Wallenberg Laboratory for Cardiovascular Research (A.T.) and Center for Bone Research (C.O., L.V., D.M.), Institute of Medicine, University of Gothenburg, S-413 45 Gothenburg, Sweden; Laboratory of Molecular Endocrinology and Oncology (F.L.), Laval University, Québec, Canada G1K 7P4; Department of Family and Preventive Medicine (E.B.-C.), School of Medicine, University of California, San Diego, La Jolla, California 92093; Department of Clinical Sciences (M.K.K.), Lund University, SE-205 02 Malmö, Sweden; and Department of Medical Sciences (O.L.), University of Uppsala, SE-751 05 Uppsala, Sweden.
Context: The age-related decline in dehydroepiandrosterone (DHEA) levels is thought to be of importance for general and vascular aging. However, data on the association between DHEA and mortality are conflicting. Objectives: We tested the hypothesis that low serum DHEA and DHEA sulfate (DHEA-S) levels predict all-cause and cardiovascular disease (CVD) death in elderly men. Design, Setting, and Participants: We used gas/liquid chromatography-mass spectrometry to analyze baseline levels of DHEA and DHEA-S in the prospective population-based MrOS Sweden study (2644 men, aged 69-81 yr). Mortality data were obtained from central registers and analyzed using Cox proportional hazards regressions. Main Outcome Measures: All-cause and CVD mortality by serum DHEA(-S) levels. Results: During a mean 4.5-yr follow-up, 328 deaths occurred. Low levels of DHEA-S (quartile 1 vs. quartiles 2-4), predicted death from all causes [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.21-1.96; adjusted for traditional cardiovascular risk factors], from CVD (n = 123 deaths; HR 1.61, 95% CI 1.10-2.37) and ischemic heart disease (n = 73; HR 1.67, 95% CI 1.02-2.74) but not cancer. Analyses with DHEA gave similar results. The association between low DHEA-S and CVD death remained after adjustment for C-reactive protein and circulating estradiol and testosterone levels. When stratified by the median age of 75.4 yr, the mortality prediction by low DHEA-S was more pronounced among younger (age adjusted HR for CVD death 2.64, 95% CI 1.37-5.09) than older men (HR 1.30, 95% CI 0.83-2.04). Conclusions: Low serum levels of DHEA(-S) predict death from all causes, CVD, and ischemic heart disease in older men.