Thomas G Travison1, Christopher J O'Donnell1, Shalender Bhasin1, Joseph M Massaro1, Udo Hoffmann1, Ramachandran S Vasan1, Ralph B D'Agostino1, Shehzad Basaria1. 1. Hebrew SeniorLife Institute for Aging Research (T.G.T.), Roslindale, Massachusetts 02131; Research Program on Men's Health, Aging and Metabolism (T.G.T., S.Bh., S.Ba.), Brigham and Women's Hospital, Boston, Massachusetts 02115; Harvard Medical School (T.G.T., C.J.O., S.Bh., U.H., S.Ba.), Boston, Massachusetts 02115; National Heart, Lung and Blood Institute's Framingham Heart Study (C.J.O., J.M.M., R.S.V., R.B.D.), Framingham, Massachusetts 01702; Cardiology Division (C.J.O.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Department of Biostatistics (J.M.M.), Boston University School of Public Health, Boston, Massachusetts 02118; Department of Radiology (U.H.), Massachusetts General Hospital, Boston, Massachusetts 02114; Section of Preventive Medicine and Epidemiology (R.S.V.), Boston University School of Medicine, Boston, Massachusetts 02118; and Department of Mathematics (R.B.D.), Boston University, Boston, Massachusetts 02215.
Abstract
CONTEXT: The relationship between sex steroids and atherosclerosis is poorly understood. OBJECTIVE: To describe the association of serum total T (TT), calculated free T (cFT), estrone (E1), estradiol (E2), and SHBG to vascular calcification in adult men. DESIGN: Observational study (Framingham Heart Study). Analyses are cross-sectional. TT, E1, and E2 were measured by liquid chromatography-tandem mass spectrometry, and SHBG by immunofluorometric assay. Estimates of association were obtained by Tobit regression, which acknowledges the influence of floor effects on outcomes. SETTING: General community. PARTICIPANTS: A total of 1654 community-dwelling men from the Offspring and Third Generation cohorts of the Framingham Heart Study. MAIN OUTCOME MEASURES: Coronary artery calcification (CAC), abdominal aortic calcification, and thoracic aortic calcification were measured by computed tomography. RESULTS: Mean (standard deviation [SD]) age was 49 (10) years. Mean (SD) TT, cFT, and SHBG were: 616 (224) ng/dL, 111 (45) pg/mL, and 46 (23) nmol/L, respectively. Mean (SD) E2 and E1 were 28 (10) and 39 (14) pg/mL. Vascular calcification at all sites was negatively associated with TT and cFT and positively associated with E2 and E1. A 100-ng/dL between-subjects increase in TT was associated with a mean (95% confidence interval) age-adjusted difference in CAC of -23% (-41%, -4%) (P = .02). After model adjustment for other cardiovascular risk factors, the estimated associations between T and vascular calcification scores were statistically nonsignificant. CONCLUSIONS: Decreased circulating T and E2 levels are associated with an age-adjusted increase in CAC, but these associations appear to express relationships either attributable to or mediated by established cardiovascular risk factors.
CONTEXT: The relationship between sex steroids and atherosclerosis is poorly understood. OBJECTIVE: To describe the association of serum total T (TT), calculated free T (cFT), estrone (E1), estradiol (E2), and SHBG to vascular calcification in adult men. DESIGN: Observational study (Framingham Heart Study). Analyses are cross-sectional. TT, E1, and E2 were measured by liquid chromatography-tandem mass spectrometry, and SHBG by immunofluorometric assay. Estimates of association were obtained by Tobit regression, which acknowledges the influence of floor effects on outcomes. SETTING: General community. PARTICIPANTS: A total of 1654 community-dwelling men from the Offspring and Third Generation cohorts of the Framingham Heart Study. MAIN OUTCOME MEASURES: Coronary artery calcification (CAC), abdominal aortic calcification, and thoracic aortic calcification were measured by computed tomography. RESULTS: Mean (standard deviation [SD]) age was 49 (10) years. Mean (SD) TT, cFT, and SHBG were: 616 (224) ng/dL, 111 (45) pg/mL, and 46 (23) nmol/L, respectively. Mean (SD) E2 and E1 were 28 (10) and 39 (14) pg/mL. Vascular calcification at all sites was negatively associated with TT and cFT and positively associated with E2 and E1. A 100-ng/dL between-subjects increase in TT was associated with a mean (95% confidence interval) age-adjusted difference in CAC of -23% (-41%, -4%) (P = .02). After model adjustment for other cardiovascular risk factors, the estimated associations between T and vascular calcification scores were statistically nonsignificant. CONCLUSIONS: Decreased circulating T and E2 levels are associated with an age-adjusted increase in CAC, but these associations appear to express relationships either attributable to or mediated by established cardiovascular risk factors.
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