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Aortic Valve Calcium Associates with All-Cause Mortality Independent of Coronary Artery Calcium and Inflammation in Patients with End-Stage Renal Disease.

ABSTRACT: BACKGROUND:Aortic valve calcium (AVC) and coronary artery calcium (CAC) are common complications in end-stage renal disease (ESRD). We investigated the prognostic significance of overlapping presence of AVC and CAC, and whether AVC was associated with all-cause mortality independent of the presence of CAC in ESRD. METHODS:259 ESRD patients (median age 55 years, 67% males) undergoing cardiac computed tomography were included. Framingham risk score (FRS), presence of cardiovascular disease (CVD), statin use, nutritional status and other relevant laboratory data were determined at baseline. During follow-up for median 36 months, 44 patients died, and 68 patients underwent renal transplantation. RESULTS:The baseline overlap presence of AVC and CAC was 37%. Multivariate regression analysis showed that FRS (odds ratio (OR) 2.25; 95% confidence interval (95% CI), 1.43-3.55) and CAC score (OR (95% CI), 2.18 (1.34-3.59)) were independent determinants of AVC. In competing-risk regression models adjusted for presence of CAC, inflammation, nutritional status, CVD, FRS and statin use, AVC remained independently associated with all-cause mortality (sub-hazard ratio (95% CI), 2.57 (1.20-5.51)). CONCLUSIONS:The overlap of AVC and CAC was 37% in this ESRD cohort. AVC was associated with increased all-cause mortality independent of presence of CAC, traditional risk factors and inflammation.

SUBMITTER: Dai L

PROVIDER: S-EPMC7074421 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Aortic Valve Calcium Associates with All-Cause Mortality Independent of Coronary Artery Calcium and Inflammation in Patients with End-Stage Renal Disease.

Dai Lu L Plunde Oscar O Qureshi Abdul Rashid AR Lindholm Bengt B Brismar Torkel B TB Schurgers Leon J LJ Söderberg Magnus M Ripsweden Jonaz J Bäck Magnus M Stenvinkel Peter P

Journal of clinical medicine 20200224 2

<h4>Background</h4>Aortic valve calcium (AVC) and coronary artery calcium (CAC) are common complications in end-stage renal disease (ESRD). We investigated the prognostic significance of overlapping presence of AVC and CAC, and whether AVC was associated with all-cause mortality independent of the presence of CAC in ESRD.<h4>Methods</h4>259 ESRD patients (median age 55 years, 67% males) undergoing cardiac computed tomography were included. Framingham risk score (FRS), presence of cardiovascular ...[more]

PMID: 32102408

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Project description:Located at the junction of left ventricle and ascending aorta, aortic root is a central cardiovascular structure consisting of aortic valve and coronary ostium that are essential for systemic and coronary circulation, respectively. Malformations of aortic valve and coronary ostium are common birth defects and may occur together in human patients, leading to complex complications including aortic valve stenosis, myocardial ischemia, heart failure and sudden cardiac death. Despite of their physiological and clinical significances, the developmental and molecular mechanisms by which coordinate the formation of aortic valve and coronary ostium remain poorly understood. Here we report that SOX17 (SRY-box 17) is an essential transcription factor required for the maturation of aortic root, as well as the patterning of aortic valve and coronary ostium. We show in mouse that deletion of Sox17 in the aortic root endothelium results in defective aortic valve with underdeveloped non-coronary leaflet (NCL) or bicuspid aortic valve (BAV) without NCL. The valve defects are accompanied by misplaced left coronary ostium that reduces coronary blood flow, leading to myocardial hypoxia and death of embryos. Mechanistically, deletion of Sox17 decreases the expression of Pdgfb (Platelet derived growth factor, B polypeptide) in the aortic root endothelium and the PDGF growth signaling in the NCL mesenchyme and aortic root smooth muscle, both of which are derived from the second heart field (SHF) cardiomyocyte precursors. Furthermore, the deletion upregulates the expression of Ctgf (Connective tissue growth factor) and the extracellular matrix (ECM) genes, whereas downregulates the vascular smooth muscle genes, in the forming aortic root. Together, these findings support a developmental disease mechanism in which delayed growth and maturation of aortic root, due to lack of SOX17-PDGF/CTGF signaling, contributes to BAV and CAAs, two common congenital cardiovascular defects.

Dataset Information

Aortic Valve Calcium Associates with All-Cause Mortality Independent of Coronary Artery Calcium and Inflammation in Patients with End-Stage Renal Disease.

Publications

Aortic Valve Calcium Associates with All-Cause Mortality Independent of Coronary Artery Calcium and Inflammation in Patients with End-Stage Renal Disease.

Similar Datasets

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