Background Observational studies and meta-analyses of trials suggest daily aspirin use may affect cancer risk, particularly for colorectal cancer, but evidence regarding alternate-day use is scant. Objective To examine the association between long-term use of alternate-day low-dose aspirin and cancer incidence in healthy women. Design Observational follow-up of a randomized controlled trial. Setting U.S. female health professionals. Participants 39,876 women aged 45 and over in the Women’s Health Study, 33,682 of whom continued observational follow-up. Intervention 100 mg of aspirin or placebo administered every other day until March 2004, with a median 10-year follow-up. Post-trial observational follow-up continued through March 2012. Measurements Incidence of cancer. Results 5,071 cancers were confirmed throughout follow-up, including 2,070 breast, 451 colorectal, 431 lung cancers, and 1,391 cancer deaths. Over the entire follow-up there was no overall effect of aspirin on total (hazard ratio (HR) = 0.97, 95% confidence interval (CI) = 0.92-1.03, p=0.31), breast (HR=0.98, 95% CI = 0.90-1.07 p=0.65) or lung (HR=1.04, 95% CI = 0.86-1.26, p=0.67) cancer. Incidence of colorectal cancer was lower in the aspirin group (HR=0.80, 95% CI = 0.67-0.97, p=0.021), primarily due to a reduction in proximal colon cancer (HR=0.73, 95% CI = 0.55-0.95, p=0.022), with the effect emerging after 10 years. The post-trial reduction in colorectal cancer was 42% (HR=0.58, 95% CI = 0.42-0.80, p<0.001). There was no extended effect on cancer deaths or colorectal polyps. There were more reported gastrointestinal bleeds (HR=1.14, 95% CI=1.06-1.22, p<0.001) and peptic ulcers (HR=1.17, 95% CI=1.09-1.27, p<0.001) in the aspirin group. Limitations Data were available only for women. Not all women received extended follow-up, and the possibility of ascertainment bias post-trial cannot be ruled out. Gastrointestinal bleeding, peptic ulcer, and polyp information was obtained only from self-report during extended follow-up. Conclusions Long-term use of alternate-day, low-dose aspirin may reduce risk for colorectal cancer in healthy women.

Lipids were associated with total, lung, and colorectal cancer risks in women. Lifestyle interventions for heart-disease prevention, which reduce apo B-100 or raise HDL cholesterol, may be associated with reduced cancer risk. The Women's Health Study was registered at clinicaltrials.gov as NCT00000479.

Context Previous studies suggest that consuming moderate-to-large amounts of alcohol on a regular basis might increase the risk of developing atrial fibrillation (AF) in men, but not in women. However, these studies were not powered to investigate the association of alcohol consumption and AF among women. Objective To prospectively assess the association between regular alcohol consumption and incident AF among women. Design, Setting and Participants 34715 initially healthy women participating in the Women’s Health Study who were >45 years and free of AF at baseline were prospectively followed from 1993 to October 31, 2006. Alcohol intake was assessed via questionnaires at baseline and 48 months of follow-up and grouped into the following categories: 0, >0 and <1, ≥1 and <2, and ≥2 drinks per day. Main outcome measure Time to a first episode of AF. AF was self-reported on the yearly questionnaires and subsequently confirmed by electrocardiogram and medical record review. Results Over a median follow-up of 12.4 years, 653 incident AF cases were confirmed. Age-adjusted incidences among women consuming 0 (n=15370), >0 and <1 (n=15758), ≥1 and <2 (n=2228), and ≥2 (n=1359) drinks per day were 1.59, 1.55, 1.27 and 2.25 events/1000 person-years of follow-up. Thus, compared with non-drinking women, women consuming ≥2 drinks per day had an absolute risk increase of 0.66 events/1000 person-years. The corresponding multivariable-adjusted hazard ratios (HR) (95% confidence interval (CI)) for incident AF were 1.0, 1.05 (0.88–1.25), 0.84 (0.58–1.22) and 1.60 (1.13–2.25), respectively. The increased hazard in the small group of women consuming ≥2 drinks persisted when alcohol intake was updated at 48 months (HR (95% CI) (1.49 (1.05–2.11)) or when women were censored at their first cardiovascular event (HR (95% CI) 1.68 (1.18–2.39)). Conclusion Among healthy middle-aged women, consumption of up to two alcoholic beverages per day was not associated with an increased risk of incident AF. Heavier consumption of two or more drinks per day, however, was associated with a small but statistically significant increased AF risk.

Rationale Circulating glycoprotein N-acetyl glucosamine residues have recently been associated with incident cardiovascular disease (CVD) and diabetes mellitus. Objective Using a plasma glycan biosignature (GlycA) to identify circulating N-acetyl glycan groups, we examined the longitudinal association between GlycA and mortality among initially-healthy individuals. Methods and Results We quantified GlycA by 400 MHz 1H nuclear magnetic resonance (NMR) spectroscopy in 27,524 participants in the Women's Health Study (WHS; NCT00000479). The primary outcome was all-cause mortality. We replicated the findings in an independent cohort of 12,527 individuals in the JUPITER trial (NCT00239681). We also undertook secondary examination of CVD and cancer mortality in WHS. In WHS, during 524,515 person-years of follow-up (median 20.5 years) there were 3,523 deaths. Risk-factor adjusted multivariable Cox proportional hazard ratio (95% confidence interval) per standard deviation increment in GlycA for all-cause mortality was significantly increased at 5-years (1.21 [1.06, 1.40]) and during maximal follow-up (1.14 [1.09, 1.16]). Similar risk for all-cause mortality was observed in the replication cohort (1.33 [1.21, 1.45]). In WHS, risk of CVD mortality was increased at 5-years (1.43 [1.05, 1.95]) and during maximal follow-up (1.15 [1.04, 1.26]); and of cancer mortality at 5-years (1.23 [1.02, 1.47]) and during maximal follow-up (1.08 [1.01, 1.16]). Examination of correlations and mortality associations adjusted for hsCRP, fibrinogen, and ICAM-1, suggested that GlycA reflects summative risk related to multiple pathways of systemic inflammation. Conclusions Among initially-healthy individuals, elevated baseline circulating glycoprotein N-acetyl methyl groups were associated with longitudinal risk of all-cause, cardiovascular, and cancer mortality.

Background-Physical activity (PA) is well known to reduce the risk of cardiovascular disease. We hypothesized that regular PA, possibly acting through reductions in blood pressure and body mass index (BMI), would reduce the risk of incident atrial fibrillation (AF) in women. Methods and Results-We prospectively followed 34 759 women who reported their leisure-time PA levels for the occurrence of AF. We estimated energy expenditure in metabolic equivalent (MET)-h/wk and validated self-reported AF with medical records. The mean (SD) age of the 34 759 participants was 54.6 (7.0) years, the mean BMI was 26.0 (5.0) kg/m

BackgroundLimited data exist directly comparing the relative benefits of moderate‐ and vigorous‐intensity activities with all‐cause and cardiovascular (CV) disease mortality rates when controlling for physical activity volume.Methods and ResultsWe followed 7979 men (Harvard Alumni Health Study, 1988–2008) and 38 671 women (Women's Health Study, 1992–2012), assessing their physical activity and health habits through repeated questionnaires. Over a mean follow‐up of 17.3 years in men and 16.4 years in women, there were 3551 deaths (1077 from CV disease) among men and 3170 deaths (620 from CV disease) among women. Those who met or exceeded an equivalent of the federal guidelines recommendation of at least 150 minutes of moderate‐intensity activity, 75 minutes of vigorous‐intensity activity, or a combination of the 2 that expended similar energy experienced significantly lower all‐cause and CV disease–related mortality rates (men, 28% to 36% and 31% to 34%, respectively; women: 38% to 55% and 22% to 44%, respectively). When comparing different combinations of moderate‐ and vigorous‐intensity activity and all‐cause mortality rates, we observed sex‐related differences. Holding constant the volume of moderate‐ to vigorous‐intensity physical activity, men experienced a modest additional benefit when expending a greater proportion of moderate‐ to vigorous‐intensity physical activity in vigorous‐intensity activities (Ptrend=0.04), but women did not (Ptrend<0.001). Moderate‐ to vigorous‐intensity physical activity composition was not associated with further cardiovascular mortality rate reductions in either men or women.ConclusionsThe present data support guidelines recommending 150 minutes of moderate‐intensity activity per week, 75 minutes of vigorous‐intensity activity per week, or an equivalent combination for mortality benefits. Among men, but not women, additional modest reductions in all‐cause mortality rates are associated with a greater proportion of moderate‐ to vigorous‐intensity physical activity performed at a vigorous intensity.

Key Points Question Is the Mediterranean diet (MED) associated with lower risk of cardiovascular disease (CVD) events in a US population, and, if so, what are the underlying mechanisms? Findings In this cohort study of 25 994 US women, higher baseline MED intake was associated with up to 28% relative risk reduction in CVD events. For the MED-CVD risk reduction, biomarkers of inflammation, glucose metabolism and insulin resistance, and adiposity contributed most to explaining the association. Meaning Higher MED intake was associated with approximately one-fourth relative risk reduction in CVD, which could be explained in part by known risk factors, both traditionally measured and novel ones.

IMPORTANCE Risk profiles for premature coronary heart disease (CHD) are unclear.OBJECTIVE To examine baseline risk profiles for incident CHD in women by age at onset. DESIGN, SETTING, AND PARTICIPANTSA prospective cohort of US female health professionals participating in the Women's Health Study was conducted; median follow-up was 21.4 years.