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Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease

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Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease. / Zewinger, Stephen; Kleber, Marcus E; Rohrer, Lucia; Lehmann, Marlene; Triem, Sarah; Jennings, Richard T; Petrakis, Ioannis; Dressel, Alexander; Lepper, Philipp M; Scharnagl, Hubert; Ritsch, Andreas; Thorand, Barbara; Heier, Margit; Meisinger, Christa; de Las Heras Gala, Tonia; Koenig, Wolfgang; Wagenpfeil, Stefan; Schwedhelm, Edzard; Böger, Rainer H; Laufs, Ulrich; Eckardstein, Arnold von; Landmesser, Ulf; Lüscher, Thomas F; Fliser, Danilo; März, Winfried; Meinitzer, Andreas; Speer, Thimoteus.

In: EUR HEART J, Vol. 38, No. 20, 21.05.2017, p. 1597-1607.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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, Eckardstein, AV, Landmesser, U, Lüscher, TF, Fliser, D, März, W, Meinitzer, A & Speer, T 2017, 'Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease', EUR HEART J, vol. 38, no. 20, pp. 1597-1607. https://doi.org/10.1093/eurheartj/ehx118

APA

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., ... Speer, T. (2017). Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease. EUR HEART J, 38(20), 1597-1607. https://doi.org/10.1093/eurheartj/ehx118

Vancouver

Zewinger S, Kleber ME, Rohrer L, Lehmann M, Triem S, Jennings RT et al. Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease. EUR HEART J. 2017 May 21;38(20):1597-1607. https://doi.org/10.1093/eurheartj/ehx118

Bibtex

@article{92f00a9fcbc0471b961624ac6e6f02c8,
title = "Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease",
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 = "Journal Article",
author = "Stephen Zewinger and Kleber, {Marcus E} and Lucia Rohrer and Marlene Lehmann and Sarah Triem and Jennings, {Richard T} and Ioannis Petrakis and Alexander Dressel and Lepper, {Philipp M} and Hubert Scharnagl and Andreas Ritsch and Barbara Thorand and Margit Heier and Christa Meisinger and {de Las Heras Gala}, Tonia and Wolfgang Koenig and Stefan Wagenpfeil and Edzard Schwedhelm and B{\"o}ger, {Rainer H} and Ulrich Laufs and Eckardstein, {Arnold von} and Ulf Landmesser and L{\"u}scher, {Thomas F} and Danilo Fliser and Winfried M{\"a}rz and Andreas Meinitzer and Thimoteus Speer",
year = "2017",
month = may,
day = "21",
doi = "10.1093/eurheartj/ehx118",
language = "English",
volume = "38",
pages = "1597--1607",
journal = "EUR HEART J",
issn = "0195-668X",
publisher = "Oxford University Press",
number = "20",

}

RIS

TY - JOUR

T1 - Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease

AU - Zewinger, Stephen

AU - Kleber, Marcus E

AU - Rohrer, Lucia

AU - Lehmann, Marlene

AU - Triem, Sarah

AU - Jennings, Richard T

AU - Petrakis, Ioannis

AU - Dressel, Alexander

AU - Lepper, Philipp M

AU - Scharnagl, Hubert

AU - Ritsch, Andreas

AU - Thorand, Barbara

AU - Heier, Margit

AU - Meisinger, Christa

AU - de Las Heras Gala, Tonia

AU - Koenig, Wolfgang

AU - Wagenpfeil, Stefan

AU - Schwedhelm, Edzard

AU - Böger, Rainer H

AU - Laufs, Ulrich

AU - Eckardstein, Arnold von

AU - Landmesser, Ulf

AU - Lüscher, Thomas F

AU - Fliser, Danilo

AU - März, Winfried

AU - Meinitzer, Andreas

AU - Speer, Thimoteus

PY - 2017/5/21

Y1 - 2017/5/21

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1093/eurheartj/ehx118

DO - 10.1093/eurheartj/ehx118

M3 - SCORING: Journal article

C2 - 28379378

VL - 38

SP - 1597

EP - 1607

JO - EUR HEART J

JF - EUR HEART J

SN - 0195-668X

IS - 20

ER -