Increased serum angiopoietin-2 is associated with abdominal aortic aneurysm prevalence and cardiovascular mortality in older men
Vascular Biology Unit, School of Medicine and Dentistry, James Cook University, Townsville, Australia.International journal of cardiology (Impact Factor: 4.04). 04/2012; 167(4). DOI: 10.1016/j.ijcard.2012.03.120
BACKGROUND: Angiopoietin-2 (Angpt2) has been implicated in the mediation and regulation of angiogenesis and inflammation which are believed to be critical mechanisms in the pathogenesis of both abdominal aortic aneurysm (AAA) and cardiovascular events. The aim of this study was to assess whether serum Angpt2 was associated with the prevalence of AAA and the occurrence of cardiovascular mortality in older men. METHODS: A cohort of 997 elderly men was recruited in 1996-99. Aortic ultrasound identified an AAA in 308 (31%). In 2001-04, blood was collected and serum Angpt2 later measured by immunoassay. The association of Angpt2 with AAA was assessed using multiple regression analysis. All men were followed by means of the Western Australia Data Linkage System until July 31st 2009. The association of Angpt2 with cardiovascular mortality was assessed using Cox proportional hazard analysis. RESULTS: Median serum Angpt2 was significantly higher (3.16ng/ml, inter-quartile range 2.51-4.54) in men with AAA compared with men without AAA (2.70ng/ml, inter-quartile range 2.03-3.72; p<0.001). After adjusting for cardiovascular risk factors, men with serum Angpt2 in the highest quartile (>3.95ng/ml) had a 2.57-fold (95% CI 1.66-3.97, p<0.001) increased odds of AAA and a 4.12-fold (95% CI 1.90-8.94, p<0.001) increased relative risk of cardiovascular mortality compared to men with serum Angpt2 in the lowest quartile (<2.13ng/ml). CONCLUSIONS: Serum Angpt2 is elevated in men with AAA and associated with an increased risk of cardiovascular mortality in older men.
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ABSTRACT: Background: In diabetic patients with renal artery arteriosclerosis (RAAS), the factors associated with a greater risk for cardiovascular-renal events (CVREs) remain unclear: the decline in estimated glomerular filtration rate (eGFR) caused by RAAS or the advance of arteriosclerosis that causes RAAS. Hence, the features to determine which best predicts the onset of CVREs in such patients were compared. Methods and results: The renal arteries of 162 type 2 diabetes patients were assessed by using magnetic resonance angiography (RAAS diagnosed as arteriosclerotic stenosis ≥50%) and they were studied longitudinally over 7 years. The influence of the presence/absence of RAAS, a decline in eGFR, clinical factors, surrogate arteriosclerotic markers and ischemic markers on patient's CVREs were assessed. A Cox regression analysis showed the detection of RAAS to be an independent risk factor for CVREs (bilateral RAAS was an extremely strong risk factor for the development of CVREs within 1,000 days), as was the decline in eGFR in a logistic regression analysis; the latter being a more powerful risk factor for CVREs. A multiple regression analysis revealed angiopoietin-2, a marker of ischemia, to be a risk factor for the decline in eGFR. Conclusions: A decline in renal function but not the renal arterial stenotic lesion itself appears to be associated with an increased incidence of CVREs in type 2 diabetic patients with RAAS.
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ABSTRACT: Background Angiopoietin 2 (Angpt2) impairs endothelial function by preventing Angiopoietin 1 from binding to their common endothelial-specific receptor Tie2. Here we examined whether circulating Angpt2 predicts outcome in kidney transplant recipients. Materials and Methods For this case-cohort study we selected 130 kidney transplant recipients who had died or returned to dialysis within the first two years of follow-up of our cohort study, as well as 130 age and gender-matched kidney transplant recipients without an event (controls) from a total of 993 kidney transplant recipients. The total of 260 selected patients were followed in median 4 years. Serum Angpt2 at baseline was measured using an in-house immuno-luminometric assay. ResultsMedian Angpt2 concentrations were significantly higher in patients who died (median [interquartile range – IQR] 3.6[2.8-5.9] ng/mL) as compared to patients who did not die during the study period (2.8[2.1-4.1] ng/mL; p<0.001). Ln (natural log) Angpt2 levels correlated positively with C-reactive protein levels (r=0.315, p<0.001), and the Charlson Comorbidity Index (r=0.188, p=0.002), and were inversely associated with eGFR (r=-0.301, p<0.001) hemoglobin (r=-0.269, p<0.001) and serum albumin concentrations (r=-0.382, p<0.001). On multivariate analyses baseline Angpt2 levels independently predicted all-cause mortality (multivariable adjusted hazard ratio associated with one natural log unit higher Angpt2 level: 1.70 (95% confidence interval: 1.10-2.61). Conclusions In our analysis circulating Angpt2 was an independent predictor of all-cause mortality in stable, prevalent kidney transplant recipients.This article is protected by copyright. All rights reserved.
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ABSTRACT: Chronic kidney disease (CKD) is an independent risk factor for the development and severity of coronary artery disease (CHD) and endothelial dysfunction. There is an increase in the circulating angiogenesis inhibitors endostatin (END), thrombospondin-2 (TSP), angiopoietin-2 (ANG) and the nitric oxide (NO) inhibitor asymmetric dimethyl arginine (ADMA) in CKD patients. The aim of this study was to evaluate associations of the serum level of these factors and of the related angiogenesis inhibitor, endoglin (ENG), with burden of coronary atherosclerosis. One hundred twenty-two patients undergoing coronary angiography were recruited from the cardiac catheterization lab at a single center. The total burden of coronary plaque (mm(2)) and the presence of coronary collaterals were quantified using quantitative coronary angiography (QCA). Serum levels of angiogenesis inhibitors were measured by ELISA (ENG, END, and ANG), Luminex assay (TSP), or HLPC (ADMA), respectively. Associations with plaque burden and coronary collateral supply were analyzed in multi-variable linear and logistic regression models. There was no significant association found between levels of circulating ADMA, ENG, END, ANG, or TSP and coronary plaque burden or collateral formation. Our findings suggest that associations of circulating END, ENG, TSP, and ANG with cardiovascular mortality are unlikely to be mediated via direct effects on coronary plaque formation or by inhibition of collateral formation. Whether associations of these factors with mortality are mediated via local concentrations, myocardial tissue, or intra-plaque expression of these factors or by an effect on plaque vulnerability merits additional investigation.
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