Both Low and High Serum Insulin-like Growth Factor I Levels Associate with Increased Risk of Cardiovascular Events in Elderly Men

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 758-779-Cardiometabolic Risk & Vascular Biology
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-769
Daniel Carlzon*1, Johan Svensson2, Ã…sa Tivesten3, Max Petzold4, Osten Ljunggren5, Magnus Karlsson6, Dan Mellström7 and Claes Ohlsson8
1Sahlgrenska University Hospital, Göteborg, Sweden, 2Sahlgrenska Univerisity Hospital, Goteborg, Sweden, 3Sahlgrenska University Hospital, Gothenburg, Sweden, 4Göteborg University, 5Uppsala University Hospital, Uppsala, Sweden, 6Inst of Clinical Sciences, Malmö, Sweden, 7Sahlgrenska University Hospital, 8Sahlgrenska University Hospital, Gothenburg, Sweden
Background: Circulating insulin-like growth factor-I (IGF-I) is mainly liver-derived and declines with age. Since the prevalence of atherosclerosis increases with increasing age, one may speculate that decreasing serum IGF-I is involved in the development of atherosclerosis. Although most previous prospective studies suggest that low serum IGF-I is associated with increased risk of cardiovascular (CV) events, some studies suggest that high serum IGF-I is associated with increased risk of CV events. As previous publications have shown conflicting results we aimed to evaluate the association between serum IGF-I and risk of CV events in a well-powered prospectively followed cohort of community-dwelling elderly Swedish men. We tested the hypothesis that both low and high serum IGF-I associate with increased risk of CV events.

Methods:Serum IGF-I levels were measured in 2901 elderly men (age 69 to 81 years) included in the prospective population-based MrOS-Sweden. Data for CV events were obtained from central Swedish registers with no loss of follow-up. The statistical analyses included Cox proportional hazards regressions with or without a spline approach.

Results:During the follow-up (median 5.1 yrs) 589 of the participants experienced a CV event. The association between serum IGF-I and risk of CV events was non-linear, and restricted cubic spline Cox regression analysis revealed a U-shaped association between serum IGF-I levels and CV events (p<0.01 for non-linearity). Low as well as high serum IGF-I (quintile 1 or 5 vs. quintiles 2-4)  associated with significantly increased risk for CV 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 CV disease and multiple other CV risk factors.

In exploratory post hoc analyses, we examined whether IGF-I was associated with the risk of coronary heart disease (CHD, n=367 events) and/or cerebrovascular (n=273 events) events. High serum IGF-I was associated with increased risk of CHD events (quintile 5 vs. quintiles 2-4, HR = 1.64, 95% CI 1.28-2.10). In contrast, serum IGF-I was not significantly associated with the risk of cerebrovascular events.

Conclusion: Both low and high serum IGF-I levels are risk markers for CV events in elderly men. The association between high serum IGF-I and CV events is mainly driven by CHD events.

Nothing to Disclose: DC, JS, T, MP, OL, MK, DM, CO

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm