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

Abstract

Objective: Abdominal aortic aneurysm (AAA) is most prevalent in older men. GH secretion declines with age resulting in reduced IGF1 levels. IGF1 and its binding proteins (IGFBPs) are expressed in vasculature, and lower IGF1 levels have been associated with cardiovascular risk factors and disease. However, the relationship of the IGF1 system with aortic dilation and AAA is unclear. We tested the hypothesis that circulating IGF1 and IGFBPs are associated with AAA and aortic diameter in older men. Design: A cross-sectional analysis involving 3981 community-dwelling men aged 70-89 years was performed. Methods: Abdominal aortic diameter was measured by ultrasound. Plasma total IGF1, IGFBP1 and IGFBP3 were measured by immunoassays. Results: After adjustment for age, body mass index, waist:hip ratio, smoking, hypertension, dyslipidemia, diabetes, coronary heart disease and serum creatinine, a higher IGF1 level was associated with AAA (odds ratio (OR)/1 S.D. increase 1.18, 95% confidence interval (CI) 1.05-1.33, PZ0.006), as was the ratio of IGF1/IGFBP3 (ORZ1.22, 95% CI 1.10-1.35, P!0.001). Highest IGF1 concentrations compared with lowest quintile were significantly associated with AAA (quintile (Q) 5 vs Q1: ORZ1.80, 95% CI 1.20-2.70, PZ0.004) as were IGF1/IGFBP3 ratios (Q5 vs Q1: ORZ2.52, 95% CI 1.59-4.02, P!0.001). IGF1 and IGFBP1 were independently associated with aortic diameter (bZ0.200, 95% CI 0.043-0.357, PZ0.012 and bZ0.274, 95% CI 0.098-0.449, PZ0.002 respectively). Conclusions: In older men, higher IGF1 and an increased ratio of IGF1/IGFBP3 are associated with AAA, while IGFBP1 is independently associated with increased aortic diameter. Components of the IGF1 system may contribute to, or be a marker for, aortic dilation in ageing men.

Meta-analysis and meta-regression analysis of biomarkers for abdominal aortic aneurysm

“…Circulating levels of insulin‐like growth factor (IGF) 1 were raised in patients with AAA. Studies examining IGF‐1 levels within the aortic wall itself, however, yielded conflicting results.…”

“…A total of 106 studies evaluating the levels of proteases, inflammatory markers, acute‐phase reactants and lipids formed the basis for this study ( Fig. ; Table S1, supporting information).…”

A Pilot Study of Protein Microarray for Simultaneous Analysis of 274 Cytokines Between Abdominal Aortic Aneurysm and Normal Aorta

“…The growth factors ferritin, GDF-15, EGF, BMP-4, IGFBP-6, and PDGF-AA have not been studied in AAAs before. Ramos-Mozo et al 38 reported that serum IGFBP-1 in patients with an AAA is significantly higher than in control patients, and Yeap et al 39 determined that IGFBP-1 is independently associated with increased aortic diameter, which makes IGFBP-1 a potential novel AAA biomarker.…”

Identification of the miRNA-target gene regulatory network in intracranial aneurysm based on microarray expression data

“…TSC1 also has a role in arterial remodeling events by affecting the inflammatory and the growth-promoting response of angiotensin II (43). Insulin-like growth factor 1 (IGF1) expression has been indicated in the vasculature and lower IGF1 expression levels increased the risk of cardiovascular and abdominal aortic aneurysm in a previous study (44). Histological analysis in a swine aneurysm model has demonstrated that IGF1 is upregulated (4-fold) in thrombus organization (45).…”