PMID- 27796501 OWN - NLM STAT- MEDLINE DCOM- 20180101 LR - 20180305 IS - 1438-2199 (Electronic) IS - 0939-4451 (Linking) VI - 49 IP - 1 DP - 2017 Jan TI - Higher serum asymmetric dimethylarginine is related to higher risk of heart failure in the EPIC-Potsdam study. PG - 173-182 LID - 10.1007/s00726-016-2348-3 [doi] AB - L-Arginine is the substrate of endothelial nitric oxide (NO) synthase forming NO which inherits various biological cardio-protective functions. The dimethylarginines asymmetric (ADMA) and symmetric dimethylarginine (SDMA) can impair the synthesis of NO and are elevated in patients with cardiovascular disease, including heart failure (HF). We investigated the association between dimethylarginines and HF risk in a case-cohort study of the European Prospective Investigation into Cancer and Nutrition (n = 27,548), comprising a random subcohort (n = 2224 including 19 HF cases), and all remaining HF cases (n = 176) that occurred within 8.3 years of follow-up. Serum concentrations of dimethylarginines were measured using liquid chromatography-tandem mass spectrometry. Hazards ratios (HRs) and 95% confidence intervals (CI) were estimated across quartiles and per doubling of ADMA and SDMA concentrations using Cox's proportional hazards regression. After multivariable adjustment, each doubling of ADMA was associated with a 60% higher HF risk (HR [95% CI] 1.60 [1.10-2.31]). Between SDMA and HF risk a U-shaped association was observed (HR [95% CI] for the second, third and fourth quartile compared to the first: 0.52 [0.33-0.82], 0.63 [0.40-0.99], and 0.71 [0.46-1.10], p for nonlinearity <0.01). We provide substantiated evidence for a relationship between ADMA and cardiovascular endpoints. In addition to the established relation between ADMA and myocardial infarction, our findings indicate a positive association between ADMA and HF incidence in persons without apparent myocardial infarction. Targeting the ADMA metabolism might open up new therapeutic perspective for HF prevention and treatment. Further investigations are needed to shed more light on mechanisms involved in the pathogenesis of HF related to elevated ADMA levels. FAU - Wirth, Janine AU - Wirth J AUID- ORCID: 0000-0001-7075-9686 AD - Department of Nutrition, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA, 02115, USA. jwirth@hsph.harvard.edu. AD - German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. jwirth@hsph.harvard.edu. AD - DZHK, Partner Site Berlin/Potsdam, Potsdam, Germany. jwirth@hsph.harvard.edu. FAU - Atzler, Dorothee AU - Atzler D AD - Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. AD - DZHK, Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany. AD - Department of Cardiovascular Medicine, University of Oxford, Oxford, UK. FAU - di Giuseppe, Romina AU - di Giuseppe R AD - German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. AD - DZHK, Partner Site Berlin/Potsdam, Potsdam, Germany. AD - Institute of Epidemiology, Christian-Albrechts University Kiel, Kiel, Germany. FAU - Cordts, Kathrin AU - Cordts K AD - Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. AD - DZHK, Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany. FAU - Menzel, Juliane AU - Menzel J AD - German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. AD - Institute for Social Medicine, Epidemiology and Health Economics, Charite University Medical Center, Berlin, Germany. FAU - Boger, Rainer H AU - Boger RH AD - Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. AD - DZHK, Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany. FAU - Boeing, Heiner AU - Boeing H AD - German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. FAU - Weikert, Cornelia AU - Weikert C AD - German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. AD - DZHK, Partner Site Berlin/Potsdam, Potsdam, Germany. AD - Institute for Social Medicine, Epidemiology and Health Economics, Charite University Medical Center, Berlin, Germany. AD - Federal Institute of Risk Assessment, Department of Food Safety, Berlin, Germany. FAU - Schwedhelm, Edzard AU - Schwedhelm E AD - Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. AD - DZHK, Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161028 PL - Austria TA - Amino Acids JT - Amino acids JID - 9200312 RN - 0 (Biomarkers) RN - 49787G1ULV (symmetric dimethylarginine) RN - 63CV1GEK3Y (N,N-dimethylarginine) RN - 94ZLA3W45F (Arginine) SB - IM MH - Adult MH - Aged MH - Arginine/*analogs & derivatives/*blood MH - Biomarkers/blood MH - Feeding Behavior/physiology MH - Female MH - Germany MH - Heart Failure/blood/*diagnosis/mortality MH - Humans MH - Male MH - Middle Aged MH - Myocardial Infarction/blood/*diagnosis/mortality MH - Prognosis MH - Proportional Hazards Models MH - Prospective Studies MH - Risk OTO - NOTNLM OT - ADMA OT - Dimethylarginine OT - Heart failure OT - Myocardial infarction OT - Nitric oxide OT - SDMA EDAT- 2016/11/01 06:00 MHDA- 2018/01/02 06:00 CRDT- 2016/11/01 06:00 PHST- 2016/03/21 00:00 [received] PHST- 2016/10/05 00:00 [accepted] PHST- 2016/11/01 06:00 [pubmed] PHST- 2018/01/02 06:00 [medline] PHST- 2016/11/01 06:00 [entrez] AID - 10.1007/s00726-016-2348-3 [pii] AID - 10.1007/s00726-016-2348-3 [doi] PST - ppublish SO - Amino Acids. 2017 Jan;49(1):173-182. doi: 10.1007/s00726-016-2348-3. Epub 2016 Oct 28.