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Biomedical subjects

J E Buring

Publications and source records attributed to J E Buring.

At least 73 records · Page 4Linked to original sources
PubMed1998

Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians' Health Study.

BACKGROUND: In contrast to most observational studies, the randomized Physicians' Health Study found no association between aspirin use and colorectal cancer after 5 years. OBJECTIVE: To determine the effect of randomly assigned aspirin treatment and self-selected aspirin use on the incidence of colorectal cancer after 12 years and to identify factors influencing the self-selection of regular aspirin use. DESIGN: Randomized clinical trial and prospective cohort study. SETTING: Male physicians throughout the United States. PATIENTS: 22071 healthy male physicians who were 40 to 84 years of age in 1982. INTERVENTION: 325 mg of aspirin every other day. In 1988, the aspirin arm of the randomized trial was stopped early. Participants then chose to receive either aspirin or placebo for the rest of the study. MEASUREMENTS: Annual questionnaires asking about aspirin use and other variables, including occurrence of cancer. RESULTS: Colorectal cancer was diagnosed in 341 patients during the study period. Over 12 years of follow-up, random assignment to aspirin was associated with a relative risk for colorectal cancer of 1.03 (95% CI, 0.83 to 1.28). Various gastrointestinal symptoms and diagnoses were strong predictors of less frequent aspirin use in 1988. The relative risk for colorectal cancer in persons who used aspirin frequently after 1988 was 1.07 (CI, 0.75 to 1.53). CONCLUSIONS: In the Physicians' Health Study, both randomized and observational analyses indicate that there is no association between the use of aspirin and the incidence of colorectal cancer. The low dose of aspirin used and the short treatment period may account for the null findings. However, other characteristics associated with the use of aspirin in observational studies remain a plausible alternative explanation.

Adult↗
PubMed1998

Alcohol intake, lipids and risks of myocardial infarction.

The health effects of alcohol consumption remain complex for several reasons: the risks and benefits accrue over many years, assessment of drinking is generally based on self-report, drinking habits change over time and studies estimate average daily drinking disregarding how or when the beverage was consumed. In addition, alcohol consumption is associated with lifestyle factors which may confound relationship with disease. Despite these methodological difficulties, epidemiological studies are surprisingly consistent, showing that light to moderate intake is associated with a lower risk of total mortality compared with those who drink heavily or do not drink at all. Thus there is a J-shaped association of alcohol intake with risk of total mortality whose basis is likely to be the effect of summing the cause-specific effects at the various drinking levels. Studies using a diversity of methods and populations have consistently reported an inverse relationship between coronary heart disease and light to moderate drinking, with the depth and width of the J-shaped mortality curve depending on the underlying risk of coronary heart disease for that population. The higher risk of death at heavy drinking levels is due to increased risk of cancer, liver diseases, cardiomyopathy and stroke. The precise mechanisms behind these effects of alcohol are only now beginning to be understood. The most plausible mechanism by which alcohol reduces the risk of coronary heart disease is by its effects on blood lipids, particularly increases in high density lipoprotein (HDL) cholesterol: about 50% of the risk reduction attributable to alcohol is explained by changes in total HDL. Further support for the HDL hypothesis comes from the lack of a differential effect of alcohol by beverage type. While the association of alcohol and cardiovascular disease is likely to be causal, any public health recommendations must consider the complexity of alcohol's metabolic, physiological and psychological effects.

Alcohol Drinking↗
PubMed1998

Low-dose aspirin and risk of cataract and subtypes in a randomized trial of U.S. physicians.

PURPOSE: To examine whether low-dose aspirin (325 mg on alternate days) reduces the risk of age-related cataract and subtypes. This report extends previous findings, including both subtypes and additional newly identified incident cases since the earlier report. METHODS: All 20,979 participants in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among U.S. male physicians age 40-84 in 1982, who did not report cataract at baseline were included. Average follow-up was five years. The main outcome measure was incident, age-related cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. RESULTS: 501 age-related cataracts were diagnosed during follow-up, including 416 with nuclear sclerosis and 212 with a posterior subcapsular component; 318 cataracts progressed to surgical extraction. Overall, there were 245 cataracts in the aspirin group and 256 in the placebo group (relative risk [RR], 0.94; 95% confidence interval [CI], 0.79 to 1.13; P = 0.52). Cataract extractions were 19% less frequent in the aspirin than in the placebo group (RR, 0.81; 95% CI, 0.65 to 1.01; P = 0.06). In subgroup analyses of subtypes, aspirin takers had a lower risk of posterior subcapsular cataract (RR, 0.74; 95% CI, 0.57 to 0.98; P = 0.03) but not nuclear sclerosis (RR, 0.96; 95% CI, 0.79 to 1.16; P = 0.65) cataract. CONCLUSIONS: Overall, these randomized trial data tend to exclude a large benefit of five years of low-dose aspirin therapy on cataract development and extraction. The data are compatible with a modest benefit on cataract extraction for this duration of aspirin therapy. Subgroup analyses raise the possibility of a modest, but potentially important, protective effect of aspirin on posterior subcapsular cataract, a particularly disabling subtype.

Adult↗
PubMed1997

Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction.

BACKGROUND: Recent data suggest that triglyceride-rich lipoproteins may play a role in atherogenesis. However, whether triglycerides, as a marker for these lipoproteins, represent an independent risk factor for coronary heart disease remains unclear, despite extensive research. Several methodological issues have limited the interpretability of the existing data. METHODS AND RESULTS: We examined the interrelationships of fasting triglycerides, other lipid parameters, and nonlipid risk factors with risk of myocardial infarction among 340 cases and an equal number of age-, sex-, and community-matched control subjects. Cases were men or women of <76 years of age with no prior history of coronary disease who were discharged from one of six Boston area hospitals with the diagnosis of a confirmed myocardial infarction. In crude analyses, we observed a significant association of elevated fasting triglycerides with risk of myocardial infarction (relative risk [RR] in the highest compared with the lowest quartile=6.8; 95% confidence interval [CI]=3.8 to 12.1; P for trend <.001). Results were not materially altered after control for nonlipid coronary risk factors. As expected, the relationship was attenuated after adjustment for HDL but remained statistically significant (RR in the highest quartile=2.7; 95% confidence interval [CI]=1.4 to 5.5; P for trend=.016). Furthermore, the ratio of triglycerides to HDL was a strong predictor of myocardial infarction (RR in the highest compared with the lowest quartile=16.0; 95% CI=7.7 to 33.1; P for trend <.001). CONCLUSIONS: Our data indicate that fasting triglycerides, as a marker for triglyceride-rich lipoproteins, may provide valuable information about the atherogenic potential of the lipoprotein profile, particularly when considered in context of HDL levels.

Adult↗
PubMed1997

Moderate alcohol consumption and risk for angina pectoris or myocardial infarction in U.S. male physicians.

BACKGROUND: Although previous studies have found that moderate alcohol intake decreases the risk for myocardial infarction, many clinicians question the validity of this finding. Furthermore, the relation of moderate drinking to the risk for other events, such as angina pectoris, is not known. OBJECTIVE: To determine whether moderate alcohol intake decreases the risk for angina pectoris or myocardial infarction in apparently healthy men. DESIGN: Prospective cohort study. SETTING: United States. PARTICIPANTS: 22,071 apparently healthy male physicians who were 40 to 84 years of age between 1981 and 1984. MEASUREMENTS: Responses to annual questionnaires. RESULTS: Through 1994, 1368 cases of new-onset angina and 690 cases of myocardial infarction had been documented. In multivariate analyses that controlled for several potential confounders, alcohol intake was strongly and inversely associated with the risk for each event (P for trend < 0.001). Compared with men who consumed less than one drink per week, those who consumed one drink per day had relative risks of 0.69 (95% CI, 0.59 to 0.81) for angina and 0.65 (CI, 0.52 to 0.81) for myocardial infarction. These associations were seen when either nondrinkers or occasional drinkers were used as the reference group. CONCLUSIONS: Moderate drinking decreases the risk for angina pectoris and myocardial infarction in apparently healthy men.

Adult↗
PubMed1997

Physical activity and risk of colon cancer: the Physicians' Health Study (United States).

Previous studies indicate that physical activity is related inversely to colon cancer risk. However, details regarding that association--whether a dose-response relation exists, whether the relation differs between non-obese and obese persons, the effect of long-term physical activity--are unclear. We examined these issues in the Physicians' Health Study (United States). Physical activity was assessed at baseline among 21,807 men, aged 40 to 84 years, and again 36 months later. Men were followed for an average of 10.9 years (from baseline) during which 217 developed colon cancer. After adjusting for potential confounders (including age, obesity, and alcohol intake), the relative risks for colon cancer associated with vigorous exercise in times per week (< 1, 1, 2-4, 5+, at baseline) were 1.0 (referent); 1.1 (95% confidence interval [CI] = 0.7-1.7); 1.2 (CI = 0.8-1.6); and 1.1 (CI = 0.7-1.6), respectively; P trend = 0.6. Physical activity was not associated significantly with colon cancer risk either among non-obese or obese men. When we used physical activity assessments at baseline as well as at 36 months, physical activity again was unrelated to colon cancer risk. These data do not support the hypothesis that physical activity reduces the risk of colon cancer. Plausible alternate explanations for the null finding include misclassification of physical activity and the potential for increased surveillance for colon cancer ('screening effect') among those physically active.

Adult↗
PubMed1996

A prospective study of cigarette smoking and risk of age-related macular degeneration in men.

OBJECTIVE: To examine the association between cigarette smoking and the incidence of age-related macular degeneration (AMD) in men. DESIGN: Prospective cohort study with average person-years of follow-up for AMD of 12.2 years. PARTICIPANTS: A total of 21 157 US male physicians participating in the Physicians' Health Study who did not have a diagnosis of AMD at baseline, were followed for at least 7 years, and had known levels of baseline smoking. Based on information reported at baseline, 11% were current smokers, 39% were past smokers, and 50% were never smokers. MAIN OUTCOME MEASURE: Incident AMD, defined as a self-report that was confirmed by medical record, review, first diagnosed after randomization, and responsible for vision loss to 20/30 or worse. RESULTS: A total of 268 incident cases of AMD with vision loss were confirmed. In multivariate analysis, current smokers of 20 or more cigarettes per day, compared with never smokers, had an increased risk of AMD (relative risk [RR], 2.46; 95% confidence interval [CI], 1.60-3.79). Past smokers had a modest elevation in risk of AMD (RR, 1.30; 95% CI, 0.99-1.70). For current smokers of fewer than 20 cigarettes per day, there was a nonsignificant 26% increased risk of AMD (RR, 1.26; 95% CI, 0.61-2.59). CONCLUSIONS: These prospective data provide support for the hypothesis that cigarette smoking increases the risk of developing AMD.

Adult↗
PubMed1996

Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease.

BACKGROUND: Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease, and earlier basic research suggested plausible mechanisms. Because large randomized trials of long duration were necessary to test this hypothesis directly, we conducted a trial of beta carotene supplementation. METHODS: In a randomized, double-blind, placebo-controlled trial of beta carotene (50 mg on alternate days), we enrolled 22,071 male physicians, 40 to 84 years of age, in the United States; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982. By December 31, 1995, the scheduled end of the study, fewer than 1 percent had been lost to follow-up, and compliance was 78 percent in the group that received beta carotene. RESULTS: Among 11,036 physicians randomly assigned to receive beta carotene and 11,035 assigned to receive placebo, there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease, or in overall mortality. In the beta carotene group, 1273 men had any malignant neoplasm (except nonmelanoma skin cancer), as compared with 1293 in the placebo group (relative risk, 0.98; 95 percent confidence interval, 0.91 to 1.06). There were also no significant differences in the number of cases of lung cancer (82 in the beta carotene group vs. 88 in the placebo group); the number of deaths from cancer (386 vs. 380), deaths from any cause (979 vs. 968), or deaths from cardiovascular disease (338 vs. 313); the number of men with myocardial infarction (468 vs. 489); the number with stroke (367 vs. 382); or the number with any one of the previous three end points (967 vs. 972). Among current and former smokers, there were also no significant early or late differences in any of these end points. CONCLUSIONS: In this trial among healthy men, 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms, cardiovascular disease, or death from all causes.

Adult↗
PubMed1996

Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate.

Elevated plasma homocyst(e)ine levels are an independent risk factor for vascular disease. In a case-control study, the authors studied the associations of fasting plasma homocyst(e)ine and vitamins, which are important cofactors in homocysteine metabolism, with the risk of myocardial infarction. The cases were 130 Boston area patients hospitalized with a first myocardial infarction and 118 population controls, less than 76 years of age, enrolled in 1982 and 1983. Dietary intakes of vitamins B6, B12, and folate were estimated from a food frequency questionnaire. After adjusting for sex and age, the authors found that the geometric mean plasma homocyst(e)ine level was 11% higher in cases compared with controls (p = 0.006). There was no clear excess of cases with extremely elevated levels. The age- and sex-adjusted odds ratio for each 3-mumol/liter (approximately 1 standard deviation) increase in plasma homocyst(e)ine was 1.35 (95% confidence interval 1.05-1.75; p trend = 0/007). After further control for several risk factors, the odds ratio was not affected, but the confidence interval was wider and the p value for trend was less significant. Dietary and plasma levels of vitamin B6 and folate were lower in cases than in controls, and these vitamins were inversely associated with the risk of myocardial infarction, independently of other potential risk factors. Vitamin B12 showed no clear association with myocardial infarction, although methylmalonic acid levels were significantly higher in cases. Comparing the mean levels of several homocysteine metabolites among cases and controls, the authors found that impairment of remethylation of homocyst(e)ine (dependent of folate and vitamin B12 rather than on vitamin B6-dependent transsulfuration) was the predominant cause of high homocyst(e)ine levels in cases. Accordingly, plasma folate and, to a lesser extent, plasma vitamin B12, but not vitamin B6, correlated inversely with plasma homocyst(e)ine, even for concentrations at the high end of normal values. These data provide further evidence that plasma homocyst(e)ine is an independent risk factor for myocardial infarction. In this population, folate was the most important determinant of plasma homocyst(e)ine, even in subjects with apparently adequate nutritional status of this vitamin.

Case-Control Studies↗
PubMed1996

Self-reported breast implants and connective-tissue diseases in female health professionals. A retrospective cohort study.

OBJECTIVE: To evaluate the association of breast implants with connective-tissue diseases. DESIGN AND PARTICIPANTS: Retrospective cohort study of 395,543 female health professionals who completed mailed questionnaires for potential participation in the Women's Health Study. A total of 10,830 women reported breast implants and 11,805 reported connective-tissue diseases between 1962 and 1991. Cox proportional hazards regression models were used in analyses. MAIN OUTCOME MEASURE: Self-reported connective-tissue diseases. RESULTS: Compared with women who did not report breast implants, the relative risk (RR) of the combined end point of any connective-tissue disease among those who reported breast implants was 1.24 (95% confidence interval, 1.08 to 1.41, P = .0015). With respect to the individual diseases, the finding for other connective-tissue diseases (including mixed) was statistically significant (P = .017), the findings for rheumatoid arthritis, Sjogren's syndrome, dermatomyositis or polymyositis, or scleroderma were of borderline statistical significance (.05 < P < .10), and the finding for systemic lupus erythematosus was not statistically significant (P = .44). There were no clear trends in RR with increasing duration of breast implants. CONCLUSION: These self-reported data from female health professionals are compatible with prior reports from other cohort studies that exclude a large hazard, but do suggest small increased risks of connective-tissue diseases among women with breast implants. The very large sample size makes chance an unlikely explanation for the results, but bias due to differential overreporting of connective-tissue diseases or selective participation by affected women with breast implants remains a plausible alternative explanation. The major contribution of this and other observational analytic studies has been to exclude large risks of connective-tissue diseases following breast implants.

Adult↗
PubMed1996

Ways of measuring rates of recurrent events.

Recurrent events are common in medical research, yet the best ways to measure their occurrence remain controversial. Moreover, the correct statistical techniques to compare the occurrence of such events across populations or treatment groups are not widely known. In both observational studies and randomised clinical trials one natural and intuitive measure of occurrence is the event rate, defined as the number of events (possibly including multiple events per person) divided by the total person-years of experience. This is often a more relevant and clinically interpretable measure of disease burden in a population than considering only the first event that occurs. Appropriate statistical tests to compare such event rates among treatment groups or populations require the recognition that some individuals may be especially likely to experience recurrent events. Straightforward approaches are available to account for this tendency in crude and stratified analyses. Recently developed regression models can appropriately examine the association of several variables with rates of recurrent events.

Health Services Research↗
PubMed1996

Interobserver agreement in the classification of stroke in the physicians' health study.

BACKGROUND AND PURPOSE: The evaluation of cerebrovascular end points in prospective studies is often based exclusively on medical record examination and may be made by more than one observer over time. To address the issues of adequacy of medical record information and consistency in diagnosis over time, we evaluated interobserver agreement for the main items of the stroke classification system used in the Physicians' Health Study. This trial included 22,071 physicians randomly assigned in 1982 to receive either aspirin or placebo to assess the subsequent risk of cardiovascular events, including stroke. METHODS: Stroke subtype, stroke severity, and certainty of diagnosis were first classified from medical records from the years 1982 through 1988. The 216 stroke events reported in this period were independently reclassified in 1994 and compared with the initial classification using kappa statistics. RESULTS: Overall agreement in major stroke types (hemorrhagic, ischemic, undetermined stroke) as well as in hemorrhagic stroke subtypes was excellent (kappa = 0.81 and kappa = 0.95, respectively). A wide range of values for the ischemic stroke subtypes (kappa = 0.13 to kappa = 0.96) was obtained. Agreement was substantial in assessment of stroke severity (kappa = 0.71), and it was fair (kappa = 0.33) for certainty of diagnosis. CONCLUSIONS: Interobserver agreement is high for major stroke types as well as for categories of hemorrhagic stroke on the basis of review of medical records and results of imaging data. The classification of ischemic stroke subtypes, however, is subject to substantial interobserver disagreement. Periodic reclassification of random samples of end points might be considered in long-term prospective studies to assess potential misclassification of events by different observers.

Adult↗