We have summarized the evolution of the Nurses' Health Study (NHS), a prospective cohort study of 121 700 married registered nurses launched in 1976; NHS II, which began in 1989 and enrolled 116 430 nurses; and NHS3, which began in 2010 and has ongoing enrollment. Over 40 years, these studies have generated long-term, multidimensional data, including lifestyle- and health-related information across the life course and an extensive repository of various biological specimens. We have described the questionnaire data collection, disease follow-up methods, biorepository resources, and data management and statistical procedures. Through integrative analyses, these studies have sustained a high level of scientific productivity and substantially influenced public health recommendations. We have highlighted recent interdisciplinary research projects and discussed future directions for collaboration and innovation.

Context Previous studies have examined the associations of individual clinical risk factors with risk of peripheral artery disease (PAD), but the combined effects of these risk factors are largely unknown. Objective To estimate the degree to which four conventional cardiovascular risk factors, smoking, hypertension, hypercholesterolemia and type 2 diabetes, are associated with the risk of PAD among men. Design, settings and participants We prospectively followed 44,985 men from the Health Professionals Follow-up Study without a history of cardiovascular disease at baseline for 25 years (1986-2011). The presence of risk factors was updated biennially during follow-up. Main outcome measure Clinically significant PAD (defined as limb amputation/revascularization, angiogram reporting vascular obstruction of ≥50%, ankle-brachial index<0.90 or physician-diagnosed PAD). Results During a median follow-up of 24.2 years (interquartile range 20.8-24.7 years), 537 PAD cases occurred. Each risk factor was significantly and independently associated with a higher risk of PAD after adjustment for the other three risk factors and confounders. The age-adjusted incidence rates per 100,000 person years were 6 cases for 0 risk factors, 18 cases for 1 risk factor, 39 cases for 2 risk factors, 76 cases for 3 risk factors and 139 cases for 4 risk factors. The multivariable-adjusted hazard ratio (HR) for each additional risk factor compared was 2.06 (95% confidence interval [95% CI], 1.92-2.32). Men without any of the four risk factors had a HR of PAD of 0.23 (95% CI, 0.14-0.36) compared with all other men in the cohort. In 96% (95% CI, 94-98%) of PAD cases, at least one of the four risk factors was present at the time of PAD diagnosis. The population-attributable risk associated with these four risk factors was 75% (95% CI, 64-87%). The incidence of PAD among men with all four risk factors was 1.4/1,000. Conclusion Among men in this cohort, smoking, hypertension, hypercholesterolemia and type 2 diabetes account for most of the risk associated with development of clinically significant PAD.

BackgroundCurrent dietary guidelines recommend eating a variety of fruits and vegetables. However, based on nutrient composition, some particular fruits and vegetables may be more or less beneficial for maintaining or achieving a healthy weight. We hypothesized that greater consumption of fruits and vegetables with a higher fiber content or lower glycemic load would be more strongly associated with a healthy weight.Methods and FindingsWe examined the association between change in intake of specific fruits and vegetables and change in weight in three large, prospective cohorts of 133,468 United States men and women. From 1986 to 2010, these associations were examined within multiple 4-y time intervals, adjusting for simultaneous changes in other lifestyle factors, including other aspects of diet, smoking status, and physical activity. Results were combined using a random effects meta-analysis. Increased intake of fruits was inversely associated with 4-y weight change: total fruits -0.53 lb per daily serving (95% CI -0.61, -0.44), berries -1.11 lb (95% CI -1.45, -0.78), and apples/pears -1.24 lb (95% CI -1.62, -0.86). Increased intake of several vegetables was also inversely associated with weight change: total vegetables -0.25 lb per daily serving (95% CI -0.35, -0.14), tofu/soy -2.47 lb (95% CI, -3.09 to -1.85 lb) and cauliflower -1.37 lb (95% CI -2.27, -0.47). On the other hand, increased intake of starchy vegetables, including corn, peas, and potatoes, was associated with weight gain. Vegetables having both higher fiber and lower glycemic load were more strongly inversely associated with weight change compared with lower-fiber, higher-glycemic-load vegetables (p < 0.0001). Despite the measurement of key confounders in our analyses, the potential for residual confounding cannot be ruled out, and although our food frequency questionnaire specified portion size, the assessment of diet using any method will have measurement error.ConclusionsIncreased consumption of fruits and non-starchy vegetables is inversely associated with weight change, with important differences by type suggesting that other characteristics of these foods influence the magnitude of their association with weight change.

Background: Although increased fruit intake reduces cardiovascular disease (CVD) risk, which fruits are most beneficial and what key constituents are responsible are unclear. Habitual intakes of flavonoids, specifically anthocyanins and flavanones, in which >90% of habitual intake is derived from fruit, are associated with decreased CVD risk in women, but associations in men are largely unknown.Objective: We examined the relation between habitual anthocyanin and flavanone intake and coronary artery disease and stroke in the Health Professionals Follow-Up Study.Design: We followed 43,880 healthy men who had no prior diagnosed CVD or cancer. Flavonoid intake was calculated with the use of validated food-frequency questionnaires.Results: During 24 y of follow-up, 4046 myocardial infarction (MI) and 1572 stroke cases were confirmed by medical records. Although higher anthocyanin intake was not associated with total or fatal MI risk, after multivariate adjustment an inverse association with nonfatal MI was observed (HR: 0.87; 95% CI: 0.75, 1.00; P = 0.04; P-trend = 0.098); this association was stronger in normotensive participants (HR: 0.81; 95% CI: 0.69, 0.96; P-interaction = 0.03). Anthocyanin intake was not associated with stroke risk. Although flavanone intake was not associated with MI or total stroke risk, higher intake was associated with a lower risk of ischemic stroke (HR: 0.78; 95% CI: 0.62, 0.97; P = 0.03, P-trend = 0.059), with the greatest magnitude in participants aged ≥65 y (P-interaction = 0.04).Conclusions: Higher intakes of fruit-based flavonoids were associated with a lower risk of nonfatal MI and ischemic stroke in men. Mechanistic studies and clinical trials are needed to unravel the differential benefits of anthocyanin- and flavanone-rich foods on cardiovascular health.