Biomedical subjects

F E Speizer

Publications and source records attributed to F E Speizer.

At least 37 records · Page 2Linked to original sources

PubMed2001

Being breastfed in infancy and breast cancer incidence in adult life: results from the two nurses' health studies.

Events during perinatal and early life may influence the incidence of breast cancer in adult life, and some case-control studies suggest that having been breastfed may reduce breast cancer risk. The authors studied this association among premenopausal and postmenopausal women by using data from the two Nurses' Health Studies, the Nurses' Health Study (using data from 1992 to 1996) and the Nurses' Health Study II (using data from 1991 to 1997). A history of being breastfed was self-reported by the study participants. During a total of 695,655 person-years, 1,073 cases of invasive breast cancer were diagnosed. The authors did not observe any important overall association between having been breastfed and the development of breast cancer later in life among premenopausal women (covariate-adjusted relative risk = 0.97, 95% confidence interval (CI): 0.78, 1.20) or postmenopausal women (covariate-adjusted relative risk = 1.12, 95% CI: 0.92, 1.37). No significant trend was observed with increasing duration of breastfeeding. The authors also used data on breastfeeding retrospectively collected from 2,103 mothers of participants of the two Nurses' Health Studies. With the mothers' reports, the covariate-adjusted odds ratio of breast cancer was 1.11 (95% CI: 0.88, 1.39) for women who were breastfed compared with those who were not. Data from these two large cohorts do not support the hypothesis that being breastfed confers protection against subsequent breast cancer.

Adult↗

PubMed2001

Intake of fish and omega-3 fatty acids and risk of stroke in women.

CONTEXT: Some prospective studies have shown an inverse association between fish intake and risk of stroke, but none has examined the relationship of fish and omega-3 polyunsaturated fatty acid intake with risk of specific stroke subtypes. OBJECTIVE: To examine the association between fish and omega-3 polyunsaturated fatty acid intake and risk of stroke subtypes in women. DESIGN, SETTING, AND SUBJECTS: Prospective cohort study of women in the Nurses' Health Study cohort, aged 34 to 59 years in 1980, who were free from prior diagnosed cardiovascular disease, cancer, and history of diabetes and hypercholesterolemia and who completed a food frequency questionnaire including consumption of fish and other frequently eaten foods. The 79 839 women who met our eligibility criteria were followed up for 14 years. MAIN OUTCOME MEASURE: Relative risk of stroke in 1980-1994 compared by category of fish intake and quintile of omega-3 polyunsaturated fatty acid intake. RESULTS: After 1 086 261 person-years of follow-up, 574 incident strokes were documented, including 119 subarachnoid hemorrhages, 62 intraparenchymal hemorrhages, 303 ischemic strokes (264 thrombotic and 39 embolic infarctions), and 90 strokes of undetermined type. Among thrombotic infarctions, 90 large-artery occlusive infarctions and 142 lacunar infarctions were identified. Compared with women who ate fish less than once per month, those with higher intake of fish had a lower risk of total stroke: the multivariate relative risks (RRs), adjusted for age, smoking, and other cardiovascular risk factors, were 0.93 (95% confidence interval [CI], 0.65-1.34) for fish consumption 1 to 3 times per month, 0.78 (95% CI, 0.55-1.12) for once per week, 0.73 (95% CI, 0.47-1.14) for 2 to 4 times per week, and 0.48 (95% CI, 0.21-1.06) for 5 or more times per week (P for trend =.06). Among stroke subtypes, a significantly reduced risk of thrombotic infarction was found among women who ate fish 2 or more times per week (multivariate RR, 0.49; 95% CI, 0.26-0.93). Women in the highest quintile of intake of long-chain omega-3 polyunsaturated fatty acids had reduced risk of total stroke and thrombotic infarction, with multivariate RRs of 0.72 (95% CI, 0.53-0.99) and 0.67 (95% CI, 0.42-1.07), respectively. When stratified by aspirin use, fish and omega-3 polyunsaturated fatty acid intakes were inversely associated with risk of thrombotic infarction, primarily among women who did not regularly take aspirin. There was no association between fish or omega-3 polyunsaturated fatty acid intake and risk of hemorrhagic stroke. CONCLUSIONS: Our data indicate that higher consumption of fish and omega-3 polyunsaturated fatty acids is associated with a reduced risk of thrombotic infarction, primarily among women who do not take aspirin regularly, but is not related to risk of hemorrhagic stroke.

Adult↗

PubMed2001

Physical activity and risk for cardiovascular events in diabetic women.

BACKGROUND: Increased physical activity has been associated with reduced risk for cardiovascular disease in the general population, but data are limited on its role among persons with type 2 diabetes mellitus. OBJECTIVE: To determine whether physical activity decreases risk for cardiovascular disease among diabetic women. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study. PATIENTS: 5125 female nurses with diabetes. MEASUREMENTS: Physical activity was first assessed in 1980 and was updated in 1982, 1986, 1988, and 1992 through validated questionnaires. Average hours of moderate or vigorous exercise and a metabolic equivalent of task (MET) score were computed. RESULTS: During 14 years of follow-up (31 432 person-years), 323 new cases of cardiovascular disease were documented (225 cases of coronary heart disease and 98 cases of stroke). The age-adjusted relative risks according to average hours of moderate or vigorous activity per week (<1, 1 to 1.9, 2 to 3.9, 4 to 6.9, >/=7) were 1.0, 0.93 (95% CI, 0.69 to 1.26), 0.82 (CI, 0.61 to 1.10), 0.54 (CI, 0.39 to 0.76), and 0.52 (CI, 0.25 to 1.09) (P < 0.001 for trend). These figures did not change materially after adjustment for smoking, body mass index, and other cardiovascular risk factors (1.0, 1.02, 0.87, 0.61, and 0.55, respectively; P = 0.001 for trend). In separate analyses, levels of physical activity were inversely associated with coronary heart disease and ischemic stroke. Among women who did not exercise vigorously, the multivariate relative risks for cardiovascular disease across quartiles of MET score for walking were 1.0, 0.85, 0.63, and 0.56 (P = 0.03 for trend). Faster usual walking pace was independently associated with lower risk. CONCLUSION: Among diabetic women, increased physical activity, including regular walking, is associated with substantially reduced risk for cardiovascular events.

Adult↗

PubMed2001

Cigarette smoking and the incidence of Parkinson's disease in two prospective studies.

An inverse association between cigarette smoking and idiopathic Parkinson's disease has been reported in several retrospective studies, but prospective evidence is available only for men. We assessed the association between the incidence of Parkinson's disease and smoking in two large prospective cohort studies comprising men and women. New cases of Parkinson's disease were identified in the Nurses' Health Study for 1976-1996, and in the Health Professionals Follow-up Study for 1986-1996. Smoking history was assessed at baseline and updated on subsequent biennial questionnaires. In women, the age-adjusted rate ratios (95% confidence intervals) for Parkinson's disease relative to never-smokers were 0.7 (0.5, 1.0) for past smokers, and 0.4 (0.2, 0.7) for current smokers. In men, the age-adjusted rate ratios for Parkinson's disease relative to never-smokers were 0.5 (0.4, 0.7) for past smokers, and 0.3 (0.1, 0.8) for current smokers. In both cohorts, the strength of the association decreased with time since quitting (among past smokers), increased with number of cigarettes per day (among current smokers), and increased with pack-years of smoking. These prospective findings confirm that an inverse association between smoking and the incidence of Parkinson's disease exists in both men and women.

Adult↗

PubMed2001

Prospective study of caffeine consumption and risk of Parkinson's disease in men and women.

Results of case-control studies and of a prospective investigation in men suggest that consumption of coffee could protect against the risk of Parkinson's disease, but the active constituent is not clear. To address the hypothesis that caffeine is protective against Parkinson's disease, we examined the relationship of coffee and caffeine consumption to the risk of this disease among participants in two ongoing cohorts, the Health Professionals' Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). The study population comprised 47,351 men and 88,565 women who were free of Parkinson's disease, stroke, or cancer at baseline. A comprehensive life style and dietary questionnaire was completed by the participants at baseline and updated every two to four years. During the follow-up (10 years in men, 16 years in women), we documented a total of 288 incident cases of Parkinson's disease. Among men, after adjustment for age and smoking, the relative risk of Parkinson's disease was 0.42 (95% CI: 0.23-0.78; p for trend < 0.001) for men in the top one-fifth of caffeine intake compared to those in the bottom one-fifth. An inverse association was also observed with consumption of coffee (p for trend = 0.004), caffeine from noncoffee sources (p for trend < 0.001), and tea (p for trend = 0.02) but not decaffeinated coffee. Among women, the relationship between caffeine or coffee intake and risk of Parkinson's disease was U-shaped, with the lowest risk observed at moderate intakes (1-3 cups of coffee/day, or the third quintile of caffeine consumption). These results support a possible protective effect of moderate doses of caffeine on risk of Parkinson's disease.

Adult↗

PubMed2001

Standardized submaximal exercise testing in never smokers: a normative study.

In a population survey on the south-western coast of Norway, 373 never smokers aged 18-73 years (230 women) without respiratory symptoms performed a standardized, progressive, incremental submaximal bicycle exercise test. All individuals were able to do an exercise involving oxygen uptake of 1.0 l min(-1), 80% of the subjects reached 1.5 l min(-1) and 50% of the subjects reached 2.0 l min(-1). The respiratory frequency (RF), ventilation (VE) and heart rate (HR) for a given oxygen uptake were all higher in women than in men. Significant predictors of failure to reach oxygen uptake of 1.5 and 2.0 l min(-1) were sex, age, body height and weight. Prediction equations are given for respiratory frequency, heart rate and ventilation for an oxygen uptake of 1.0 l min(-1) in women and 1.5 l min(-1) in men; and body height is a strong predictor for all dependent variables. A multiple linear regression analysis in women showed that age was a significant predictor of respiratory frequency (P<0.05), ventilation (P<0.001) and heart rate (P<0.001), while in men age was a significant predictor only of ventilation (P<0.001) during the bicycle exercise protocol.

Adolescent↗

PubMed2001

Expiratory and inspiratory forced vital capacity and one-second forced volume in asymptomatic never-smokers in Norway.

The objectives of this study were to examine within and between individual variation detected during forced expiratory (FE) and forced inspiratory (FI) manoeuvers in a general population and to investigate the dependence of these variables on age, body size, and gender. A random sample of asymptomatic never smokers who had never been exposed occupationally to quartz or asbestos and who were living on the south-western coast of Norway were examined by spirometry; 81% of the individuals invited to attend did so. Of the 488 subjects between 18 and 73 years of age, 98% contributed three acceptable recordings for forced expiratory vital capacity (FVC) and one-second forced expiratory volume (FEV1), 94% contributed three acceptable recordings for forced inspiratory vital capacity (FIVC) and 85% contributed three acceptable recordings for one-second forced inspiratory volume (FIV(1)). The within-subject variation increased with body height and was considerably larger for FIV(1) than for FVC, FEV(1) or FIVC. A four-parameter model of pulmonary function measurement divided by height squared, including a gender term and a linear and quadratic term of age, fit the median of the observed values well. The residuals had a close-to-normal distribution, and the fifth-percentile values were estimated as the lower limit of normal. The peak value of dynamic lung volumes was observed into the middle of the fourth decade of life, and the decline thereafter did not differ greatly between the genders or among the different indices. The forced inspiratory volumes are the first reported in any reference population.

Adolescent↗

PubMed2001

Twenty-four-hour urine chemistries and the risk of kidney stones among women and men.

BACKGROUND: Results of a 24-hour urine collection are integral to the selection of the most appropriate intervention to prevent kidney stone recurrence. However, the currently accepted definitions of normal urine values are not firmly supported by the literature. In addition, little information is available about the relationship between risk of stone formation and the levels of urinary factors. Unfortunately, the majority of previous studies of 24-hour urine chemistries were limited by the inclusion of recurrent stone formers and poorly defined controls. METHODS: We obtained 24-hour urine collections from 807 men and women with a history of kidney stone disease and 239 without a history who were participants in three large ongoing cohort studies: the Nurses' Health Study I (NHS I; mean age of 61 years), the Nurses' Health Study II (NHS II; mean age of 42 years), and the Health Professionals Follow-up Study (HPFS; mean age of 59 years). RESULTS: Mean 24-hour urine calcium excretion was higher and urine volume was lower in cases than controls in NHS I (P < or = 0.01), NHS II (P < or = 0.13) and HPFS (P < or = 0.01), but urine oxalate and citrate did not differ. Among women, urine uric acid was similar in cases and controls but was lower in cases in men (P = 0.06). The frequency of hypercalciuria was higher among the cases in NHS I (P = 0.26), NHS II (P = 0.03), and HPFS (P = 0.02), but 27, 17, and 14% of the controls, respectively, also met the definition of hypercalciuria. The frequency of hyperoxaluria did not differ between cases and controls, but was three times more common among men compared with women. After adjusting for the other urinary factors, the relative risk of stone formation increased with increasing urine calcium levels and concentration in all three cohorts but not in a linear fashion. Compared with individuals with a urine calcium concentration of <75 mg/L, the relative risk of stone formation among those with a urine calcium concentration of > or =200 mg/L for NHS I was 4.34 (95% CI, 1.59 to 11.88), for NHS II was 51.09 (4.27 to 611.1), and for HPFS was 4.30 (1.71 to 10.84). There was substantial variation in the relative risks for stone formation for the concentration of other urine factors within the different cohorts. CONCLUSIONS: The traditional definitions of normal 24-hour urine values need to be reassessed, as a substantial proportion of controls would be defined as abnormal, and the association with risk of stone formation may be continuous rather than dichotomous. The 24-hour urine chemistries are important for predicting risk of stone formation, but the significance and the magnitudes of the associations appear to differ by age and gender.

Adult↗

PubMed2001

Beta(2)-adrenoceptor polymorphism and body mass index are associated with adult-onset asthma in sedentary but not active women.

STUDY OBJECTIVE: Beta(2)-adrenoceptor Gly16 polymorphism has been associated with asthma severity and beta(2)-adrenoceptor receptor downregulation, but not with the diagnosis of asthma. Glu27 polymorphism may limit beta(2)-adrenoceptor downregulation and predict body mass index (BMI), particularly among sedentary persons. In addition, BMI predicts asthma. We hypothesized that these DNA sequence variants predict adult-onset asthma only in sedentary women. DESIGN: Nested case-control study. SETTING: Nurses' Health Study, a large, prospective cohort study with participants throughout the United States. PARTICIPANTS: Among lifelong nonsmokers, 171 women with adult-onset, medication-requiring asthma and 137 age-matched control subjects. MEASUREMENTS: Physical activity and BMI were self-reported by previously validated questionnaire items. Genomic DNA was obtained from buccal brushings collected via first-class mail. RESULTS: Of 76 sedentary women, the adjusted odds ratios of Gly16 allele were 7.4 (p = 0.047) for asthma and 13.8 (p = 0.02) for steroid-requiring asthma. No similar associations were observed among 232 active women (p = 0.91). Sedentary individuals with both Gly16 and Glu27 alleles had a less elevated risk for asthma. BMI was associated with asthma and Glu27 allele among sedentary women. CONCLUSION: This exploratory analysis suggests an important gene/environment interaction for asthma involving physical activity level. Further study in larger populations is warranted to confirm if sedentary lifestyle unmasks a genetic risk for asthma.

Adult↗

PubMed2001

Smoking and mortality among women with type 2 diabetes: The Nurses' Health Study cohort.

OBJECTIVE: To assess the relationship between cigarette smoking and mortality among women with type 2 diabetes in the Nurses' Health Study cohort. RESEARCH DESIGN AND METHODS: The Nurses' Health Study, a prospective cohort of U.S. female registered nurses, included 7,401 women with type 2 diabetes diagnosed at baseline or during follow-up from 1976 to 1996. Total and cause-specific mortality of these diabetic women were the outcomes of interest. RESULTS: We documented 724 deaths during 20 years of follow-up (67,420 person-years) among women with type 2 diabetes. In multivariate analyses, adjusting for age, history of high blood pressure and high cholesterol, and other cardiovascular risk factors, compared with never smokers, the RRs of mortality were 1.31 (95% CI 1.11-1.55) for past smokers, 1.43 (0.96-2.14) for current smokers of 1-14 cigarettes/day, 1.64 (1.24-2.17) for current smokers of 15-34 cigarettes/day, and 2.19 (1.32-3.65) for current smokers of > or =35 cigarettes/day (P for trend = 0.0002). Women with type 2 diabetes who had stopped smoking for > or =10 years had a mortality RR of 1.11 (0.92-1.35) compared with diabetic women who were never smokers. CONCLUSIONS: Cigarette smoking is associated in a dose-response manner with an increased mortality among women with type 2 diabetes. Furthermore, quitting smoking appears to decrease this excess risk substantially. Diabetes patients should be strongly advised against smoking.

Adult↗

PubMed2000

A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease.

BACKGROUND: Most primary prevention studies have found that long-term users of postmenopausal hormone therapy are at lower risk for coronary events, but numerous questions remain. An adverse influence of hormone therapy on cardiovascular risk has been suggested during the initial year of use; however, few data are available on short-term hormone therapy. In addition, the cardiovascular effects of daily doses of oral conjugated estrogen lower than 0.625 mg are unknown, and few studies have examined estrogen plus progestin in this regard. OBJECTIVE: To investigate duration, dose, and type of postmenopausal hormone therapy and primary prevention of cardiovascular disease. DESIGN: Prospective, observational cohort study. SETTING: Nurses' Health Study, with follow-up from 1976 to 1996. PATIENTS: 70 533 postmenopausal women, in whom 1258 major coronary events (nonfatal myocardial infarction or fatal coronary disease) and 767 strokes were identified. MEASUREMENTS: Details of postmenopausal hormone use were ascertained by using biennial questionnaires. Cardiovascular disease was established by using a questionnaire and was confirmed by medical record review. Logistic regression models were used to calculate relative risks and 95% CIs, adjusted for confounders. RESULTS: When all cardiovascular risk factors were considered, the risk for major coronary events was lower among current users of hormone therapy, including short-term users, compared with never-users (relative risk, 0.61 [95% CI, 0.52 to 0.71]). Among women taking oral conjugated estrogen, the risk for coronary events was similarly reduced in those currently taking 0.625 mg daily (relative risk, 0.54 [CI, 0.44 to 0.67]) and those taking 0.3 mg daily (relative risk, 0.58 [CI, 0. 37 to 0.92]) compared with never-users. However, the risk for stroke was statistically significantly increased among women taking 0.625 mg or more of oral conjugated estrogen daily (relative risk, 1.35 [CI, 1.08 to 1.68] for 0.625 mg/d and 1.63 [CI, 1.18 to 2.26] for >/=1.25 mg/d) and those taking estrogen plus progestin (relative risk, 1.45 [CI, 1.10 to 1.92]). Overall, little relation was observed between combination hormone therapy and risk for cardiovascular disease (major coronary heart disease plus stroke) (relative risk, 0.91 [CI, 0.75 to 1.11]). CONCLUSIONS: Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease. Furthermore, 0.3 mg of oral conjugated estrogen daily is associated with a reduction similar to that seen with the standard dose of 0.625 mg. However, estrogen at daily doses of 0.625 mg or greater and in combination with progestin may increase risk for stroke.

Adult↗

PubMed2000

Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women.

BACKGROUND: Diets high in fruits and vegetables have been shown to be associated with a lower risk of lung cancer. beta-Carotene was hypothesized to be largely responsible for the apparent protective effect, but this hypothesis was not supported by clinical trials. METHODS: We examined the association between lung cancer risk and fruit and vegetable consumption in 77 283 women in the Nurses' Health Study and 47 778 men in the Health Professionals' Follow-up Study. Diet was assessed with the use of a food-frequency questionnaire that included 15 fruits and 23 vegetables. We used logistic regression models to estimate relative risks (RRs) of lung cancer within each cohort. All statistical tests were two-sided. RESULTS: We documented 519 lung cancer cases among the women and 274 among the men. Total fruit and vegetable consumption was associated with a modestly lower risk of lung cancer among the women but not among the men. The RR for the highest versus lowest quintile of intake was 0.79 (95% confidence interval [CI] = 0.59-1.06) among the women and 1.12 (95% CI = 0.74-1.69) among the men after adjustment for smoking status, quantity of cigarettes smoked per day, time since quitting smoking, and age at initiation of smoking. However, total fruit and vegetable consumption was associated with a lower risk of lung cancer among never smokers in the combined cohorts, although the reduction was not statistically significant (RR = 0.63; 95% CI = 0.35-1.12 in the highest tertile). CONCLUSION: Higher fruit and vegetable intakes were associated with lower risks of lung cancer in women but not in men. It is possible that the inverse association among the women remained confounded by unmeasured smoking characteristics, although fruits and vegetables were protective in both men and women who never smoked.

Adult↗

PubMed2000

Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers.

BACKGROUND: Frequent consumption of fruit and vegetables has been associated with a reduced risk of colorectal cancer in many observational studies. METHODS: We prospectively investigated the association between fruit and vegetable consumption and the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (88 764 women) and the Health Professionals' Follow-up Study (47 325 men). Diet was assessed and cumulatively updated in 1980, 1984, 1986, and 1990 among women and in 1986 and 1990 among men. The incidence of cancer of the colon and rectum was ascertained up to June or January of 1996, respectively. Relative risk (RR) estimates were calculated with the use of pooled logistic regression models accounting for various potential confounders. All statistical tests were two-sided. RESULTS: With a follow-up including 1 743 645 person-years and 937 cases of colon cancer, we found little association of colon cancer incidence with fruit and vegetable consumption. For women and men combined, a difference in fruit and vegetable consumption of one additional serving per day was associated with a covariate-adjusted RR of 1.02 (95% confidence interval [CI] = 0.98-1.05). A difference in vegetable consumption of one additional serving per day was associated with an RR of 1.03 (95% CI = 0.97-1.09). Similar results were obtained for women and men considered separately. A difference in fruit consumption of one additional serving per day was associated with a covariate-adjusted RR for colon cancer of 0.96 (95% CI = 0.89-1.03) among women and 1. 08 (95% CI = 1.00-1.16) among men. For rectal cancer (total, 244 cases), a difference in fruit and vegetable consumption of one additional serving per day was associated with an RR of 1.02 (95% CI = 0.95-1.09) in men and women combined. None of these associations was modified by vitamin supplement use or smoking habits. CONCLUSIONS: Although fruits and vegetables may confer protection against some chronic diseases, their frequent consumption does not appear to confer protection from colon or rectal cancer.

Adult↗

PubMed2000

Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk.

The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (CI): 0.96, 1.10) in premenopausal women and 1.07 (95% CI: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% CI: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% CI: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.

Adult↗

PubMed2000

Trends in the incidence of coronary heart disease and changes in diet and lifestyle in women.

BACKGROUND: Previous studies have found concurrent declines in blood pressure, serum cholesterol levels, and the incidence of and mortality from coronary disease. However, the effects of changes in diet and lifestyle on trends in coronary disease are largely unknown. METHODS: We followed 85,941 women who were 34 to 59 years old and had no previously diagnosed cardiovascular disease or cancer from 1980 to 1994 in the Nurses' Health Study. Diet and lifestyle variables were assessed at base line and updated during follow-up. RESULTS: After adjustment for the effect of age, the incidence of coronary disease declined by 31 percent from the two-year period 1980-1982 to the two-year period 1992-1994. From 1980 to 1992, the proportion of participants currently smoking declined by 41 percent, the proportion of postmenopausal women using hormone therapy increased by 175 percent, and the prevalence of overweight, defined as a body-mass index (the weight in kilograms divided by the square of the height in meters) of 25 or more, increased by 38 percent. During the study period, diet improved substantially. Statistically, changes in these variables--when considered simultaneously--explained a 21 percent decline in the incidence of coronary disease, representing 68 percent of the overall decline from 1980-1982 to 1992-1994. Taken individually, the reduction in smoking explained a 13 percent decline in the incidence of coronary disease; improvement in diet explained a 16 percent decline; and increase in postmenopausal hormone use explained a 9 percent decline. On the other hand, the increase in body-mass index explained an 8 percent increase in the incidence of coronary disease. CONCLUSIONS: Reduction in smoking, improvement in diet, and an increase in postmenopausal hormone use accounted for much of the decline in the incidence of coronary disease in this group of women. An increasing prevalence of obesity, however, appears to have slowed the decline in the incidence of coronary disease.

Adult↗

PubMed2000

Moderate alcohol consumption and risk of coronary heart disease among women with type 2 diabetes mellitus.

BACKGROUND: Moderate alcohol consumption is associated with reduced risk for coronary heart disease (CHD) in generally healthy populations. We assessed prospectively the association between moderate alcohol intake and CHD risk in women with type 2 diabetes mellitus, a group at high risk for cardiovascular disease. METHODS AND RESULTS: We studied women in the Nurses' Health Study who reported a diagnosis of diabetes mellitus at >/=30 years of age. During 39 092 person-years of follow-up from 1980 to 1994, there were 295 CHD events documented among this population, including 194 cases of nonfatal myocardial infarction and 101 cases of fatal CHD. Odds ratios derived from logistic regression were used to estimate relative risks (RRs) for CHD as a function of usual alcohol intake, with adjustment for potential confounders. Compared with diabetic women reporting no alcohol intake, the age-adjusted RR for nonfatal or fatal CHD among diabetic women reporting usual intake of 0.1 to 4.9 g (<0.5 drinks) of alcohol daily was 0.74 (95% CI 0.56 to 0.98), and among those reporting usual intake >/=5 g/d, it was 0.48 (95% CI 0.32 to 0.72) (P for trend <0.0001). Inverse associations between alcohol intake and CHD risk remained significant in multivariate analysis adjusting for several other coronary risk factors (0.1 to 4. 9 g/d: RR 0.72 [95% CI 0.54 to 0.96]; >/=5 g/d: RR 0.45 [0.29 to 0.68]). CONCLUSIONS: Although potential risks of alcohol consumption must be considered, these data suggest that moderate alcohol consumption is associated with reduced CHD risk in women with diabetes and should not be routinely discouraged.

Adult↗

PubMed2000

A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk.

The CYP19 gene codes for aromatase, a key steroidogenic enzyme involved in the conversion of androgens to estrogens. A tetranucleotide (TTTA) repeat polymorphism is present in intron 4 of CYP19; 2 out of 4 breast cancer case-control studies have reported a greater frequency of 2 specific alleles among affected women. We evaluated associations between CYP19 repeat alleles and breast cancer risk in a case-control study nested within the Nurses' Health Study cohort (incident cases: n=462; controls: n=618). We observed seven different CYP19 alleles (TTTA(7-13)). Compared to controls, cases had a statistically significant greater frequency of the 10 (TTTA)(10) repeat allele (10 allele: 2.3% vs. 0.7%, p = 0.005) and a nonsignificant increase in the frequency of the 12 (TTTA)(12) allele (12 allele: 3.1% vs. 2.1%, p = 0.11). A higher frequency of the 10 allele was observed in more advanced cancer cases defined as four or more involved nodes or distant metastasis [4+ nodes: 5/36 (13.9%) vs. 0-3 nodes: 13/330 (3.9%), p = 0.02]. Among controls, we found women with the 7 repeat allele to have decreased levels of estrone sulfate (-16.4%, p = 0.02), estrone (-6.1%, p = 0.22) and estradiol (-9.9%, p = 0.10), and a lower estrone/androstenedione ratio (E1/A) (-10.5%, p = 0.08) compared to non-carriers. A higher E1/A ratio and elevated estrogen levels were observed among carriers of the 8 repeat allele; E1/A ratio (+21.0%, p = 0.003), estrone (+7.5%, p = 0.16) and estradiol (+10.8%, p = 0.08). However, we observed no evidence of an association between these alleles and breast cancer risk. We were unable to make inferences regarding the effect of the 10 allele on hormone levels due to the small number of allele carriers in the subgroup with hormone levels. As this repeat polymorphism is not close to the splice sites in intron 4, linkage disequilibrium with other functional polymorphisms in CYP19 may explain the findings of an increased association between breast cancer and the 10 allele variant of CYP19. We did not detect any sequence variants in the regulatory region or in the adipose-specific exon I.4. The lack of an established effect on CYP19 function associated with the 10 allele means that these findings should be interpreted with caution.

Alleles↗

PubMed2000

Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density.

Insulin-like growth factors (IGFs) and insulin-like growth factor-binding proteins (IGFBPs) play a role in the normal development of breast tissue and possibly in the etiology of breast cancer. Breast density is one of the strongest predictors of breast cancer. In a cross-sectional analysis within the Nurses' Health Study, we compared the associations of plasma levels of endogenous IGF-I and IGFBP-3 with breast density in 65 premenopausal and 192 postmenopausal women. The digitized film screen mammograms were evaluated by the computer-assisted Toronto method, in which visually selected gray-scale cut points are used to assess breast density. Generalized linear models and Spearman's partial correlation coefficients described the associations between breast density and IGF-I, IGFBP-3, and the IGF-I:IGFBP-3 ratio. Premenopausal breast density was positively correlated with IGF-I and inversely correlated with IGFBP-3; the association was strongest for the IGF-I:IGFBP-3 ratio and breast density (r = 0.39; P = 0.004). In contrast, the correlation between breast density and the IGF-I:IGFBP-3 ratio among postmenopausal women was -0.02 (P = 0.83). The associations of IGF-I:IGFBP-3 ratio with breast density differed significantly between premenopausal and postmenopausal women (P = 0.01). Mammographic density is positively associated with plasma IGF-I levels and inversely associated with plasma IGFBP-3 levels among premenopausal women, but not among postmenopausal women. These results are consistent with previous studies that showed a positive association between a higher IGF-I:IGFBP-3 ratio and subsequent risk of breast cancer only among premenopausal women. The findings raise the possibility that premenopausal levels of IGF-I and IGFBP-3 could be in the etiological pathway that relates higher breast density with increased breast cancer risk.

Aged↗