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Biomedical subjects

J E Manson

Publications and source records attributed to J E Manson.

At least 235 records · Page 13Linked to original sources

Family history, age, and risk of breast cancer. Prospective data from the Nurses' Health Study.

OBJECTIVE: To examine prospectively the risk of breast cancer as influenced by a maternal history of breast cancer, the mother's age at diagnosis, or a sister's history of breast cancer. DESIGN: Prospective cohort study with biennial follow-up. SETTING/PARTICIPANTS: 117,988 women in the Nurses' Health Study aged 30 to 55 years in 1976, followed up through 1988 (1.3 million person-years of follow-up). RESULTS: We identified 2389 incident cases of invasive breast cancer. Compared with women without a maternal history of breast cancer, the age-adjusted relative risk (RR) of breast cancer was highest among women whose mother was diagnosed before the age of 40 years (RR, 2.1 [95% confidence interval, 1.6 to 2.8]). The RR decreased with advancing maternal age at time of diagnosis to 1.5 (95% confidence interval, 1.1 to 2.2) for maternal diagnosis after the age of 70 years. Having a sister with a history of breast cancer also was related to increased risk; for women with one sister with breast cancer compared with those with one sister without such a history, the age-adjusted RR was 2.3 (95% confidence interval, 1.6 to 3.4). Women whose mother and sister both had a history of breast cancer had an RR of 2.5 (95% confidence interval, 1.5 to 4.2) compared with those without a family history. These associations did not differ appreciably when stratified by age; menopausal status; history of benign breast disease; body mass index; age at menarche; or parity or age at first birth of the women at risk. The results remained unchanged when we controlled for these risk factors in multivariate models. Despite slightly greater mammography surveillance and earlier detection of tumors among women with a family history of breast cancer, detection bias is unlikely to account for more than a small part of the observed association. CONCLUSIONS: Risk of breast cancer is approximately doubled among women whose mother had breast cancer diagnosed before the age of 40 years or who have a sister with breast cancer, and remains elevated even for those whose mothers were diagnosed with breast cancer at the age of 70 years or older. However, the risk associated with a mother or sister history of breast cancer is smaller than suggested by earlier retrospective studies. Overall, within this population of middle-aged women, only 2.5% of breast cancer cases are attributable to a positive family history.

Adult↗

Vitamin E consumption and the risk of coronary disease in women.

BACKGROUND: Interest in the antioxidant vitamin E as a possible protective nutrient against coronary disease has intensified with the recognition that oxidized low-density lipoprotein may be involved in atherogenesis. METHODS: In 1980, 87,245 female nurses 34 to 59 years of age who were free of diagnosed cardiovascular disease and cancer completed dietary questionnaires that assessed their consumption of a wide range of nutrients, including vitamin E. During follow-up of up to eight years (679,485 person-years) that was 97 percent complete, we documented 552 cases of major coronary disease (437 nonfatal myocardial infarctions and 115 deaths due to coronary disease). RESULTS: As compared with women in the lowest fifth of the cohort with respect to vitamin E intake, those in the top fifth had a relative risk of major coronary disease of 0.66 (95 percent confidence interval, 0.50 to 0.87) after adjustment for age and smoking. Further adjustment for a variety of other coronary risk factors and nutrients, including other antioxidants, had little effect on the results. Most of the variability in intake and reduction in risk was attributable to vitamin E consumed as supplements. Women who took vitamin E supplements for short periods had little apparent benefit, but those who took them for more than two years had a relative risk of major coronary disease of 0.59 (95 percent confidence interval, 0.38 to 0.91) after adjustment for age, smoking status, risk factors for coronary disease, and use of other antioxidant nutrients (including multi-vitamins). CONCLUSIONS: Although these prospective data do not prove a cause-and-effect relation, they suggest that among middle-aged women the use of vitamin E supplements is associated with a reduced risk of coronary heart disease. Randomized trials of vitamin E in the primary and secondary prevention of coronary disease are being conducted; public policy recommendations about the widespread use of vitamin E should await the results of these trials.

Adult↗

Endogenous tissue-type plasminogen activator and risk of myocardial infarction.

Endogenous tissue-type plasminogen activator (tPA) has been hypothesised to be a marker of baseline fibrinolytic capacity. We therefore tested whether tPA antigen is associated with the occurrence of future myocardial infarction (MI) among apparently healthy individuals. tPA antigen concentrations were measured at baseline in plasma samples from 231 apparently healthy men from the Physicians' Health Study cohort who later developed MI, and in an equal number of controls matched for age and smoking habit who remained free of reported cardiovascular disease during a follow-up of 60.2 months. In crude matched-pair analyses, baseline concentrations of tPA antigen were higher in cases than controls (p = 0.03) and strongly associated with risk of future MI. Specifically, the relative risks of developing a first MI from lowest (referent) to highest quintiles of tPA antigen were 1.00, 1.27, 1.75, 1.88, and 2.81 (p for trend 0.0008, 95% CI for the relative risk in the fifth as compared with first quintile 1.47 to 5.37, p = 0.002). Analyses which adjusted for risk factors that affect progression of atherosclerosis, particularly HDL-cholesterol, abolished the statistical significance of this association, a finding which suggests that elevations of tPA antigen are a result rather than a cause of atherosclerotic coronary disease. These prospective data suggest that endogenous tPA concentrations increase as a consequence of important preclinical atherosclerosis and therefore may be a marker for risk of future MI.

Adult↗

Intake of trans fatty acids and risk of coronary heart disease among women.

Trans isomers of fatty acids, formed by the partial hydrogenation of vegetable oils to produce margarine and vegetable shortening, increase the ratio of plasma low-density-lipoprotein to high-density-lipoprotein cholesterol, so it is possible that they adversely influence risk of coronary heart disease (CHD). To investigate this possibility, we studied dietary data from participants in the Nurses' Health Study. We calculated intake of trans fatty acids from dietary questionnaires completed by 85,095 women without diagnosed CHD, stroke, diabetes, or hypercholesterolaemia in 1980. During 8 years of follow-up, there were 431 cases of new CHD (non-fatal myocardial infarction or death from CHD). After adjustment for age and total energy intake, intake of trans isomers was directly related to risk of CHD (relative risk for highest vs lowest quintile 1.50 [95% Cl 1.12-2.00], p for trend = 0.001). Additional control for established CHD risk factors, multivitamin use, and intakes of saturated fat, monounsaturated fat, and linoleic acid, dietary cholesterol, vitamins E or C, carotene, or fibre did not change the relative risk substantially. The association was stronger for the 69,181 women whose margarine consumption over the previous 10 years had been stable (1.67 [1.05-2.66], p for trend = 0.002). Intakes of foods that are major sources of trans isomers (margarine, cookies [biscuits], cake, and white bread) were each significantly associated with higher risks of CHD. These findings support the hypothesis that consumption of partially hydrogenated vegetable oils may contribute to occurrence of CHD.

Age Factors↗

A comparison of prospective and retrospective assessments of diet in the study of breast cancer.

Fat intake was examined in relation to risk of breast cancer using dietary questionnaires administered both before and after the diagnosis of breast cancer. Among the Nurses' Health Study cohort members who completed a food frequency questionnaire and were free of cancer in 1986, 398 were diagnosed with breast cancer during 2 years of follow-up. These cases and 798 age-matched controls (cohort members who also completed a dietary questionnaire in 1986 but did not develop breast cancer) were sent another food frequency questionnaire in 1989 inquiring about their diet in 1985. Three hundred cases and 602 controls responded to the second questionnaire. The age-adjusted analysis using the prospective (1986) questionnaire demonstrated no appreciable associations between breast cancer incidence and intakes of total fat (odds ratio (OR) between highest and lowest quintiles = 0.87; 95% confidence interval (CI) 0.54-1.40) and saturated fat (OR = 0.97; CI 0.64-1.46). The age-adjusted analysis using the retrospective (1989) questionnaire suggested positive associations between breast cancer incidence and intakes of total fat (OR = 1.43; 95% CI 0.90-2.27) and saturated fat (OR = 1.38; 95% CI 0.89-2.13). When nutrients were adjusted for total energy intake, the direction and magnitude of the differences between the prospective and retrospective analyses were similar to the analyses unadjusted for energy intake. These results suggest that case-control studies of diet and breast cancer may yield biased associations between fat intake and the risk of breast cancer.

Adult↗

Smoking cessation and decreased risk of stroke in women.

OBJECTIVE: To prospectively examine the relationship of time since stopping smoking with risk of stroke in middle-aged women. DESIGN: An ongoing prospective cohort of women with 12 years' follow-up data (1976 to 1988), in which information on smoking habits was updated every 2 years by postal questionnaire. POPULATION STUDIED: A total of 117,006 female registered nurses aged 30 to 55 years in 1976 and free of coronary heart disease, stroke, and cancer at baseline. MAIN OUTCOME MEASURES: Incident strokes (fatal and nonfatal), further subdivided into ischemic stroke, subarachnoid hemorrhage, and cerebral hemorrhage. RESULTS: The age-adjusted relative risk of total stroke among current smokers compared with never smokers was 2.58 (95% confidence interval, 2.08 to 3.19). The corresponding relative risk among former smokers was 1.34 (95% confidence interval, 1.04 to 1.73). For total and ischemic stroke, the excess risks among former smokers largely disappeared from 2 to 4 years after cessation. The same patterns of decline were observed regardless of number of cigarettes smoked, the age at starting, or the presence of other risk factors for stroke. CONCLUSIONS: The risk of suffering among cigarette smokers declines soon after cessation and the benefits are independent of the age at starting and the number of cigarettes smoked per day.

Adult↗

Recall and selection bias in reporting past alcohol consumption among breast cancer cases.

Recall and selection bias are well-recognized potential problems in case-control studies of alcohol and cancer, but few analyses have attempted to assess the direction and the magnitude of these potential biases. We thus examined alcohol consumption in relation to risk of breast cancer using dietary questionnaires administered both before and after the diagnosis of breast cancer in the Nurses' Health Study (United States). Among cohort members who completed a dietary questionnaire in 1986 and who were free of cancer, 616 were diagnosed with breast cancer during follow-up to December 1989. These cases and 1,277 controls (a random sample of cohort members who did not develop cancer up to 1990) then were sent another questionnaire inquiring about their diet in 1985. Four hundred and ninety-four cases (80.2 percent) and 999 controls (78.2 percent) responded to the second questionnaire. The analysis based on the prospective (1986) questionnaire demonstrated an elevated risk of breast cancer among women who drank 30 or more g of alcohol daily (about two drinks) relative to nondrinkers (odds ratio [OR] = 1.55, 95 percent confidence interval [CI] = 1.01-2.39). The analysis based on the retrospective questionnaire also indicated a similar but slightly attenuated elevation of risk of breast cancer among women who drank at least 30 g daily (OR = 1.42, CI = 0.85-2.40). In these data, bias due to selection and recall had only minor effects on reported intake of alcohol consumption.

Adult↗

Antioxidant micronutrients and breast cancer.

We reviewed epidemiologic evidence on the relationship between four antioxidant micronutrients (vitamin A, vitamin C, vitamin E, and selenium) and breast cancer risk. Available data support a modest protective effect of vitamin A, although more studies are needed to examine further this association and to assess the relative contributions of preformed vitamin A (retinol) and carotenoids. In addition, the possibility that some other component of vitamin A-rich foods may account for this observed association should be explored. Data on the relationship between vitamins C and E and breast cancer risk are limited and inconsistent, and further information is necessary. A substantial body of evidence indicates a lack of any appreciable effect of selenium intake on breast cancer risk, at least within the range of human diets. Future observational studies should ideally be prospective in design, as prospective studies are less prone to selection and recall bias than are case-control studies, and should address methodologic issues such as confounding by other micronutrients and appropriate storage conditions of blood specimens. Although hypotheses relating micronutrient intake to risk of breast cancer should be tested in randomized trials, ethical and logistical constraints make these studies difficult to perform.

Antioxidants↗

Antioxidants and cardiovascular disease: a review.

In spite of the significant decline in cardiovascular disease (CVD) mortality over the past several decades, CVD remains the leading cause of death in the United States. Although age-specific CVD rates are higher in men than women, CVD is nonetheless the leading cause of death for both sexes, and is responsible for approximately one-third of all fatalities in women as well as men. Antioxidant vitamins are a promising area of current research in the prevention of CVD. The postulated mechanism for such an effect derives from basic research demonstrating the ability of antioxidants to inhibit the oxidation of low-density lipoprotein cholesterol. Epidemiologic studies that have explored the antioxidant vitamin hypothesis include descriptive and cross-sectional studies, analytic investigations using case-control and prospective cohort study designs, as well as several small randomized clinical trials. Findings from these studies are not totally consistent, but generally support the hypothesis that antioxidant vitamins reduce the risk of CVD. Overall, there are fewer data in women than men. Large-scale randomized trials are now ongoing that will provide reliable evidence on this question. The ongoing Physicians' Health Study of over 22,000 men is testing beta-carotene, while the recently begun Women's Health Study of 40,000 women will test, utilizing a factorial design, beta-carotene as well as vitamin E. A trial has also recently been funded to test beta-carotene, vitamin E and vitamin C in secondary prevention among a high-risk population of 8,000 women with prior CVD events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Height and incidence of cardiovascular disease in male physicians.

BACKGROUND: An inverse association between height and risk of coronary heart disease (CHD) has been reported in several case-control and cohort studies, but the reasons for the association remain uncertain. We evaluated this association among 22,071 male physicians, a population homogeneous for high educational attainment and socioeconomic status in adulthood. METHODS AND RESULTS: The study population was comprised of participants in the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of low-dose aspirin and beta-carotene in the primary prevention of cardiovascular disease and cancer among US male physicians, aged 40 to 84 years, in 1982. Participants were classified into five height categories at study entry, from shortest to tallest, and were followed an average of 60.2 months to determine the incidence of myocardial infarction (MI), stroke, and death from cardiovascular disease. Men in the tallest (> or = 73 in. or 185.4 cm) compared with the shortest (< or = 67 in. or 170.2 cm) height category had a 35% lower risk of MI (relative risk, 0.65; 95% confidence interval, 0.44 to 0.99; P = .04), after adjusting for known cardiovascular risk factors. Further, a marginally significant inverse trend (P trend = .05) across the height categories was observed. Although the relationship was not strictly linear, for every inch of added height, there was an approximate 2% to 3% decline in risk of MI. In contrast, men in the tallest compared with the shortest height category had only small and nonsignificant decreases in risk of stroke and cardiovascular death. While no significant trend in risks of these end points across the height categories was observed, the numbers of events for these end points were far less than for MI, and thus the confidence intervals were wide. CONCLUSIONS: These data indicate that height is inversely associated with subsequent risk of MI. At this time, a few mechanisms are plausible, but none are convincing. Other epidemiological and basic research efforts are needed to explore a variety of physiological correlates of height that may be responsible for mediating the height-MI association. In the meantime, while height is not modifiable, it is easy to measure and may be useful to evaluate CHD disease risk profiles and target lifestyle interventions.

Adjuvants, Immunologic↗

Cigarette smoking and the risk of diabetes in women.

OBJECTIVES: Noninsulin-dependent diabetes mellitus, a major risk factor for cardiovascular disease, is prevalent in more than 12 million Americans. A voluminous amount of data demonstrates that cigarette smoking is an important cause of cancer and coronary heart disease. However, the association between cigarette smoking and the risk of diabetes is virtually unexplored, especially in women. METHODS: We examined the association between smoking and the incidence of noninsulin-dependent diabetes mellitus among 114,247 female nurses who were free of diabetes, cardiovascular disease, and cancer in 1976. We collected exposure information and disease status prospectively for 12 years from biennially self-administered questionnaires. RESULTS: Current smokers had an increased risk of diabetes, and we observed a significant dose-response trend for higher risk among heavier smokers. During 1,277,589 person-years of follow-up, 2333 women were clinically diagnosed with diabetes. The relative risk of diabetes, adjusted for obesity and other risk factors, was 1.42 among women who smoked 25 or more cigarettes per day compared with nonsmokers. CONCLUSIONS: These data suggest that cigarette smoking may be an independent, modifiable risk factor for noninsulin-dependent diabetes mellitus.

Adult↗

Comparison of diets of diabetic and nondiabetic women.

OBJECTIVE: To assess the dietary habits of diabetic women. RESEARCH DESIGN AND METHODS: Participants in the Nurses Health Study, a cohort of 121,700 registered female nurses, were followed since 1976. We compared the usual dietary intakes of women who had been diagnosed with diabetes mellitus by 1980 and age-matched nondiabetic control women; diets of these women were assessed in 1980 and 1984 by a semiquantitative food frequency questionnaire. The study examined 162 IDDM women and 738 NIDDM women. Similar comparisons were made for 429 women who developed NIDDM between 1980 and 1984. RESULTS: Although differences were small, women with IDDM in 1984 and women with NIDDM in 1980 and 1984 consumed less energy from carbohydrates, especially from sucrose, and more energy from protein and fat than did control women. Similar results were also found in 1984 for the 429 women who developed NIDDM between 1980 and 1984. In 1980, energy from nonsucrose carbohydrate was slightly higher in both IDDM and NIDDM women than in the control women. However, in 1984, using a dietary questionnaire designed to assess more complete dietary intake, less consistent results were obtained. Diabetic women tended to avoid desserts and sweets, sugar-containing beverages, and alcoholic beverages but consumed more meat and meat products. Intakes of foods high in complex carbohydrates (e.g., bread, rice, pasta, and potatoes) were similar between diabetic and control women. CONCLUSIONS: The results suggest that these diabetic women did not consume the high-carbohydrate, low-fat diets that the American Diabetes Association has been recommending over the past decade.

Adult↗

Dietary fat and fiber in relation to risk of breast cancer. An 8-year follow-up.

OBJECTIVE: To address the hypotheses that dietary fat increases and fiber decreases the risk of breast cancer. DESIGN: Prospective cohort study with dietary assessment at baseline, using a validated, self-administered food frequency questionnaire. SETTING/PARTICIPANTS: 89,494 women in the Nurses' Health Study who were 34 through 59 years of age in 1980 and who were followed up for 8 years (> 95% complete). RESULTS: 1439 incident cases of breast cancer were diagnosed, including 774 among postmenopausal women. After adjustment for age, established risk factors, and total energy intake, we observed no evidence of any positive association between total fat intake and breast cancer incidence (relative risks [RRs] for increasing quintiles of fat intake were 1.0, 0.85, 0.96, 0.91, and 0.90; 95% confidence interval for highest vs lowest quintile, 0.77 to 1.07). Among postmenopausal women alone, corresponding RRs were 1.0, 0.89, 1.00, 0.95, and 0.91. Comparing extreme deciles of total fat intake (> or = 49% vs < 29% of total energy intake), the RR was 0.86 (95% confidence interval, 0.67 to 1.08). A similar absence of any positive association was observed without adjustment for energy intake; for tumors less than 2 cm as well as 2 cm or greater in diameter; for saturated, monounsaturated, and polyunsaturated fat; and after excluding the first 4 years of follow-up. Also, we found no suggestion of any positive association when using a more detailed and precise dietary questionnaire completed in 1984 (666 subsequent cases), even when women consuming less than 25% of energy from fat were used as the comparison group. No suggestion of a protective effect of dietary fiber was observed (RRs for increasing quintiles were 1.0, 0.95, 0.93, 1.02, and 1.02). CONCLUSIONS: These data provide evidence against both an adverse influence of fat intake and a protective effect of fiber consumption by middle-aged women on breast cancer incidence over 8 years. Nevertheless, the positive association between intake of animal fat and risk of colon cancer observed in many studies provides ample reason to limit this source of energy.

Adult↗

A prospective study of cigarette smoking and risk of cataract in men.

OBJECTIVE: To examine the association between cigarette smoking and the incidence of cataract. DESIGN, SETTING, AND PARTICIPANTS: The design was a prospective cohort study using data from the Physicians' Health Study, a randomized trial of aspirin and beta carotene among 22,071 US male physicians aged 40 to 84 years that began in 1982. This analysis includes the 17,824 physicians who did not report cataract at baseline and did provide complete risk factor information. Based on information reported at baseline, 10% were current smokers, 39% were past smokers, and 51% were never smokers. MAIN OUTCOME MEASURE: An incident cataract was defined as a self-report confirmed by medical record review to have been first diagnosed after randomization, age-related in origin, and responsible for a decrease in best corrected visual acuity to 20/30 or worse. MAIN RESULTS: During 60 months of follow-up, 557 incident cataracts among 371 participants were confirmed. Compared with never smokers, current smokers of 20 or more cigarettes per day had a statistically significant increase in the risk of cataract (relative risk [RR], 2.16; 95% confidence interval [Cl], 1.46 to 3.20; P less than .001). Similar results were obtained after simultaneously controlling for other potential cataract risk factors in a logistic regression model (RR, 2.05; 95% Cl, 1.38 to 3.05; P less than .001). Among the 557 eyes with cataract, nuclear sclerotic changes were present in 442 while posterior subcapsular changes were present in 204. After controlling for other potential cataract risk factors, current smokers of 20 or more cigarettes per day had statistically significant increases in nuclear sclerosis (RR, 2.24; 95% Cl, 1.47 to 3.41; P less than .001) and posterior subcapsular (RR, 3.17; 95% Cl, 1.81 to 5.53; P less than .001) cataract. Past smokers had an elevated risk of posterior subcapsular (RR, 1.44; 95% Cl, 0.97 to 2.13; P = .07) but not nuclear sclerosis cataract. For current smokers of fewer than 20 cigarettes per day, no increased risks were observed of total, nuclear sclerosis, or posterior subcapsular cataract. CONCLUSIONS: These data provide support for the hypothesis that cigarette smoking increases the risk of developing both nuclear sclerosis and posterior subcapsular cataract.

Adult↗

Low-dose aspirin and subsequent peripheral arterial surgery in the Physicians' Health Study.

In the US Physicians' Health Study the early termination of the aspirin arm has provided the opportunity to test the hypothesis that low-dose aspirin (325 mg on alternate days) might affect the subsequent occurrence of peripheral arterial surgery. In the study, a randomised double-blind placebo-controlled trial among 22,071 healthy US male physicians aged 40-84, there were, during an average of 60.2 months of treatment and follow-up, 56 participants who underwent peripheral arterial surgery (20 aspirin, 36 placebo). The relative risk of peripheral artery surgery in the aspirin group was 0.54 (95% confidence intervals 0.30-0.95; p = 0.03). These data indicate that chronic administration of low-dose aspirin to apparently healthy men reduced the need for peripheral arterial surgery.

Adult↗

Comparison of delay times to hospital presentation for physicians and nonphysicians with acute myocardial infarction.

To evaluate whether patients who recognize the symptoms of myocardial ischemia and have easy access to medical care have shortened time delays between onset of symptoms and hospital presentation, the total time interval between symptom onset and hospital arrival for 258 U.S. male physicians experiencing a first acute myocardial infarction (AMI) in the Physicians' Health Study (PHS) was compared with that of a comparable group of 240 men enrolled in the U.S. component of the Second International Study of Infarct Survival (ISIS-2), as well as with those of previously published series of patients with AMI. For patients presenting for medical care within 24 hours of symptom onset, the median time delay from onset of symptoms to presentation for medical care was 1.8 hours in the PHS, and 4.9 hours in the U.S. component of ISIS-2 (p less than 0.001). Furthermore, 56% of participants in the PHS presented for medical care within 2 hours and 72% within 4 hours of symptom onset compared with 20% (p less than 0.001) and 44% (p less than 0.001), respectively, for ISIS-2 participants. In previously published series, the average time to presentation was comparable to that in the ISIS-2 trial, with variation depending on country of origin and on local population density. The median time to medical presentation in any previous series was not shorter than that in the PHS. Thus, physicians in the PHS had significantly shorter time delays between onset of symptoms and presentation for medical care. This difference may help explain the far lower than expected cardiovascular mortality rates among physician participants in the PHS.(ABSTRACT TRUNCATED AT 250 WORDS)

Chi-Square Distribution↗