A prospective study of past use of oral contraceptive agents and risk of cardiovascular diseases

We evaluated the effects of past use of oral contraceptive agents on the risk of various cardiovascular diseases among women in the Nurses' Health Study cohort. We studied 119,061 women who were 30 to 55 years of age in 1976, who provided information on their use of oral contraceptives, and who at entry had had no previous coronary disease or stroke. End points were documented by medical records. During eight years of follow-up (484,096 person-years among those who had never used oral contraceptives, 415,488 among past users, and 22,376 among current users), there were 485 new cases of major coronary disease (380 nonfatal myocardial infarctions and 105 deaths from coronary disease), 282 strokes (205 nonfatal and 77 fatal), and 48 other deaths from cardiovascular causes. We found no evidence to suggest an increase in the risk of cardiovascular diseases among past users of oral contraceptives, even with prolonged previous use. After adjustment for a variety of risk factors, the relative risk of major coronary disease for women who had used oral contraceptives in the past, as compared with those who had never used such agents, was 0.8 (95 percent confidence interval, 0.6 to 1.0); of stroke, 1.0 (95 percent confidence interval, 0.7 to 1.3); and of death from all cardiovascular causes, 0.9 (95 percent confidence interval, 0.7 to 1.2). We found neither evidence of increased risk with longer use nor any trend with the amount of time since the last use. According to these prospective data, the use of oral contraceptive agents in the past does not materially raise a woman's risk of subsequent cardiovascular disease.     

Interaction between a peroxisome proliferator-activated receptor gamma gene polymorphism and dietary fat intake in relation to body mass

The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a critical regulator of adipogenesis. PPAR gamma+/- mice are resistant to high-fat diet-induced obesity and thus PPAR gamma may mediate physiological responses to dietary fat in other mammals. The aim of this study was to determine whether the human PPAR gamma proline to alanine substitution polymorphism (Pro12Ala) modifies the association between dietary fat and adiposity and plasma lipids. Subjects (n=2141) were controls selected for three case-control studies nested within the Nurses' Health Study, a large ongoing prospective cohort study. Associations between intake of total fat, fat subtypes and BMI were different in PPAR gamma 12Ala variant allele-carriers compared with non-carriers. Among homozygous wild-type Pro/Pro individuals, those in the highest quintile of total fat intake, had significantly higher mean body mass index (BMI) compared with those in the lowest quintile (27.3 versus 25.4 kg/m2, respectively; P-trend<0.0001) whereas among 12Ala variant allele-carriers there was no significant trend observed between dietary fat intake and BMI (P-trend=0.99; P-interaction=0.003). In contrast, intake of monounsaturated fat was not associated with BMI among homozygous wild-type women but was inversely associated with BMI among 12Ala variant allele-carriers (mean in lowest quintile=27.6 versus mean in highest quintile=25.5 kg/m2; P-trend=0.006; P-interaction=0.003). The relationship between dietary fat intake and plasma lipid concentrations also differed according to PPAR gamma genotype. These data suggest that PPAR gamma genotype is an important factor in physiological responses to dietary fat in humans.     

Long or highly irregular menstrual cycles as a marker for risk of type 2 diabetes mellitus.

CONTEXT: Although oligomenorrhea has been associated cross-sectionally with insulin resistance and glucose intolerance, it is not known whether oligomenorrhea is a marker for increased future risk of type 2 diabetes mellitus (DM). OBJECTIVE: To prospectively assess risk of type 2 DM in women with a history of long or highly irregular menstrual cycles. DESIGN AND SETTING: The Nurses' Health Study II, a prospective observational cohort study. PARTICIPANTS: A total of 101 073 women who had no prior history of DM and who reported their usual menstrual cycle pattern at age 18 to 22 years on the baseline (1989) questionnaire. MAIN OUTCOME MEASURE: Incident reports of DM, with follow-up through 1997, compared among women categorized by menstrual cycle length (5 categories). RESULTS: During 564 333 person-years of follow-up, there were 507 cases of type 2 DM. Compared with women with a usual cycle length of 26 to 31 days (referent category) at age 18 to 22 years, the relative risk (RR) of type 2 DM among women with a menstrual cycle length that was 40 days or more or was too irregular to estimate was 2.08 (95% confidence interval [CI], 1.62-2.66), adjusting for body mass index at age 18 years and several other potential confounding variables. The RR of type 2 DM associated with long or highly irregular menstrual cycles was greater in obese women, but was also increased in nonobese women (at body mass indexes at age 18 years of <25, 25-29, and >/=30 kg/m, RRs were 1.67 [95% CI, 1.14-2.45], 1.74 [95% CI, 1.07-2.82], and 3.86 [95% CI, 2.33-6.38], respectively). CONCLUSION: Women with long or highly irregular menstrual cycles have a significantly increased risk for developing type 2 DM that is not completely explained by obesity.     

Alcohol intake in early adulthood and risk of colorectal cancer: three large prospective cohort studies of men and women in the United States

European Journal of Epidemiology - Heavy alcohol consumption in mid-adulthood is an established risk factor of colorectal cancer (CRC). Alcohol use in early adulthood is common, but its association...     

The Role of Radiation Therapy and 5-Fluorouracil in Colon and Rectal Cancer

Since the original report improved survival of patients with locally unresectable gastric cancer treated with irradiation and 5-fluorouacil (5-FU) in 1968, there has been extensive investigation of this treatment combination in a variety of gastrointestinal tumors, including colon and rectal cancer. There are now extensive data supporting the use of 5-FU-based chemotherapy with irradiation in the adjuvant treatment of rectal cancer and increasing experience defining its role in negotiant therapy. The value of adjuvant 5-FU-based chemotherapy and irradiation in colonies cancer is controversial, but there may be subsets of patients who benefit from this treatment. Ongoing studies in rectal and colon cancer are evaluating the role of irradiation with various modes of 5-FU adminstration (bolus v short or continuous infusion) as well as its modulation with other agents.     

Risk factors for basal cell carcinoma of the skin in men: results from the health professionals follow-up study.

The authors examined the relation of constitutional factors and sun exposure to risk of basal cell carcinoma of the skin (BCC) in a prospective cohort of 44,591 predominantly Caucasian US male health professionals, 40-75 years of age and free of cancer at enrollment in 1986. During 8 years of follow-up, 3,273 cases of self-reported BCC were documented. The following variables were each associated with an elevated risk of BCC: having red hair; green, hazel, or blue eyes; a tendency to sunburn; and north European ancestry. The lifetime number of blistering sunburns was also positively associated with BCC risk (p trend < 0.0001). Compared with men who as teenagers had been outside less than once a week, men who had been outside weekly (relative risk (RR) = 1.30; 95% confidence interval (CI): 1.14, 1.47) and daily (RR = 1.42; 95% CI: 1.24, 1.63) had an elevated risk of BCC. Living in a region of residence with high solar radiation as an adult was also associated with an increased risk of BCC (RR = 1.48; 95% CI: 1.36, 1.60), whereas living in such a region only in childhood did not increase BCC risk. These results confirm the role of constitutional factors and suggest that adult sun exposure increases BCC risk.     

Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women

BACKGROUND: Experimental studies in laboratory animals and humans suggest that alpha-linolenic acid (18:3n-3) may reduce the risk of arrhythmia. OBJECTIVE: The objective was to examine the association between dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease (IHD). DESIGN: This was a prospective cohort study. The intake of alpha-linolenic acid was derived from a 116-item food-frequency questionnaire completed in 1984 by 76283 women without previously diagnosed cancer or cardiovascular disease. RESULTS: During 10 y of follow-up, we documented 232 cases of fatal IHD and 597 cases of nonfatal myocardial infarction. After adjustment for age, standard coronary risk factors, and dietary intake of linoleic acid and other nutrients, a higher intake of alpha-linolenic acid was associated with a lower relative risk (RR) of fatal IHD; the RRs from the lowest to highest quintiles were 1.0, 0.99, 0.90, 0.67, and 0.55 (95% CI: 0.32, 0.94; P for trend = 0.01). For nonfatal myocardial infarction there was only a modest, nonsignificant trend toward a reduced risk when extreme quintiles were compared (RR: 0.85; 95% CI: 0.61, 1.19; P for trend = 0.50). A higher intake of oil and vinegar salad dressing, an important source of alpha-linolenic acid, was associated with reduced risk of fatal IHD when women who consumed this food > or =5-6 times/wk were compared with those who rarely consumed this food (RR: 0.46; 95% CI: 0.27, 0.76; P for trend = 0.001). CONCLUSIONS: This study supports the hypothesis that a higher intake of alpha-linolenic acid is protective against fatal IHD. Higher consumption of foods such as oil-based salad dressing that provide polyunsaturated fats, including alpha-linolenic acid, may reduce the risk of fatal IHD.     

Presenting statistical uncertainty in trends and dose-response relations.

When one estimates the effects of a polytomous exposure, it is common practice to express all effects relative to a baseline or reference level. Certain authors have challenged this practice and proposed alternatives, which we review here. One alternative, the "floating absolute risk" method, can supply useful statistics and trend graphs, but it does not yield valid confidence intervals for relative risks. All categorical methods have further shortcomings when the exposure is continuous, however. These shortcomings can be addressed by plotting or tabulating confidence limits for points on a flexible curve fitted to the uncategorized data.     

Predicting outcome of care in the neonatal intensive care unit

The accuracy of a neonatal intensive care unit (NICU) staff in predicting the outcome and length of stay of infants admitted to the NICU, and the factors they felt were important in making these predictions, were evaluated. This prospective study used a questionnaire to survey 44 nurses, residents, and attending neonatologists working in the NICU about the predicted outcomes of 52 infants admitted to the NICU at the University of Nebraska Medical Center over a 1-month period. Factors previously identified by the staff as important indicators of infant outcome were assigned points of importance by the respondents, and specific values for these factors were recorded for each infant. The NICU staff indicated that gestational age was the most important indicator of infant outcome. The attending neonatologists placed more value on gestational age (analysis of variance [ANOVA] P less than .0001) than did the nurses or residents. Among the staff groups, there were significant differences in the weight or points assigned to a given factor for pulmonary function, renal function, number of resuscitations, and the "other" category (ANOVA P less than .05). The nurses ranked pulmonary function criteria lower than the residents did (P less than .04), but considered renal function more important than either the residents (P = .005) or the attending neonatologists considered it to be (P = .01). The number of resuscitations was ranked higher by the nursing staff than by other groups, whereas the attending neonatologists assigned less importance to the "other" category.(ABSTRACT TRUNCATED AT 250 WORDS)