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.

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.

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.

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.

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.