Oral contraceptives and myocardial infarction--the search for the smoking gun.
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Biomedical subjects
Publications and source records attributed to L Chasan-Taber.
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As rates of diabetes mellitus and obesity continue to increase, physical activity continues to be a fundamental form of therapy. Exercise influences several aspects of diabetes, including blood glucose concentrations, insulin action and cardiovascular risk factors. Blood glucose concentrations reflect the balance between skeletal muscle uptake and ambient concentrations of both insulin and counterinsulin hormones. Difficulties in predicting the relative impact of these factors can result in either hypoglycemia or hyperglycemia. Despite the variable impact of exercise on blood glucose, exercise consistently improves insulin action and several cardiovascular risk factors. Beyond the acute impact of physical activity, long-term exercise behaviors have been repeatedly associated with decreased rates of type 2 diabetes. While exercise produces many benefits, it is not without risks for patients with diabetes mellitus. In addition to hyperglycemia, from increased hepatic glucose production, insufficient insulin levels can foster ketogenesis from excess concentrations of fatty acids. At the opposite end of the glucose spectrum, hypoglycemia can result from excess glucose uptake due to either increased insulin concentrations, enhanced insulin action or impaired carbohydrate absorption. To decrease the risk for hypoglycemia, insulin doses should be reduced prior to exercise, although some insulin is typically still needed. Although precise risks of exercise on existing diabetic complications have not been well studied, it seems prudent to consider the potential to worsen nephropathy or retinopathy, or to precipitate musculoskeletal injuries. There is more substantive evidence that autonomic neuropathy may predispose patients to arrhythmias. Of clear concern, increased physical activity can precipitate a cardiac event in those with underlying CAD. Recognizing these risks can prompt actions to minimize their impact. Positive actions that are part of exercise programs for diabetic patients emphasize SMBG, foot care and cardiovascular functional assessment. SMBG provides critical information on the impact of exercise and is recommended for all patients before, during and after exercise. More frequent monitoring (and for longer periods following exercise) is recommended for those with hypoglycemia unawareness or those performing high-intensity exercise. Preventing the sequelae of an exercise-induced severe hypoglycemic reaction can be as simple as carrying glucose tablets or gel, a diabetic identification bracelet or card, or exercising with an individual who is aware of the circumstances. In addition to blood glucose concentrations, proper foot care is critical to people with diabetes who exercise and includes considering type of shoe, type of exercise, inspection of skin surfaces and appropriate evaluation and treatment of lesions (calluses and others). Those with severe neuropathy can consider alternatives to weight-bearing exercises. Precipitation of clinical CAD is of great concern for all diabetic patients participating in exercise activities. Although a sufficiently sensitive and specific screening test for coronary disease has not been identified, those planning an exercise program of moderate intensity or greater should be evaluated. Initial cardiac assessment should include exercise testing as well as identifying risk for autonomic neuropathy. In addition to noting maximal heart rate and blood pressure as well as ischemic changes, exercise tolerance testing can identify anginal thresholds and patients with asymptomatic ischemia. Those without symptoms should be counseled regarding target pulse rates to avoid inducing ischemia. Ischemic changes need to be evaluated for either further diagnostic testing or pharmacological intervention. For patients with diabetes mellitus, the overall benefits of exercise are clearly significant. Clinicians and patients must work together to maximize these benefits while minimizing risks for negative consequences. Identifying and preventing potential problems beforehand can reduce adverse outcomes and promote this important approach to healthy living.
OBJECTIVES: The relation of personal characteristics, health and lifestyle behaviors, and cancer screening practices to current colorectal cancer (CRC) screening was assessed and compared with those factors' relation to current mammography screening in women and prostate-specific antigen (PSA) screening in men. METHODS: A cross-sectional random-digit-dialed telephone survey of 954 Massachusetts residents aged 50 and older was conducted. RESULTS: The overall prevalence of current CRC screening was 55.3%. Logistic regression results indicated that family history of CRC (odds ratio [OR] = 1.98; 95% confidence interval [CI] = 1.02, 3.86), receiving a regular medical checkup (OR = 3.07; 95% CI = 2.00, 4.71), current screening by mammography in women and PSA in men (OR = 4.40; 95% CI = 2.94, 6.58), and vitamin supplement use (OR = 1.87; 95% CI = 1.27, 2.77) were significant predictors of CRC screening. CONCLUSIONS: Health and lifestyle behaviors were related to increased current CRC, mammography, and PSA screening. Personal factors independently related to CRC screening were not consistent with those related to mammography and PSA screening. This lack of consistency may reflect different stages of adoption of each type of screening by clinicians and the public.
PURPOSE: Alcohol consumption has been implicated in the pathogenesis of cataract in some, but not all analytic studies. To date, no prospective analysis of the relationship between alcohol consumption and cataract has been conducted in women. METHODS: We examined the association between alcohol consumption and cataract extraction in a prospective cohort of female registered nurses. In 1980, 50,461 women were included and others were added as they became 45 years of age for a total of 77,466 women. Information on alcohol consumption and incidence of senile cataract extraction was ascertained during 12 years of follow-up with biennial questionnaires. RESULTS: We observed 1468 cases of cataract extraction in 761,036 person-years of follow-up. Compared to nondrinkers, those consuming alcohol were not at increased risk of cataract, even up to 25 grams or more per day (2 or more drinks). Results remained unchanged after controlling for cataract risk factors including cigarette smoking, body mass index, and diabetes. When risk was examined for specific cataract subtypes only, those in the highest category of consumption had a multivariate relative risk of 1.10 for nuclear cataracts and 1.50 for posterior subcapsular cataracts only. CONCLUSIONS: These prospective data suggest that there is no substantial overall increased risk of senile cataract due to alcohol intake. The possibility that alcohol consumption leads to a modest increased risk of posterior subcapsular type opacities requiring extraction merits further exploration.
Oral contraceptive use is associated with hypertension, dyslipidemias, and insulin resistance, all of which also characterize hypertensive disorders of pregnancy. In this prospective cohort study, the association of oral contraceptive use before pregnancy and the risk of gestational hypertension and preeclampsia was assessed. Between 1991 and 1995, 3973 nulliparous women who reported their first pregnancy lasting > or = 6 months were studied. Pregravid exposures were collected by biennial mailed questionnaires, and cases were confirmed by medical record review. Recent oral contraceptive use was defined as use within 2 years of pregnancy. Proportional hazards analysis was used to adjust for potential confounding variables. During the 4 years of follow-up, 133 (3.3%) women with gestational hypertension and 62 (1.6%) with preeclampsia were identified. Twenty-five percent of women who did not develop these disorders were recent users of oral contraceptives, compared with 19% (p = 0.11) of women who developed gestational hypertension and 30% (p = 0.38) who developed preeclampsia. Mean duration of prior oral contraceptive use was similar for cases and noncases. Compared with never and past users, the multivariate relative risk among recent users for developing gestational hypertension was 0.7 (95% confidence interval (CI), 0.4-1.0) and for preeclampsia was 1.3 (95% CI, 0.8-2.4). Among recent users who had used oral contraceptives for > or = 8 years, the relative risk for gestational hypertension was 0.6 (95% CI, 0.3-1.2) and for preeclampsia was 2.1 (95% CI, 1.1-4.2). When the analysis was restricted to women who had never smoked, the risk for gestational hypertension was 0.2 (95% CI, 0.1-0.9) and for preeclampsia was 4.1 (95% CI, 1.9-8.7). Thus, recent use of oral contraceptives was associated with a reduced risk for developing gestational hypertension. In contrast, there was a suggestion that recent use was associated with an increased risk of developing preeclampsia, but only among women who had used these agents for > or = 8 years.
BACKGROUND: Oxidation of lens proteins plays a central role in the formation of age-related cataracts, suggesting that dietary antioxidants may play a role in prevention. However, the relation between specific antioxidants and risk of cataract remains uncertain. OBJECTIVE: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in women. METHODS: A prospective cohort of registered female nurses aged 45-71 y and free of diagnosed cancer was followed; in 1980, 50461 were included and others were added as they became 45 y of age for a total of 77466. Information on nutrient intake was assessed by repeated administration of a food-frequency questionnaire during 12 y of follow-up. RESULTS: During 761762 person-years of follow-up, 1471 cataracts were extracted. After age, smoking, and other potential cataract risk factors were controlled for, those with the highest intake of lutein and zeaxanthin had a 22% decreased risk of cataract extraction compared with those in the lowest quintile (relative risk: 0.78; 95% CI: 0.63, 0.95; P for trend = 0.04). Other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin), vitamin A, and retinol were not associated with cataract in multivariate analysis. Increasing frequency of intakes of spinach and kale, foods rich in lutein, was associated with a moderate decrease in risk of cataract. CONCLUSIONS: Lutein and zeaxanthin and foods rich in these carotenoids may decrease the risk of cataracts severe enough to require extraction.
BACKGROUND: Dietary antioxidants, including carotenoids, are hypothesized to decrease the risk of age-related cataracts by preventing oxidation of proteins or lipids within the lens. However, prospective epidemiologic data concerning this phenomenon are limited. OBJECTIVE: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in men. DESIGN: US male health professionals (n = 36644) who were 45-75 y of age in 1986 were included in this prospective cohort study. Others were subsequently included as they became 45 y of age. A detailed dietary questionnaire was used to assess intake of carotenoids and other nutrients. During 8 y of follow-up, 840 cases of senile cataract extraction were documented. RESULTS: We observed a modestly lower risk of cataract extraction in men with higher intakes of lutein and zeaxanthin but not of other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin) or vitamin A after other potential risk factors, including age and smoking, were controlled for. Men in the highest fifth of lutein and zeaxanthin intake had a 19% lower risk of cataract relative to men in the lowest fifth (relative risk: 0.81; 95% CI: 0.65, 1.01; P for trend = 0.03). Among specific foods high in carotenoids, broccoli and spinach were most consistently associated with a lower risk of cataract. CONCLUSIONS: Lutein and zeaxanthin may decrease the risk of cataracts severe enough to require extraction, although this relation appears modest in magnitude. The present findings add support for recommendations to consume vegetables and fruit high in carotenoids daily.
A half-million children are believed to be sexually abused each year in the United States. In 1995, the American Medical Association declared sexual assault "a silent violent epidemic." The majority of efforts to stop child sexual abuse have focused on punishing abusers and treating victims and their families; prevention programs are uncommon and rely on educating children to report sexual abuse. This case study describes the evaluation of the first public health campaign designed to target adults for prevention. A baseline assessment of attitudes, awareness, knowledge, and policies was conducted in Vermont to identify facilitators and barriers to adult prevention of child sexual abuse. These included predisposing factors (50% of Vermont residents did not know the characteristics of an abuser), enabling factors (60% of Vermont residents did not know where to refer someone who may have sexual behavior problems), and reinforcing factors (when focus group participants knew an abuser, they were less likely to take action). This process guided the intervention, which included a broad-based media campaign targeting adults; a one-to-one communications strategy that provided information to agencies working with families at risk and a toll-free helpline for adults in an abuse situation; and a systems change strategy designed to educate decision-makers and leaders. Program evaluation measures included a random-digit dial survey, focus groups, a survey of Vermont decision-makers, and other data sets. The successes and limitations of these interventions, both as strategies in themselves and as data sources for evaluation, are discussed.
We prospectively examined the association between vitamin supplement intake and the incidence of cataract extraction during 12 years of follow-up in a cohort of 47,152 female nurses. Women were 45 years or older and free of diagnosed cancer in 1980; others were added as they reached 45 years of age, for a total of 73,956 women. During 720,082 years of follow-up, 1,377 senile cataracts were diagnosed and extracted. Those who used multivitamins or separate supplements of vitamin C, E, or A did not have decreased risks of cataract as compared with nonusers even for use of 10 or more years. After adjusting for cataract risk factors, including cigarette smoking, body mass index, and diabetes mellitus, users of vitamin C supplements for 10 or more years had a relative risk (RR) of 0.95 [95% confidence interval (CI) = 0.76-1.20]. Associations were stronger among long-term vitamin C supplement users who were never-smokers (RR = 0.71; 95% CI = 0.47-1.08) and less than 60 years of age (RR = 0.72; 95% CI = 0.49-1.04). These findings suggest that there is little overall benefit of long-term use of vitamin supplements for risk of cataracts requiring extraction.
PURPOSE: To review the association between combined oral contraceptives and cardiovascular disease, with emphasis on oral contraceptives containing low doses of estrogen (low-dose oral contraceptives). DATA SOURCES: A systematic search of the MEDLINE database was done for all relevant articles published between 1967 (when low-dose oral contraceptives were introduced in the United States) and June 1997. Textbooks, meeting proceedings, and reference lists were also searched. STUDY SELECTION: All English-language human epidemiology studies of oral contraceptives that used cardiovascular disease as an end point were reviewed. Animal and metabolic studies were reviewed only if they were especially relevant to the mechanism of action of oral contraceptives. DATA EXTRACTION: Descriptive and analytic data from each study were collected. DATA SYNTHESIS: Data were organized by cardiovascular end point, study design, estrogen dose, and type of progestogen. Data on relative and absolute risk are presented to address current prescription guidelines. CONCLUSIONS: The risk for cardiovascular disease is lower with current preparations of oral contraceptives, including those that contain the new progestogens, than with older oral contraceptives containing high doses of estrogen. Among users of low-dose oral contraceptives, cardiovascular diseases occur mainly in smokers and women with predisposing factors. Every effort should be made to encourage smoking cessation among potential users of oral contraceptives.
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.
Histories of oral contraceptive (OC) use were reported by 116,686 women aged 25 to 42 years in the Nurses' Health Study II on a self-administered questionnaire accompanied by a color photo booklet of all OC preparations ever marketed in the US. To evaluate the quality of this information, we compared the responses of a randomly selected sample of 215 participants with their data from a subsequent, detailed telephone interview using a structured life events calendar. Agreement for a history of ever having used OC was high between the two methods (exact agreement 99%). Reported durations of use were equivalent (mean duration 42.7 months by telephone interview and 44.6 months by questionnaire). The Spearman correlation for duration of use calculated from the two methods was 0.94 (p < 0.0001). For a subset of women for whom we were able to obtain OC prescription records, the medical record confirmed the use of an identical or equivalent brand in 75% of intervals of reported use. Acceptably valid OC histories were obtained with a self-administered questionnaire.
OBJECTIVE: To examine prospectively the association between modern oral contraceptives with low doses of estrogen and progestin and subsequent incidence of NIDDM. RESEARCH DESIGN AND METHODS: In a prospective cohort study, 98,590 U.S. female nurses aged 25 to 42 and free of diagnosed diabetes, coronary heart disease, stroke, and cancer at baseline in 1989 were followed for 4 years. Endpoint was incidence of confirmed NIDDM. Oral contraceptive use was reported on mailed questionnaires. RESULTS: During 352,067 person-years follow-up, we confirmed 185 incident cases of NIDDM. After adjusting for age, BMI, cigarette smoking, family history of diabetes, parity, physical activity, alcohol intake, ethnicity, history of diagnosis of infertility, elevated cholesterol, and hypertension, women currently using oral contraceptives had a relative risk (RR) of 1.6 (95% CI, 0.9-3.1). For past users, the multivariate RR was 1.2 (95% CI, 0.8-1.8). This association was attenuated after restricting the analysis to symptomatic cases of NIDDM. For current users, RR = 1.3 (95% CI, 0.6-2.8), and for past users, RR = 0.9 (95% CI, 0.6-1.4), suggesting that increased surveillance may explain at least part of any excess risk. CONCLUSIONS: In this large prospective study, we found no appreciable increase in the 4-year risk of NIDDM among current users of oral contraceptives. There was no apparent increase in risk among past users. The small number of cases reflect the low absolute risk of NIDDM in this population of young women.
BACKGROUND: Oral contraceptives induce hypertension in approximately 5% of users of high-dose pills that contain at least 50 micrograms estrogen and 1 to 4 mg progestin, and small increases in blood pressure have been reported even among users of modern low-dose formulations. However, neither the responsible hormone in the oral contraceptive nor particular subgroups of women who might be susceptible to the hypertensive effect of oral contraceptives have been identified. METHODS AND RESULTS: In a prospective cohort study in the United States, 68 297 female nurses aged 25 to 42 years and free of diagnosed hypertension, diabetes, coronary heart disease, stroke, and cancer at baseline were followed up for 4 years. During 231 006 person-years of follow-up, 1567 incident cases of hypertension were diagnosed. Compared with women who had never used oral contraceptives, the age-adjusted relative risk was 1.5 (95% CI = 1.2 to 1.8) for current use and 1.1 (95% CI = 0.9 to 1.2) for past use. After adjustment for age, body mass index, hormones cigarette smoking, family history of hypertension, parity, physical activity, alcohol intake, and ethnicity, current users of oral contraceptives had an increased risk of development of hypertension (RR = 1.8; 95% CI = 1.5 to 2.3) compared with women who had never used them. The multivariate relative risk for past users was 1.2 (95% CI = 1.0 to 1.4). There were no important modifying effects of age, family history of hypertension, ethnicity, or body mass index. CONCLUSIONS: Current users of oral contraceptives had a significant, moderately increased risk of hypertension. However, among this group, only 41.5 cases per 10 000 person-years could be attributed to oral contraceptive use. Risk decreased quickly with cessation of oral contraceptives, and past users appeared to have only a slightly increased risk.
OBJECTIVE: To assess prospectively the risk of myocardial infarction (MI) associated with decreased plasma levels of folate and pyridoxal phosphate (PLP, a form of vitamin B6) in relation to elevated levels of total homocysteine (tHcy). DESIGN: Nested case-control study using prospectively collected blood samples. SETTING: Participants in the Physicians' Health Study. SUBJECTS: 14,916 male physicians, aged 40-84 years, with no prior MI or stroke provided plasma samples at baseline and were followed for 7.5 years. Samples from 333 men who subsequently developed MI, and their paired controls matched by age and smoking, were analyzed for folate and PLP levels. MEASURES OF OUTCOME: Acute MI or death due to coronary disease. RESULTS: In a model controlling for diabetes, angina, hypertension, Quetelet's index, and total/high-density lipoprotein cholesterol, men with the lowest 20% of folate levels (< 2.0 ng/mL) had a relative risk of 1.4 (95% confidence interval 0.9-2.3) compared with those in the top 80%. For the lowest 20% of vitamin B6 values, the relative risk was 1.5 (95% CI: 1.0-2.2). When we included both folate and B6 in a model with cardiovascular risk factors, the relative risk of MI for low as compared to high levels of folate was 1.3 (95% CI: 0.8-2.1) and for PLP, 1.3 (95% CI: 0.9-2.1). Adding tHcy to this model did not add significant predictive value (chi sq = 2.0, p > 0.05), except in the first half of the follow-up interval when men with the top 5% of tHcy values had an almost three-fold increase in risk of MI. CONCLUSIONS: Although not statistically significant, these prospective data are compatible with the hypothesis that low dietary intake of folate and/or vitamin B6 contribute to risk of MI.
Given concerns about survey nonresponse bias as well as the need to plan resources for participant recruitment, this study tracked each step of the recruitment process (location, response, consent, and completion) of sociodemographically diverse older women for a survey concerning mammography experience. Younger, less educated poor women were likely to be lost due to inability to locate them, while older middle- and upper-economic-group women were more likely to be lost due to refusal to participate. Hispanic and Black women were significantly more likely to respond on successive attempts to recruit them than were White, non-Hispanic women. There was no significant difference in refusal rates by minority women over the successive contacts, as contrasted with White women, who refused at significantly higher rates with each attempt.