Antithrombotic therapy for acute myocardial infarction.

Antithrombotic therapy is clearly beneficial in the treatment of acute myocardial infarction, but the optimal regimen is controversial. Treatment with aspirin leads to substantial and significant reductions in rates of mortality, reinfarction and stroke in patients with acute myocardial infarction, and the benefits are additive with those of thrombolytic therapy. It is unclear whether heparin confers additional net benefits over aspirin alone.

Current issues concerning thrombolytic therapy for acute myocardial infarction.

Data are now available from three large-scale randomized trials that directly compare the risks and benefits of thrombolytic agents in acute myocardial infarction. In the interpretation of results from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial and its International Extension, the Third International Study of Infarct Survival (ISIS-3), and the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial, there are areas of both agreement and controversy. It is generally agreed that the agents most commonly used in the United States--tissue-type plasminogen activator (t-PA), streptokinase and anisoylated plasminogen streptokinase activator complex (APSAC)--all reduce mortality when given to patients with acute evolving myocardial infarction.

Discrimination in absorption or transport of beta-carotene isomers after oral supplementation with either all-trans- or 9-cis-beta-carotene.

Human subjects (n = 24) were supplemented with 100 mg beta-carotene/d for 6 d, either as synthetic all-trans-beta-carotene or a natural beta-carotene preparation derived from the alga Dunaliella salina, which consists of a 50:50 mixture of all-trans- and 6-cis-beta-carotene. This loading dose was followed by a 23-d maintenance dose consisting of alternate-day supplementation with 50 mg all-trans-beta-carotene or either 66 or 100 mg of the natural 50:50 isomeric mixture. The loading dose resulted in significant increases in plasma concentrations of both isomers, with the all-trans-beta-carotene-supplemented group showing a 7.

Man-made vitreous fibers and risk of respiratory system cancer: a review of the epidemiologic evidence.

Because asbestos has been demonstrated to cause lung cancer, the issue regarding safety of other fibers, including man-made vitreous fibers (MMVF), has been raised. We reviewed the available evidence, in particular the epidemiologic data, on MMVF and the risk of respiratory system cancer. Glass fibers (especially glass wool) have been studied most extensively.

Alcohol consumption and mortality among women.

Background: Studies in men suggest that light-to-moderate alcohol intake is associated with a reduction in overall mortality, due primarily to a reduced risk of coronary heart disease. Among women with similar levels of alcohol consumption, an increased risk of breast cancer has been noted that complicates the balance of risks and benefits.

Methods: We conducted a prospective study among 85,709 women, 34 to 59 years of age and without a history of myocardial infarction, angina, stroke, or cancer, who completed a dietary questionnaire in 1980.

Relationship of alcohol intake with blood pressure in young adults.

The objective of this study was to examine the relationship of usual current alcohol intake with systolic and diastolic pressures among young adults. Participants were 316 men and women, aged 18 to 26 years, from East Boston, Mass. At each of three weekly visits we obtained three blood pressure measurements on each subject using a random-zero sphygmomanometer.

Plasma concentration of lipoprotein(a) and the risk of future stroke.

Objective: To assess prospectively the risk of future stroke associated with baseline concentration of lipoprotein(a), abbreviated Lp(a).

Design: Nested case-control study using baseline plasma samples.

Setting: Men in the Physicians' Health Study.

Implications of small reductions in diastolic blood pressure for primary prevention.

Objectives: To estimate the impact of small reductions in the population distribution of diastolic blood pressure (DBP), such as those potentially achievable by population-wide lifestyle modification, on incidence of coronary heart disease (CHD) and stroke.

Design: Published data from the Framingham Heart Study, a longitudinal cohort study, and from the National Health and Nutrition Examination Survey II, a national population survey, were used to examine the impact of a population-wide strategy aimed at reducing DBP by an average of 2 mm Hg in a population including normotensive subjects.

Setting/participants: White men and women aged 35 to 64 years in the United States.

Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men.

Background: A specific point mutation in the gene coding for coagulation factor V is associated with resistance to degradation by activated protein C, a recently described abnormality of coagulation that may be associated with an increased risk of venous thrombosis. Whether this mutation also predisposes patients to arterial thrombosis is unknown, as is the value of screening for the mutation in order to define the risk of venous thrombosis among unselected healthy people.

Methods: Among 14,916 apparently healthy men in the Physicians' Health Study who provided base-line blood samples, 374 had myocardial infarctions, 209 had strokes, and 121 had deep venous thrombosis, pulmonary embolism, or both, during a mean follow-up of 8.

Evidence for a positive linear relation between blood pressure and mortality in elderly people.

Many studies of blood pressure in the elderly have found higher death rates in groups with the lowest blood pressure than in those with intermediate values. In a large community study, we examined whether these findings are real or artifacts of short follow-up, co-morbidity, or low blood pressure in people near death. In 1982-83, we assessed drug use, medical history, disability, physical function, and blood pressure in 3657 residents of East Boston, Massachusetts, aged 65 and older.

A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease.

Background: In a previous study, men with a history of myocardial infarction were found to have an increased prevalence of homozygosity for the deletional allele (D) of the angiotensin-converting-enzyme (ACE) gene. The D allele is associated with higher levels of ACE, which may predispose a person to ischemic heart disease. We investigated the association between the ACE genotype and the incidence of myocardial infarction, as well as other manifestations of ischemic heart disease, in a large, prospective cohort of U.

Lack of blood pressure effect with calcium and magnesium supplementation in adults with high-normal blood pressure. Results from Phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase I of the Trials of Hypertension Prevention (TOHP) was a randomized, multicenter investigation that included double-blind, placebo-controlled testing of calcium and magnesium supplementation among 698 healthy adults (10.5% blacks and 31% women) aged 30 to 54 years with high-normal diastolic blood pressure (DBP) (80 to 89 mm Hg). Very high compliance (94 to 96% by pill counts) with daily doses of 1 g of calcium (carbonate), 360 mg of magnesium (diglycine), or placebos was corroborated for the active supplements by significant net increases in all urine and serum compliance measures in white men and for urine compliance measures in white women.

Weight, weight change, and coronary heart disease in women. Risk within the 'normal' weight range.

OBJECTIVE--To assess the validity of the 1990 US weight guidelines for women that support a substantial gain in weight at approximately 35 years of age and recommend a range of body mass index (BMI) (defined as weight in kilograms divided by the square of height in meters) from 21 to 27 kg/m2, in terms of coronary heart disease (CHD) risk in women. DESIGN--Prospective cohort study. SETTING--Female registered nurses in the United States.

Migraine and subsequent risk of stroke in the Physicians' Health Study.

Objective: To evaluate, in a prospective design, whether migraine is an independent risk factor for subsequent stroke.

Design: Evaluated as part of the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in the primary prevention of cardiovascular disease and cancer begun in 1982. The aspirin component of the study was terminated in 1988, with average follow-up of 60.

A prospective study of plasma fish oil levels and incidence of myocardial infarction in U.S. male physicians.

Objectives: This study evaluated whether increased intake of fish oils (eicosapentaenoic and docosahexaenoic acids) might reduce the risk of coronary heart disease.

Background: Observational and clinical studies have suggested that increased intake of fish oils, as reflected in plasma levels of fish oils, may reduce the risk of myocardial infarction.

Methods: A nested case-control study was conducted among the 14,916 participants in the Physicians' Health Study with a sample of plasma before randomization.

Childhood socioeconomic status and risk of cardiovascular disease in middle aged US women: a prospective study.

Objective: To examine prospectively the relationship of childhood socioeconomic status and risk of cardiovascular disease in middle aged women.

Design: A prospective cohort of women with 14 years follow up data (1976-90).

Subjects: A total of 117,006 registered female nurses aged 30 to 55 years in 1976 and free of diagnosed coronary heart disease, stroke, and cancer at baseline.

A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer.

Objective: To evaluate the validity of prostate-specific antigen (PSA) in identifying men who subsequently were or were not clinically diagnosed with prostate cancer, assess optimal test cutoff, measure lead time, and estimate relative risks (RRs) associated with discrete PSA levels.

Designs: Nested case-control study of men providing plasma samples before a 10-year follow-up.

Setting: The Physicians' Health Study, an ongoing randomized trial that enrolled 22,071 men aged 40 to 84 years in 1982.

Supplementation with beta-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation.

The inhibition of low density lipoprotein (LDL) oxidation has been postulated as one mechanism by which antioxidants may prevent the development of atherosclerosis. Available data on the ability of beta-carotene to inhibit LDL oxidation are conflicting. We examined the role of in vivo and in vitro supplementation with beta-carotene on metal ion-dependent (cupric ions, Cu2+) and metal ion-independent (2,2'-azobis[2-amidinopropane]dihydrochloride, AAPH) oxidation of LDL as measured by the formation of conjugated dienes (absorbance at 234 nm).

An overview of trials of cholesterol lowering and risk of stroke.

Background: While blood cholesterol level predicts coronary heart disease, whether there is any association with the risk of stroke is unclear. Some, but not all, observational studies suggest that cholesterol level predicts risk of stroke, particularly ischemic stroke. This hypothesis is attractive because ischemic events constitute the vast majority of all strokes and, like coronary heart disease, involve atherogenic processes.

Direct Comparison of Aspirin Plus Hirudin, Aspirin Plus Heparin, and Aspirin Alone Among 12,000 Patients with Acute Myocardial Infarction Not Receiving Thrombolysis: Rationale and Design of the First American Study of Infarct Survival (ASIS-1).

While antithrombotic therapy of acute myocardial infarction is clearly beneficial, substantial controversy exists regarding the optimal regimen. In particular, while aspirin alone has proven highly effective in reducing rates of reinfarction, stroke, and death following acute coronary occlusion, heparin has not clearly been shown to have additional benefit when added to aspirin but is associated with increased rates of hemorrhagic stroke and major bleeding. At the same time, available data for newer specific thrombin inhibitors such as hirudin suggest greater benefits than aspirin alone or aspirin plus heparin in terms of maintaining coronary flow, but possibly higher risks of hemorrhagic stroke and major bleeding.

beta-carotene and cancer chemoprevention.

Evidence supports the potential role of beta-carotene in cancer prevention. Basic research has demonstrated that beta-carotene can trap organic free radicals and/or deactivate excited oxygen molecules which may have an anticancer effect by preventing tissue damage. Although observational epidemiologic studies are not entirely consistent, many show an inverse association between dietary intake or blood levels of beta-carotene and subsequent cancer risk.

Intermittent claudication and subsequent cardiovascular disease in the elderly.

Background: This study reports the prevalence of intermittent claudication (IC) in ambulatory community-resident adults age 65 years or older, compares cardiovascular risk factors and comorbidity of persons with and without IC, and examines the independent association of IC in predicting all cause and cardiovascular mortality, myocardial infarction, stroke, and disability.

Methods: Data are from a pooled sample of 8996 older adults from the East Boston, New Haven, and Iowa sites of the Established Populations for Epidemiologic Studies of the Elderly, conducted between 1982 and 1988.

Results: 2.