Risk of Mortality According to Body Mass Index and Body Composition Among Postmenopausal Women.

Obesity, often defined as a body mass index (BMI; weight (kg)/height (m)(2)) of 30 or higher, has been associated with mortality, but age-related body composition changes can be masked by stable BMI. A subset of Women's Health Initiative participants (postmenopausal women aged 50-79 years) enrolled between 1993 and 1998 who had received dual-energy x-ray absorptiometry scans for estimation of total body fat (TBF) and lean body mass (LBM) (n = 10,525) were followed for 13.6 (standard deviation, 4.6) years to test associations between BMI, body composition, and incident mortality. Overall, BMI ≥35 was associated with increased mortality (adjusted hazard ratio (HR) = 1.45, 95% confidence interval (CI): 1.16, 1.82), while TBF and LBM were not. However, an interaction between age and body composition (P < 0.001) necessitated age stratification. Among women aged 50-59 years, higher %TBF increased risk of death (HR = 2.44, 95% CI: 1.38, 4.34) and higher %LBM decreased risk of death (HR = 0.41, 95% CI: 0.23, 0.74), despite broad-ranging BMIs (16.4-69.1). However, the relationships were reversed among women aged 70-79 years (P < 0.05). BMI did not adequately capture mortality risk in this sample of postmenopausal women. Our data suggest the clinical utility of evaluating body composition by age group to more robustly assess mortality risk among postmenopausal women.

Genetic Variant in ACVR2B Is Associated with Lean Mass.

INTRODUCTION: Low lean mass (LM) is a risk factor for chronic disease, a major cause of disability and diminished quality of life, and is a heritable trait. However, relatively few specific genetic factors have been identified as potentially influencing this trait. METHODS: In this study, we selected 1493 single-nucleotide polymorphisms (SNP) in 155 candidate genes involved in anabolic, catabolic, growth hormone, and other related pathways and examined their association with LM, assessed by dual-energy x-ray absorptiometry, in a sample of 2760 non-Hispanic and Hispanic white postmenopausal women from the Women's Health Initiative (WHI) Observational Study. We assessed the replication of our top findings in a meta-analysis of 20 genome-wide association studies (n = 38,292) conducted by the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium Musculoskeletal Working Group. RESULTS: We identified 32 SNPs that had nominally significant associations with LM in the WHI cohort. In the replication stage, we find that SNP rs2276541 in the activin A receptor, type IIB (ACVR2B), was significantly associated with LM (ß = 0.15, P = 2.17 × 10). ACVR2B codes for a receptor for a negative regulator of skeletal muscle, myostatin, and has previously been identified in a candidate gene study as a determinant of skeletal muscle mass. CONCLUSIONS: Our findings support a previously proposed role of ACVR2B allelic variation as a determinant of muscle mass and extend prior findings in men and women. Additional large-scale studies will be needed to confirm our findings in different populations.

The relationship between incidence of fractures and anemia in older multiethnic women.

OBJECTIVES: To prospectively examine the relationship between anemia and incident fractures of the hip, spine, and all skeletal sites in women from diverse racial and ethnic backgrounds enrolled in the Women's Health Initiative (WHI) Observational Study and Clinical Trials. DESIGN: Prospective cohort study. SETTING: Forty WHI clinical centers across the United States. PARTICIPANTS: Postmenopausal women (n=160,080), mean age 63.2±7.2, were recruited and followed for an average of 7.8 years. MEASUREMENTS: Anemia was defined as hemoglobin levels at baseline less than 12 g/dL. All fractures were self-reported. Trained physicians further confirmed hip fractures using medical records. RESULTS: Eight thousand seven hundred thirty-nine of the participants (5.5%) were anemic. The age-adjusted incidence rate of hip fractures per 10,000 person-years was 21.4 in women with anemia and 15.0 in women without anemia; higher incidence rates for spine and all fractures were also observed in anemic women. After multiple covariates were included in the Cox proportional hazards models, significantly greater fracture risk associated with anemia still existed, as demonstrated by hazard ratios of fractures associated with anemia of 1.38 (95% confidence interval (CI)=1.13-1.68) for hip, 1.30 (95% CI=1.09-1.55) for spine, and 1.07 (95% CI=1.01-1.14) for all types. No significant racial or ethnic difference was found in these relationships. CONCLUSION: A significantly greater fracture risk was observed in multiethnic postmenopausal women with anemia. Given the high prevalence of anemia in the elderly population, it is important to better understand the relationship and mechanisms linking anemia to fracture risk.