Showing papers by "Frank E. Speizer published in 1991"

Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study.

Abstract: Background The effect of postmenopausal estrogen therapy on the risk of cardiovascular disease remains controversial. Our 1985 report in the Journal, based on four years of follow-up, suggested that estrogen therapy reduced the risk of coronary heart disease, but a report published simultaneously from the Framingham Study suggested that the risk was increased. In addition, studies of the effect of estrogens on stroke have yielded conflicting results. Methods We followed 48,470 postmenopausal women, 30 to 63 years old, who were participants in the Nurses' Health Study, and who did not have a history of cancer or cardiovascular disease at base line. During up to 10 years of follow-up (337,854 person-years), we documented 224 strokes, 405 cases of major coronary disease (nonfatal myocardial infarctions or deaths from coronary causes), and 1263 deaths from all causes. Results After adjustment for age and other risk factors, the overall relative risk of major coronary disease in women currently taking estrogen was 0.56 (95 percent confidence interval, 0.40 to 0.80); the risk was significantly reduced among women with either natural or surgical menopause. We observed no effect of the duration of estrogen use independent of age. The findings were similar in analyses limited to women who had recently visited their physicians (relative risk, 0.45; 95 percent confidence interval, 0.31 to 0.66) and in a low-risk group that excluded women reporting current cigarette smoking, diabetes, hypertension, hypercholesterolemia, or a Quetelet index above the 90th percentile (relative risk, 0.53; 95 percent confidence interval, 0.31 to 0.91). The relative risk for current and former users of estrogen as compared with those who had never used it was 0.89 (95 percent confidence interval, 0.78 to 1.00) for total mortality and 0.72 (95 percent confidence interval, 0.55 to 0.95) for mortality from cardiovascular disease. The relative risk of stroke when current users were compared with those who had never used estrogen was 0.97 (95 percent confidence interval, 0.65 to 1.45), with no marked differences according to type of stroke. Conclusions Current estrogen use is associated with a reduction in the incidence of coronary heart disease as well as in mortality from cardiovascular disease, but it is not associated with any change in the risk of stroke.

A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women.

Abstract: We examined the relationship of maturity-onset clinical diabetes mellitus with the subsequent incidence of coronary heart disease, stroke, total cardiovascular mortality, and all-cause mortality in a cohort of 116177 US women who were 30 to 55 years of age and free of known coronary heart disease, stroke, and cancer in 1976. During 8 years of follow-up (889 255 personyears), we identified 338 nonfatal myocardial infarctions, 111 coronary deaths, 259 strokes, 238 cardiovascular deaths, and 1349 deaths from all causes. Diabetes was associated with a markedly increased risk of nonfatal myocardial infarction and fatal coronary heart disease (age-adjusted relative risk [RR] = 6.7; 95% confidence interval [CI], 5.3 to 8.4), ischemic stroke (RR = 5.4; 95% CI, 3.3 to 9.0), total cardiovascular mortality (RR 6.3; 95% CI, 4.6 to 8.6), and all-cause mortality (RR 3.0; 95% CI, 2.5 to 3.7). A major independent effect of diabetes persisted in multivariate analyses after simultaneous control for other known coronary risk factors (for these end points, RR [95% CI] = 3.1 [2.3 to 4.2], 3.0 [1.6 to 5.7], 3.0 [1.9 to 4.8], and 1.9 [1.4 to 2.4], respectively). The absolute excess coronary risk due to diabetes was greater in the presence of other risk factors, including cigarette smoking, hypertension, and obesity. These prospective data indicate that maturity-onset clinical diabetes is a strong determinant of coronary heart disease, ischemic stroke, and cardiovascular mortality among middle-aged women. The adverse effect of diabetes is amplified in the presence of other cardiovascular risk factors, many of which are modifiable. (Arch Intern Med.1991;151:1141-1147)

A prospective study of aspirin use and primary prevention of cardiovascular disease in women.

Abstract: Objective. —The aim of the study was to examine prospectively the association between regular aspirin use and the risk of a first myocardial infarction and other cardiovascular events in women. Design. —Prospective cohort study including 6 years of follow-up. Setting.—Registered nurses residing in 11 US states. Participants. —US registered nurses (n = 87 678) aged 34 to 65 years and free of diagnosed coronary heart disease, stroke, and cancer at baseline. Follow-up was 96.7% of total potential person-years of follow-up. Main Outcome Measures. —Incidence of myocardial infarction, stroke, cardiovascular death, and all important vascular events. Results. —During 475 265 person-years of follow-up, we documented 240 nonfatal myocardial infarctions, 146 nonfatal strokes, and 130 deaths due to cardiovascular disease (total, 516 important vascular events). Among women who reported taking one through six aspirin per week, the age-adjusted relative risk (RR) of a first myocardial infarction was 0.68 (95% confidence interval [CI], 0.52 to 0.89; P =.005), as compared with those women who took no aspirin. After simultaneous adjustment for risk factors for coronary disease, the RR was 0.75 (95% CI, 0.58 to 0.99; P =.04). For women aged 50 years and older, the age-adjusted RR was 0.61 (95% CI, 0.45 to 0.84; P =.002) and the multivariate RR was 0.68 (95% CI, 0.50 to 0.93; P =.02). We observed no alteration in the risk of stroke (multivariate RR = 0.99; P =.94). The multivariate RR of cardiovascular death was 0.89 (P =.56) and of important vascular events was 0.85 (P =.12). When examined separately, the results were nearly identical for the subgroups who took one through three and four though six aspirin per week. Among women who took seven or more aspirin per week, there were no apparent reductions in risk. Conclusions. —The use of one through six aspirin per week appears to be associated with a reduced risk of a first myocardial infarction among women. A randomized trial in women is necessary, however, to provide conclusive data on the role of aspirin in the primary prevention of cardiovascular disease in women. (JAMA. 1991;266:521-527)

Association of Indoor Nitrogen Dioxide with Respiratory Symptoms and Pulmonary Function in Children

Abstract: The effect of indoor nitrogen dioxide on the cumulative incidence of respiratory symptoms and pulmonary function level was studied in a cohort of 1,567 white children aged 7-11 years examined in six US cities from 1983 through 1988. Week-long measurements of nitrogen dioxide were obtained at three indoor locations over 2 consecutive weeks in both the winter and the summer months. The household annual average nitrogen dioxide concentration was modeled as a continuous variable and as four ordered categories. Multiple logistic regression analysis of symptom reports from a questionnaire administered after indoor monitoring showed that a 15-ppb increase in the household annual nitrogen dioxide mean was associated with an increased cumulative incidence of lower respiratory symptoms (odds ratio (OR) = 1.4, 95% confidence interval (95% Cl) 1.1-1.7). The response variable indicated the report of one or more of the following symptoms: attacks of shortness of breath with wheeze, chronic wheeze, chronic cough, chronic phlegm, or bronchitis. Girls showed a stronger association (OR = 1.7, 95% Cl 1.3-2.2) than did boys (OR = 1.2, 95% Cl 0.9-1.5). An analysis of pulmonary function measurements showed no consistent effect of nitrogen dioxide. These results are consistent with earlier reports based on categorical indicators of household nitrogen dioxide sources and provide a more specific association with nitrogen dioxide as measured in children's homes.

Peak Expiratory Flow Rate and 5-Year Mortality in an Elderly Population

Abstract: During a population survey in 1982-1983 among all community-dwelling elderly aged 65 years and over in East Boston, Massachusetts, measurements of peak expiratory flow rate using the mini-Wright peak flow meter were made on 3,582 participants (80% of those eligible). The average peak flow rate was 315 liters/minute, and a measure of peak flow rate adjusted for age, sex, height, and weight was computed. This was a highly significant (p less than 0.0001) predictor of 5-year total mortality, whose ascertainment was virtually complete. The relative risk was 1.27 (95 percent confidence interval 1.19-1.36) per 100 liters/minute decrease in peak flow rate, using a proportional hazards model including terms for age, sex, and smoking. There was no apparent modification of the effect of this measure in various categories of smoking, with relative risks of 1.24 for nonsmokers, 1.29 for ex-smokers, and 1.26 for current smokers. This finding also persisted after adjustments for other covariates, including respiratory symptoms such as cough, phlegm, and wheeze; cardiovascular risk factors such as history of myocardial infarction and stroke; and systolic and diastolic blood pressures; socioeconomic status; scores on simple tests of cognitive function; measures of physical activity and functional ability; and self-assessed state of health. In a stepwise model including all of these variables, the relative risk was 1.16 (p less than 0.0001) per 100 liters/minute decrease in peak flow rate, indicating that peak flow rate is a strong independent predictor of total mortality in the elderly.

A prospective study of reproductive history and exogenous estrogens on the risk of colorectal cancer in women.

Abstract: Among 118,404 female registered nurses who responded to a mailed questionnaire and had no history of cancer in 1976, 191 colon cancers and 49 rectal cancers were diagnosed during 8 years of follow-up We observed no material association between parity and colon cancer risk; women who bore four or more children had a risk similar to that of nulliparous women (age-adjusted RR = 11, 95% confidence limits (CL): 06, 19) No consistent patterns of colorectal cancer risk were associated with age at menarche or at first birth Current or past use of oral contraceptives did not appreciably alter the risk of colorectal cancer; past use of postmenopausal estrogens was associated with a reduced risk of colorectal cancer (RR = 05, 95% CL: 03, 10) These and other data do not support any substantial effect of reproductive history or oral contraceptive use on the risk of large bowel cancer; however, the possible protective role of postmenopausal estrogen therapy merits further investigation

A prospective study of body mass, height, and smoking on the risk of colorectal cancer in women.

Abstract: Female registered nurses in the United States who responded to a questionnaire in 1976 that inquired about height, weight, and smoking history were followed for the development of colon or rectal cancers through May of 1984. Among the 118,404 respondents free of cancer in 1976, 191 colon cancers and 49 rectal cancers were observed during 916,170 person-years of follow-up. After omitting cases diagnosed within two years of weight report, we found little overall relation of body mass (Quetelet's) index to colon cancer risk; however there was a suggestion of elevated risk for the heaviest category of body mass index (greater than or equal to 29 kg/m2, relative risk (RR) = 1.5; 95 percent confidence interval = 0.8 - 2.7) relative to the lowest category (less than 21 kg/m2). Self-reported body mass index from adolescence had a slightly more pronounced, although not significant, association with risk of colon cancer. Increasing height was significantly associated with colon cancer (RR = 1.6, 95 percent confidence interval = 1.1 - 2.5 for the tallest category [greater than or equal to 168 cm] versus the shortest (less than 160 cm], trend, P = 0.04). Measures of current or past smoking failed to demonstrate any consistent relationship with colon cancer.

Recall (Report) Bias and Reliability in the Retrospective Assessment of Melanoma Risk

Abstract: In a case-control study nested in the Nurses' Health Study cohort, the authors assessed recall bias in the ascertainment of two risk factors for melanoma: hair color and ability to tan. Participants reported on these risk factors in a 1982 questionnaire and in a subsequent case-control questionnaire or telephone interview. The test-retest reliability among controls was high for both questions (Spearman's r = 0.76). Among women diagnosed with melanoma after the first questionnaire and before the second, there was a substantial shift toward reporting a reduced ability to tan when participants were questioned after the diagnosis of melanoma (p = 0.035). No shift was noted for the hair color question (p = 0.8). The authors conclude that recall bias was observed among female nurses with cutaneous melanoma in the assessment of tanning ability, a major risk factor for melanoma.

Melanoma and the Sun: The Effect of Swimsuits and a “Healthy” Tan on the Risk of Nonfamilial Malignant Melanoma in Women

Abstract: The authors examined the relation between sun exposure and melanoma risk and tested the previously published site-specific association of bikini use and melanoma of the trunk in a study of 130 cases incident between 1976 and 1984 and 300 controls nested within the Nurses' Health Study. A summary variable derived from four measures of sun sensitivity was more closely associated with melanoma than any component measure. There was no association of bikini use at ages 15-20 years with trunk melanoma risk (relative risk (RR) = 0.8, p = 0.7), and the 95% confidence interval (CI) (0.3-2.6) excludes the previously published estimate. High frequency of swimsuit use outdoors at ages 15-20 years was associated with increased melanoma risk among sun-sensitive women (RR = 6.4, 95% CI 1.7-23.8, p = 0.006), but appeared to be protective among sun-resistant women (RR = 0.3, 95% CI 0.1-1.0, p = 0.06). These findings suggest that the risk of trunk melanoma associated with bikini use is at most modest and that sun-sensitive women may increase their risk of melanoma with frequent sun exposures, but that sun-resistant women do not, presumably because they develop a photoprotective tan.

Sensitive subgroups and normal variation in pulmonary function response to air pollution episodes.

Abstract: The Clean Air Act requires that sensitive subgroups of exposed populations be protected from adverse health effects of air pollution exposure. Hence, data suggesting the existence of sensitive subgroups can have an important impact on regulatory decisions. Some investigators have interpreted differences among individuals in observed pulmonary function response to air pollution episodes as evidence that individuals differ in their sensitivity. An alternative explanation is that the differences are due entirely to normal variation in repeated pulmonary function measurements. This paper investigates this question by reanalyzing data from three studies of children exposed to air pollution episodes to determine whether the observed variability in pulmonary function response indicates differences in sensitivity or natural interoccasion variability. One study investigated exposures to total suspended particulates (TSP), the other two investigated exposure to ozone. In all studies, each child's response to air pollution exposures was summarized by regressing that child's set of pulmonary function measurements on the air pollution concentrations on the day or days before measurement. The within-child and between-child variances of these slopes were used to test the hypothesis of variable sensitivity. Regression slopes did not vary significantly among children exposed to episodes of high TSP concentration, but there was evidence of heterogeneity in both studies of ozone exposures. The finding of heterogeneous response to ozone exposure is consistent with the epidemiologic and chamber studies of ozone exposures, but the lack of evidence for heterogeneous response to TSP exposures implies that observed variation in response can be explained by sampling variability rather than the presence of sensitive subgroup.

Parental age at birth and risk of breast cancer in daughters: a prospective study among US women

Abstract: We examined the relation between parental age at birth and risk of breast cancer among daughters in a population of 118,309 US women who were 30 to 55 years of age in 1976 and without prior diagnosis of cancer. During 1,140,239 person-years of follow-up, we documented 1,799 incident cases of breast cancer in this population. After adjusting for established breast cancer risk factors, we observed only a weak and nonsignificant trend in risk of breast cancer with increasing maternal age at birth and no relation for paternal age. After adjusting for other risk factors, the chi trend was 1.10, P = 0.27 for increasing maternal age at birth. Daughters born to mothers 30 to 34 years of age had an age-adjusted relative risk of breast cancer of 1.11 (95% confidence interval: 0.89, 1.37) compared to daughters born to mothers less than 20 years of age. The weak positive trend in risk with increasing maternal age was present among both pre- and postmenopausal women. These findings suggest that there is little or no association between maternal age and risk of breast cancer, and that paternal age is not related to risk of breast cancer.

Estrogen Replacement Therapy and Risk of Breast Cancer-Reply

Abstract: In Reply. —We appreciate the concern expressed by Drs Bush and Helzlsouer regarding the elevated risk of breast cancer among women currently using estrogen replacement therapy. They raise the question of differential rates of mammography among the women who are current users of postmenopausal hormones (64%) compared with nonusers (49%). Actually, this modest difference in rates initially concerned us as well. After a detailed examination, we concluded that it cannot explain the association between estrogen use and breast cancer incidence. As of 1988, among women in the Nurses' Health Study who reported having a mammogram, two thirds indicated that they had had more than one previous mammogram, suggesting that the population is approaching the steady state in which mammography increases lead time but not the total number of cases of breast cancer that are diagnosed. In the Health Insurance Plan on New York, 1 after 5 years, the excess incidence

Selenium and Breast Cancer-Reply

Abstract: In Reply.— The women in our study live in 11 large, geographically diverse US states, including Texas, a state with a high soil selenium level, 1 and thus their selenium intake is broadly representative of the average intake for US women. The median toenail selenium concentration of the upper quintile in our study was 0.99 μg/g, approximately equal to the value of toenail selenium (0.999 μg/g) among women consuming more than 90 μg/d of selenium supplements in the Nurses' Health Study. 2 Dr Schrauzer states that our study "actually suggests" a reduced risk of breast cancer in subjects with the highest selenium levels. In fact, the relative risk in the highest quintile of toenail selenium is 1.10, in the opposite direction to that hypothesis. We agree that the confidence interval (0.70 to 1.69) does not exclude a modest protective association, as stated in our original article. Indeed, we are conducting