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Objective:The objective of this study is to estimate the accuracy of early oral glucose tolerance testing (GTT), to predict impaired glucose tolerance.Study Design:This was a prospective cohort study. Women received an early 75 g 2 h GTT between postpartum days 2–4 and again 6–12 weeks postpartum. The ability of the early GTT to accurately detect impaired glucose tolerance and diabetes was assessed by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPVs). The routine 6–12-week postpartum GTT was considered the gold standard.Results:The early GTT was completed by 100% of subjects, whereas only 31 of 58 (53%) women returned to complete the 6–12-week postpartum GTT. The early GTT had modest sensitivity for impaired glucose tolerance (62.5%) and overt diabetes (50%). However, it had excellent specificity (100%), PPV (100%) and NPV (96.7%) for diabetes. The NPV for impaired glucose tolerance with the early GTT was 80%.Conclusion:Rates of 6–12 week postpartum GTT completion among patients with gestational diabetes is poor. Appropriate postpartum management may improve by using the early GTT as a screening test.

(Abstracted from J Perinatol2018;38:118–121)Women with pregnancies complicated by gestational diabetes mellitus (GDM) are at a significantly increased risk of developing type 2 diabetes mellitus (T2DM), hypertension, and cardiovascular disease. Diabetes screening for women with GDM is recommended 6 to 12 weeks following delivery, although this is an arbitrary time point developed to coincide with the routine postpartum visit.

A polymorphism (G to A transition) in intron 13 of the mitochondrial enzyme monoamine oxidase B (MAOB) gene may modify, alone or by interacting with the catechol-O-methyltransferase (COMTLL) genotype (low enzymatic activity), the risk of idiopathic PD. Also, the association between never smoking and PD risk may be present only in people with the MAOB G allele.

OBJECTIVE: The diagnostic value of tests for antimyeloperoxidase antibodies (anti-MPO) for systemic vasculitis is less established than that for cytoplasmic antineutrophil cytoplasmic antibody (cANCA)/antiproteinase 3 antibodies (anti-PR3). Controversy exists regarding the optimal utilization of indirect immunofluorescence (IIF) ANCA testing versus antigen-specific ANCA testing. To summarize the pertinent data, we conducted a metaanalysis examining the diagnostic value of ANCA testing systems that include assays for anti-MPO. METHODS: We performed a structured Medline search and reference list review. Target articles in the search strategy were those reporting the diagnostic value of immunoassays for anti-MPO for the spectrum of systemic necrotizing vasculitides that includes Wegener's granulomatosis, microscopic polyangiitis, the Churg-Strauss syndrome, and isolated pauci-immune necrotizing or crescentic glomerulonephritis, regardless of other types of ANCA tests. Inclusion criteria required specification of a consecutive or random patient selection method and the use of acceptable criteria for the diagnosis of vasculitis exclusive of ANCA test results. Weighted pooled summary estimates of sensitivity and specificity were calculated for anti-MPO alone, anti-MPO + perinuclear ANCA (pANCA), and anti-MPO/pANCA + anti-PR3/cANCA. RESULTS: Of 457 articles reviewed, only 7 met the selection criteria. Summary estimates of sensitivity and specificity (against disease controls only) of assays for anti-MPO for the diagnosis of systemic necrotizing vasculitides were 37.1% (confidence interval 26.6% to 47.6%) and 96.3% (CI 94.1% to 98.5%), respectively. When the pANCA pattern by IIF was combined with anti-MPO testing, the specificity improved to 99.4%, with a lower sensitivity, 31.5%. The combined ANCA testing system (anti-PR3/cANCA + anti-MPO/pANCA) increased the sensitivity to 85.5% with a specificity of 98.6%. CONCLUSION: These results suggest that while anti-MPO is relatively specific for the diagnosis of systemic vasculitis, the combination system of immunoassays for anti-MPO and IIF for pANCA is highly specific and both tests should be used together given the high diagnostic precision required for these conditions. Because patients with ANCA associated vasculitis have either anti-MPO with pANCA or anti-PR3 with cANCA, and rarely both, a combined ANCA testing system including anti-PR3/cANCA and anti-MPO/pANCA is recommended to optimize the diagnostic performance of ANCA testing.

To compare pathologic features of the cancers arising after different types of benign breast disease (BBD), we reviewed the invasive breast cancer slides of 169 women with a previous benign biopsy result. Lesions were categorized previously as nonproliferative, proliferative without atypia, or atypical hyperplasia. Pathologic features of the cancers were evaluated without knowledge of the previous BBD category. Estrogen and progesterone receptor immunohistochemistry was performed on available tissue blocks. The median times between a benign result and cancer were 100, 124, and 92 months for women with nonproliferative lesions, proliferative lesions without atypia, and atypical hyperplasia, respectively. Cancers in the 3 groups did not differ significantly in tumor size, axillary lymph node status, or histologic grade, and there was no significant difference in the distribution of histologic types of breast cancer. Lymphatic vessel invasion, extensive intraductal component, and hormone receptor status did not differ among BBD categories. The pathologic features of breast cancers that develop in women with a previous benign biopsy result do not vary according to the histologic category of the previous BBD.

There is conflicting evidence on whether stress is a risk factor for breast cancer. The present study examined prospectively the relationship between stress at work and risk of breast cancer.

The role of 123I-N-isopropyl-p-iodoamphetamine (123I-IMP), a new agent used in brain imaging with single-photon emission computed tomography (SPECT), has been assessed in the early diagnosis of acute infarctive stroke and Alzheimer's disease (AD). The diagnosis of these conditions in their early stages has remained problematic, principally due to limitations of existing technologies. To more formally assess this new technology, we estimated the sensitivity and specificity of 123I-IMP SPECT scanning in the diagnosis of stroke and AD. We based our assessment on a review of all published studies that reported on 123I-IMP SPECT scans and which included three or more patients. The results from three major studies indicate that 123I-IMP SPECT scanning has a higher sensitivity (92 to 100) than computerized tomography (55 to 86) in the early diagnosis of acute cerebral infarction. Preliminary findings from studies using 123I-IMP SPECT in the diagnosis of early AD are promising and show a sensitivity of at least 69. Furthermore, 123I-IMP SPECT scanning clearly discriminates patients with advanced AD from normals: sensitivity has ranged from 50 to 100, while specificity has ranged from 97 to 100. Studies also suggest that it can discriminate AD patients from those with multi-infarct dementia. Our review indicates that 123I-IMP SPECT may have an important future role in the early diagnosis and management of patients with acute infarctive stroke and AD.

To examine prospectively the relationship of childhood socioeconomic status and risk of cardiovascular disease in middle aged women.

Previous studies have established a relationship between low levels of social networks and total mortality, but few have examined cause specific mortality or disease incidence. This study aimed to examine prospectively the relationships between social networks and total and cause specific mortality, as well as cardiovascular disease incidence.

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.

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.

Abdominal obesity increases the estrogen-to-androgen ratio and may increase sympathetic nervous activity, both hypothesized to influence the development of benign prostatic hyperplasia and the severity of urinary obstructive symptoms. In 1986 and 1987, men aged 40-75 years who were participants in the Health Professionals Follow-up Study and who were without prior diagnosis of cancer or prostatectomy provided data on weight, height, and waist and hip circumferences. The men were followed for incidence of prostatectomy for benign prostatic hyperplasia up to January 1992. In addition, the frequency and severity of symptoms of urinary obstruction were assessed among respondents to a questionnaire in 1992. Among 25,892 men who provided complete information for both surgery and symptoms, 837 men had surgery for benign prostatic hyperplasia, and 2,581 of those without surgery reported frequent urinary symptoms. After adjustment for age, smoking, and body mass index, abdominal obesity was related to prostatectomy (odds ratio (OR) = 2.38, 95% confidence interval (CI) 1.42-3.99, for those with a waist circumference > or = 43 inches (109 cm) relative to those with a waist circumference < 35 inches (89 cm); p trend < 0.0001) and with frequent urinary symptoms among those without prostatectomy (OR = 2.00, 95% CI 1.47-2.72; p < 0.0001). Body mass index, hip circumference, and waist-to-hip ratio were not associated with benign prostatic hyperplasia independently of waist circumference. These results suggest that abdominal obesity in men may increase the frequency and severity of urinary obstructive symptoms and may increase the likelihood that such obese men will undergo a prostatectomy.

A high intake of calcium, vitamin D, or specific dairy products is thought to reduce the incidence of colorectal cancer. The association of these nutrients and foods with the occurrence of colorectal adenomas, precursors of cancer, was studied in two large US cohort studies. Cases were patients with a diagnosis of adenomatous polyps of the left colon or rectum (331 men, 1986-1990; 350 women, 1980-1988), and controls were persons with endoscopic findings negative for adenoma (9,159 men and 8,585 women). After adjustment for age, total energy, family history of colorectal cancer, body mass index, alcohol consumption, folate, intake of saturated fat and fiber, indications for endoscopy, and previous endoscopy, total calcium intake was not associated with the risk for adenoma (relative risk (RR), highest vs. lowest quintile of intake: men, 1.13, 95% confidence interval (CI) 0.76-1.66; women, 1.17, 95% CI 0.81-1.69). Total vitamin D intake was unrelated to the risk for adenoma in men (RR = 1.29, 95% CI 0.87-1.93). An inverse nonsignificant association was observed in women in the 1980-1988 analyses (RR = 0.68, 95% CI 0.41-1.13, trend p = 0.09), mainly attributable to the intake of multivitamin supplements, but an analysis of 4-year data (1984-1988) using a more detailed dietary assessment showed no association with vitamin D (RR = 1.04, 95% CI 0.65-1.67). Milk consumption and intake of total fermented dairy products were not related to adenoma risk. In conclusion, the occurrence of colorectal adenoma was neither related to calcium intake nor to milk consumption, whereas vitamin D from supplements but not diet was slightly, but not significantly, inversely associated with risk among women only.

The authors evaluated the reproducibility and validity of alcohol consumption measured by a mailed, self-administered questionnaire in two large prospective studies. Subsamples of 173 women and 136 men from these cohorts completed two food-frequency questionnaires and multiple 1-week diet records (four for women and two for men) and provided a fasting blood sample. Intakes of alcohol reported over the previous year by food frequency questionnaire 2 correlated highly with intake assessed by multiple week diet records completed over this period (Spearman r = 0.90 in women and 0.86 in men). Mean daily alcohol intake as assessed by the diet records and the questionnaires was very similar. Serum high density lipoprotein cholesterol levels were significantly correlated with alcohol intakes estimated from the questionnaire (r = 0.40 in women and 0.35 in men) and for the diet records (r = 0.33 in women and 0.38 in men). Four years after completing the diet records, women were asked to report their alcohol intake of 4 years earlier; this estimate was highly correlated with the diet records (r = 0.84) and with the earlier high density lipoprotein cholesterol (r = 0.40). These data suggest that a simple self-administered questionnaire can provide useful estimates of alcohol intake over an extended period of time in subjects participating in prospective epidemiologic studies.

To assess the validity of the selenium concentration in human toenails as a measure of selenium intake and to determine other correlates of toenail selenium level, the authors examined the predictors of toenail selenium within two subgroups of a large cohort study of US women. Mean toenail selenium was higher among 38 consumers of selenium supplements (0.904 micrograms/g, standard deviation (SD) 0.217) than among 96 nonusers (0.748 micrograms/g, SD 0.149; p less than 0.001), and a dose-response relation was observed among supplement users (Spearman's r = 0.32; p = 0.05). In a second subgroup of 677 women, selenium supplement use was also associated with higher mean toenail selenium (0.906 micrograms/g, SD 0.214, among 18 users and 0.801 micrograms/g, SD 0.148, among 659 nonusers; p = 0.02), and the dose-response relation was also significant (Spearman's r = 0.50; p = 0.03). The geographic variation in toenail selenium levels was consistent with the geographic distribution of selenium in forage crops. Toenail selenium declined with age and was significantly reduced among cigarette smokers (mean = 0.746, SD 0.124, among 146 current smokers and mean = 0.817, SD 0.159, among 311 never smokers; p less than 0.001) but was not materially affected by alcohol consumption. A dietary selenium score calculated from a food frequency questionnaire failed to predict toenail selenium level, demonstrating the suspected inability of diet questionnaires to measure individual selenium intake because of the highly variable selenium composition of different samples of the same food.(ABSTRACT TRUNCATED AT 250 WORDS)

The relation between lactation and risk of breast cancer was examined in a cohort of 89,413 parous female US registered nurses aged 30-55 years and free from cancer in 1976 who provided information on total duration of lactation in 1986. Between 1976 and 1986, 1,262 cases of breast cancer occurred during 785,958 person-years of follow-up. There was no independent association between lactation and the risk of breast cancer. After adjustment for age and parity, compared with women who had never lactated, the relative risks (and 95% confidence intervals (CI] were 0.95 (95% CI 0.84-1.08) for women with less than 7 months of lactation, 0.87 (95% CI 0.71-1.08) for 7-11 months, 0.94 (95% CI 0.77-1.14) for 12-23 months, and 0.98 (95% CI 0.76-1.28) for greater than or equal to 24 months (test for trend: z = -0.80, p = 0.42). The association did not differ by age or menopausal status. These results do not confirm reports that relatively short durations of lactation reduce the risk of breast cancer among younger women.

To determine the relation of body mass index (weight/height2) with the risk of clinical non-insulin-dependent diabetes, the authors analyzed data from a cohort of 113,861 US women aged 30-55 years in 1976. During 8 years of follow-up (826,010 person-years), 873 definite cases were identified among women initially free from diagnosed diabetes. Among women of average body mass index, 23-23.9 kg/m2, the relative risk was 3.6 times that of women having a body mass index less than 22 kg/m2. The risk continued to increase above this level of body mass index. The authors observed a much weaker positive association with weight at age 18, and this association was eliminated after adjustment for current body mass index. Thus, weight gain after age 18 was a major determinant of risk. For an increase of 20-35 kg, the relative risk was 11.3, and for an increase of more than 35 kg, the relative risk was 17.3. Adjusting for family history did not appreciably alter the strong relation observed among women at average levels of body mass index. These data indicate that, at even average weight, women are at increased risk of clinical non-insulin-dependent diabetes and that the relation between body mass index and risk of diabetes is continuous.

Evidence for an independent role of increased physical activity in the primary prevention of coronary heart disease has grown in recent years. The authors apply the techniques of meta-analysis to data extracted from the published literature by Powell et al. (Ann Rev Public Health 1987;8:253-87), as well as more recent studies addressing this relation, in order to make formal quantitative statements and to explore features of study design that influence the observed relation between physical activity and coronary heart disease risk. They find, for example, a summary relative risk of death from coronary heart disease of 1.9 (95% confidence interval 1.6-2.2) for sedentary compared with active occupations. The authors also find that methodologically stronger studies tend to show a larger benefit of physical activity than less well-designed studies.

Obesity is associated with an increased risk of many major chronic diseases. We estimated the economic costs of obesity-associated non-insulin-dependent diabetes mellitus, cardiovascular disease, gallbladder disease, cancer, and musculoskeletal disorders in 1990 US dollars, using a prevalence-based approach to cost-of-illness. In addition to direct costs, indirect costs were also estimated. The indirect cost of morbidity was estimated by calculating the costs associated with work days lost, and mortality costs were estimated on the basis of lifetime earnings lost. In 1990, the direct cost of obesity-associated disease in the US was $US45.8 billion, and the indirect cost of obesity was estimated to be $US23.0 billion. Therefore the total economic cost of obesity was estimated to be $US68.8 billion in 1990.

The relation of the presence of moles (nevi) on all four limbs to risk of cutaneous malignant melanoma was explored among 98 incident cases aged 32-59 years at diagnosis and 190 age-matched controls drawn from the Nurses' Health Study, a prospective cohort of female nurses in the United States. Cases diagnosed during follow-up from 1976 to 1982 were included in this study. Participants reported counts of all moles and raised moles alone on postal questionnaires. Distributions of moles were similar for right and left sides on upper and lower limbs for cases and controls. Counts declined with increasing age for all women, from a median of 15 for the youngest tertile of controls (aged 36-46 years) to three for the oldest (aged 54-62 years). Cases had more moles than did controls (medians of 23 and 9, respectively, for total moles on all four limbs): The presence of any mole on a limb gave relative risks for melanoma ranging from 2.2 (95% confidence interval (CI) = 1.2-4.0) for one or more moles on an arm to 2.9 (95% CI = 1.6-5.3) for one or more moles on the lower limb. For raised moles, relative risks were 1.7 (95% CI = 1.0-2.7) for arm, 2.1 (95% CI = 1.3-3.5) for lower limb, and 3.5 (95% CI = 2.0-6.3) for leg (below knee). The highest site-specific risk (i.e., for any moles on the same limb as the melanoma vs. no moles on that limb) was for moles on the lower limb (relative risk = 5.0 (95% CI = 1.8-13.5)). There were positive and significant trends in overall and site-specific risk with increasing numbers of moles on all limbs when absolute mole counts were considered, e.g., for total moles on all four limbs combined, chi for trend = 4.0, one-sided p less than 0.001, with relative risk for more than 100 moles versus none of 6.0. Inclusion of sun exposure and other constitutional factors in logistic regression analyses did not alter these observed relations between the presence of moles and risk of melanoma.

The use of food frequency questionnaires for measuring dietary intake has become widespread in epidemiologic studies. It has been suggested that inquiring about a person's usual serving size of each food, in addition to the frequency of consumption, will improve the accuracy of this method. This approach implies that individuals characteristically eat a specific amount of any particular food, and that this amount can be reported with reasonable accuracy. To investigate the variability of portion sizes, the authors analyzed data for 68 commonly consumed foods, based on four one-week weighed diet histories recorded by 194 Boston-area women aged 34-59 years during 1980 and 1981. For each food, total population variance in portion size was partitioned into within-person (intraindividual) and between-person (interindividual) components. For all but seven food items (yogurt, liver, mixed vegetables, watermelon, pancakes/waffles, cold cereal, and cooked cereal) the within-person variance in portion size exceeded the between-person variance. The mean of the within-person to between-person variance ratios, after exclusion of two outlying foods, was 3.4 for untransformed portion sizes, and 3.2 after portion sizes were loge-transformed. Foods with a high within-person variance also tended to have a high between-person variance. The dominance of within-person variance in portion sizes suggests that the concept of usual portion size is complex, and that subjects may experience substantial difficulty in specifying their "usual" portion size. The smaller contribution of between-person variance to the total variance in portion size suggests that specification of a standard portion size by the investigator may not introduce a large error in the estimation of food and nutrient intake.

Polymorphisms in the N-acetyltransferase 2 (NAT2) gene are determinants of the rate of metabolic activation of carcinogenic compounds such as aryl aromatic amines. Homozygosity for any combination of three variant alleles in Caucasians defines 'slow' acetylators; presence of one or two wild-type alleles characterizes 'rapid' acetylators. Although most previous studies have not observed an overall elevation in risk of breast cancer among slow acetylators, a recent study observed that cigarette smoking was associated with a large increase in risk of breast cancer among slow acetylators. We assessed the relation between NAT2 acetylation status and breast cancer risk, and its interaction with smoking, in a prospective study of mainly Caucasian US women. Four hundred and sixty-six incident cases who were diagnosed with breast cancer after giving a blood specimen in 1989-90 were matched to 466 controls in a nested case-control study. NAT2 genotype was determined using PCR-RFLP assays. The multivariate relative risk (RR) comparing slow with rapid acetylators was 0.9 (95% CI 0.7-1.2). Among slow acetylators, current smoking immediately prior to diagnosis was not associated with a significant elevation in risk compared with never smoking rapid acetylators (RR = 1.4, 95% CI 0.7-2.6). No significant association was seen between pack-years of smoking and risk of breast cancer among either slow or fast acetylators. A non-significant elevation in risk was observed among women who smoked for > or = 5 years prior to first pregnancy and were rapid acetylators, compared with never smoking rapid acetylators (RR = 1.5, 95% CI 0.9-2.6). In analyses limited to 706 post-menopausal women, the elevated risks for current smokers immediately prior to diagnosis who were slow acetylators compared with never smokers who were fast acetylators were slightly stronger but still not statistically significant. In summary, we observed little evidence of an association between NAT2 genotype and breast cancer. In this prospective study, cigarette smoking was not appreciably associated with breast cancer among either slow or fast NAT2 acetylators.

Earlier work showed how to perform fixed‐effects meta‐analysis of studies or trials when each provides results on more than one outcome per patient and these multiple outcomes are correlated. That fixed‐effects generalized‐least‐squares approach analyzes the multiple outcomes jointly within a single model, and it can include covariates, such as duration of therapy or quality of trial, that may explain observed heterogeneity of results among the trials. Sometimes the covariates explain all the heterogeneity, and the fixed‐effects regression model is appropriate. However, unexplained heterogeneity may often remain, even after taking into account known or suspected covariates. Because fixed‐effects models do not make allowance for this remaining unexplained heterogeneity, the potential exists for bias in estimated coefficients, standard errors and p‐values. We propose two random‐effects approaches for the regression meta‐analysis of multiple correlated outcomes. We compare their use with fixed‐effects models and with separate‐outcomes models in a meta‐analysis of periodontal clinical trials. A simulation study shows the advantages of the random‐effects approach. These methods also facilitate meta‐analysis of trials that compare more than two treatments. © 1998 John Wiley & Sons, Ltd.

OBJECTIVE: To examine the association between birth weight and non-fatal adult cardiovascular disease while controlling for potential confounders such as socioeconomic group and adult lifestyle. DESIGN: Retrospective self report of birth weight in an ongoing longitudinal cohort of nurses followed up by postal questionnaire every two years. SETTING: Nurses' health study, a cohort of 121700 women followed up since 1976. MAIN OUTCOME MEASURES: Non-fatal cardiovascular disease, including myocardial infarction, coronary revascularisation, and stroke. RESULTS: Among the 70297 women free of cardiovascular disease at baseline who reported birth weight in the 1992 questionnaire there were 1309 first cases of non-fatal cardiovascular disease. Increasing birth weight was associated with decreasing risk of non-fatal cardiovascular disease. There were 1216 first cases of non-fatal cardiovascular disease among women who were singletons and had been born full term; their relative risks adjusted for several cardiovascular risk factors were 1.49 (95% confidence interval 1.05 to 2.10) for birth weight &lt; 2268 g (&lt; 5 lb 0 oz); 1.25 (0.98 to 1.61) for birth weight 2268-2495 g (5 lb 0 oz to 5 lb 8 oz); 1.12 (0.98 to 1.27) for birth weight > 2495-3175 g (> 5 lb 8 oz to 7 lb 0 oz); 1.00 (referent) for birth weight > 3175-3856 g (> 7 lb 0 oz to 8 lb 8 oz); 0.96 (0.80 to 1.15) for birth weight > 3856-4536 g (> 8 lb 8 oz to 10 lb 0 oz); and 0.68 (0.46 to 1.00) for birth weight > 4536 g (> 10 lb 0 oz) (P value for trend = 0.0004). The inverse trend was apparent for both coronary heart disease and stroke. CONCLUSIONS: These data provide strong evidence of an association between birth weight and adult coronary heart disease and stroke.

Obesity, android fat distribution, and other anthropometric measures have been associated with coronary heart disease in long-term prospective studies. However, fluctuations in weight due to age-related hormonal changes and changes in lifestyle practices may bias relative risk estimates over a long follow-up period. The authors prospectively studied the association between body mass index (BMI) (kg/m2), waist-to-hip ratio, and height as independent predictors of incident coronary heart disease in a 3-year prospective study among 29,122 US men aged 40-75 years in 1986. The authors documented 420 incident coronary events during the follow-up period. Body mass index, waist-to-hip ratio, short stature, and weight gain since age 21 were associated with an increased risk of coronary heart disease. Among men younger than 65, after adjusting for other coronary risk factors, the relative risk was 1.72 (95% confidence interval (CI) 1.10-2.69) for men with BMI of 25-28.9, 2.61 (95% CI 1.54-4.42) for BMI of 29.0-32.9, and 3.44 (95% CI 1.67-7.09) for obese men with BMI > or = 33 compared with lean men with BMI < 23.0. Among men > or = 65 years of age, the association between BMI and risk of coronary heart disease was much weaker. However, in this age group, the waist-to-hip ratio was a much stronger predictor of risk (relative risk = 2.76, 95% CI 1.22-6.23 between extreme quintiles). These results suggest that for younger men, obesity, independent of fat distribution, is a strong risk factor for coronary heart disease. For older men, measures of fat distribution may be better than body mass index at predicting risk of coronary disease.

We examined the association between oral contraceptive use and incidence of Type 2 (non-insulin-dependent) diabetes mellitus among 115117 female nurses free of diabetes, cardiovascular disease and cancer in 1976 and followed-up for 12 years. During 1237440 person years of follow-up, 2276 women who provided information on oral contraceptive use were clinically diagnosed with Type 2 diabetes. Women who used oral contraceptives in the past had only a slight and marginally increased relative risk of 1.10 (95% confidence interval 1.01, 1.21) compared to those women who had never used oral contraceptives after controlling for known risk factors of disease. We found no evidence of increased risk with longer duration of use or with shorter interval since last use. Current users did not have an increased risk of Type 2 diabetes (relative risk = 0.86, 95% confidence interval 0.46, 1.61) when compared to women who had never used the drug. There was no effect modification by obesity, family history of diabetes, or physical activity. These data suggest that past or current oral contraceptive use does not substantially influence subsequent risk of Type 2 diabetes.

Fat intake was examined in relation to risk of breast cancer using dietary questionnaires administered both before and after the diagnosis of breast cancer. Among the Nurses' Health Study cohort members who completed a food frequency questionnaire and were free of cancer in 1986, 398 were diagnosed with breast cancer during 2 years of follow-up. These cases and 798 age-matched controls (cohort members who also completed a dietary questionnaire in 1986 but did not develop breast cancer) were sent another food frequency questionnaire in 1989 inquiring about their diet in 1985. Three hundred cases and 602 controls responded to the second questionnaire. The age-adjusted analysis using the prospective (1986) questionnaire demonstrated no appreciable associations between breast cancer incidence and intakes of total fat (odds ratio (OR) between highest and lowest quintiles = 0.87; 95% confidence interval (CI) 0.54-1.40) and saturated fat (OR = 0.97; CI 0.64-1.46). The age-adjusted analysis using the retrospective (1989) questionnaire suggested positive associations between breast cancer incidence and intakes of total fat (OR = 1.43; 95% CI 0.90-2.27) and saturated fat (OR = 1.38; 95% CI 0.89-2.13). When nutrients were adjusted for total energy intake, the direction and magnitude of the differences between the prospective and retrospective analyses were similar to the analyses unadjusted for energy intake. These results suggest that case-control studies of diet and breast cancer may yield biased associations between fat intake and the risk of breast cancer.

Height has been inversely associated with coronary heart disease in several prospective studies in men, but data in women are sparse. The relation between height and cardiovascular disease was examined in 14 years of follow-up data from the Nurses' Health Study, a prospective cohort of 121,700 US female nurses aged 30-55 years in 1976. The relative risks associating height with coronary heart disease (nonfatal myocardial infarction (n = 1,000), fatal myocardial infarction (n = 304), confirmed angina (n = 1,343), or coronary revascularization (n = 901)) were estimated after adjustment for a large number of cardiovascular risk factors, including age and body mass index. Compared with the shortest women (< or = 61 inches (< or = 1.55 m)), the relative risk of coronary heart disease was 0.82 (95% confidence interval (CI) 0.73-0.92) for women 62-63 inches (1.57-1.60 m) tall, 0.74 (95% CI 0.65-0.85) for women 64 inches (1.63 m) tall, 0.79 (95% CI 0.70-0.89) for women 65-66 inches (1.65-1.68 m) tall, and 0.73 (95% CI 0.65-0.83) for women 67 or more inches (> or = 1.70 m) tall (p for trend < 0.0001). The inverse association was more pronounced for angina/coronary revascularization (p for trend < 0.0001; relative risk for 67 or more inches = 0.67 (95% CI 0.58-0.78)) than for myocardial infarction (p for trend = 0.03; relative risk for 67 or more inches = 0.78 (95% CI 0.64-0.95)). No trend was evident for height in relation to risk of stroke. These data support the hypothesis that height is inversely related to risk of coronary heart disease in women.

In 1986-1987, the authors assessed the fatty acid intake of 118 Boston-area men, aged 40-75 years, by a semiquantitative food frequency questionnaire administered twice, by two 7-day diet records, and by capillary gas chromatography of subcutaneous fat samples obtained by needle aspirate from the lateral buttock. Spearman correlation coefficients between diet record estimates of fatty acid intake (as a percentage of total fat) and fat aspirate measures (as a percentage of total peak area) were as follows: saturated fat, r = 0.16 (p = 0.09); monounsaturated fat, r = 0.22 (p = 0.01); and polyunsaturated fat, r = 0.49 (p = 0.0001). Spearman correlation coefficients between estimates derived from the food frequency questionnaire were as follows: saturated fat, r = 0.18 ( p = 0.05); monounsaturated fat, r = 0.14 (p = 0.14); polyunsaturated fat, r = 0.50 (p = 0.0001); and eicosapentaenoic acid, r = 0.47 (p = 0.0001). These data confirm that the polyunsaturated and eicosapentaenoic fatty acid content of subcutaneous fat is a measure of dietary intake of these fats. Although diet records are commonly thought to be the "gold standard" method of dietary assessment, the similar correlations observed between the fatty acid composition of adipose tissue and estimates of intake from the food frequency questionnaire and from diet records suggest that these two dietary assessment methods have similar validity in the measurement of polyunsaturated fatty acid intake.

The authors assessed the reproducibility and validity of an expanded 131-item semiquantitative food frequency questionnaire used in a prospective study among 51,529 men. The form was administered by mail twice to a sample of 127 participants at a one-year interval. During this interval, men completed two one-week diet records spaced approximately 6 months apart. Mean values for intake of most nutrients assessed by the two methods were similar. Intraclass correlation coefficients for nutrient intakes assessed by questionnaires one year apart ranged from 0.47 for vitamin E without supplements to 0.80 for vitamin C with supplements. Correlation coefficients between the energy-adjusted nutrient intakes measured by diet records and the second questionnaire (which asked about diet during the year encompassing the diet records) ranged from 0.28 for iron without supplements to 0.86 for vitamin C with supplements (mean r = 0.59). These correlations were higher after adjusting for week-to-week variation in diet record intakes (mean r = 0.65). These data indicate that the expanded semiquantitative food frequency questionnaire is reproducible and provides a useful measure of intake for many nutrients over a one-year period.

The relation of self-reported high blood pressure to the subsequent development of coronary heart disease and stroke was examined in a cohort of 119,963 women, aged 30-55 years, who were initially free from cardiovascular disease. Participants in the Nurses' Health Study reported high blood pressure and other cardiovascular risk factors on baseline questionnaires mailed in 1976. During six years of follow-up, there were 308 incident cases of coronary heart disease (66 fatal and 242 nonfatal myocardial infarctions) and 175 strokes (50 fatal and 125 nonfatal). Fatal as well as nonfatal coronary heart disease and stroke were all significantly more frequent among the women who had reported high blood pressure. After adjusting simultaneously for age and other risk factors, the relative risks were 3.5 (95% confidence interval (Cl) 2.8-4.5) for total coronary heart disease and 2.6 (95% Cl 1.8-3.5) for total stroke. This association was evident at all levels of relative weight. The results emphasize the importance of high blood pressure as an independent predictor of coronary heart disease and stroke in middle-aged women and suggest that the increased risk occurs in both lean and obese women.

Several investigators have observed an association between alcohol consumption and elevated glucose levels, raising the possibility that alcohol may increase the risk of diabetes. This hypothesis was evaluated prospectively among 85,051 women participating in the Nurses' Health Study who were 34 to 59 years of age in 1980 and had no history of cancer, coronary heart disease, or diabetes. At baseline, participants completed an independently validated dietary questionnaire which included information on the consumption of beer, wine, and liquor. Incident cases of non-insulin-dependent diabetes were reported on follow-up questionnaires sent in 1982 and 1984 (98% response to at least one follow-up); 526 cases were confirmed by a supplementary questionnaire regarding symptoms, laboratory values, and treatment. The risk of diabetes decreased monotonically with increasing alcohol consumption (chi trend = -9.4, p less than 0.0001). Compared with nondrinkers, women consuming 5-14.9 g of alcohol per day (about 4-10 drinks per week) had an age-adjusted relative risk of diabetes of 0.4 (95% confidence interval (CI) 0.3-0.6); for 15 g or more per day, the relative risk was 0.3 (95% CI 0.2-0.4). However, a strong inverse association between alcohol drinking and body weight explained much of the apparent protective effect of alcohol. After simultaneous adjustment for Quetelet index (weight (kg)/height (m)2), family history of diabetes, total caloric intake, and age, the relative risk of diabetes for consumers of 5-14.9 g per day was 0.8 (95% CI 0.6-1.2), and for women who drank 15+ g per day, the relative risk was 0.6 (95% CI 0.3-0.9). These data provide no support for the hypothesis that moderate alcohol intake increases the risk of non-insulin-dependent diabetes.

Although higher relative weight is generally considered to increase the risk of breast cancer, several case-control studies have suggested that the reverse may be true among premenopausal women. The association between Quetelet's index (a measure of relative weight calculated as weight/height) and the subsequent incidence of breast cancer was therefore examined during four years of follow-up among a cohort of 121,964 US women who were 30-55 years of age in 1976. In contrast to women who had experienced natural menopause or bilateral oophorectomy, the incidence of breast cancer among premenopausal women decreased with higher levels of relative weight. Age-adjusted relative risks for increasing quintiles of Quetelet's index were 1.00, 0.90, 0.90, 0.73, and 0.66 (Mantel extension test for trend = -2.82, p = 0.005). This inverse association was not explained by known risk factors for breast cancer and was somewhat stronger when Quetelet's index was computed using reported weight at age 18 years. The excess incidence of breast cancer among lean premenopausal women, however, was limited to tumors that were less than 2.0 cm in diameter, were not associated with metastases to lymph nodes, and were well-differentiated. These findings suggest that the apparent excess risk of breast cancer among lean premenopausal women may result at least in part from easier, and thus earlier, diagnosis of less aggressive tumors.

A modification of the model of Pike et al. (Nature 1983;303: 767-70) was applied to 91,523 women in the Nurses' Health Study who did not report prevalent cancer initially and who were followed for 14 years (1,212,855 person-years and 2,341 incident breast cancers). The model took into account current age, age at all births, age at menopause, and age at menarche in predicting the annual and cumulative incidence of breast cancer. The authors found that ages both at first birth and at subsequent births have long-term influence on breast cancer incidence. The incidence density for parous women was greater than for nulliparous women for 20-30 years after the time of the first birth. However, cumulative incidence up to age 70 years was about 20% lower, 10% lower, or 5% higher for parous versus nulliparous women if their first birth was at age 20, 25, or 35 years, respectively. The authors also observed a significantly lower incidence after each additional birth as well as after menopause for women of the same age. Overall, the effect of reproductive factors (other than age at menarche) appears to influence cumulative incidence to age 70 years by a maximum of approximately 50% when women with multiple births with an early age at first birth are compared with women with a single birth at a late age.

OBJECTIVE: To examine the relation between nut consumption and risk of coronary heart disease in a cohort of women from the Nurses' Health Study. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. SUBJECTS: 86 016 women from 34 to 59 years of age without previously diagnosed coronary heart disease, stroke, or cancer at baseline in 1980. MAIN OUTCOME MEASURES: Major coronary heart disease including non-fatal myocardial infarction and fatal coronary heart disease. RESULTS: 1255 major coronary disease events (861 cases of non-fatal myocardial infarction and 394 cases of fatal coronary heart disease) occurred during 14 years of follow up. After adjusting for age, smoking, and other known risk factors for coronary heart disease, women who ate more than five units of nuts (one unit equivalent to 1 oz of nuts) a week (frequent consumption) had a significantly lower risk of total coronary heart disease (relative risk 0.65, 95% confidence interval 0.47 to 0.89, P for trend=0.0009) than women who never ate nuts or who ate less than one unit a month (rare consumption). The magnitude of risk reduction was similar for both fatal coronary heart disease (0.61, 0.35 to 1.05, P for trend=0.007) and non-fatal myocardial infarction (0.68, 0.47 to 1.00, P for trend=0.04). Further adjustment for intakes of dietary fats, fibre, vegetables, and fruits did not alter these results. The inverse association persisted in subgroups stratified by levels of smoking,use of alcohol, use of multivitamin and vitamin E supplements, body mass index, exercise, and intake of vegetables or fruits. CONCLUSIONS: Frequent nut consumption was associated with a reduced risk of both fatal coronary heart disease and non-fatal myocardial infarction. These data, and those from other epidemiological and clinical studies, support a role for nuts in reducing the risk of coronary heart disease.