Frank E. Speizer

An association between air pollution and mortality in six U.S. cities

BACKGROUND Recent studies have reported associations between particulate air pollution and daily mortality rates. Population-based, cross-sectional studies of metropolitan areas in the United States have also found associations between particulate air pollution and annual mortality rates, but these studies have been criticized, in part because they did not directly control for cigarette smoking and other health risks. METHODS In this prospective cohort study, we estimated the effects of air pollution on mortality, while controlling for individual risk factors. Survival analysis, including Cox proportional-hazards regression modeling, was conducted with data from a 14-to-16-year mortality follow-up of 8111 adults in six U.S. cities. RESULTS Mortality rates were most strongly associated with cigarette smoking. After adjusting for smoking and other risk factors, we observed statistically significant and robust associations between air pollution and mortality. The adjusted mortality-rate ratio for the most polluted of the cities as compared with the least polluted was 1.26 (95 percent confidence interval, 1.08 to 1.47). Air pollution was positively associated with death from lung cancer and cardiopulmonary disease but not with death from other causes considered together. Mortality was most strongly associated with air pollution with fine particulates, including sulfates. CONCLUSIONS Although the effects of other, unmeasured risk factors cannot be excluded with certainty, these results suggest that fine-particulate air pollution, or a more complex pollution mixture associated with fine particulate matter, contributes to excess mortality in certain U.S. cities.

A Prospective Study of Obesity and Risk of Coronary Heart Disease in Women

We examined the incidence of nonfatal and fatal coronary heart disease in relation to obesity in a prospective cohort study of 115,886 U.S. women who were 30 to 55 years of age in 1976 and free of diagnosed coronary disease, stroke, and cancer. During eight years of follow-up (775,430 person-years), we identified 605 first coronary events, including 306 nonfatal myocardial infarctions, 83 deaths due to coronary heart disease, and 216 cases of confirmed angina pectoris. A higher Quetelet index (weight in kilograms divided by the square of the height in meters) was positively associated with the occurrence of each category of coronary heart disease. For increasing levels of current Quetelet index (less than 21, 21 to less than 23, 23 to less than 25, 25 to less than 29, and greater than or equal to 29), the relative risks of nonfatal myocardial infarction and fatal coronary heart disease combined, as adjusted for age and cigarette smoking, were 1.0, 1.3, 1.3, 1.8, and 3.3 (Mantel-extension chi for trend = 7.29; P less than 0.00001). As expected, control for a history of hypertension, diabetes mellitus, and hypercholesterolemia--conditions known to be biologic effects of obesity--attenuated the strength of the association. The current Quetelet index was a more important determinant of coronary risk than that at the age of 18; an intervening weight gain increased risk substantially. These prospective data emphasize the importance of obesity as a determinant of coronary heart disease in women. After control for cigarette smoking, which is essential to assess the true effects of obesity, even mild-to-moderate overweight increased the risk of coronary disease in middle-aged women.

Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women.

BACKGROUND The rates of colon cancer in various countries are strongly correlated with the per capita consumption of red meat and animal fat and, to a lesser degree, inversely associated with the consumption of fiber. METHODS We conducted a prospective study among 88,751 women 34 to 59 years old and without a history of cancer, inflammatory bowel disease, or familial polyposis who completed a dietary questionnaire in 1980. By 1986, during 512,488 person-years of follow-up, 150 incident cases of colon cancer had been documented. RESULTS After adjustment for total energy intake, animal fat was positively associated with the risk of colon cancer (P for trend = 0.01); the relative risk for the highest as compared with the lowest quintile was 1.89 (95 percent confidence interval, 1.13 to 3.15). No association was found for vegetable fat. The relative risk of colon cancer in women who ate beef, pork, or lamb as a main dish every day was 2.49 (95 percent confidence interval, 1.24 to 5.03), as compared with those reporting consumption less than once a month. Processed meats and liver were also significantly associated with increased risk, whereas fish and chicken without skin were related to decreased risk. The ratio of the intake of red meat to the intake of chicken and fish was particularly strongly associated with an increased incidence of colon cancer (P for trend = 0.0005); the relative risk for women in the highest quintile of this ratio as compared with those in the lowest quintile was 2.49 (95 percent confidence interval, 1.50 to 4.13). A low intake of fiber from fruits appeared to contribute to the risk of colon cancer, but this relation was not statistically independent of meat intake. CONCLUSIONS These prospective data provide evidence for the hypothesis that a high intake of animal fat increases the risk of colon cancer, and they support existing recommendations to substitute fish and chicken for meats high in fat.

Menopause and the Risk of Coronary Heart Disease in Women

To determine the relation of menopause to the risk of coronary heart disease, we analyzed data on a prospective cohort of 121,700 U.S. women 30 to 55 years old who were followed from 1976 to 1982. Information on menopausal status, the type of menopause, and other risk factors was obtained in 1976 and updated every two years by mailing questionnaires. Through 1982, the follow-up rate was 98.3 percent for mortality and 95.4 percent for nonfatal events. After we controlled for age and cigarette smoking, women who had had a natural menopause and who had never taken replacement estrogen had no appreciable increase in the risk of coronary heart disease, as compared with premenopausal women (adjusted rate ratio, 1.2; 95 percent confidence limits, 0.8 and 1.8). Again compared with premenopausal women, the occurrence of a natural menopause together with the use of estrogens did not affect the risk (rate ratio, 0.8, 95 percent confidence limits, 0.4 and 1.3). Women who had undergone bilateral oophorectomy and who had never taken estrogens after menopause had an increased risk (rate ratio, 2.2; 95 percent confidence limits, 1.2 and 4.2). However, the use of estrogens in the postmenopausal period appeared to eliminate this increased risk among these women as compared with premenopausal women (rate ratio, 0.9; 95 percent confidence limits, 0.6 and 1.6). These data suggest that, in contrast to a natural menopause, bilateral oophorectomy increases the risk of coronary heart disease. This increase appears to be prevented by estrogen-replacement therapy.

Physical activity and incidence of non-insulin-dependent diabetes mellitus in women

The potential role of physical activity in the primary prevention of non-insulin-dependent diabetes mellitus (NIDDM) is largely unknown. We examined the association between regular vigorous exercise and the subsequent incidence of NIDDM in a prospective cohort of 87,253 US women aged 34-59 years and free of diagnosed diabetes, cardiovascular disease, and cancer in 1980. During 8 years of follow-up, we confirmed 1303 cases of NIDDM. Women who engaged in vigorous exercise at least once per week had an age-adjusted relative risk (RR) of NIDDM of 0.67 (p less than 0.0001) compared with women who did not exercise weekly. After adjustment for body-mass index, the reduction in risk was attenuated but remained statistically significant (RR = 0.84, p = 0.005). When analysis was restricted to the first 2 years after ascertainment of physical activity level and to symptomatic NIDDM as the outcome, age-adjusted RR of those who exercised was 0.5, and age and body-mass index adjusted RR was 0.69. Among women who exercised at least once per week, there was no clear dose-response gradient according to frequency of exercise. Family history of diabetes did not modify the effect of exercise, and risk reduction with exercise was evident among both obese and nonobese women. Multivariate adjustments for age, body-mass index, family history of diabetes, and other variables did not alter the reduced risk found with exercise. Our results indicate that physical activity may be a promising approach to the primary prevention of NIDDM.

A Prospective Study of Walking as Compared with Vigorous Exercise in the Prevention of Coronary Heart Disease in Women

BACKGROUND The role of walking, as compared with vigorous exercise, in the prevention of coronary heart disease remains controversial, and data for women on this topic are sparse. METHODS We prospectively examined the associations between the score for total physical activity, walking, and vigorous exercise and the incidence of coronary events among 72,488 female nurses who were 40 to 65 years old in 1986. Participants were free of diagnosed cardiovascular disease or cancer at the time of entry and completed serial detailed questionnaires about physical activity. During eight years of follow-up, we documented 645 incident coronary events (nonfatal myocardial infarction or death from coronary disease). RESULTS There was a strong, graded inverse association between physical activity and the risk of coronary events. As compared with women in the lowest quintile group for energy expenditure (expressed as the metabolic-equivalent [MET] score), women in increasing quintile groups had age-adjusted relative risks of 0.77, 0.65, 0.54, and 0.46 for coronary events (P for trend <0.001). In multivariate analyses, the inverse gradient remained strong (relative risks, 0.88, 0.81, 0.74, and 0.66 for women in increasing quintile groups as compared with those in the lowest quintile group; P for trend=0.002). Walking was inversely associated with the risk of coronary events; women in the highest quintile group for walking, who walked the equivalent of three or more hours per week at a brisk pace, had a multivariate relative risk of 0.65 (95 percent confidence interval, 0.47 to 0.91) as compared with women who walked infrequently. Regular vigorous exercise (> or =6 MET) was associated with similar risk reductions (30 to 40 percent). Sedentary women who became active in middle adulthood or later had a lower risk of coronary events than their counterparts who remained sedentary. CONCLUSIONS These prospective data indicate that brisk walking and vigorous exercise are associated with substantial and similar reductions in the incidence of coronary events among women.

A Prospective Study of Moderate Alcohol Consumption and the Risk of Coronary Disease and Stroke in Women

In 1980, 87,526 female nurses 34 to 59 years of age completed a dietary questionnaire that assessed their consumption of beer, wine, and liquor. By 1984, during 334,382 person-years of follow-up, we had documented 200 incident cases of severe coronary heart disease (164 nonfatal myocardial infarctions and 36 deaths due to coronary disease), 66 ischemic strokes, and 28 subarachnoid hemorrhages. Follow-up was 98 percent complete. As compared with nondrinkers, women who consumed 5 to 14 g of alcohol per day (three to nine drinks per week) had a relative risk of coronary disease of 0.6 (95 percent confidence interval, 0.4 to 0.9); for 15 to 24 g per day the relative risk was 0.6 (0.3 to 1.1), and for 25 g or more per day it was 0.4 (0.2 to 0.8), after adjustment for risk factors for coronary disease. Alcohol intake was also associated with a decreased risk of ischemic stroke. For 5 to 14 g of alcohol per day the relative risk was 0.3 (0.1 to 0.7), and for 15 g per day or more it was 0.5 (0.2 to 1.1). In contrast, although the number of cases of subarachnoid hemorrhage was small, alcohol intake tended to be associated with an increased risk of this disorder; for 5 to 14 g per day the relative risk was 3.7 (1.0 to 13.8). These prospective data suggest that among middle-aged women, moderate alcohol consumption decreases the risks of coronary heart disease and ischemic stroke but may increase the risk of subarachnoid hemorrhage.

A Prospective Study of Postmenopausal Estrogen Therapy and Coronary Heart Disease

To clarify the possible role of postmenopausal estrogen use in coronary heart disease, we surveyed 121,964 female nurses, aged 30 to 55 years, with mailed questionnaires, beginning in 1976. Information on hormone use and other potential risk factors was updated and the incidence of coronary heart disease was ascertained through additional questionnaires in 1978 and 1980, with a 92.7 per cent follow-up. End points were documented by medical records. During 105,786 person-years of observation among 32,317 postmenopausal women who were initially free of coronary disease, 90 women had either nonfatal myocardial infarctions (65 cases) or fatal coronary heart disease (25 cases). As compared with the risk in women who had never used postmenopausal hormones, the age-adjusted relative risk of coronary disease in those who had ever used them was 0.5 (95 per cent confidence limits, 0.3 and 0.8; P = 0.007), and the risk in current users was 0.3 (95 per cent confidence limits, 0.2 and 0.6; P = 0.001). The relative risks were similar for fatal and nonfatal disease and were unaltered after adjustment for cigarette smoking, hypertension, diabetes, high cholesterol levels, a parental history of myocardial infarction, past use of oral contraceptives, and obesity. These data support the hypothesis that the postmenopausal use of estrogen reduces the risk of severe coronary heart disease.

A Prospective Study of Family History and the Risk of Colorectal Cancer

BACKGROUND A family history of colorectal cancer is recognized as a risk factor for the disease. However, as a result of the retrospective design of prior studies, the strength of this association is uncertain, particularly as it is influenced by characteristics of the person at risk and the affected family members. METHODS We conducted a prospective study of 32,085 men and 87,031 women who had not previously been examined by colonoscopy or sigmoidoscopy and who provided data on first-degree relatives with colorectal cancer, diet, and other risk factors for the disease. During the follow-up period, colorectal cancer was diagnosed in 148 men and 315 women. RESULTS The age-adjusted relative risk of colorectal cancer for men and women with affected first-degree relatives, as compared with those without a family history of the disease, was 1.72 (95 percent confidence interval, 1.34 to 2.19). The relative risk among study participants with two or more affected first-degree relatives was 2.75 (95 percent confidence interval, 1.34 to 5.63). For participants under the age of 45 years who had one or more affected first-degree relatives, the relative risk was 5.37 (95 percent confidence interval, 1.98 to 14.6), and the risk decreased with increasing age (P for trend, < 0.001). CONCLUSIONS A family history of colorectal cancer is associated with an increased risk of the disease, especially among younger people.

Cohort Studies of Fat Intake and the Risk of Breast Cancer — A Pooled Analysis

BACKGROUND Experiments in animals, international correlation comparisons, and case-control studies support an association between dietary fat intake and the incidence of breast cancer. Most cohort studies do not corroborate the association, but they have been criticized for involving small numbers of cases, homogeneous fat intake, and measurement errors in estimates of fat intake. METHODS We identified seven prospective studies in four countries that met specific criteria and analyzed the primary data in a standardized manner. Pooled estimates of the relation of fat intake to the risk of breast cancer were calculated, and data from study-specific validation studies were used to adjust the results for measurement error. RESULTS Information about 4980 cases from studies including 337,819 women was available. When women in the highest quintile of energy-adjusted total fat intake were compared with women in the lowest quintile, the multivariate pooled relative risk of breast cancer was 1.05 (95 percent confidence interval, 0.94 to 1.16). Relative risks for saturated, monounsaturated, and polyunsaturated fat and for cholesterol, considered individually, were also close to unity. There was little overall association between the percentage of energy intake from fat and the risk of breast cancer, even among women whose energy intake from fat was less than 20 percent. Correcting for error in the measurement of nutrient intake did not materially alter these findings. CONCLUSIONS We found no evidence of a positive association between total dietary fat intake and the risk of breast cancer. There was no reduction in risk even among women whose energy intake from fat was less than 20 percent of total energy intake. In the context of the Western lifestyle, lowering the total intake of fat in midlife is unlikely to reduce the risk of breast cancer substantially.