Associations of IGF1 and IGFBPs 1 and 3 with all-cause and cardiovascular mortality in older men: the Health In Men Study

Abstract

Objective: Circulating IGF1 declines with age while ill-health increases. Controversy remains whether differences in the levels of IGF1 and its binding proteins 1 and 3 (IGFBP1 and IGFBP3) determine health outcomes during ageing. We examined associations of IGF1, IGFBP1 and IGFBP3 with all-cause and cardiovascular mortality in older men. Design: We conducted a prospective cohort study of community-dwelling men aged R70 years. Methods: Plasma collected at baseline (2001)(2002)(2003)(2004) was assayed for total IGF1, IGFBP1 and IGFBP3. Incidence and causes of death from time of recruitment to 31 December 2008 were ascertained using the Western Australian Data Linkage System. Cox regression analyses were performed, adjusting for conventional cardiovascular risk factors. Results: Among 3983 men followed for 5.2 years (median), 694 deaths occurred, 243 from cardiovascular disease (CVD). There was no difference in survival according to quintiles of IGF1. Increased IGFBP1 predicted increased all-cause mortality (highest versus lowest quintile: adjusted hazard ratio (HR)Z1.98, 95% confidence interval (CI)Z1.52-2.57, P!0.001 for trend) and increased cardiovascular mortality (HRZ3.42 (2.03-5.77), P!0.001 for trend). Decreased IGFBP3 predicted increased all-cause mortality (lowest versus highest quintile: HRZ1.57, 95% CIZ1.23-2.01, PZ0.007 for trend). Associations of IGFBP1 and IGFBP3 with all-cause mortality were not attenuated by adjustment for IGF1 levels. Conclusions: In older men, higher IGFBP1 and lower IGFBP3 levels predict overall and CVD-related mortality, while IGF1 levels are not associated with mortality. Further studies are needed to clarify the underlying mechanisms by which IGFBP1 and IGFBP3 levels are associated with mortality risk, and whether this occurs independently of IGF1.

ω-3 fatty acid differentially modulated serum levels of IGF1 and IGFBP3 in men with CVD: A randomized, double-blind placebo-controlled study

“…At the baseline our findings confirmed previous investigation by revealing a low serum IGF1 in CVD patients[1][2][3][11][12][13]. The present study indicated increasing effect of IGF1 and lowering impact of this supplement on IGFBP3 in CVD patients.…”

Increased IGF1 levels in relation to heart failure and cardiovascular mortality in an elderly population: impact of ACE inhibitors

“…In the study by Bunderen et al (4) mentioned above, an increased risk for allcause mortality was found for elderly subjects with the lowest IGF1 levels in the 1st quintile compared with the 3rd quintile. Other studies have failed to show an association between IGF1 levels and all-cause mortality (9,(30)(31)(32). These conflicting results could be explained by differences in population age (O17 years in Saydah et al (32), 51-89 years in Laughlin et al (9) and O65 in Kaplan et al (28), race, and unrecognized differences in lifestyle factors that modulate IGF levels.…”

“…Low IGF1 levels were associated with increased risk for fatal IHD among elderly subjects regardless of prevalent IHD and CVD risk factors (9). A recent population study in Australia, conducted on elderly men, failed to find a difference in CV mortality based on IGF1 levels according to quintiles (30).…”

Associations of IGF1 and its binding proteins with abdominal aortic aneurysm and aortic diameter in older men

“…Reduced IGFBP1 level has been associated with thickening of the carotid wall in patients with type 2 diabetes (31), and with metabolic syndrome in older men (17). Paradoxically, older adults with higher IGFBP1 levels experience increased all-cause and cardiovascular mortality despite the association of higher IGFBP1 with more favourable metabolic status (32,33,34). The association of higher IGFBP1 with aortic diameter is consistent with this counterintuitive concept and IGFBP1 may act independently of IGF1 on a cellular level to influence the vasculature (35).…”