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Zewinger, S.* ; Kleber, M.E.* ; Rohrer, L.* ; Lehmann, M.* ; Triem, S.* ; Jennings, R.T.* ; Petrakis, I.* ; Dressel, A.* ; Lepper, P.M.* ; Scharnagl, H.* ; Ritsch, A.* ; Thorand, B. ; Heier, M. ; Meisinger, C. ; de Las Heras Gala, T. ; Koenig, W.* ; Wagenpfeil, S.* ; Schwedhelm, E.* ; Böger, R.H.* ; Laufs, U.* ; von Eckardstein, A.* ; Landmesser, U.* ; Lüscher, T.F.* ; Fliser, D.* ; März, W.* ; Meinitzer, A.* ; Speer, T.*

Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease.

Eur. Heart J. 38, 1597-1607 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Aims: The vascular effects of high-density lipoproteins (HDL) differ under certain clinical conditions. The composition of HDL is modified in patients with chronic kidney disease (CKD). As a consequence, uremic HDL induces endothelial dysfunction. We have previously shown that accumulation of symmetric dimethylarginine (SDMA) in HDL causes these adverse effects of HDL in CKD. The aim of the study is to determine the impact of the accumulation of SDMA on the association between HDL and mortality. Methods and results: Mortality, renal function, serum SDMA and HDL-cholesterol (HDL-C) were assessed in the LURIC study including 3310 subjects undergoing coronary angiography. All-cause mortality was 30.0% during median follow-up of 9.9 years. Serum SDMA levels significantly predicted all-cause and cardiovascular mortality, and were significantly correlated with SDMA accumulation in HDL. Notably, higher serum SDMA was independently associated with lower cholesterol efflux (P = 0.004) as a measure of HDL functionality. In subjects with low SDMA levels, higher HDL-C was associated with significantly lower mortality. In contrast, in subjects with high SDMA, HDL-C was associated with higher mortality. These findings were confirmed in 1424 participants of the MONICA/KORA S3 cohort. Of note, we derived an algorithm allowing for calculation of biologically effective HDL-C' based on measured HDL-C and SDMA. We corroborated these clinical findings with in vitro evidence showing that SDMA accumulation abolishes the anti-inflammatory and regenerative properties of HDL. Conclusion: The data identify SDMA as a marker of HDL dysfunction. These findings highlight on the pivotal role of SDMA accumulation in HDL as a mediator of pre-mature cardiovascular disease in patients with CKD.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cardiovascular Risk ; High-density Lipoproteins ; Kidney Disease ; Symmetric Dimethylarginine; Coronary-artery-disease; Chronic Kidney-disease; Glomerular-filtration-rate; Stage Renal-disease; Asymmetrical Dimethylarginine; Endothelial Dysfunction; European Guidelines; Clinical-practice; Risk; Mortality
ISSN (print) / ISBN 0195-668X
e-ISSN 1522-9645
Journal European Heart Journal
Quellenangaben Volume: 38, Issue: 20, Pages: 1597-1607 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Oxford
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Independent Research Group Clinical Epidemiology (KEPI)