Although a growing body of evidence indicates strong links between psychological stress (stress) and untoward cardiovascular disease (CVD) outcomes, comprehensive examination of these effects remains lacking. The "Cumulative Psychological Stress and Cardiovascular Disease Risk in Middle Aged and Older Women" study is embedded within the landmark Women's Health Study (WHS) follow-up cohort and seeks to evaluate the individual and joint effects of stressors (cumulative stress) on incident CVD risk, including myocardial infarction, stroke, coronary revascularization and CVD death. GWAS data will be used for exploratory analyses to identify any genes associated with stress and CVD. This study prospectively follows 25,335 women (mean age 72.2 ± 6.04 years) without CVD who returned a short mailed stress questionnaire at baseline and 3 years of follow-up inquiring about their experiences with stress including perceived stress, work stress, work-family spillover, financial stress, traumatic and major life events, discrimination and neighborhood environment/stressors. Other domains ascertained were sleep, anger, cynical hostility, depression, anxiety, social support, intimate partner relations, and volunteer and social activities. Higher levels of cumulative stress were associated with younger age and black race/ethnicity, divorced or separated marital status, increased prevalence of obesity, smoking, diabetes, depression and anxiety (p<0.001 for each). Findings from this study will provide clinically important, new information about associations of cumulative stress, environmental, lifestyle and genetic factors with incident CVD risk in aging women.

Objectives

Research about work-related stressors and cardiovascular disease (CVD) has produced mixed findings. Moreover, a paucity of data exists regarding the long-term associations between job strain and job insecurity and CVD among women.

Methods

We used Cox proportional hazard models to examine the relationship between job strain, job insecurity, and incident CVD over 10 years of follow-up among 22,086 participants in the Women's Health Study (mean age 57±5 years).

Results

During 10 years of follow-up there were 170 myocardial infarctions (MI), 163 ischemic strokes, 440 coronary revascularizations, and 52 CVD deaths. In models adjusted for age, race, education, and income, women with high job strain (high demand, low control) were 38% more likely to experience a CVD event than their counterparts who reported low job strain (low demand, high control; Rate Ratio (RR) = 1.38, 95% Confidence Interval (CI) = 1.08-1.77), and women with active jobs (high demand, high control) were 38% more likely to experience a CVD event relative to women who reported low job strain (95% CI = 1.07-1.77). Outcome-specific analyses revealed that high job strain predicted non-fatal myocardial infarction (RR = 1.67, CI = 1.04-2.70), and coronary revascularization (RR = 1.41, CI = 1.05-1.90). No evidence of an association between job insecurity and long-term CVD risk was observed.

Conclusion

High strain and active jobs, but not job insecurity, were related to increased CVD risk among women. Both job strain and job insecurity were significantly related to CVD risk factors. With the increase of women in the workforce, these data emphasize the importance of addressing job strain in CVD prevention efforts among working women.

Background

Use of some non-steroidal anti-inflammatory drugs (NSAIDs) has been linked to an increased risk of stroke. However, information on the impact of NSAID use on functional outcomes from stroke is limited.

Methods

Using women enrolled in the Women's Healthy Study who were free of a history of stroke or TIA at baseline, a prospective cohort study was performed to examine the impact of NSAID use on functional outcomes from stroke. Women were classified as NSAID non-user (<11 days of use in the past month), user (≥ 11 days of use in the past month), and missing (did not answer the question about NSAID use) during each year of the study. Possible functional outcomes were TIA or ischemic stroke with modified Rankin scale (mRS) score of 0 to 1, 2 to 3, or 4 to 6.

Results

After 15.7 mean years of follow-up, 702 TIAs, 292 ischemic strokes with mRS 0-1, 233 ischemic strokes with mRS 2-3 and 98 ischemic strokes with mRS 4-6 occurred. Compared to women who were NSAID non-users, women who were NSAID users had multivariable-adjusted (95% CI) of 1.00 (0.77, 1.29) for TIA, 1.48 (1.04, 2.10) for mRS 0-1, 0.83 (0.52, 1.33) for mRS 2-3, and 1.33 (0.68, 2.59) for mRS 4-6.

Conclusion

Results from this large cohort study suggest than NSAID use may be associated with an increased risk of ischemic stroke with mild functional outcome.

Short sleep duration is associated with increased cardiovascular disease (CVD) risk. However, it is uncertain whether sleep debt, a measure of sleep deficiency during the week compared to the weekend, confers increased cardiovascular risk. Because sleep disturbances increase with age particularly in women, we examined the relationship between sleep debt and ideal cardiovascular health (ICH) in older women. Sleep debt is defined as the difference between self-reported total weekday and weekend sleep hours of at least 2 hours among women without apparent CVD and cancer participating in the Women's Health Stress Study follow-up cohort of female health professionals (N = 22 082). The ICH consisted of seven health factors and behaviors as defined by the American Heart Association Strategic 2020 goals including body mass index, smoking, physical activity, diet, blood pressure, total cholesterol, and glucose. Mean age was 72.1 ± 6.0 years. Compared to women with no sleep debt, women with sleep debt were more likely to be obese and have hypertension (pall < .05). Linear regression models adjusted for age and race/ethnicity revealed that sleep debt was significantly associated with poorer ICH (B = -0.13 [95% CI = -0.18 to -0.08]). The relationship was attenuated but remained significant after adjustment for education, income, depression/anxiety, cumulative stress, and snoring. Sleep debt was associated with poorer ICH, despite taking into account socioeconomic status and psychosocial factors. These results suggest that weekly sleep duration variation, possibly leading to circadian misalignment, may be associated with cardiovascular risk in older women.

Objectives

We prospectively examined whether socioeconomic status (SES) predicts incident type II diabetes (diabetes), a cardiovascular risk equivalent and burgeoning public health epidemic among women.

Methods

Participants include 23,992 women with Hb(A1c) levels <6% and no CVD or diabetes at baseline followed from February 1993 to March 2007. SES was measured by education and income while diabetes was self-reported.

Results

Over 12.3 years of follow-up, 1,262 women developed diabetes. In age and race adjusted models, the relative risk of diabetes decreased with increasing education (<2 years of nursing, 2 to <4 years of nursing, bachelor's degree, master's degree, and doctorate: 1.0, 0.7 [95% Confidence Interval (CI), 0.6-0.8], 0.6 (95% CI, 0.5-0.7), 0.5 (95% CI, 0.4-0.6), 0.4 (95% CI, 0.3-0.5); p(trend)<0.001). Adjustment for traditional and non-traditional cardiovascular risk factors attenuated this relationship (education: p(trend) = 0.96). Similar associations were observed between income categories and diabetes.

Conclusion

Advanced education and increasing income were both inversely associated with incident diabetes even in this relatively well-educated cohort. This relationship was largely explained by behavioral factors, particularly body mass index.

Background

Vitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent.

Methods

In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D₃ would result in a lower risk of fractures than placebo. VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D₃ (2000 IU per day), n-3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were reported by participants on annual questionnaires and adjudicated by centralized medical-record review. The primary end points were incident total, nonvertebral, and hip fractures. Proportional-hazards models were used to estimate the treatment effect in intention-to-treat analyses.

Results

Among 25,871 participants (50.6% women [13,085 of 25,871] and 20.2% Black [5106 of 25,304]), we confirmed 1991 incident fractures in 1551 participants over a median follow-up of 5.3 years. Supplemental vitamin D₃, as compared with placebo, did not have a significant effect on total fractures (which occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group; hazard ratio, 0.98; 95% confidence interval [CI], 0.89 to 1.08; P = 0.70), nonvertebral fractures (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.50), or hip fractures (hazard ratio, 1.01; 95% CI, 0.70 to 1.47; P = 0.96). There was no modification of the treatment effect according to baseline characteristics, including age, sex, race or ethnic group, body-mass index, or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in adverse events as assessed in the parent trial.

Conclusions

Vitamin D₃ supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; VITAL ClinicalTrials.gov number, NCT01704859.).

Background

Elevated postprandial triglycerides reflect a proatherogenic milieu, but underlying mechanisms are unclear.

Objective

We examined differences between fasting and nonfasting profiles of directly measured lipoprotein size and subfractions to assess if postprandial triglycerides reflected increases in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and remnants, or small dense lipid depleted LDL (sdLDL) particles.

Methods

We conducted a cross-sectional analysis of 15,397 participants (10,135 fasting; 5262 nonfasting [<8 hours since last meal]) from the VITamin D and OmegA-3 TriaL. Baseline cholesterol subfractions were measured by the vertical auto profile method and particle subfractions by ion mobility. We performed multivariable linear regression adjusting for cardiovascular and lipoprotein-modifying risk factors.

Results

Mean age (SD) was 68.0 years (±7.0), with 50.9% women. Adjusted mean triglyceride concentrations were higher nonfasting by 17.8 ± 1.3%, with higher nonfasting levels of directly measured VLDL cholesterol (by 3.5 ± 0.6%) and total VLDL particles (by 2.0 ± 0.7%), specifically large VLDL (by 12.3 ± 1.3%) and medium VLDL particles (by 5.3 ± 0.8%), all P < .001. By contrast, lower concentrations of low density lipoprotein (LDL) and IDL cholesterol and particles were noted for nonfasting participants. sdLDL cholesterol levels and particle concentrations showed no statistically significant difference by fasting status (-1.3 ± 2.1% and 0.07 ± 0.6%, respectively, P > .05).

Conclusions

Directly measured particle and cholesterol concentrations of VLDL, not sdLDL, were higher nonfasting and may partly contribute to the proatherogenicity of postprandial hypertriglyceridemia. These differences, although statistically significant, were small and may not fully explain the increased risk of postprandial hypertriglyceridemia.

To evaluate the effect of vitamin D₃ supplementation on cancer mortality in the general population and on prognosis in cancer patients, a systematic review and meta-analysis of randomised, placebo-controlled trials (RCTs) and individual patient data (IPD) was conducted. Overall, 14 RCTs with a total of 104,727 participants (2015 cancer deaths) were identified and 7 RCTs, including 90 % of all study participants (n = 94,068), could be included in the IPD meta-analyses. The main meta-analysis of the 14 RCTs yielded a statistically non-significant reduction in cancer mortality by 6 % (risk ratio (RR) [95%-confidence interval (95%CI)]: 0.94 [0.86-1.02]). Subgroup analyses revealed a 12 % lower cancer mortality in the vitamin D₃ group compared with the placebo group in 10 trials with a daily dosing regimen (RR [95%CI]: 0.88 [0.78-0.98]), whereas no mortality reduction was seen in 4 trials using a bolus regimen (RR [95%CI]: 1.07 [0.91-1.24]; p-value for interaction: 0.042). The IPD meta-analysis (RR [95%CI]: 0.93 [0.84; 1.02]) confirmed the finding of all trials. The IPD were used to test effect modification by age, sex, body mass index, ethnicity, baseline serum 25-hydroxyvitamin D concentration, adherence and cancer-related factors but no statistically significant findings were obtained in meta-analyses of all trials. When restricted to trials with daily dosing in a post-hoc analysis, adults aged ≥ 70 years (RR [95%CI]: 0.83 [0.77; 0.98]) and subjects with vitamin D₃ therapy initiation before cancer diagnosis (RR [95%CI]: 0.87 [0.69; 0.99]) appeared to benefit most from daily vitamin D₃ supplementation. Measurements of baseline 25-hydroxyvitamin D levels and inclusion of other than non-Hispanic White adults were too sparse in the trials to draw conclusions. Results for all-cause and cancer-specific survival of participants with cancer were comparable to those obtained in the general population for cancer mortality. In conclusion, vitamin D₃ did not reduce cancer mortality in the main meta-analysis of all RCTs because the observed risk reduction by 6 % was not statistically significant. However, a subgroup analysis revealed that vitamin D₃ administered daily, in contrast to bolus supplementation, reduced cancer mortality by 12 %.

In 2012, the National Cancer Institute (NCI) engaged the scientific community to provide a vision for cancer epidemiology in the 21st century. Eight overarching thematic recommendations, with proposed corresponding actions for consideration by funding agencies, professional societies, and the research community emerged from the collective intellectual discourse. The themes are (i) extending the reach of epidemiology beyond discovery and etiologic research to include multilevel analysis, intervention evaluation, implementation, and outcomes research; (ii) transforming the practice of epidemiology by moving toward more access and sharing of protocols, data, metadata, and specimens to foster collaboration, to ensure reproducibility and replication, and accelerate translation; (iii) expanding cohort studies to collect exposure, clinical, and other information across the life course and examining multiple health-related endpoints; (iv) developing and validating reliable methods and technologies to quantify exposures and outcomes on a massive scale, and to assess concomitantly the role of multiple factors in complex diseases; (v) integrating "big data" science into the practice of epidemiology; (vi) expanding knowledge integration to drive research, policy, and practice; (vii) transforming training of 21st century epidemiologists to address interdisciplinary and translational research; and (viii) optimizing the use of resources and infrastructure for epidemiologic studies. These recommendations can transform cancer epidemiology and the field of epidemiology, in general, by enhancing transparency, interdisciplinary collaboration, and strategic applications of new technologies. They should lay a strong scientific foundation for accelerated translation of scientific discoveries into individual and population health benefits.