Daniel Carlzon1, Johan Svensson, Max Petzold, Magnus K Karlsson, Östen Ljunggren, Åsa Tivesten, Dan Mellström, Claes Ohlsson. 1. Center for Bone and Arthritis Research (D.C., J.S., D.M., C.O.), Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Center for Applied Biostatistics (M.P.), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical and Molecular Osteoporosis Research Unit (M.K.K.), Department of Orthopaedics and Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden; Department of Medical Sciences (Ö.L.), University of Uppsala, Uppsala, Sweden; and Wallenberg Laboratory for Cardiovascular Research (Å.T.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Abstract
CONTEXT: Most previous prospective studies suggest that low serum IGF-1 associates with increased risk of cardiovascular disease (CVD) events whereas other studies suggest that high serum IGF-1 associates with increased risk of CVD events. OBJECTIVE: We tested the hypothesis that not only low, but also high serum IGF-1 levels associate with increased risk of CVD events in elderly men. SETTING AND DESIGN: Serum IGF-1 levels were measured in 2901 elderly men (age 69-81 years) included in the Swedish cohort of the prospective, population-based Osteoporotic Fractures in Men Study (MrOS), Sweden cohort. Data for CVD events were obtained from national Swedish registers with no loss of followup. RESULTS: During followup (median, 5.1 y) 589 participants experienced a CVD event. The association between serum IGF-1 and risk of CVD events was nonlinear, and restricted cubic spline Cox regression analysis revealed a U-shaped association between serum IGF-1 levels and CVD events (P < .01 for nonlinearity). Low as well as high serum IGF-1 (quintile 1 or 5 vs quintiles 2-4) significantly associated with increased risk for CVD events (hazard ratio [HR] = 1.25, 95% confidence interval, [CI], 1.02-1.54; and HR = 1.35, 95% CI 1.10-1.66, respectively). These associations remained after adjustment for prevalent CVD and multiple risk factors. High serum IGF-1 associated with increased risk of coronary heart disease (CHD) events but not with risk of cerebrovascular events. CONCLUSIONS: Both low and high serum IGF-1 levels are risk markers for CVD events in elderly men. The association between high serum IGF-1 and CVD events is mainly driven by CHD events.
CONTEXT: Most previous prospective studies suggest that low serum IGF-1 associates with increased risk of cardiovascular disease (CVD) events whereas other studies suggest that high serum IGF-1 associates with increased risk of CVD events. OBJECTIVE: We tested the hypothesis that not only low, but also high serum IGF-1 levels associate with increased risk of CVD events in elderly men. SETTING AND DESIGN: Serum IGF-1 levels were measured in 2901 elderly men (age 69-81 years) included in the Swedish cohort of the prospective, population-based Osteoporotic Fractures in Men Study (MrOS), Sweden cohort. Data for CVD events were obtained from national Swedish registers with no loss of followup. RESULTS: During followup (median, 5.1 y) 589 participants experienced a CVD event. The association between serum IGF-1 and risk of CVD events was nonlinear, and restricted cubic spline Cox regression analysis revealed a U-shaped association between serum IGF-1 levels and CVD events (P < .01 for nonlinearity). Low as well as high serum IGF-1 (quintile 1 or 5 vs quintiles 2-4) significantly associated with increased risk for CVD events (hazard ratio [HR] = 1.25, 95% confidence interval, [CI], 1.02-1.54; and HR = 1.35, 95% CI 1.10-1.66, respectively). These associations remained after adjustment for prevalent CVD and multiple risk factors. High serum IGF-1 associated with increased risk of coronary heart disease (CHD) events but not with risk of cerebrovascular events. CONCLUSIONS: Both low and high serum IGF-1 levels are risk markers for CVD events in elderly men. The association between high serum IGF-1 and CVD events is mainly driven by CHD events.
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