Association of serum IGF1 with endothelial function: results from the population-based study of health in Pomerania.
ABSTRACT IGF1 mediates multiple physiological and pathophysiological responses in the cardiovascular system. The aim of this study was to analyze the association between serum IGF1 as well as IGF-binding protein 3 (IGFBP3) levels and endothelial function measured by flow-mediated dilation (FMD).
Cross-sectional population-based observational study.
The study population comprised 1482 subjects (736 women) aged 25-85 years from the Study of Health in Pomerania. Serum IGF1 and IGFBP3 levels were determined by chemiluminescence immunoassays. FMD measurements were performed using standardized ultrasound techniques. FMD values below the sex-specific median were considered low.
In males, logistic regression analyses revealed an odds ratio (OR) of 1.27 (95% confidence interval (CI) 1.07-1.51; P=0.008) for decreased FMD for each decrement of IGF1 s.d. after adjustment for major cardiovascular confounders. In females, no significant relationship between serum IGF1 and FMD was found (OR 0.88, CI 0.74-1.05; P=0.147). After exclusion of subjects with the current use of antihypertensive medication, these findings were similar (males: OR 1.40, CI 1.12-1.75; P=0.003; females: OR 0.95, CI 0.77-1.16; P=0.595). There was no association between serum IGFBP3 levels and FMD in both sexes.
Low serum IGF1 levels are associated with impaired endothelial function in males. In women, serum IGF1 is not associated with endothelial function.
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ABSTRACT: Context: Measurement of IGF-1 is a cornerstone in diagnosis and monitoring of GH-related diseases, but considerable discrepancies exist between analytical methods. A recent consensus conference defined criteria for validation of IGF-1 assays and for establishment of normative data. Objectives: Our objectives were development and validation of a novel automated IGF-1 immunoassay (iSYS; Immunodiagnostic Systems) according to international guidelines and establishment of method-specific age- and sex-adjusted reference intervals and analysis of their robustness. Setting and Participants: We conducted a multicenter study with samples from 12 cohorts from the United States, Canada, and Europe including 15ü014 subjects (6697 males and 8317 females, 0-94 years of age). Main Outcome Measures: We measured concentrations of IGF-1 as determined by the IDS iSYS IGF-1 assay. Results: A new IGF-1 assay calibrated against the recommended standard (02/254) and insensitive to the 6 high-affinity IGF binding proteins was developed and rigorously validated. Age- and sex-adjusted reference intervals derived from a uniquely large cohort reflect the age-related pattern of IGF-1 secretion: a decline immediately after birth followed by an increase until a pubertal peak (at 15 years of age). Later in life, values decrease continuously. The impact of gender is small, although across the lifespan, women have lower mean IGF-1 concentrations. Geographical region, sampling setting (community or hospital based), and rigor of exclusion criteria in our large cohort did not affect the reference intervals. Conclusions: Using large cohorts of well-characterized subjects from different centers allowed construction of robust reference ranges for a new automated IGF-1 assay. The strict adherence to recent consensus criteria for IGF-1 assays might facilitate clinical application of the results.The Journal of Clinical Endocrinology and Metabolism 02/2014; 99(5):jc20133059. DOI:10.1210/jc.2013-3059 · 6.31 Impact Factor
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ABSTRACT: Accumulating evidence now indicates that insulin-like growth factors (IGF) and their regulatory proteins are growth promoters for arterial cells and mediators of cardiovascular diseases. We hypothetised that IGF-1 levels could play a role in the development of stent thrombosis (ST), and aimed to investigate the associations between stent thrombosis under effective dual antiplatelet therapy and IGF-1 levels and other related factors such as disease severity and LV ejection fraction in patients undergoing coronary stent placement. A total of 128 patients undergoing coronary stent implantation were included in the analysis. Seventy-seven patients experiencing ST in the first year after stent implantation were defined as the ST group. Fifty-one patients without ST at least 1 year after stent implantation were defined as the no-thrombosis (NT) group. The IGF-1 levels, Gensini scores, and other related factors were measured. The IGF-1 levels were significantly higher in the stent thrombosis group than in the no-thrombosis group (122.22 ±50.61 ng/ml vs. 99.52 ±46.81 ng/ml, respectively, p < 0.039). The left ventricle ejection fraction (LVEF) values were significantly lower (44.13 ±9.25% vs. 55.81 ±8.77%, p < 0.0001) and Gensini scores were significantly higher (63.74 ±26.54 vs. 48.87 ±23.7, p < 0.004) in the ST group than in the NT group, respectively. In the linear regression analysis, IGF-1, Gensini score, LVEF, total cholesterol, and triglycerides were found to be independent risk factors for ST. This study revealed that the plasma IGF-1 levels, disease severity, were significantly higher and LVEF was lower in patients with ST. High IGF-1 levels may identify patients who are at increased risk for ST. Future trials are necessary to confirm these results.Postepy w Kardiologii Interwencyjnej / Advances in Interventional Cardiology 12/2014; 10(4):242-249. DOI:10.5114/pwki.2014.46765 · 0.07 Impact Factor
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ABSTRACT: Context: Measurement of IGFBP-3 can aid the diagnosis of growth hormone related diseases. Furthermore, epidemiological studies suggest that IGFBP-3 and the molar IGF-I/IGFBP-3 ratio are associated with clinical endpoints like cancer or cardiovascular disease. However, their clinical use is limited by the lack of validated reference intervals. Objectives: Establishment of age- and sex-specific reference intervals for IGFBP-3 and the molar IGF-I/IGFBP-3 ratio by newly developed automated immunoassays. Setting: Multicentre study with samples from 11 cohorts from the USA, Canada and Europe Participants: 14,970 subjects healthy subjects covering all ages from birth to senescence. Main outcome measures: Concentrations of IGFBP-3 and the IGF-I/IGFBP-3 ratio as determined by the IDS iSYS IGF-I and IGFBP-3 assays. Results: Both the concentration of IGFBP-3 and the IGF-I/IGFBP-3 ratio are mainly determined by age. IGFBP-3 concentrations increase until the age of 22 years, with a plateau being visible between 15 and 25 years. Determined by the high peripubertal peak in IGF-I, the peak in the IGF-I/IGFBP-3 ratio occurs already around the age of 15, with a slightly earlier and higher peak in females. Beyond the age of 60, IGFBP-3 concentrations remain higher in females, whereas IGF-I as well as the IGF-I/IGFBP-3 ratio remain significantly higher in males. Conclusions: We present an extensive set of assay specific, age and sex-adjusted normative data for concentrations of IGFBP-3 and the molar IGF-I/IGFBP-3 ratio and demonstrate distinct sex specific differences across lifespan.The Journal of Clinical Endocrinology and Metabolism 01/2014; 99(5):jc20133060. DOI:10.1210/jc.2013-3060 · 6.31 Impact Factor