Participants in the Health, Aging, and Body Composition Study (Health ABC Study) were aged between 69 and 79 years at the baseline visit and were recruited between April 1997 and June 1998 from a random sample of Medicare beneficiaries from Pittsburgh (PA, USA) and Memphis (TN, USA). To be eligible, participants had to report no difficulty in walking 400 m, climbing ten steps or performing basic activities of daily living. Individuals requiring assistive ambulatory devices, those with life-threatening cancers and those planning to move were excluded. The study was approved by the institutional review boards of the University of California, San Francisco, the University of Pittsburgh and the University of Tennessee. All study participants provided informed consent.
Participants reported their racial group, age, sex, smoking history and comorbid conditions, including asthma/chronic obstructive pulmonary disease, cancer, chronic kidney disease, congestive heart failure, CVD, diabetes, hypertension and stroke/transient ischaemic attack. Hypertension was defined as the use of an antihypertensive medication or systolic BP >140 mmHg or diastolic BP >90 mmHg. Diabetes was defined by self-report, use of drugs to control diabetes, or fasting plasma glucose ≥6.9 mmol/l or 2 h post-challenge glucose ≥11.0 mmol/l. Body composition (both regional adiposity and lean mass) was measured by computed tomography using standardised protocols as previously reported .
Participants underwent venipuncture after an overnight fast. Total adiponectin levels were assayed in 2002–2003 from frozen serum specimens; adiponectin was measured in duplicate by RIA (Linco, St Charles, MO, USA) with an intra-assay coefficient of variation of 1.8–3.6%.
Mortality outcomes were assessed until 31 August 2005. Deaths were adjudicated by a central committee for immediate and underlying causes of death using established criteria, including review of death certificate, all recent hospital records, and interview with the next of kin. Cardiovascular mortality was defined as atherosclerotic cardiovascular disease (definite fatal myocardial infarction, or definite or possible fatal CHD), stroke, atherosclerotic disease other than coronary or cerebrovascular, and other CVD.
Associations of baseline covariates with total and CVD mortality were assessed using Cox models. We rescaled body composition measures by their standard deviations and assessed correlations among the body composition variables to identify and eliminate collinearity. We used multivariable Cox proportional hazards models to examine associations between adiponectin and total mortality and mortality from CVD. In nested sequences of models using only those with all covariates (n = 2,548), we adjusted for age, sex, race, site, smoking, hypertension, diabetes, CHD, LDL-cholesterol and estimated GFR. Then, we adjusted our models for body composition, including BMI, abdominal visceral fat, thigh intermuscular fat and thigh muscle area. Last, models were adjusted for HDL-cholesterol, insulin and triacylglycerol.
We checked whether sex, race, diabetes, CVD, smoking status, body composition, weight loss and use of medications may modify the association between adiponectin and mortality. Participants taking a medication known to increase adiponectin (insulin, thiazolidinedione, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, beta blockers, and/or statins) were compared with those not using any of these medications. We also evaluated adiponectin’s association with mortality per year and by tertile of follow-up time.
The proportional hazards assumption was verified by examining plots of Schoenfeld residuals vs transformed time and assessing interactions of the all predictors with log transformed time. We used SAS Version 9.1 (SAS Institute, Cary, NC, USA) and SPlus Version 6.1 (Insightful, Seattle, WA, USA).