Dorothee Atzler1, M Odette Gore2, Colby R Ayers2, Chi-un Choe2, Rainer H Böger2, James A de Lemos2, Darren K McGuire2, Edzard Schwedhelm2. 1. From the Departments of Clinical Pharmacology and Toxicology (D.A., R.H.B., E.S.) and Neurology, Experimental Neuropediatrics (C.U.C.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.), Partner Site Hamburg/Kiel/Lübeck, Germany (D.A., R.H.B., E.S.); and Division of Cardiology, Department of Internal Medicine (M.O.G., J.A.d.L., D.K.M.) and Department of Clinical Sciences (C.R.A., D.K.M.), University of Texas Southwestern Medical Center, Dallas. dorothee.atzler@well.ox.ac.uk. 2. From the Departments of Clinical Pharmacology and Toxicology (D.A., R.H.B., E.S.) and Neurology, Experimental Neuropediatrics (C.U.C.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.), Partner Site Hamburg/Kiel/Lübeck, Germany (D.A., R.H.B., E.S.); and Division of Cardiology, Department of Internal Medicine (M.O.G., J.A.d.L., D.K.M.) and Department of Clinical Sciences (C.R.A., D.K.M.), University of Texas Southwestern Medical Center, Dallas.
Abstract
OBJECTIVE: The nonproteinogenic amino acid homoarginine has been postulated to have antiatherosclerotic effects as a weak substrate of nitric oxide synthase. This investigation in the population-based Dallas Heart Study (DHS) aimed to evaluate the association of homoarginine with clinical and subclinical cardiovascular outcomes. APPROACH AND RESULTS: Plasma homoarginine was measured in 3514 participants of the DHS using liquid chromatography-tandem mass spectrometry. Associations between homoarginine and major adverse cardiovascular events and all-cause mortality were analyzed using Cox proportional hazard models adjusting for cardiovascular risk factors. Linear regression was used to assess cross-sectional associations between homoarginine and subclinical cardiovascular disease, including coronary artery calcium measured by electron beam-computed tomography, and aortic plaque burden and aortic wall thickness by MRI. Median age was 43 (interquartile range, 36-52) years, with 56% women and 52% black participants. Median follow-up was 9.4 (9.0-9.8) years. Median plasma homoarginine was 2.80 (2.14-3.54) μmol/L. In multivariable models, higher homoarginine was associated with lower rate of major adverse cardiovascular events (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98) and lower all-cause mortality (hazard ratio, 0.82; 0.73-0.92; per 1 log SD increase in homoarginine). Homoarginine was inversely and independently associated with aortic wall thickness (β-estimate, -0.04; P<0.01) but not with aortic plaque burden and coronary artery calcium. CONCLUSIONS: Homoarginine is inversely associated with subclinical vascular disease and with risk for cardiovascular disease events. Additional studies are needed to evaluate whether the regulation of plasma homoarginine could emerge as a novel therapeutic option to improve outcomes in cardiovascular disease.
OBJECTIVE: The nonproteinogenic amino acid homoarginine has been postulated to have antiatherosclerotic effects as a weak substrate of nitric oxide synthase. This investigation in the population-based Dallas Heart Study (DHS) aimed to evaluate the association of homoarginine with clinical and subclinical cardiovascular outcomes. APPROACH AND RESULTS: Plasma homoarginine was measured in 3514 participants of the DHS using liquid chromatography-tandem mass spectrometry. Associations between homoarginine and major adverse cardiovascular events and all-cause mortality were analyzed using Cox proportional hazard models adjusting for cardiovascular risk factors. Linear regression was used to assess cross-sectional associations between homoarginine and subclinical cardiovascular disease, including coronary artery calcium measured by electron beam-computed tomography, and aortic plaque burden and aortic wall thickness by MRI. Median age was 43 (interquartile range, 36-52) years, with 56% women and 52% black participants. Median follow-up was 9.4 (9.0-9.8) years. Median plasma homoarginine was 2.80 (2.14-3.54) μmol/L. In multivariable models, higher homoarginine was associated with lower rate of major adverse cardiovascular events (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98) and lower all-cause mortality (hazard ratio, 0.82; 0.73-0.92; per 1 log SD increase in homoarginine). Homoarginine was inversely and independently associated with aortic wall thickness (β-estimate, -0.04; P<0.01) but not with aortic plaque burden and coronary artery calcium. CONCLUSIONS:Homoarginine is inversely associated with subclinical vascular disease and with risk for cardiovascular disease events. Additional studies are needed to evaluate whether the regulation of plasma homoarginine could emerge as a novel therapeutic option to improve outcomes in cardiovascular disease.
Authors: Jeanney Lew; Monika Sanghavi; Colby R Ayers; Darren K McGuire; Torbjørn Omland; Dorothee Atzler; Maria O Gore; Ian Neeland; Jarett D Berry; Amit Khera; Anand Rohatgi; James A de Lemos Journal: Circulation Date: 2017-02-07 Impact factor: 29.690
Authors: Ilkka Seppälä; Niku Oksala; Antti Jula; Antti J Kangas; Pasi Soininen; Nina Hutri-Kähönen; Winfried März; Andreas Meinitzer; Markus Juonala; Mika Kähönen; Olli T Raitakari; Terho Lehtimäki Journal: Sci Rep Date: 2017-04-25 Impact factor: 4.379
Authors: Kiterie M E Faller; Dorothee Atzler; Debra J McAndrew; Sevasti Zervou; Hannah J Whittington; Jillian N Simon; Dunja Aksentijevic; Michiel Ten Hove; Chi-Un Choe; Dirk Isbrandt; Barbara Casadei; Jurgen E Schneider; Stefan Neubauer; Craig A Lygate Journal: Cardiovasc Res Date: 2018-03-01 Impact factor: 10.787
Authors: Dorothee Atzler; Christina Baum; Francisco Ojeda; Till Keller; Kathrin Cordts; Renate B Schnabel; Chi-un Choe; Karl J Lackner; Thomas Münzel; Rainer H Böger; Stefan Blankenberg; Edzard Schwedhelm; Tanja Zeller Journal: J Am Heart Assoc Date: 2016-04-13 Impact factor: 5.501