Contributions of the Women's Health Initiative to Cardiovascular Research: JACC State-of-the-Art Review.

The WHI (Women's Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementation) for the primary prevention of major chronic diseases, including cardiovascular disease, in older women. In the WHI observational study, numerous clinical, behavioral, and social factors have been evaluated as predictors of incident chronic disease and mortality. Although the original interventions have been completed, the WHI data and biomarker resources continue to be leveraged and expanded through ancillary studies to yield novel insights regarding cardiovascular disease prevention and healthy aging in women.

Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative.

Research findings remain inconsistent whether caffeine consumption is associated with invasive breast cancer. We aimed to examine the association between caffeine intake from coffee and tea and incident invasive breast cancer among postmenopausal women. We included 79 871 participants in the Women's Health Initiative Observational Study in the current analysis. Incident invasive breast cancers were identified through September 30, 2015. Caffeine intake (mg/day) from caffeinated and decaffeinated coffee and tea was estimated based on self-reported frequency (cups/day) and average caffeine amount in each beverage. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses were conducted to explore whether associations of caffeine intake from coffee and tea with invasive breast cancer were different by age, race and ethnicity, smoking status, body mass index, history of hormone therapy use, alcohol intake and subtypes of breast cancer. During a median follow-up of 16.0 years, 4719 incident invasive breast cancers were identified. No significant association was found between caffeine intake from coffee and tea and invasive breast cancer incidence after adjusting for demographic, lifestyle and reproductive factors: HRs (95% CIs) for increasing quartiles of caffeine intake compared to the lowest were 1.03 (0.94, 1.12), 1.04 (0.95, 1.13) and 1.03 (0.94, 1.13), respectively (P-for-trend = .54). No significant associations of coffee and tea intake (cups/day) with overall breast cancer risk were found. Our findings are consistent with others showing no clear association of caffeine consumption with invasive breast cancer among postmenopausal women.

Adequate vitamin D status is associated with the reduced odds of prevalent diabetic retinopathy in African Americans and Caucasians.

BACKGROUND: Vitamin D status has been hypothesized to protect against development of diabetic retinopathy via its anti-inflammatory and anti-angiogenic properties. Additionally, in vitro and in vivo studies suggest vitamin D favorably influences blood pressure and blood glucose control, strong risk factors for diabetic retinopathy. We examined the association between vitamin D status and prevalent diabetic retinopathy in participants with diabetes from a population-based cohort. METHODS: Among participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes at visit 3 (1993-1995), 1339 (906 Caucasians, 433 African Americans) had serum 25-hydroxyvitamin (25[OH]D) concentrations assessed at visit 2 (1989-1992) and nonmydriatic retinal photographs taken at visit 3. Dietary intake of vitamin D was assessed at visit 1 (1987-1989). Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for diabetic retinopathy by categories of season-adjusted 25(OH)D (<30 [referent], 30-<50, 50-<75 and ≥75 nmol/L), by quartile of vitamin D intake (IU/day), and use of vitamin D or fish oil supplements (yes/no). P for trend was estimated using continuous 25(OH)D or vitamin D intake. ORs were adjusted for race, and duration of diabetes. We further adjusted for HBA1c and hypertension to examine if 25(OH)D influenced diabetic retinopathy via its effects on either glycemic control or blood pressure. RESULTS: ORs (95 % CIs) for retinopathy, adjusted for race and duration, were 0.77 (0.45-1.32), 0.64 (0.37-1.10), and 0.39 (0.20-0.75), p for trend = 0.001, for participants with 25(OH)D of 30-<50, 50-<75, and ≥75 nmol/L, respectively. Further adjustment for hypertension minimally influenced results (data not show), but adjustment for HBA1c attenuated the OR among those with 25(OH)D ≥75 (0.47 [0.23-0.96], p for trend = 0.030). No statistically significant association was observed between vitamin D intake from foods or supplements and retinopathy. CONCLUSIONS: 25(OH)D concentrations ≥75 nmol/L were associated with lower odds of any retinopathy assessed 3 years later. We speculate this may be due in part to vitamin D's influence on blood glucose control.

TNF Receptors Predict Hip Fracture Risk in the WHI Study and Fatty Acid Intake Does Not Modify This Association.

CONTEXT: Chronic inflammation may increase the risk of fracture, and omega-3 polyunsaturated fatty acids (PUFAs) may reduce fracture risk via down-regulation of inflammatory cytokine gene expression and other mechanisms. OBJECTIVE: We investigated associations between baseline samples of inflammatory markers, TNFα soluble receptors 1 and 2 (TNFα-sR1 and -sR2), and incident hip fracture. These associations were then tested for effect modification by dietary PUFA intake estimated by a baseline food frequency questionnaire. DESIGN AND SETTING: A nested case-control study was conducted among participants of the Women's Health Initiative Observational Study (ages, 50-79 y). Multivariable conditional logistic regression models were constructed to account for the paired design. PARTICIPANTS: This study sampled 400 pairs of hip fracture cases and controls without incident hip fracture, matched on age, year of enrollment, and menopausal hormone use. MAIN OUTCOME MEASURES: Odds ratio of hip fracture by quartile of TNF soluble receptors. RESULTS: The odds ratio of hip fracture comparing the highest to lowest quartiles was 2.24 (95% confidence interval, 1.05-4.79; P for linear trend, .048) for TNFα-sR1 and 2.83 (95% confidence interval, 1.34-5.99; P for linear trend, .011) for TNFα-sR2, adjusted for FRAX hip fracture score, nutritional variables, and selected factors impacting inflammation; there was a gradient of risk by increasing quartile in TNFα-sR1. PUFA intake did not modify these associations. CONCLUSIONS: Women with the highest levels of TNFα-sR1 and TNFα-sR2 had a greater than 2-fold increased hip fracture risk, independent of other fracture risk factors. These associations did not differ by high vs low PUFA intake.

Associations between smoking and tooth loss according to the reason for tooth loss: the Buffalo OsteoPerio Study.

BACKGROUND: Smoking is associated with tooth loss. However, smoking's relationship to the specific reason for tooth loss in postmenopausal women is unknown. METHODS: Postmenopausal women (n = 1,106) who joined a Women's Health Initiative ancillary study (The Buffalo OsteoPerio Study) underwent oral examinations for assessment of the number of missing teeth, and they reported the reasons for tooth loss. The authors obtained information about smoking status via a self-administered questionnaire. The authors calculated odds ratios (ORs) and 95 percent confidence intervals (CIs) by means of logistic regression to assess smoking's association with overall tooth loss, as well as with tooth loss due to periodontal disease (PD) and with tooth loss due to caries. RESULTS: After adjusting for age, education, income, body mass index, history of diabetes diagnosis, calcium supplement use and dental visit frequency, the authors found that heavy smokers (≥ 26 pack-years) were significantly more likely to report having experienced tooth loss compared with never smokers (OR = 1.82; 95 percent CI, 1.10-3.00). Smoking status, packs smoked per day, years of smoking, pack-years and years since quitting smoking were significantly associated with tooth loss due to PD. For pack-years, the association for heavy smokers compared with that for never smokers was OR = 6.83 (95 percent CI, 3.40 -13.72). The study results showed no significant associations between smoking and tooth loss due to caries. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Smoking may be a major factor in tooth loss due to PD. However, smoking appears to be a less important factor in tooth loss due to caries. Further study is needed to explore the etiologies by which smoking is associated with different types of tooth loss. Dentists should counsel their patients about the impact of smoking on oral health, including the risk of experiencing tooth loss due to PD.

Intraindividual variation in plasma 25-hydroxyvitamin D measures 5 years apart among postmenopausal women.

BACKGROUND: Current literature examining associations between vitamin D and chronic disease generally use a single assessment of 25-hydroxyvitamin D [25(OH)D], assuming the 25(OH)D concentration of an individual is consistent over time. METHODS: We investigated the intraindividual variability between two measures of plasma 25(OH)D concentrations collected approximately five years apart (1997-2000 to 2002-2005) in 672 postmenopausal women participating in the Women's Health Initiative. Plasma 25(OH)D was assessed using the DiaSorin LIAISON® chemiluminescence immunoassay. The within-pair coefficient of variation (CV) was 4.9% using blinded quality control samples. Mean and SDs of 25(OH)D at the two time points were compared using a paired t test. An intraindividual CV and intraclass correlation coefficient (ICC) were used to assess intraindividual variability. A Spearman correlation coefficient (r) assessed the strength of the association between the two measures, and concordance in vitamin D status at two time points was compared. RESULTS: Mean 25(OH)D concentrations (nmol/L) significantly increased over time from 60.0 (SD = 22.2) to 67.8 (SD = 22.2; P < 0.05). The CV was 24.6%, the ICC [95% confidence interval (CI)] was 0.59 (0.54-0.64), and the Spearman r was 0.61 (95% CI = 0.56-0.66). Greater concordance over five years was observed in participants with sufficient compared with deficient or inadequate baseline 25(OH)D concentrations (weighted kappa = 0.39). Reliability measures were moderately influenced by season of blood draw and vitamin D supplement use. CONCLUSION: There is moderate intraindividual variation in 25(OH)D concentrations over approximately five years. IMPACT: These data support the use of a one-time measure of blood 25(OH)D in prospective studies with ≤ five years of follow-up.