RDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases. The biologic mechanisms underlying this association merit investigation.

Background In contrast to many observational studies, women in the Women’s Health Initiative (WHI) trial randomised to oestrogen-alone had lower invasive breast cancer incidence than those assigned placebo. Influence of oestrogen use on breast cancer mortality has not been reported. Methods Between 1993 and 1998, the WHI enrolled 10,739 postmenopausal women from 40 US centres into a randomized, double-masked, placebo-controlled trial evaluating oral conjugated equine oestrogen (0·625 mg/d). Women aged 50–79 years with prior hysterectomy, anticipated 3-year survival, and mammography clearance were randomized by a computerized, permuted block algorithm, stratified by age group and centre, to receive oestrogen or matching placebo. The trial was terminated early, in 2004, for an adverse effect on stroke. In extended follow-up through August 2009, we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumor characteristics, and mortality. Cox regression models were used to estimate intention-to-treat hazard ratios [HRs]. Findings After a median 11.8 (interquartile range [IQR], 9·1 to 12·9) years of follow-up, conjugated equine oestrogen-alone use for a median of 5·9 (IQR, 2·5 to 7·3) years was associated with lower invasive breast cancer incidence compared to placebo (151 vs. 199 breast cancers; annualized rates, 0·27% vs. 0·35%; HR, 0·77; 95% confidence interval [CI], 0·62 to 0·95; P=0·02) with no difference (P=0·76) between intervention-phase (HR, 0·79; 95% CI, 0·61 to 1·02) and post-intervention effects (HR, 0·75; 95% CI: 0·51 to 1·09) ). Potential effect modification by benign breast disease (P=0·01) and family history of breast cancer (P=0·02) was observed. In the oestrogen-alone group fewer women died from breast cancer (6 vs.16 deaths; annualized rates 0·009% vs. 0·024%; HR, 0·37; 95% CI, 0·13 to 0·91; P=0.03) and fewer died from all causes after a breast cancer diagnosis (30 vs. 50 deaths; annualized rates, 0·046% vs. 0·076%; HR, 0·62; 95% CI, 0·39 to 0·9;, P=0·04). Interpretation Women with hysterectomy seeking relief of climacteric symptoms may be given reassurance regarding breast cancer influence of oestrogen use consistent with durations observed in this trial. However, these findings do not support oestrogen use for breast cancer risk reduction since this benefit may not apply to populations at higher risk. Funding US National Heart, Lung and Blood Institute. Wyeth provided study medications.

Calcium plus vitamin D3 supplementation did not reduce the risk of developing diabetes over 7 years of follow-up in this randomized placebo-controlled trial. Higher doses of vitamin D may be required to affect diabetes risk, and/or associations of calcium and vitamin D intake with improved glucose metabolism observed in nonrandomized studies may be the result of confounding or of other components of foods containing these nutrients.

Abstract-Experimental and epidemiological studies suggest that calcium and vitamin D supplements may lower blood pressure. We examined the effect of calcium plus vitamin D supplementation on blood pressure and the incidence of hypertension in postmenopausal women. The Women's Health Initiative Calcium/Vitamin D Trial randomly assigned 36 282 postmenopausal women to receive 1000 mg of elemental calcium plus 400 IU of vitamin D3 daily or placebo in a double-blind fashion. Change in blood pressure and the incidence of hypertension were ascertained. Over a median follow-up time of 7 years, there was no significant difference in the mean change over time in systolic blood pressure (0.22 mm Hg; 95% CI: Ϫ0.05 to 0.49 mm Hg) and diastolic blood pressure (0.11 mm Hg; 95% CI: Ϫ0.04 to 0.27 mm Hg) between the active and placebo treatment groups. This null result was robust in analyses accounting for nonadherence to study pills and in baseline subgroups of interest, including black subjects and women with hypertension or high levels of blood pressure, with low intakes of calcium and vitamin D or low serum levels of vitamin D. In 17 122 nonhypertensive participants at baseline, the hazard ratio for incident hypertension associated with calcium/vitamin D treatment was 1.01 (95% CI T he role of calcium in the prevention and treatment of hypertension is controversial, despite decades of study. An overall healthy dietary pattern that is rich in calcium from low-fat dairy products, fruits, and vegetables has been shown to lower blood pressure substantially compared with a typical diet higher in fat and sodium and lower in calcium, magnesium, potassium, and fiber. 1-4 However, meta-analyses [5][6][7][8][9][10][11][12] and systematic reviews 13 of the epidemiological and clinical trial evidence regarding dietary intake of calcium as a single nutrient have generally concluded that the effect on systolic blood pressure (BP) lowering is small, on the order of 2 mm Hg. The effect on diastolic BP, if any, may be even smaller. Nevertheless, at a population level, sustained BP lowering of this degree by calcium supplementation could have important benefits on cardiovascular disease.:Although the relation between vitamin D and BP has been less studied, 2 small, short-term intervention studies suggest that vitamin D, either as ultraviolet light exposure or as an oral supplement, may lower BP. 14,15 In addition, the risk of incident hypertension was lower in a 4-year prospective study among men and women with higher plasma levels of 25(OH) vitamin D. 16 Animal studies have also shown that oral supplementation with vitamin D lowered BP in hypertensive rats; in this model vitamin D inhibited renin expression in the juxtaglomerular apparatus and inhibited smooth muscle proliferation. [17][18][19][20]