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Biomedical subjects

M J Stampfer

Publications and source records attributed to M J Stampfer.

At least 199 records · Page 11Linked to original sources
PubMed1997

Oral contraceptives and ovulatory causes of delayed fertility.

The return of fertility for women who discontinue oral contraceptives takes longer as compared with women who discontinue other methods of contraception. It remains unclear, however, whether subsequent fertility differs according to duration or age at first use. The authors performed a nested case-control study within a cohort of 116,686 female registered nurses residing in 14 US states. Baseline information was reported on mailed questionnaires in 1989. Cases comprised 1,917 married nurses without previous pregnancy who were unable to become pregnant for at least 1 year and were subsequently diagnosed with primary ovulatory infertility. Controls comprised 44,521 married parous nurses with no history of infertility and no pregnancies lasting less than 6 months. After allowing for 2 years of suppressed fertility following discontinuation of oral contraceptive use and excluding women with signs of menstrual or hormonal disorder, the authors found that the multivariate relative risk for ovulatory causes of delayed fertility was 1.2 (95% confidence interval 0.7-1.9) for ever users. There was no statistically significant trend of increasing risk with increasing duration of use and younger age at first use. The fact that 88 percent of cases reported an eventual pregnancy by 1993 suggests that absolute fertility was not impaired.

Adult↗
PubMed1997

Postmenopausal hormone therapy and mortality.

BACKGROUND: Postmenopausal hormone therapy has both benefits and hazards, including decreased risks of osteoporosis and cardiovascular disease and an increased risk of breast cancer. METHODS: We examined the relation between the use of postmenopausal hormones and mortality among participants in the Nurses' Health Study, who were 30 to 55 years of age at base line in 1976. Data were collected by biennial questionnaires beginning in 1976 and continuing through 1992. We documented 3637 deaths from 1976 to 1994. Each participant who died was matched with 10 controls alive at the time of her death. For each death, we defined the subject's hormone status according to the last biennial questionnaire before her death or before the diagnosis of the fatal disease; this reduced bias caused by the discontinuation of hormone use between the time of diagnosis of a potentially fatal disease and death. RESULTS: After adjustment for confounding variables, current hormone users had a lower risk of death (relative risk, 0.63; 95 percent confidence interval, 0.56 to 0.70) than subjects who had never taken hormones; however, the apparent benefit decreased with long-term use (relative risk, 0.80; 0.67 to 0.96, after 10 or more years) because of an increase in mortality from breast cancer among long-term hormone users. Current hormone users with coronary risk factors (69 percent of the women) had the largest reduction in mortality (relative risk, 0.51; 95 percent confidence interval, 0.45 to 0.57), with substantially less benefit for those at low risk (13 percent of the women; relative risk, 0.89; 95 percent confidence interval, 0.62 to 1.28). CONCLUSIONS: On average, mortality among women who use postmenopausal hormones is lower than among nonusers; however, the survival benefit diminishes with longer duration of use and is lower for women at low risk for coronary disease.

Adult↗
PubMed1997

A prospective study of body mass index, weight change, and risk of stroke in women.

OBJECTIVE: To examine the associations of body mass index (BMI) and weight change with risk of stroke in women. SETTING AND DESIGN: Prospective cohort study among US female registered nurses participating in the Nurses' Health Study. PARTICIPANTS: A total of 116759 women aged 30 to 55 years in 1976 who were free from diagnosed coronary heart disease, stroke, and cancer. MAIN OUTCOME MEASURE: Incidence of ischemic stroke, hemorrhagic stroke (subarachnoid or intraparenchymal hemorrhage), and total stroke. RESULTS: During 16 years of follow-up, 866 total strokes (including 403 ischemic strokes and 269 hemorrhagic strokes) were documented. In multivariate analyses adjusted for age, smoking, postmenopausal hormone use, and menopausal status, women with increased BMI (> or =27 kg/m2) had significantly increased risk of ischemic stroke, with relative risks (RRs) of 1.75 (95% confidence interval [CI], 1.17-2.59) for BMI of 27 to 28.9 kg/m2; 1.90 (95% CI, 1.28-2.82) for BMI of 29 to 31.9 kg/m2; and 2.37 (95% CI, 1.60-3.50) for BMI of 32 kg/m2 or more (P for trend<.001), as compared with those with a BMI of less than 21 kg/m2. For hemorrhagic stroke there was a nonsignificant inverse relation between obesity and hemorrhagic stroke, with the highest risk among women in the leanest BMI category (P for trend=.20). For total stroke the RRs were somewhat attenuated compared with those for ischemic stroke but remained elevated for women with higher BMI (P for trend<.001). In multivariate analyses that also adjusted for BMI at age 18 years, weight gain from age 18 years until 1976 was associated with an RR for ischemic stroke of 1.69 (95% CI, 1.26-2.29) for a gain of 11 to 19.9 kg and 2.52 (95% CI, 1.80-3.52) for a gain of 20 kg or more (P for trend<.001), as compared with women who maintained stable weight (loss or gain <5 kg). Although weight change was not related to risk of hemorrhagic stroke (P for trend=.20), a direct relationship was observed between weight gain and total stroke risk (P for trend<.001). CONCLUSIONS: These prospective data indicate that both obesity and weight gain in women are important risk factors for ischemic and total stroke but not hemorrhagic stroke. The relationship between obesity and total stroke depends on the distribution of stroke subtypes in the population.

Adult↗
PubMed1997

A prospective study of passive smoking and coronary heart disease.

BACKGROUND: Several epidemiological studies have suggested an association of passive smoking with coronary heart disease (CHD). However, few studies have taken account of exposure to passive smoking in the workplace. Additionally, several studies have been unable to control for the full range of potential confounding factors. We examined prospectively the relationship of passive smoking with risk of CHD in a cohort of women. METHODS AND RESULTS: The study was carried out in an ongoing prospective cohort of US female nurses, in whom we assessed exposure to passive smoking at home and at work as well as duration of years spent living with someone who smoked regularly. We studied 32046 women 36 to 61 years of age in 1982 who had never smoked and were free of diagnosed CHD, stroke, and cancer. During 10 years of follow-up (1982 to 1992), 152 incident cases of CHD (127 nonfatal myocardial infarction and 25 fatal CHD) occurred. Compared with women not exposed to passive smoking, the relative risks of total CHD-adjusted for a broad range of cardiovascular risk factors-were 1.58 (95% CI, 0.93 to 2.68) among those reporting occasional exposure and 1.91 (95% CI, 1.11 to 3.28) among women reporting regular exposure to passive smoking at home or work. There was no relation apparent between duration of living with a smoker and risk of CHD. CONCLUSIONS: Despite the fact that exposure to passive smoking was assessed by self-report and only at baseline (as well as other limitations), these data suggest that regular exposure to passive smoking at home or work increases the risk of CHD among nonsmoking women.

Adult↗
PubMed1997

Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.

BACKGROUND: Inflammation may be important in the pathogenesis of atherothrombosis. We studied whether inflammation increases the risk of a first thrombotic event and whether treatment with aspirin decreases the risk. METHODS: We measured plasma C-reactive protein, a marker for systemic inflammation, in 543 apparently healthy men participating in the Physicians' Health Study in whom myocardial infarction, stroke, or venous thrombosis subsequently developed, and in 543 study participants who did not report vascular disease during a follow-up period exceeding eight years. Subjects were randomly assigned to receive aspirin or placebo at the beginning of the trial. RESULTS: Base-line plasma C-reactive protein concentrations were higher among men who went on to have myocardial infarction (1.51 vs. 1.13 mg per liter, P<0.001) or ischemic stroke (1.38 vs. 1.13 mg per liter, P=0.02), but not venous thrombosis (1.26 vs. 1.13 mg per liter, P=0.34), than among men without vascular events. The men in the quartile with the highest levels of C-reactive protein values had three times the risk of myocardial infarction (relative risk, 2.9; P<0.001) and two times the risk of ischemic stroke (relative risk, 1.9; P=0.02) of the men in the lowest quartile. Risks were stable over long periods, were not modified by smoking, and were independent of other lipid-related and non-lipid-related risk factors. The use of aspirin was associated with significant reductions in the risk of myocardial infarction (55.7 percent reduction, P=0.02) among men in the highest quartile but with only small, nonsignificant reductions among those in the lowest quartile (13.9 percent, P=0.77). CONCLUSIONS: The base-line plasma concentration of C-reactive protein predicts the risk of future myocardial infarction and stroke. Moreover, the reduction associated with the use of aspirin in the risk of a first myocardial infarction appears to be directly related to the level of C-reactive protein, raising the possibility that antiinflammatory agents may have clinical benefits in preventing cardiovascular disease.

Adult↗
PubMed1997

The CAG repeat within the androgen receptor gene and its relationship to prostate cancer.

The length of a polymorphic CAG repeat sequence, occurring in the androgen receptor gene, is inversely correlated with transcriptional activity by the androgen receptor. Because heightened androgenic stimulation may increase risk of prostate cancer development and progression, we examined whether shorter CAG repeats in the androgen receptor gene are related to higher risk of prostate cancer. We conducted a nested case-control study of 587 newly diagnosed cases of prostate cancer detected between 1982 and 1995, and 588 controls without prostate cancer, within the Physician's Health Study. An association existed between fewer androgen receptor gene CAG repeats and higher risk of total prostate cancer [relative risk (RR) = 1.52; 95% confidence interval (CI) = 0.92-2.49; P trend = 0.04; for men with CAG repeat lengths < or = 18 relative to > or = 26 repeats]. In particular, a shorter CAG repeat sequence was associated with cancers characterized by extraprostatic extension or distant metastases (stage C or D) or high histologic grade (RR = 2.14; CI = 1.14-4.01; P trend = 0.001). This association was observed individually both for high stage (RR = 2.23) and high grade prostate cancer (RR = 1.89). Men with shorter repeats were at particularly high risk for distant metastatic and fatal prostate cancer. Variability in the CAG repeat length was not associated with low grade or low stage disease. These results demonstrate that a shorter CAG repeat sequence in the androgen receptor gene predicts higher grade and advanced stage of prostate cancer at diagnosis, and metastasis and mortality from the disease. The clinical implications of these results should be evaluated further.

Adult↗
PubMed1997

Interrelation of hyperhomocyst(e)inemia, factor V Leiden, and risk of future venous thromboembolism.

BACKGROUND: Because patients with rare familial homocystinuria who also carry factor V Leiden have an increased incidence of venous thromboembolism (VTE), we hypothesized an interrelation of moderate hyperhomocyst(e)inemia, factor V Leiden, and risk of VTE in the general population. METHODS AND RESULTS: In a large prospective cohort, we determined total homocysteine level and factor V Leiden mutation in baseline blood samples from 145 initially healthy men who subsequently developed VTE and among 646 men who remained free of vascular disease during a 10-year follow-up period. Hyperhomocyst(e)inemia was defined as a total homocysteine level above the 95th percentile (17.25 mumol/L). Compared with men with normal total homocysteine levels, those with hyperhomocyst(e)inemia had no increase in risk of any VTE but were at increased risk of idiopathic VTE (relative risk [RR] = 3.4, P = .002). Compared with men without Leiden mutation, those with mutation were at increased risk of developing any VTE (RR = 2.3, P = .005) as well as idiopathic VTE (RR = 3.6, P = .0002). Compared with men with neither abnormality, those affected by both disorders had a 10-fold increase in risk of any VTE (RR = 9.65, P = .009) and a 20-fold increase in risk of idiopathic VTE (RR = 21.8, P = .0004). CONCLUSIONS: Apparently healthy men with coexistent hyperhomocyst(e)inemia and Leiden mutation are at substantially increased risk of developing future VTEs, particularly those events considered idiopathic. In these data, the risk of VTE among doubly affected individuals was far greater than the sum of the individual risks associated with either abnormality alone.

Aged↗
PubMed1997

Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women.

BACKGROUND: Calcium intake is believed to play an important role in the formation of kidney stones, but data on the risk factors for stone formation in women are limited. OBJECTIVE: To examine the association between intake of dietary and supplemental calcium and the risk for kidney stones in women. DESIGN: Prospective cohort study with 12-year follow-up. SETTING: Several U.S. states. PARTICIPANTS: 91,731 women participating in the Nurses' Health Study I who were 34 to 59 years of age in 1980 and had no history of kidney stones. MEASUREMENTS: Self-administered food-frequency questionnaires were used to assess diet in 1980, 1984, 1986, and 1990. The main outcome measure was incident symptomatic kidney stones. RESULTS: During 903,849 person-years of follow-up, 864 cases of kidney stones were documented. After adjustment for potential risk factors, intake of dietary calcium was inversely associated with risk for kidney stones and intake of supplemental calcium was positively associated with risk. The relative risk for stone formation in women in the highest quintile of dietary calcium intake compared with women in the lowest quintile was 0.65 (95% CI, 0.50 to 0.83). The relative risk in women who took supplemental calcium compared with women who did not was 1.20 (CI, 1.02 to 1.41). In 67% of women who took supplemental calcium, the calcium either was not consumed with a meal or was consumed with meals whose oxalate content was probably low. Other dietary factors showed the following relative risks among women in the highest quintile of intake compared with those in the lowest quintile: sucrose, 1.52 (CI, 1.18 to 1.96); sodium, 1.30 (CI, 1.05 to 1.62); fluid, 0.61 (CI, 0.48 to 0.78); and potassium, 0.65 (CI, 0.51 to 0.84). CONCLUSIONS: High intake of dietary calcium appears to decrease risk for symptomatic kidney stones, whereas intake of supplemental calcium may increase risk. Because dietary calcium reduces the absorption of oxalate, the apparently different effects caused by the type of calcium may be associated with the timing of calcium ingestion relative to the amount of oxalate consumed. However, other factors present in dairy products (the major source of dietary calcium) could be responsible for the decreased risk seen with dietary calcium.

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PubMed1997

Age-specific incidence rates of venous thromboembolism among heterozygous carriers of factor V Leiden mutation.

BACKGROUND: Previous reports suggest that younger carriers of the factor V Leiden mutation are at greater risk for venous thromboembolism than are older carriers. However, available data on thromboembolic risk are limited. OBJECTIVE: To determine age-specific incidence rates of venous thromboembolism associated with the factor V Leiden mutation. DESIGN: Prospective cohort study. PATIENTS: 14,916 initially healthy men participating in the Physicians' Health Study who were followed from 1982 to August 1994 for the occurrence of deep venous thrombosis or pulmonary embolism. MEASUREMENTS: Polymerase chain reaction was used to determine factor V Leiden mutation status in 156 study participants who developed venous thromboembolism during follow-up and in 2406 study participants who remained free of vascular disease. RESULTS: Risks for venous thromboembolism in heterozygous carriers of factor V Leiden mutation increased with age at a rate significantly greater than that in noncarriers. Whereas incidence rates of venous thromboembolism were similar in men with and men without the factor V Leiden mutation who were younger than 50 years of age, incidence rate differences (per 1000 person-years of observation) between affected and unaffected men increased significantly from 1.23 (95% CI, -0.4 to 2.9) for those aged 50 to 59 years to 1.61 (CI, -0.5 to 3.7) for those aged 60 to 69 years of age to 5.97 (CI, 0.6 to 11.3) for those aged 70 years or older (P for trend = 0.008). For idiopathic venous thromboembolism, age-specific incidence rate differences between men with and without the factor V Leiden mutation increased significantly with age (P = 0.017). However, no significant relation was found for secondary events (P > 0.2). CONCLUSIONS: The findings support the hypothesis that the pathogenesis of venous thromboembolism involves acquired as well as genetic risk factors and indicate that determination of factor V Leiden mutation status should not be limited to young patients.

Adult↗
PubMed1997

Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer.

Folate derivatives are important in experimental colorectal carcinogenesis; low folate intake, particularly with substantial alcohol intake, is associated with increased risk. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate, required for purine and thymidine syntheses, to 5-methyltetrahydrofolate, the primary circulatory form of folate necessary for methionine synthesis. A common mutation (677C-->T) in MTHFR reduces enzyme activity, leading to lower levels of 5-methyltetrahydrofolate. To evaluate the role of folate metabolism in human carcinogenesis, we examined the associations of MTHFR mutation, plasma folate levels, and their interaction with risk of colon cancer. We also examined the interaction between genotype and alcohol intake. We used a nested case-control design within the Physicians' Health Study. Participants were ages 40-84 at baseline when alcohol intake was ascertained and blood samples were drawn. During 12 years of follow-up, we identified 202 colorectal cancer cases and matched them to 326 cancer-free controls by age and smoking status. We genotyped for the MTHFR polymorphism and measured plasma folate levels. Men with the homozygous mutation (15% in controls) had half the risk of colorectal cancer [odds ratio (OR), 0.49; 95% confidence interval (CI), 0.27-0.87] compared with the homozygous normal or heterozygous genotypes. Overall, we observed a marginal significant increased risk of colorectal cancer (OR, 1.78; 95% CI, 0.93-3.42) among those whose plasma folate levels indicated deficiency (<3 ng/ml) compared with men with adequate folate levels. Among men with adequate folate levels, we observed a 3-fold decrease in risk (OR, 0.32; 95% CI, 0.15-0.68) among men with the homozygous mutation compared with those with the homozygous normal or heterozygous genotypes. However, the protection due to the mutation was absent in men with folate deficiency. In men with the homozygous normal genotype who drank little or no alcohol as reference, those with the homozygous mutation who drank little or no alcohol had an 8-fold decrease in risk (OR, 0.12; 95% CI, 0.03-0.57), and for moderate drinkers, a 2-fold decrease in risk (OR, 0.42; 95% CI, 0.15-1.20); no decrease in risk was seen in those drinking 1 or more drinks/day. Our findings provide support for an important role of folate metabolism in colon carcinogenesis. In particular, these results suggest that the 677C-->IT mutation in MTHFR reduces colon cancer risk, perhaps by increasing 5,10-methylenetetrahydrofolate levels for DNA synthesis, but that low folate intake or high alcohol consumption may negate some of the protective effect.

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

A prospective study of risk factors for pulmonary embolism in women.

OBJECTIVE: To investigate risk factors for pulmonary embolism in women. DESIGN: Prospective study based on biennial, mailed questionnaires. SETTING: Nurses' Health Study with 16 years of follow-up from 1976 to 1992. PATIENTS: A group of 112822 women aged 30 to 55 years in 1976, free from diagnosed cardiovascular disease or cancer at baseline. Overall, there were 1619770 person-years of follow-up. MEASUREMENTS: Based on self-report and medical records, we documented 280 cases of pulmonary embolism, of which 125 were primary (no identified antecedent cancer, trauma, surgery, or immobilization). Information on height, weight, cigarette smoking, hypertension, diabetes, and hypercholesterolemia was collected by questionnaire. RESULTS: In multivariate analysis, obesity, cigarette smoking, and hypertension were independent predictors of pulmonary embolism. Specifically, obese women (body mass index > or = 29.0 kg/m2) had an increased risk of primary pulmonary embolism (multivariate relative risk=2.9; 95% confidence interval [CI], 1.5-5.4). Heavy cigarette smokers also had an increased risk of primary pulmonary embolism. The relative risk (RR) of primary pulmonary embolism was 1.9 (95% CI, 0.9-3.7) for women currently smoking 25 to 34 cigarettes per day and 3.3 (95% CI, 1.7-6.5) for those smoking 35 cigarettes or more daily as compared with never smokers. Hypertension, even after adjustment for body mass index, was also associated with an increased risk of primary pulmonary embolism (RR=1.9; 95% CI, 1.2-2.8). High serum cholesterol levels (RR=1.1; 95% CI, 0.62-1.8) and diabetes (RR=0.7; 95% CI, 0.3-1.9) did not appear to be related to primary pulmonary embolism. CONCLUSION: These prospective data indicate that obesity, cigarette smoking, and hypertension are associated with increased risk of pulmonary embolism in women. Control of these risk factors will decrease risks of pulmonary embolism as well as coronary heart disease.

Adult↗
PubMed1997

Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women.

OBJECTIVE: To examine prospectively the relationship between glycemic diets, low fiber intake, and risk of non-insulin-dependent diabetes mellitus. DESIGN: Cohort study. SETTING: In 1986, a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease, cancer, and diabetes completed a detailed dietary questionnaire from which we calculated usual intake of total and specific sources of dietary fiber, dietary glycemic index, and glycemic load. MAIN OUTCOME MEASURE: Non-insulin-dependent diabetes mellitus. RESULTS: During 6 years of follow-up, 915 incident cases of diabetes were documented. The dietary glycemic index was positively associated with risk of diabetes after adjustment for age, body mass index, smoking, physical activity, family history of diabetes, alcohol and cereal fiber intake, and total energy intake. Comparing the highest with the lowest quintile, the relative risk (RR) of diabetes was 1.37 (95% confidence interval [CI], 1.09-1.71, P trend=.005). The glycemic load (an indicator of a global dietary insulin demand) was also positively associated with diabetes (RR= 1.47; 95% CI, 1.16-1.86, P trend=.003). Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles (RR=0.72, 95% CI, 0.58-0.90, P trend=.001). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes (RR=2.50, 95% CI, 1.14-5.51) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS: Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes.

Adult↗
PubMed1997

PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis.

BACKGROUND: The gene encoding the platelet glycoprotein IIIa receptor (GPIIIa), shows polymorphism (PIA1/A2). In a previous study, men with acute coronary ischaemia were more likely than controls to carry the PIA2 allele. This receptor has an important role in acute thrombus formation; these findings therefore raise the possibility of inherited platelet risk factors for both arterial and venous thrombosis. We investigated whether the PIA2 allele is associated with myocardial infarction, stroke, and venous thrombosis in a large prospective cohort of men in the USA. METHODS: 14916 initially healthy men participating in the Physicians Health Study provided baseline blood specimens for DNA analysis and were followed prospectively for a mean of 8.6 years. 374 men had a first myocardial infarction, 209 stroke, and 121 venous thrombosis during follow-up (704 cases). Distribution of the PIA1/A2 polymorphism was investigated by a PCR based on restriction-fragment length polymorphism in these men and in a sample of 704 matched study participants who remained free of thrombosis during follow-up (controls). FINDINGS: The frequency of the PIA2 allele was similar to the control frequency (14.8%) among men who had myocardial infarction (13.5%, p = 0.4), stroke (13.4%, p = 0.5), or venous thrombosis (14.5%, p = 0.9). The relative risk of any vascular event among men homozygous or heterozygous for PIA2 compared with men homozygous for PIA1 was 0.96 (95% CI 0.8-1.2). We found no evidence of association between the PIA2 allele and myocardial infarction (relative risk 0.93 [95 0.7-1.2]), stroke (0.93 [0.7-1.3]), or venous thrombosis (1.07 [0.7-1.6]). There was no evidence of association in subgroup analyses by age, smoking status, and presence of family history of premature coronary disease, hypercholesterolaemia, hypertension, or diabetes. Aspirin use had no effect on these findings. INTERPRETATION: In a large cohort of apparently healthy men, carriage of the GPIIIa PIA2 allele was not associated with any increase in subsequent risk of myocardial infarction, stroke, or venous thrombosis.

Adult↗
PubMed1997

Prospective study of moderate alcohol consumption and risk of peripheral arterial disease in US male physicians.

BACKGROUND: Moderate alcohol consumption decreases the risk of coronary heart disease, but its relation to peripheral arterial disease (PAD) is uncertain. METHODS AND RESULTS: In the Physicians' Health Study, a randomized trial of the use of aspirin and beta-carotene in 22071 apparently healthy men, we documented 433 incident cases of PAD during 11 years of follow-up. After we controlled for age and treatment assignment, daily drinkers (> or = 7 drinks per week) had a relative risk (RR) of PAD of 0.92 (95% confidence interval, 0.72 to 1.17) compared with the reference group (< 1 drink per week). After additional control for smoking, however, the RR was 0.68 (0.52 to 0.89). Further control for exercise, diabetes mellitus, and parental history of myocardial infarction revealed an RR of 0.74 (0.57 to 0.97). CONCLUSIONS: Moderate alcohol consumption appears to decrease the risk of PAD in apparently healthy men.

Adult↗
PubMed1997

Prospective study of moderate alcohol consumption and mortality in US male physicians.

BACKGROUND: Although moderate alcohol consumption decreases the risk of myocardial infarction, its impact on all-cause mortality among apparently healthy men is unclear. METHODS: We performed a prospective cohort study in 22071 men in the Physicians' Health Study. Participants were aged 40 to 84 years and had no history of myocardial infarction, stroke, transient ischemic attack, or cancer. RESULTS: There were 1206 deaths (394 cardiovascular, 488 cancer, and 324 other) during 10.7 years of follow-up. Compared with participants who consumed less than 1 drink per week, the relative risk (95% confidence interval) of all-cause mortality for men who consumed 2 to 4 drinks per week was 0.72 (0.59-0.87); 5 to 6 drinks per week, 0.79 (0.64-0.99); 1 drink per day, 0.98 (0.84-1.15); and the highest drinking group (> or = 2 drinks per day), 1.51 (1.17-1.95). This association was similar with either nondrinkers or occasional drinkers used as the reference group and was not subject to material confounding or effect modification by any factor examined. The overall relationship was the result of a J-shaped association with cardiovascular mortality, an increase in cancer deaths for the highest drinking group, and a U-shaped association with other causes of mortality. CONCLUSIONS: Risk of all-cause mortality varies by level of alcohol consumption. In this apparently healthy cohort, men who consumed 2 to 6 drinks per week had the most favorable mortality profile and men who had 2 or more drinks per day the most unfavorable mortality profile. The difference between consumption of small and large amounts of alcohol may mean the difference between preventing and causing excess mortality.

Adult↗
PubMed1997

Arterial and venous thrombosis is not associated with the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor gene in a large cohort of US men.

BACKGROUND: The 4G allele of the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor (PAI-1) gene is associated with increased PAI-1 activity. In a small group of young Swedish men, this allele has been reported to predict risk of myocardial infarction. Whether this polymorphism increases risk of arterial and venous thrombosis among middle-aged men is unknown. METHODS AND RESULTS: Among 14916 men 40 to 84 years old participating in the Physicians' Health Study who provided baseline blood samples for DNA analysis, 374 suffered first myocardial infarction and 121 had venous thromboembolism during 8.6 years of follow-up. Distributions of the 4G/5G polymorphism in the PAI-1 gene promoter were assessed in these men as well as in a sample of study participants matched on age and smoking who did not develop vascular occlusion during the prospective follow-up period. The distributions of the 4G/4G, 4G/5G, and 5G/5G genotypes among men who developed myocardial infarction (0.27, 0.51, 0.22; P = .7) or venous thromboembolism (0.30, 0.49, 0.21; P = .5) were virtually identical to those of men who remained free of vascular disease (0.27, 0.50, 0.23). Thus, the relative risk of future thrombosis among those with the 4G/4G genotype compared with those without the 4G/4G genotype was 1.02 (95% CI, 0.8 to 1.3). There was no effect modification by age, smoking status, family history of premature thrombosis, history of hypertension, hypercholesterolemia, or aspirin use. CONCLUSIONS: These data indicate that the 4G/5G polymorphism in the promoter of the PAI-1 gene is not a major pathogenetic risk factor for arterial or venous thrombosis among middle-aged men.

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