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.     

Plasma viscosity and the risk of coronary heart disease: results from the MONICA-Augsburg Cohort Study, 1984 to 1992

Plasma viscosity is determined by various macromolecules, eg, fibrinogen, immunoglobulins, and lipoproteins. It may therefore reflect several aspects involved in cardiovascular diseases, including the effects of classic risk factors, hemostatic disturbances, and inflammation. We examined the association of plasma viscosity with the incidence of a first major coronary heart disease event (CHD; fatal and nonfatal myocardial infarction and cardiac death; n=50) in 933 men aged 45 to 64 years of the MONICA project of Augsburg, Germany. The incidence rate was 7.23 per 1000 person-years (95% confidence interval [CI], 5.37 to 9.53), and the subjects were followed up for 8 years. All suspected cases of an incident CHD event were classified according to the MONICA protocol. There was a positive and statistically significant unadjusted relationship between plasma viscosity and the incidence of CHD. The relative risk of CHD events associated with a 1-SD increase in plasma viscosity (0.070 mPa x s) was 1.60 (95% CI, 1.25 to 2.03). After adjustment for age, total cholesterol, high density lipoprotein cholesterol, smoking, blood pressure, and body mass index, the relative risk was reduced only moderately (1.42; 95% CI, 1.09 to 1.86). The relative risk of CHD events for men in the highest quintile of the plasma viscosity distribution in comparison with the lowest quintile was 3.31 (95% CI, 1.19 to 9.25) after adjustment for the aforementioned variables. A large proportion of events (40%) occurred among men in the highest quintile. These findings suggest that plasma viscosity may have considerable potential to identify subjects at risk for CHD events.     

Body weight and risk of nonfatal acute myocardial infarction among women: a case-control study from northern Italy

BACKGROUND: The relationship between nonfatal acute myocardial infarction (AMI) and self-reported body weight and body mass index (BMI; Quetelet index, kg/m2) has been investigated. METHODS: A case-control study was conducted between 1983 and 1992 in northern Italy on 432 women with nonfatal AMI and 867 controls in hospital for acute, noncardiovascular, nonneoplastic, nondigestive, non-hormone-related conditions. Odds ratios (OR), with their 95% confidence intervals (CI), were computed by unconditional multiple logistic regression analysis, including terms for age, education, and smoking, plus history of selected diseases. RESULTS: Women with body weight and BMI in the highest quartile had an increased risk of AMI after allowance for age, education, and smoking status (OR 1.5, 95% CI 1.0 to 2.2, and OR 1.7, 95% CI 1.2 to 2.4, respectively). Compared with leaner women, the risk was higher among women with BMI above the median, in association with a history of diabetes (OR 5.2) or hyperlipidemia (OR 6.0). Hypertensive women had similar OR in the two strata of BMI (OR 5.1 and 4.8). The association of BMI with risk of AMI was apparently stronger among women younger than 50 years and among less educated women, but was similar among smokers and never smokers. CONCLUSIONS: The results of this study confirm that AMI among women is related to excess BMI, with a population attributable risk of 17%. The excess risk was substantial among overweight women with history of diabetes or hyperlipidemia, stressing the importance of controlling body weight among these women.     

Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study

CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. OBJECTIVE: To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinics in Texas. PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION: Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. RESULTS: After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. CONCLUSIONS: Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.     

Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies

BACKGROUND AND PURPOSE: The available data on low-dose oral contraceptive pill (OCP) use and stroke risk in US women are limited by small numbers. We sought more precise estimates by conducting a pooled analysis of data from 2 US population-based case-control studies. METHODS: We analyzed interview data from 175 ischemic stroke cases, 198 hemorrhagic stroke cases, and 1191 control subjects 18 to 44 years of age. RESULTS: For ischemic stroke, the pooled odds ratio (pOR) adjusted for stroke risk factors for current use of low-dose OCPs compared with women who had never used OCP (never users) was 0.66 (95% confidence interval [CI], 0.29 to 1.47) and compared with women not currently using OCPs (nonusers) the pOR was 1.09 (95% CI, 0.54 to 2.21). For hemorrhagic stroke, the pOR for current use of low-dose OCPs compared with never users was 0.95 (95% CI, 0.46 to 1.93) and compared with nonusers the pOR was 1.11 (95% CI, 0.61 to 2.01). The pORs for current low-dose OCP use and either stroke type were not elevated among women who were >/=35 years, cigarette smokers, obese, or not receiving medical therapy for hypertension. pORs for current low-dose OCP use were 2.08 (95% CI, 1. 19 to 3.65) for ischemic stroke and 2.15 (95% CI, 0.85 to 5.45) for hemorrhagic stroke among women reporting a history of migraine but were not elevated among women without such a history. Past OCP use (irrespective of formulation) was inversely related to ischemic stroke but unrelated to hemorrhagic stroke. CONCLUSIONS: Women who use low-dose OCPs are, in the aggregate, not at increased risk of stroke. Studies are needed to clarify the risk of stroke among users who may be susceptible on the basis of age, smoking, obesity, hypertension, or migraine history.     

Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries

PURPOSE: To compare the risk for fatal myocardial infarction (MI) after adjuvant radiotherapy (RT) for left-sided breast cancer with the risk for MI after adjuvant RT for right-sided breast cancer. METHODS: We studied women with local- and regional-stage breast cancer diagnosed from 1973 to 1992 from the Surveillance, Epidemiology, and End-Results (SEER) cancer registries. We performed life-table analysis, the log-rank test, and Cox proportional hazards regression to compare the time to fatal MI from diagnosis between left-sided and right-sided cases, censoring deaths from other causes. RESULTS: Among irradiated patients, the relative risk (RR) for fatal MI in women with left-sided breast cancer was 1.17 (95% confidence interval [CI], 1.01 to 1.36), controlling for age, compared with those with right-sided breast cancer. The RR for fatal MI among left-sided cases was increased for those under the age of 60 years (RR = 1.98; 95% CI, 1.31 to 2.97) compared with right-sided cases, but not at age 60 years or older. Among women with irradiated regional-stage cancer who were younger than 60 years of age, the risk was significantly increased (RR = 2.24; 95% CI, 1.38 to 3.64) for those with left-sided compared with right-sided breast cancer, but not among patients aged 60 years or older. Among irradiated local-stage cases, the risk for those with left-sided breast cancer was not significantly elevated in either age category. Analysis of 5-year conditional survival cohorts showed an increased risk for irradiated left-sided cases among women younger than 60 years of age in the 10- to 15-year conditional survival cohort (RR = 5.28; 95% CI, 1.82 to 15.3). CONCLUSION: Adjuvant RT for left-sided breast cancer diagnosed in women younger than 60 years of age is associated with a higher risk for fatal MI 10 to 15 years later compared with adjuvant RT for right-sided cases.     

History of lactation and breast cancer risk

A self-administered questionnaire was completed by 1,018 women diagnosed with breast cancer during 1988-1989 identified through the British Columbia Cancer Registry and by 1,025 controls selected at random from the Provincial Voters List. Parous premenopausal women who had never nursed (odds ratio (OR) = 1.3, 95% confidence interval (CI) 0.9-2.0) or who had lactated for 1 month or less (OR = 1.8, 95% CI 1.3-2.5) had an increased risk of breast cancer adjusted for age and parity, compared with women who had breast-fed 2 months or longer. The risk was particularly elevated (OR = 3.0, 95% CI 1.6-5.4) among women who reported having tried to nurse, but who were unsuccessful. Among women who nursed for at least 2 months, there was an indication of decreasing risk with increasing duration of nursing. Among postmenopausal parous women, no relation between lactation history and breast cancer risk was evident.     

A prospective study of positive psychological well-being and coronary heart disease.

Objective: Research suggests that positive psychological well-being is associated with cardiovascular health. However, much of this research uses elderly samples and has not determined the pathways by which psychological well-being influences cardiovascular disease or whether effects are similar for men and women. This study investigates the association between two aspects of well-being (emotional vitality and optimism) and coronary heart disease (CHD) in a sample of middle-aged men and women, and considers potential mediating factors. Method: Between 1991 and 1994, well-being and coronary risk factors were assessed among 7,942 individuals without a prior cardiovascular event from the Whitehall II cohort. Incident CHD (fatal CHD, first nonfatal myocardial infarction, or first definite angina) was tracked during 5 person-years of follow-up. Results: Positive psychological well-being was associated with reduced risk of CHD with an apparent threshold effect. Relative to people with the lowest levels of well-being, those with the highest levels had minimally adjusted hazard ratios of 0.74, 95% confidence interval [0.55, 0.98] for emotional vitality and 0.73, 95% confidence interval [0.54, 0.99] for optimism. Moreover, the association was strong for both genders and was only weakly attenuated when accounting for ill-being. Neither health-related behaviors nor biological factors explained these associations. Conclusions: Positive psychological well-being was associated with a modest, but consistent reduced risk of incident CHD. The relationship was comparable for men and women, and was maintained after controlling for cardiovascular risk factors and ill-being. Additional research is needed to identify underlying mechanisms and investigate whether interventions to increase well-being may enhance cardiovascular health. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Treatment for infertility and risk of invasive epithelial ovarian cancer

The relationship between the use of fertility drugs and the risk of ovarian cancer was analysed using data from an Italian case-control study. The study comprised 971 women below the age of 75 years with histologically confirmed invasive epithelial ovarian cancer diagnosed within the year before the interview. The controls were 2758 women admitted to the same network of hospitals where the cases of ovarian cancer had been identified. Five cases (0.5%) and 11 controls (0.4%) reported use of fertility drugs. In comparison with women who had never used fertility drugs, the multivariate odds ratio (OR) for women who had taken fertility drugs was 1.1 [95% confidence interval (CI) 0.4-3.3]. The OR were 0.7 (95% CI 0.1-7.9) and 1.0 (95% CI 0.2-3.8) for women who had used fertility drugs for <6 and > or =6 cycles respectively. Considering the 14 cases and 45 controls reporting difficulty in conception, the risk of ovarian cancer was 0.5 (95% CI 0.1-3.6) for women who reported use of fertility drugs. Considering nulliparous women only, the estimated OR of ovarian cancer for any fertility drug use was 0.6 (95% CI 0.1-3.5). Although the present results have limitations in terms of statistical power and available information, they provide reassuring evidence of the absence of a strong association between fertility drugs and subsequent risk of developing epithelial ovarian cancer.     

Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study

OBJECTIVE: To examine the relation between nut consumption and risk of coronary heart disease in a cohort of women from the Nurses' Health Study. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. SUBJECTS: 86 016 women from 34 to 59 years of age without previously diagnosed coronary heart disease, stroke, or cancer at baseline in 1980. MAIN OUTCOME MEASURES: Major coronary heart disease including non-fatal myocardial infarction and fatal coronary heart disease. RESULTS: 1255 major coronary disease events (861 cases of non-fatal myocardial infarction and 394 cases of fatal coronary heart disease) occurred during 14 years of follow up. After adjusting for age, smoking, and other known risk factors for coronary heart disease, women who ate more than five units of nuts (one unit equivalent to 1 oz of nuts) a week (frequent consumption) had a significantly lower risk of total coronary heart disease (relative risk 0.65, 95% confidence interval 0.47 to 0.89, P for trend=0.0009) than women who never ate nuts or who ate less than one unit a month (rare consumption). The magnitude of risk reduction was similar for both fatal coronary heart disease (0.61, 0.35 to 1.05, P for trend=0.007) and non-fatal myocardial infarction (0.68, 0.47 to 1.00, P for trend=0.04). Further adjustment for intakes of dietary fats, fibre, vegetables, and fruits did not alter these results. The inverse association persisted in subgroups stratified by levels of smoking,use of alcohol, use of multivitamin and vitamin E supplements, body mass index, exercise, and intake of vegetables or fruits. CONCLUSIONS: Frequent nut consumption was associated with a reduced risk of both fatal coronary heart disease and non-fatal myocardial infarction. These data, and those from other epidemiological and clinical studies, support a role for nuts in reducing the risk of coronary heart disease.     

Prospective study of calcium channel blocker use, cardiovascular disease, and total mortality among hypertensive women: the Nurses' Health Study

BACKGROUND: In several observational studies, patients prescribed calcium channel blockers had higher risks of cardiovascular diseases and mortality than those prescribed other antihypertensive medications. We explored these associations in the Nurses' Health Study. METHODS AND RESULTS: A total of 14 617 women who reported hypertension and regular use of diuretics, beta-blockers, calcium channel blockers, ACE inhibitors, or a combination in 1988 were included in the analyses. Cardiovascular events and deaths were ascertained through May 1, 1994. We documented 234 cases of myocardial infarction. Calcium channel blocker monodrug users had an age-adjusted relative risk (RR) of myocardial infarction of 2.36 (95% CI, 1.43 to 3.91) compared with those prescribed thiazide diuretics. Women prescribed calcium channel blockers had a higher prevalence of ischemic heart disease. After adjustment for these and other coronary risk factors, the RR was 1.64 (95% CI, 0.97 to 2.77). Comparing the use of any calcium channel blocker (monodrug and multidrug users) with that of any other antihypertensive agent, the adjusted RR was 1.42 (95% CI, 1.01 to 2.01). An association between calcium channel blocker use and myocardial infarction was apparent among women who had ever smoked cigarettes (covariate-adjusted RR, 1.81; 95% CI, 1.20 to 2.72) but not among never-smokers (RR, 0.94; 95% CI, 0.48 to 1.84). CONCLUSIONS: In analyses adjusted only for age, we found a significant elevation in RR of total myocardial infarction among women who used calcium channel blockers compared with those who did not. After adjustment for comorbidity and other covariates, the RR was reduced. Whether the remaining observed elevated risk is real, or a result of residual confounding by indication, or chance, or a combination of the above cannot be evaluated with certainty on the basis of these observational data.     

Smoking associated with alcoholism: introduction to the major human dependencies

We examined the relation between Quetelet's body mass index (BMI) and age-adjusted mortality risk from specific diseases in a 26-year prospective cohort study of 12,576 non-Hispanic white women who had never smoked. To account for effects due to antecedent disease, we focused on women surviving 15-26 years after their report of body weight. High BMI (>27 kg per m2) decreased the risk of fatal respiratory disease (hazard ratios of 0.7 for ages 30-54 years and 0.6 for ages 55-74 years) but increased risk in all other disease categories. Low BMI (<21 kg per m2) increased the risk of fatal respiratory disease (hazard ratios of 2.0 for ages 30-54 years and 1.4 for ages 55-74 years). Among middle-aged women (ages 30-54 years), we found that low BMI also increased the risk of certain fatal cardiovascular diseases (hazard ratios of 1.5 for cerebrovascular death and 2.5 for hypertensive and other cardiovascular deaths), but the increase in the risk of fatal cerebrovascular disease did not remain (hazard ratio of 0.4) after exclusion of subarachnoid and intraparenchymal hemorrhage deaths from the endpoint. Although the inverse relation between BMI and risk of fatal respiratory disease was also evident in the subset who reported body weight 17 years after baseline, further restriction of this subset to stable-weight women reporting no history of respiratory disease resulted in a U-shaped relation. Data from this subset also indicated that weight loss substantially increased the risk of fatal respiratory disease. These findings implicate high and low BMI as risk factors for fatal respiratory disease but suggest that the risk due to high BMI was obscured by weight loss that followed the onset of disease. The overall findings support an association between obesity and a higher risk of fatal disease but also raise the possibility that apparently healthy, never-smoking women can experience a higher long-term risk of fatal cardiovascular and respiratory diseases due to a lower body weight.     

Cardiovascular events and mortality in newly and chronically depressed persons > 70 years of age

The role of duration of depressed mood in the prediction of cardiovascular disease (CVD) requires further study, as it has been suggested that emerging depressive symptoms may be a better predictor than persistent depressive symptoms. This prospective cohort study of 3,701 men and women aged > 70 years uses 3 measurement occasions of depressive symptomatology (Center for Epidemiologic Studies-Depression Scale) during a 6-year period to distinguish persons who were newly (depressed at baseline but not at 3 and 6 years before baseline) and chronically depressed (depressed at baseline and at 3 or 6 years before baseline). Their risk of subsequent CVD events and all-cause mortality was compared with that of subjects who were never depressed during the 6-year period. Outcome events were based on death certificates and Medicare hospitalization records. During a median follow-up of 4.0 years, there were 732 deaths (46.2/1,000 person-years) and 933 new CVD events (64.7/1,000 person-years). In men, but not in women, newly depressed mood was associated with an increased risk of CVD mortality (relative risk 1.75, 95% confidence interval [CI] 1.00 to 3.05), new CVD events (relative risk 2.07, 95% CI 1.44 to 2.96), and new coronary heart disease events (relative risk 2.03, 95% CI 1.28 to 3.24) after adjustment for traditional CVD risk factors. The association between newly depressed mood and all-cause mortality was smaller (relative risk 1.40, 95% CI 0.95 to 2.07). Chronic depressed mood was not associated with new CVD events or all-cause mortality. Our findings suggest that newly depressed older men, but not women, were approximately twice as likely to have a CVD event than those who were never depressed. In men, recent onset of depressed mood is a better predictor of CVD than long-term depressed mood.     

Effect of vitamin E and beta carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease

BACKGROUND: Oxidized low-density lipoprotein is involved in the pathogenesis of atherosclerosis. In epidemiological studies antioxidants have been inversely related with coronary heart disease. Findings from controlled trials are inconclusive. METHODS: We studied the primary preventive effect of vitamin E (alpha tocopherol) and beta carotene supplementation on major coronary events in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial undertaken primarily to examine the effects of these agents on cancer. A total of 27 271 Finnish male smokers aged 50 to 69 years with no history of myocardial infarction were randomly assigned to receive vitamin E (50 mg), beta carotene (20 mg), both agents, or placebo daily for 5 to 8 years (median, 6.1 years). The end point was the first major coronary event, either nonfatal myocardial infarction (surviving at least 28 days; n = 1204) or fatal coronary heart disease (n = 907). RESULTS: The incidence of primary major coronary events decreased 4% (95% confidence interval, -12% to 4%) among recipients of vitamin E and increased 1% (95% confidence interval, -7% to 10%) among recipients of beta carotene compared with the respective nonrecipients. Neither agent affected the incidence of nonfatal myocardial infarction. Supplementation with vitamin E decreased the incidence of fatal coronary heart disease by 8% (95% confidence interval, -19% to 5%), but beta carotene had no effect on this end point. CONCLUSIONS: Supplementation with a small dose of vitamin E has only marginal effect on the incidence of fatal coronary heart disease in male smokers with no history of myocardial infarction, but no influence on nonfatal myocardial infarction. Supplementation with beta carotene has no primary preventive effect on major coronary events.     

The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a family history of breast cancer

BACKGROUND: The risks and benefits of hormone replacement therapy (HRT) are of considerable interest and importance, especially in terms of whether they differ among subsets of women. OBJECTIVE: To determine whether HRT is associated with increased risks for breast cancer and total mortality in women with a family history of breast cancer. DESIGN: Prospective cohort study. SETTING: Population-based sample of midwestern post-menopausal women enrolled in an observational study of risk factors for cancer. PARTICIPANTS: Random sample of 41,837 female Iowa residents 55 to 69 years of age. MEASUREMENTS: Incidence rates of and relative risks for breast cancer (n = 1085) and total mortality (n = 2035) through 8 years of follow-up were calculated by using data from the State Health Registry of Iowa and the National Death Index. RESULTS: A family history of breast cancer was reported by 12.2% of the cohort at risk. Among women with a family history of breast cancer, those who currently used HRT and had done so for at least 5 years developed breast cancer at an age-adjusted annual rate of 61 cases per 10,000 person-years (95% CI, 28 to 94 cases); this rate was not statistically significantly higher than the rate in women who had never used HRT (46 cases per 10,000 person-years [CI, 36 to 55 cases]). Among women with a family history, those who used HRT had a significantly lower risk for total mortality than did women who had never used HRT (relative risk, 0.67 [CI, 0.51 to 0.89]), including total cancer-related mortality (relative risk, 0.75 [CI, 0.50 to 1.12]). The age-adjusted annual mortality rate for women using HRT for at least 5 years was 46 deaths per 10,000 person-years (CI, 19 to 74 deaths); this is roughly half the rate seen in women who had never used HRT (80 deaths per 10,000 person-years [CI, 69 to 92 deaths]). CONCLUSIONS: These data suggest that HRT use in women with a family history of breast cancer is not associated with a significantly increased incidence of breast cancer but is associated with a significantly reduced total mortality rate.     

Perinatal mortality and its relationship to the reporting of low-birthweight infants

OBJECTIVE: To determine whether diabetes defined by isolated postchallenge hyperglycemia (IPH) (2-h postchallenge plasma glucose > or = 11.1 mmol/l with fasting plasma glucose [FPG] < 7.0 mmol/l) increases the risk of fatal cardiovascular disease (CVD) in older women and men. RESEARCH DESIGN AND METHODS: In a prospective study, we followed 769 men and 1,089 women, aged 50-89 years, who had no history of diabetes or myocardial infarction and demonstrated no fasting hyperglycemia (i.e., FPG < 7.0 mmol/l) when they underwent oral glucose tolerance testing at baseline in 1984-1987. RESULTS: At baseline, 70% of 125 women and 48% of 133 men with previously undiagnosed diabetes had IPH. Over the next 7 years, women with IPH had a significantly increased risk of fatal CVD and heart disease compared with nondiabetic women. This increased risk was not observed in men with IPH. This association was independent of age, hypertension, central obesity, cigarette smoking, HDL cholesterol, and triglycerides (multiply adjusted hazard ratio and 95% CI: 2.6 and 1.4-4.7 for CVD; 2.9 and 1.3-6.4 for heart disease). CONCLUSIONS: Diabetes defined by IPH alone is common in older adults and more than doubles the risk of fatal CVD and heart disease in older women. Because the prevalence of IPH increases with age, the use of fasting glucose alone for diabetes screening or diagnosis may fail to identify most older adults at high risk for CVD and should be reevaluated.     

Association of calcium channel blocker use with increased rate of acute myocardial infarction in patients with left ventricular dysfunction

The Studies of Left Ventricular Dysfunction (SOLVD) assessed the effect of enalapril in patients with systolic left ventricular dysfunction (LVD). We performed retrospective analyses of the association between calcium channel blocker (CCB) use and fatal and nonfatal myocardial infarction (MI) in these patients. MI occurred in 11.5% of 845 patients receiving CCBs versus 7.5% of 2551 patients not receiving CCBs in the enalapril group and in 14.4% of 874 patients receiving CCBs versus 9.3% of 2527 patients not receiving CCBs in the placebo group. By multivariate Cox regression analysis, adjusting for comorbidity, cause and severity of LVD, heart failure, and concomitant drug use, CCB use was an independent predictor of MI (relative risk [RR] 1.37, confidence interval [CI] 1.14 to 1.63). The increase in MI risk was greater among patients with a higher heart rate (RR 1.46, CI 1.14 to 1.86) and lower blood pressure (RR 1.45, CI 1.14 to 1.86). The adjusted risk ratio for all-cause mortality associated with CCB use was 1.14 (CI 1.00 to 1.28; p = 0.0454). In this analysis of patients with LVD, CCB use was associated with significantly increased risk of fatal or nonfatal MI.     

Hormone replacement therapy and risk of non-fatal stroke

BACKGROUND: The effect of postmenopausal hormone replacement therapy (HRT) on the risk of subtypes of stroke is as yet unclear. To investigate the effect of oestrogen and combined oestrogen-progestagen therapy on the risk of non-fatal haemorrhagic and thromboembolic stroke, we carried out a case-control study. METHODS: From the Danish National Patient Register we identified all Danish women aged 45-64 years who had a non-fatal, first-ever cerebrovascular attack during 1990-92. Two age-matched controls were randomly selected for each case from the Danish National Person Register. Important correlates of hormone use and stroke, on which information was obtained from postal questionnaires, were controlled for by multivariate analyses based on log-linear graphical models. The analyses included data on 1422 cases classified in four subtypes of stroke (160 subarachnoid haemorrhage, 95 intracerebral haemorrhage, 846 thromboembolic infarction, 321 transient ischaemic attack) and 3171 controls. FINDINGS: After adjustment for confounding variables and correction for the trend in sales of HRT preparations, no significant associations were detected between current use of unopposed oestrogen replacement therapy and non-fatal subarachnoid haemorrhage (odds ratio 0.52 [95% CI 0.23-1.22]), intracerebral haemorrhage (0.15 [0.02-1.09]), or thromboembolic infarction (1.16 [0.86-1.58]), respectively, compared with never use. Current use of combined oestrogen-progestagen replacement therapy had no significant influence on the risk of subarachnoid haemorrhage (1.22 [0.79-1.89]), intracerebral haemorrhage (1.17 [0.64-2.13]), or thromboembolic infarction (1.17 [0.92-1.47]). A significantly increased incidence of transient ischaemic attacks among former users of HRT and among current users of unopposed oestrogen may to some extent be explained by selection--HRT users being more aware of symptoms than non-users. INTERPRETATION: Unopposed oestrogen and combined oestrogen-progestagen replacement therapy have no influence on the risk of non-fatal thromboembolic or haemorrhagic stroke in women aged 45-64 years.     

The effects of frequently rotating shiftwork on sleep and the family life of hospital nurses

The effects of three frequently rotating shifts in an irregular sequence on the daily activities of 239 Japanese female hospital nurses were studied by the time-budget method. The nurses recorded their daily activities for several consecutive days. The questionnaire was returned by 80.8% of the participants, and recordings of 1016 days were analysed. A two-way analysis of variance clarified that the shift combination influenced the daily activities. The most distinct result was that nurses spent significantly more time on free-time activities on the day when they worked the night shift followed by the evening shift than they did on the day when they worked any other shift combination. Nurses offset sleep deprivation either by sleeping during the day before and after working the night shift (82-100%) or by sleeping 2 to 4 h later in the morning after working the evening shift and on days off. There was a strong positive correlation between total sleep time (including day sleep) and the length of the interval between two consecutive shifts (r = 0.95, p < 0.001). This result suggests that more than 16 h between work shifts is required to allow more than 7 h of total sleep time. In an analysis by household status, nurses who had young children (average age, 2.8 years) slept less and spent less time on free-time activities than did other nurses.     

Activity of the enzymes participating in purine metabolism of cancerous and noncancerous human kidney tissues

CONTEXT: Heart failure is often preceded by isolated systolic hypertension, but the effectiveness of antihypertensive treatment in preventing heart failure is not known. OBJECTIVE: To assess the effect of diuretic-based antihypertensive stepped-care treatment on the occurrence of heart failure in older persons with isolated systolic hypertension. DESIGN: Analysis of data from a multicenter, randomized, double-blind, placebo-controlled clinical trial. PARTICIPANTS: A total of 4736 persons aged 60 years and older with systolic blood pressure between 160 and 219 mm Hg and diastolic blood pressure below 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP). INTERVENTION: Stepped-care antihypertensive drug therapy, in which the step 1 drug is chlorthalidone (12.5-25 mg) or matching placebo, and the step 2 drug is atenolol (25-50 mg) or matching placebo. MAIN OUTCOME MEASURES: Fatal and nonfatal heart failure. RESULTS: During an average of 4.5 years of follow-up, fatal or nonfatal heart failure occurred in 55 of 2365 patients randomized to active therapy and 105 of the 2371 patients randomized to placebo (relative risk [RR], 0.51; 95% confidence interval [CI], 0.37-0.71; P<.001; number needed to treat to prevent 1 event [NNT], 48). Among patients with a history of or electrocardiographic evidence of prior myocardial infarction (MI), the RR was 0.19 (95% CI, 0.06-0.53; P=.002; NNT, 15). Older patients, men, and those with higher systolic blood pressure or a history of or electrocardiographic evidence of MI at baseline had higher risk of developing heart failure. CONCLUSION: In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure. Among patients with prior MI, an 80% risk reduction was observed.