Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zewinger, S; Kleber, ME; Rohrer, L; Lehmann, M; Triem, S; Jennings, RT; Petrakis, I; Dressel, A; Lepper, PM; Scharnagl, H; Ritsch, A; Thorand, B; Heier, M; Meisinger, C; de Las Heras Gala, T; Koenig, W; Wagenpfeil, S; Schwedhelm, E; Böger, RH; Laufs, U; von Eckardstein, A; Landmesser, U; Lüscher, TF; Fliser, D; März, W; Meinitzer, A; Speer, T.
Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease.
Eur Heart J. 2017; 38(20):1597-1607
Doi: 10.1093/eurheartj/ehx118
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- Co-Autor*innen der Med Uni Graz
- März Winfried
- Meinitzer Andreas
- Scharnagl Hubert
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- Abstract:
- 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. 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 invitro evidence showing that SDMA accumulation abolishes the anti-inflammatory and regenerative properties of HDL. 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. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Arginine - analogs & derivatives
- Arginine - metabolism
- Biomarkers - metabolism
- Cardiovascular Diseases - etiology
- Cardiovascular Diseases - mortality
- Female -
- Glomerular Filtration Rate - physiology
- Humans -
- Lipoproteins, HDL - metabolism
- Male -
- Middle Aged -
- Prognosis -
- Renal Insufficiency, Chronic - complications
- Renal Insufficiency, Chronic - mortality
- Risk Factors -
- Find related publications in this database (Keywords)
- High-density lipoproteins
- Kidney disease
- Cardiovascular risk
- Symmetric dimethylarginine