetically determined. Analysis of the data revealed no evidence for heritability of olfactory sensitivity. However, factors significantly associated with odor perception included cigar, pipe, and cigarette smoking; body fatness; alcohol consumption; and diabetes mellitus.

The serum cholesterol-cancer relationship: an analysis of time trends in the Framingham Study.

Time trends in serum cholesterol were analyzed in the Framingham Study data to determine whether low serum cholesterol, which appears to be associated with increased cancer risk, can truly be called a precursor to the development of the disease. Serum cholesterol measured at base line was found to be associated with the risk of both fatal cancer and all cancers occurring in the subsequent 18 years in men (P less than 0.05). This inverse association seems particularly strong for colon cancer in men. Analysis of time trends in the Framingham data did not yield consistent results for all ages. Men 50--59 years old had a statistically significant lower serum cholesterol measured 16--18 years before cancer diagnosis. For men 60--65 years old, a statistically significant trend toward lower serum cholesterol was apparent as measurement was made closer to the time fo cancer diagnosis. Although the Framingham data are not conclusive, they do suggest that in some cancer cases where the serum cholesterol level was lower than that expected at as much as 16--18 years before cancer diagnosis, the depressed level was likely to be a precursor to the tumor growth. However, consistent with the metabolic consequences of tumor growth, the data show that in some cancer cases, serum cholesterol had decreased at measurements made close to the time of cancer diagnosis.

Case-control study of antihypertensive and diuretic use by women with malignant and benign breast lesions detected in a mammography screening program.

A significant but low-level association (relative odds, 2.0; P less than 0.05) was observed between the occurrence of breast cancer and the use of rauwolfia derivatives for 5 or more years in the study of 481 breast cancer cases and 1,268 controls from a joint national mammography screening project of the National Cancer Institute and the American Cancer Society. This association was confined to women over age 50 years who were also heavier than average. No confounding effects could be held responsible for this association after adjustment was made for variables such as presence of hypertension, weight, age at first pregnancy, and other breast cancer risk factors. Other antihypertensive and diuretic drugs as well as multiple drug use also exhibited some suggestive associations with breast cancer. Another group of 421 women with benign lesions at breast biopsy were also compared to the 1,268 controls. They showed a significant association between benign lesions and use of thiazides for 5 or more years (relative odds, 2.4; P less than 0.001) whether employed to treat edema or hypertension. Other antihypertensive and diuretic agents also seemed to show this association, but most of them were being used together with thiazides.

Breast cancer risk factors among screening program participants.

PIP: Data were obtained by mailed questionnaire from 405 breast cancer patients identified during the first 2 years of operation of the Breast Cancer detection Demonstration Project in the U.S. and from a sample of 1156 normal screenees (response rate = 88%) in an attempt to examine whetHer the usual risk indicators for breast cancer apply to individuals participating in screening programs. No substantial differences were found between the respondents and the nonrespondents for the variables on which information had been obtained at the time of the initial screening. Nearly all of t(e recognized risk factors were seen in this population. The relative risk (FF) of breast cancer was 3.9 among women whose mothers were also affected; this finding was statistically significant. Relative risk was increased for women reporting early menarche, late menopause, nulliparity, late age when 1st child was born, and excessive weight. The relative risk was not elevated in women with a prior breast biopsy but was excessive for those with more than 1 biopsy. No association with thyroid medications or menopausal hormones was found. Among women having undergone a natural menopause, a nonstatistically significant elevation in the relative risk was noted for long term oral contraceptive users; this excess relative risk was restricted to those using OCs in the presence of breast cancer risk indicators. The results indicate the need for further study of women with extended periods of OC use, particularly when accompanied by other known risk indicators.^ieng

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.

Review of the epidemiological evidence for a possible relationship between hypocholesterolemia and cancer.

The evidence relating hypocholesterolemia to an increased risk of cancer is controversial. Although more than a dozen populations have been studied in prospective epidemiological investigations, there is relatively little consistency relating low serum cholesterol levels to future risk or mortality from cancer. Several studies have demonstrated a significant inverse relationship, but many others have failed to do so, and there is no ready explanation for the divergence of results. The data from dietary studies, both at the group level and at the individual level, indicate that, if anything, higher intakes of cholesterol appear to be related to cancer rather than lower levels. A potential role for vitamin A and for some genetic predisposition to cancer perhaps associated with lower cholesterol absorption and decreased degradation of cholesterol in the gut may possibly explain some of these inconsistencies. It is concluded that: (a) the available data do not substantiate any direct cause and effect relationship between low blood cholesterol levels and cancer. Rather, the data suggest that low cholesterol levels may serve as a "marker," possibly genetic, and in only small numbers of male individuals in any given population; (b) the data do not preclude, countermand, or contradict the current public health message which recommends that those with elevated cholesterol levels seek to lower them through diets lower in saturated fat and cholesterol.

Race, sex, poverty, and the medical treatment of acute myocardial infarction in the elderly.

BACKGROUND: Race, sex, and poverty are associated with the use of diagnostic cardiac catheterization and coronary revascularization during treatment of acute myocardial infarction (AMI). However, the association of sociodemographic characteristics with the use of less costly, more readily available medical therapies remains poorly characterized. METHODS AND RESULTS: We evaluated 169 079 Medicare beneficiaries >/=65 years of age treated for AMI between January 1994 and February 1996 to determine the association of patient race, sex, and poverty with the use of medical therapy. Multivariable regression models were constructed to evaluate the unadjusted and adjusted influence of sociodemographic characteristics on the use of 2 admission (aspirin, reperfusion) and 2 discharge therapies (aspirin, beta-blockers) indicated during the treatment of AMI. Therapy use varied by patient race, sex, and poverty status. Black patients were less likely to undergo reperfusion (RR 0.84, 95% CI 0. 78, 0.91) or receive aspirin on admission (RR 0.97, 95% CI 0.96, 0. 99) and beta-blockers (RR 0.94, 95% CI 0.88, 1.00) at discharge. Female patients were less likely to receive aspirin on admission (RR 0.98, 95% CI 0.97, 0.99) and discharge (RR 0.98, 95% CI 0.96, 0.99). Poor patients were less likely to receive aspirin (RR 0.97, 95% CI 0. 96, 0.98) or reperfusion (RR 0.97, 95% CI 0.93, 1.00) on admission and aspirin (RR 0.98, 95% CI 0.96, 1.00), or beta-blockers (RR 0.95, 95% CI 0.91, 0.99) on discharge. CONCLUSIONS: Medical therapies are currently underused in the treatment of black, female, and poor patients with AMI.

Delay in the prehospital phase of acute myocardial infarction. Lack of influence on incidence of sudden death.

Prehospital delay is considered to be an important cause of out-of-hospital coronary mortality. Behavior of patients and physicians in response to the symptoms of myocardial infarction (MI) or impending out-of-hospital death (OHD) was studied for 107 consecutive acute coronary events in Framingham, Mass. Delay due to inappropriate patient behavior was the most important component of total delay. Delay related to patient-physician contact occurred in two thirds of MI cases and was more than 30 minutes in half of these. Office visits and inappropriate triage by nurses and receptionists were important factors in physician delay. However, 60% to 75% of OHDs occur so rapidly that their prevention by reduction of prehospital delay seems impossible. A strategy for reduction of delay that might be of benefit in preventing some of the remaining OHDs is described.

Epidemiology and genetics of hypertension.

The major decline in cardiovascular mortality during the last 20 years may be related to improved hypertension control, but a causal relationship has not been proven. Fundamental epidemiologic associations between age, sex, race, socioecomonic class, and blood pressure (BP) have been well characterized. Risk of coronary heart disease and stroke mortality and morbidity is linearly related to BP or to categorically defined hypertension. Weight is a major correlate of BP at all ages and in most populations. The relationships between hypertension and other nutritionally related factors are not so well defined. The Framingham Study (both cohort and offspring components) provides information about other BP correlates such as heart rate and clinical chemistry values as well as evidence suggesting a genetic influence on BP variability in families. Combined with observations from other studies, it appears that heredity plays a very important role in human hypertension.

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.

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.

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.

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.

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.

The magnitude and nature of the decrease in coronary heart disease mortality rate.

The age-adjusted cardiovascular mortality rate has fallen by 40% in the United States over the last 30 years, primarily since the late 1960s. Although cardiovascular disease is still the leading cause of death in this country, the rate of deaths from cardiovascular disease have dropped to below 50%, and the rate continues to decrease. In actual numbers, it has been estimated that as many as 300,000 people between the ages of 35 and 65 years would have died from coronary heart disease between 1968 and 1978 if the mortality rate had remained unchanged. The extent of the decline varies with different areas of the country and most dramatically affects the black population. Between 1970 and 1980, life expectancy increased by 2.7 years for white men, 2.5 years for white women, 3.7 years for black men, and 4.0 years for black women. Attempts to analyze the decline in mortality must take 2 features of mortality into consideration: incidence and case fatality, which reflect changes in primary prevention factors and in treatment methods, respectively. However, data on cardiovascular disease conflict and are difficult to interpret. Many methods of estimating the potential effect of altering or eliminating potential risk factors such as smoking, hypertension and cholesterol have been explored, with encouraging results.

Community surveillance for coronary heart disease: the Framingham Cardiovascular Disease survey. Comparisons with the Framingham Heart Study and previous short-term studies.

It appears likely that intervention trials on a community scale against one or more coronary heart disease risk factors will begin in the near future. Prerequisite to the evaluation of the effectiveness of these trials is the accurate determination of coronary heart disease incidence rates. The Framingham Cardiovascular Disease Survey was undertaken to test the hypothesis that a short-term surveillance study of a defined population can generate accurate incidence rates for at least some categories of cardiovascular disease and that these rates are comparable with those obtained by longitudinal survey of the same population. In conjunction with the 1970 U.S. census, a 1 year survey was made of all new coronary heart disease events occurring in the town of Framingham, Mass. Surveillance was performed by several methods that were intentionally overlapping. During the study period, 244 coronary heart disease events occurred. Despite the relatively small size of the population, many of the well established epidemiologic characteristics of this disease were evident. The rates obtained by the cardiovascular disease survey were comparable with those obtained by the Framingham Heart Study, for the harder end points of myocardial infarction and death from coronary heart disease, but much smaller for the softer end point of angina pectoris, especially in women. These data and those from similar studies indicate that periodic short-term surveillance studies of target populations of major intervention programs can provide an economic method of generating incidence data for the evaluation of the impact of such programs on myocardial infarction and death from coronary 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.

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.

Data needed for improving the health of minorities.

Identified needs for minority health data, obstacles in obtaining the data, and potential solutions are reviewed. Vital statistics for whites and blacks have been available by states for many years. Recent revisions provide data on Hispanics, and new resolutions will provide data on Asian and Pacific Islander subgroups. But limitations persist in providing accurate statistics for minority subgroups. A major obstacle is the inadequacy of census denominator estimates, due to differential undercounts, paucity of postcensal estimates for states and localities, and the validity of the race and ethnicity data. Important issues revolve around quality, comparability, and intraperson variability of self-identification in determining race and ethnicity, versus external assessment. National survey data have oversampled for black and Hispanic minorities, but not others. The Disadvantaged Minority Health Improvement Act of 1990 provides some solutions, including an extramural grants program to strengthen minority statistics, which the National Center for Health Statistics has implemented to improve minority health assessment at all levels.