Association of calcium and vitamin D supplementation with cancer incidence and cause-specific mortality in Black women: Extended follow-up of the Women's Health Initiative calcium-vitamin D trial.

Low circulating vitamin D levels are more prevalent in Black than White individuals. We analyzed the Women's Health Initiative (WHI) calcium plus vitamin D (CaD) randomized clinical trial extended follow-up data to evaluate associations between calcium plus vitamin D supplementation and incident cancer, cardiovascular disease (CVD), and cause-specific mortality endpoints among Black women. Intent-to-treat analysis was performed. Among 3325 Black women in the CaD trial who were randomized into either daily calcium (1000 mg of calcium carbonate) plus vitamin D (400 IU D3) or placebos for an average of 7 years, there were 813 deaths, 588 incident cancers, and 837 CVD events during an average of 15.7 years of follow up (52 230 total person-years). Using Cox's proportional hazards models, we calculated hazard ratios and their confidence intervals for outcomes ascertained during the trial period, posttrial follow-up period and overall periods combined. We found that total mortality, cause-specific mortality, and total cancer incidence were almost identical between CaD and placebo groups. These results suggest that calcium plus vitamin D supplementation does not reduce risks of cancer, CVD, or other major causes of death in Black women overall and, thus, other medical, behavioral or social interventions should be considered to narrow health disparities related to these outcomes. However, other finer endpoints, such as colorectal cancer, warrants further investigation.

Inflammatory, Oxidative Stress, and Cardiac Damage Biomarkers and Radiation-Induced Fatigue in Breast Cancer Survivors.

PURPOSE: Studies examining biomarkers associated with fatigue in breast cancer survivors treated with radiation are limited. Therefore, we examined the longitudinal association between serum biomarkers and post-breast cancer fatigue in survivors treated with radiation: [oxidative stress] 8-hydroxyguanosine, myeloperoxidase; [inflammation] interleukin-6 (IL-6), c-reactive protein, growth differentiation factor-15 (GDF-15), placental growth factor, transforming growth factor-beta, [cardiac damage] cystatin-C, troponin-I. METHODS: In a secondary analysis, we included participants from the Women's Health Initiative if they had: a previous breast cancer diagnosis (stages I-III), no prior cardiovascular diseases, pre-and post-breast cancer serum samples drawn approximately 3 years apart, and fatigue measured using the Short-Form 36 vitality subscale at both serum collections. Biomarkers were measured using ELISA or RT-qPCR and modeled as the log2 post-to pre-breast cancer ratio. RESULTS: Overall, 180 women with a mean (SD) age of 67.0 (5.5) years were included. The mean (SD) vitality scores were 66.2 (17.2) and 59.7 (19.7) pre- and post-breast cancer, respectively. Using multivariable weighted linear regression, higher biomarker ratios of cystatin-C, IL-6, and GDF-15 were associated with a lower vitality score (i.e., higher fatigue). For example, for each 2-fold difference in cystatin-C biomarker ratio, the vitality score was lower by 7.31 points (95% CI: -14.2, -0.45). CONCLUSION: Inflammatory and cardiac damage biomarkers are associated with fatigue in breast cancer survivors treated with radiation; however, these findings should be replicated in a larger sample. Biomarkers could be measured in clinical practice or assessed in risk prediction models to help identify patients at high risk for fatigue.

Long-Term Exposures to Air Pollution and the Risk of Atrial Fibrillation in the Women's Health Initiative Cohort.

BACKGROUND: Atrial fibrillation (AF) is associated with substantial morbidity and mortality. Short-term exposures to air pollution have been associated with AF triggering; less is known regarding associations between long-term air pollution exposures and AF incidence. OBJECTIVES: Our objective was to assess the association between long-term exposures to air pollution and distance to road on incidence of AF in a cohort of U.S. women. METHODS: We assessed the association of high resolution spatiotemporal model predictions of long-term exposures to particulate matter (PM10 and PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and distance to major roads with incidence of AF diagnosis, identified through Medicare linkage, among 83,117 women in the prospective Women's Health Initiative cohort, followed from enrollment in Medicare through December 2012, incidence of AF, or death. Using time-varying Cox proportional hazards models adjusted for age, race/ethnicity, study component, body mass index, physical activity, menopausal hormone therapy, smoking, diet quality, alcohol consumption, educational attainment, and neighborhood socioeconomic status, we estimated the relative risk of incident AF in association with each pollutant. RESULTS: A total of 16,348 incident AF cases were observed over 660,236 person-years of follow-up. Most exposure-response associations were nonlinear. NO2 was associated with risk of AF in multivariable adjusted models [Hazard Ratio (HR)=1.18; 95% confidence interval (CI): 1.13, 1.24, comparing the top to bottom quartile, p-for-trend=<0.0001]. Women living closer to roadways were at higher risk of AF (e.g., HR=1.07; 95% CI: 1.01, 1.13 for living within 50m of A3 roads, compared with ≥1,000 m, p-for-trend=0.02), but we did not observe adverse associations with exposures to PM10, PM2.5, or SO2. There were adverse associations with PM10 (top quartile HR=1.10; 95% CI: 1.05, 1.16, p-for-trend=<0.0001) and PM2.5 (top quartile HR=1.09; 95% CI: 1.03, 1.14, p-for-trend=0.002) in sensitivity models adjusting for census region. DISCUSSION: In this study of postmenopausal women, NO2 and distance to road were consistently associated with higher risk of AF. https://doi.org/10.1289/EHP7683.