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Eur Heart J. 2017 May 21;38(20):1597-1607. doi: 10.1093/eurheartj/ehx118.

Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease.

Author information

1
Department of Internal Medicine IV, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
2
Mannheim Medical Faculty, Medical Clinic V (Nephrology • Hypertensiology • Endocrinology • Diabetology • Rheumatology), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
3
Institute of Nutrition, Dornburger Strasse, 07743 Friedrich Schiller University Jena, Germany.
4
Institute of Clinical Chemistry, University Hospital Zurich, Rämistrasse, 8091 Zurich, Switzerland.
5
Department of Internal Medicine V, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
6
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz, 8036 Graz, Austria.
7
Department of Internal Medicine, Medical University of Innsbruck, Christoph-Probst-Platz, 6020 Innsbruck, Austria.
8
Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Ingolstaedter Landstrasse 1, 85764 Munich, Germany.
9
Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Albert-Einstein-Allee, 89081 Ulm, Germany.
10
German Centre of Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
11
Deutsches Herzzentrum München, Technische Universität München, Lazarettstrasse 36, 80636 Munich, Germany.
12
Epidemiology and Medical Informatics, Campus Homburg/Saar, Saarland University, Institute for Medical Biometry, Kirrberger Strasse, 66421 Homburg/Saar, Germany.
13
University Medical Center Hamburg-Eppendorf, Institute of Experimental and Clinical Pharmacology and Toxicology, Martinistrasse, 20246 Hamburg, Germany.
14
Department of Internal Medicine III, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
15
Department of Cardiology, Charité University Hospital, Hindenburgdamm, 12203 Berlin, Germany.
16
University Heart Center Zurich, Department of Cardiology, University Hospital and Center for Molecular Cardiology, University of Zurich, Rämistrasse, 8091 Zurich, Switzerland.
17
Center of Molecular Cardiology, University of Zurich, Wagistrasse, 8952 Zurich, Switzerland.
18
Synlab Academy, Synlab Holding Deutschland GmbH, P5, 7, 68161 Mannheim and Augsburg, Germany.

Abstract

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 invitro 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.

KEYWORDS:

Cardiovascular risk; High-density lipoproteins; Kidney disease; Symmetric dimethylarginine

PMID:
28379378
DOI:
10.1093/eurheartj/ehx118
[Indexed for MEDLINE]

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