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Biomedical subjects

J E Buring

Publications and source records attributed to J E Buring.

At least 19 recordsLinked to original sources

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

Decreased HDL2 and HDL3 cholesterol, Apo A-I and Apo A-II, and increased risk of myocardial infarction.

BACKGROUND: A large and consistent body of evidence supports the judgment that elevation of total plasma blood cholesterol is a cause of myocardial infarction (MI) and that high levels of low density lipoprotein (LDL) cholesterol have a positive relation and high levels of high density lipoprotein (HDL) cholesterol an inverse relation with MI. At present, however, the roles, if any, of the major subfractions of HDL, namely, HDL2 and HDL3, have not been clarified. In addition, the relation of plasma apolipoprotein concentrations to MI and whether they provide predictive information over and above their lipoprotein cholesterol associations is unknown. METHODS AND RESULTS: We evaluated these questions in a case-control study of patients hospitalized with a first MI and neighborhood controls of the same age and sex. Cases had significantly lower levels of total HDL (p less than 0.0001) as well as HDL2 (p less than 0.0001) and HDL3 (p less than 0.0001) cholesterol. These differences persisted after controlling for a large number of demographic, medical history, and behavioral risk factors and levels of other lipids. There were significant (p less than 0.0001) inverse dose-response relations with odds ratios for those in the highest quartile relative to those in the lowest of 0.15 for total HDL, 0.17 for HDL2, and 0.29 for HDL3 cholesterol levels. Levels of LDL and very low density lipoprotein cholesterol and triglycerides were also higher among cases than controls, but only for triglycerides was the difference statistically significant after adjustment for coronary risk factors and other lipids (p = 0.044). Apolipoproteins A-I and A-II were both significantly (p less than 0.0001) lower in cases, and differences remained even after adjustment for coronary risk factors and lipids. There were significant dose-response relations for both apolipoprotein A-I (p = 0.026) and A-II (p = 0.002). Neither apolipoprotein B nor E was significantly related to MI after adjustment for lipids and other coronary risk factors. When all four apolipoproteins were taken together, there was an increased level of prediction of MI over the information provided by the lipids and other coronary risk factors (p = 0.003), but this appeared present only for the individual apolipoproteins A-I (p = 0.027) and A-II (p = 0.011). CONCLUSIONS: These data indicate that both HDL2 and HDL3 cholesterol levels are significantly associated with MI. They also raise the possibility that apolipoprotein levels, especially A-I and A-II, may add importantly relevant information to determination of risk of MI.

Age Factors

Occupation and risk of nonfatal myocardial infarction.

BACKGROUND: While some analytic studies have suggested that individuals in occupations representing higher compared with lower socioeconomic status have a decreased risk of coronary heart disease, it is unclear whether occupation itself has an etiologic role in the development of coronary heart disease or whether differences in as yet uncontrolled coronary risk factors may account for these differences in risk. METHODS: White-collar vs blue-collar occupation and risk of coronary heart disease was evaluated among 230 male patients hospitalized for a first myocardial infarction and 222 control subjects of the same age, sex, and neighborhood of residence. Information on coronary risk factors was obtained from home interviews, and blood specimens were drawn to test lipid and lipoprotein levels. Usual occupation was dichotomized into white-collar and blue-collar occupation according to the Edwards' classification. RESULTS: The relative risk of myocardial infarction of white-collar compared with blue-collar workers was 0.74 (95% confidence interval, 0.46 to 1.19) after controlling for age, cigarette smoking, family history of premature myocardial infarction, history of treatment for high blood pressure, body mass index, history of diabetes, alcohol consumption, type A personality, leisure-time physical activity, total calories, and percentage of calories consumed as saturated fat. However, there was no residual association after control for high-density lipoprotein cholesterol yielding a relative risk of 0.98 (95% confidence interval, 0.59 to 1.63). CONCLUSIONS: These results suggest that white-collar occupation per se does not appear to protect from coronary heart disease. Any apparent protective effect on myocardial infarction that has been previously observed in white-collar compared with blue-collar workers may be attributable to differences in high-density lipoprotein cholesterol levels.

Alcohol Drinking

Low-dose aspirin therapy for chronic stable angina. A randomized, placebo-controlled clinical trial.

OBJECTIVE: To evaluate the efficacy of low-dose aspirin in the primary prevention of myocardial infarction among patients with chronic stable angina. DESIGN: A randomized, double-blind, trial. PATIENTS: The study included 333 men with baseline chronic stable angina but with no previous history of myocardial infarction, stroke, or transient ischemic attack who were enrolled in the Physicians' Health Study, a trial of aspirin among 22,071 male physicians. INTERVENTION: Patients were randomly assigned to receive alternate-day aspirin therapy (325 mg) or placebo and were followed for an average of 60.2 months for the occurrence of myocardial infarction, stroke, or cardiovascular death. RESULTS: During follow-up, 27 patients had confirmed myocardial infarctions; 7 were among the 178 patients with chronic stable angina who received aspirin therapy and 20 were among the 155 patients who received placebo (relative risk, 0.30; 95% CI, 0.14 to 0.63; P = 0.003). While simultaneously controlling for other cardiovascular risk factors in a proportional hazards model, an overall 87% risk reduction was calculated (relative risk, 0.13; CI, 0.04 to 0.42; P less than 0.001). For the subgroup of patients with chronic stable angina but no previous coronary bypass surgery or coronary angioplasty, an almost identical reduction in the risk for myocardial infarction was found (relative risk, 0.14; CI, 0.04 to 0.56; P = 0.006). Of 13 strokes, 11 occurred in the aspirin group and 2 in the placebo group (relative risk, 5.4; CI, 1.3 to 22.1; P = 0.02). No stroke was fatal, but 4 produced some long-term impairment of function. One stroke, in the aspirin group, was hemorrhagic. CONCLUSION: Our data indicated that alternate-day aspirin therapy greatly reduced the risk for first myocardial infarction among patients with chronic stable angina, a group of patients at high risk for cardiovascular death (P less than 0.001). Although our results for stroke were based on small numbers, they suggested an apparent increase in frequency of stroke with aspirin therapy; this finding requires confirmation in randomized trials of adequate sample size.

Adult

Low-dose aspirin and risks of cataract in a randomized trial of US physicians.

Observational studies have raised the question of a possible benefit of aspirin on the development of cataract. The Physicians' Health Study, a randomized double-masked placebo-controlled trial among 22,071 male physicians, aged 40 to 84 years, provided the opportunity to collect information about whether low-dose aspirin therapy (325 mg on alternate days) affects the development or extraction of cataract. There were 173 age-related cataracts among those physicians assigned to aspirin therapy and 180 among those given placebo (relative risk, 0.95; 95% confidence interval, 0.74 to 1.22). Cataract extractions were less frequent in the aspirin than in the placebo group, but this difference was not statistically significant (relative risk, 0.80; 95% confidence interval, 0.56 to 1.15). Among younger men (aged 40 to 59 years), the relative risks were 0.62 (95% confidence interval, 0.40 to 0.94) for cataract development and 0.67 (95% confidence interval, 0.38 to 1.31) for cataract extraction. These randomized trial data tend to exclude any large benefit of aspirin. While the overall findings concerning cataract development seem to be null, the data on extraction of age-related cataract, while not statistically significant, cannot exclude a possible small to moderate benefit of alternate-day aspirin therapy on the extraction of age-related cataract.

Adult

Estimating the effect of the run-in on the power of the Physicians' Health Study.

In the Physicians' Health Study, a randomized, placebo-controlled, double-blind trial of aspirin in the reduction of cardiovascular mortality and beta-carotene in decreasing cancer incidence, 33,223 subjects were eligible and willing to enter the trial. Instead of randomizing this group immediately, all participants received identical calendar packs that contained active aspirin and beta-carotene placebo. Following an 18-week run-in, only 22,071 subjects who remained eligible and willing and had taken at least 2/3 of their pills were randomized. We estimated the effect of the run-in as follows: pill taking compliance increased 20-41 per cent; sample size decreased 34 per cent; duration of follow-up decreased 7 per cent which resulted in a 7 per cent decrease in the expected event rate for the placebo group. To estimate these changes, we made assumptions about compliance and outcome risk for those excluded by the run-in. Our conclusion, however, about the net effect of the run-in on the power of the study remains constant across variations in a number of those assumptions. The power with the run-in, with 22,071 good compliers was typically higher, and never more than negligibly lower, than the power without the run-in, with 33,223 good and poor compliers. In addition, savings from enrolling 11,152 fewer subjects in the trial resulted from the use of the run-in.

Aspirin

The effect of chronic platelet inhibition with low-dose aspirin on atherosclerotic progression and acute thrombosis: clinical evidence from the Physicians' Health Study.

Low-dose aspirin has been postulated to decrease risks of cardiovascular disease by affecting atherosclerotic progression as well as acute thrombosis. In the Physicians' Health Study, a randomized double-blind placebo-controlled trial of alternate day aspirin (325 mg), 22,071 apparently healthy male physicians were treated and followed over a period of 5 years for the occurrence of myocardial infarction and of new angina pectoris. In an analysis of the cumulative incidence and cumulative relative risks of these end points, it was found that the full protective effect of aspirin in reducing the risk of myocardial infarction is apparent soon after initiation of therapy and does not change over time. In contrast, long-term aspirin therapy has no apparent role in decreasing the risk of developing future angina pectoris. Taken together, these clinical observations support the hypothesis that the primary effect of prophylactic low-dose aspirin therapy is to inhibit acute thrombosis, but do not support the hypothesis that long-term platelet inhibition for a duration of up to 5 years slows the initiation and progression of atherosclerosis.

Acute Disease

Clinical characteristics of nonfatal myocardial infarction among individuals on prophylactic low-dose aspirin therapy.

BACKGROUND: The influence of prophylactic low-dose aspirin on the clinical characteristics of subsequent nonfatal myocardial infarction was examined in the Physicians' Health Study, a randomized, double-blind placebo-controlled trial of alternate-day aspirin (325 mg) among 22,071 US male physicians. METHODS AND RESULTS: During 60.2 months of follow-up, 342 incident cases of nonfatal myocardial infarction were confirmed (95.2% of all reports): 129 on aspirin and 213 on placebo (p less than 0.00001). Despite this statistically extreme reduction in occurrence of a first nonfatal infarction attributable to aspirin, there were no significant differences in the size, location, electrocardiographic features, or postinfarction left ventricular ejection fraction between the aspirin and placebo groups. Furthermore, among those undergoing angiography, there were no differences in the distribution or number of coronary vessels obstructed. CONCLUSIONS: These data indicate that chronic platelet inhibition with alternate-day aspirin therapy reduces the risk of a first myocardial infarction but does not appear to have a significant effect on the clinical characteristics of events that are survived. This finding may result from a direct effect of aspirin or from an aspirin-induced shift in infarction severity. Regardless of mechanism, these clinical observations suggest that treatment decisions for acute infarction patients should be made independently of a history of aspirin use.

Adult

Low-dose aspirin for migraine prophylaxis.

The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial that studied low-dose aspirin (325 mg every other day) therapy among 22,071 US male physicians aged 40 to 84 years. Annual follow-up questionnaires requested information on the occurrence of numerous medical conditions including migraine. At the end of 60 months, morbidity follow-up was 99.7% complete, and the reported consumption of aspirin or other platelet-active drugs was 86% in the aspirin group and 14% in the placebo group. Of those randomized to aspirin, 661 (6.0%) reported migraine at some time after randomization, as compared with 818 (7.4%) of those allocated to the placebo group, representing a statistically significant 20% reduction in recurrence rate. The rate of self-report of ordinary headache was similar in the two groups. These data indicate that migraine is mediated, at least in part, by the effects of platelets and suggest that low-dose aspirin should be considered for prophylaxis among those with a history of established migraine.

Adult