Association of branched-chain amino acids with mortality-the Ludwigshafen Risk and Cardiovascular Health (LURIC) study

Angela P Moissl; Stefan Lorkowski; Andreas Meinitzer; Stefan Pilz; Hubert Scharnagl; Graciela E Delgado; Marcus E Kleber; Bernhard K Krämer; Burkert Pieske; Martin R Grübler; Helmut Brussee; Dirk von Lewinski; Hermann Toplak; Astrid Fahrleitner-Pammer; Winfried März; Andreas Tomaschitz

doi:10.1016/j.isci.2023.106459

Association of branched-chain amino acids with mortality-the Ludwigshafen Risk and Cardiovascular Health (LURIC) study

iScience. 2023 Mar 21;26(4):106459. doi: 10.1016/j.isci.2023.106459. eCollection 2023 Apr 21.

Authors

Angela P Moissl^{1

2

3}, Stefan Lorkowski^{1

2}, Andreas Meinitzer⁴, Stefan Pilz⁵, Hubert Scharnagl⁴, Graciela E Delgado^{3

6}, Marcus E Kleber^{2

3

7}, Bernhard K Krämer^{3

6

8}, Burkert Pieske^{9

10}, Martin R Grübler⁵, Helmut Brussee⁵, Dirk von Lewinski¹¹, Hermann Toplak⁵, Astrid Fahrleitner-Pammer⁵, Winfried März^{2

3

4

12}, Andreas Tomaschitz¹³

Affiliations

¹ Institute of Nutritional Sciences Friedrich Schiller University Jena, Jena, Germany.
² Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Jena, Germany.
³ Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology, Pneumology), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁴ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
⁵ Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Diabetology, Graz, Austria.
⁶ Center for Preventive Medicine and Digital Health Baden-Württemberg (CPDBW), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁷ Synlab Human Genetics Laboratory, SYNLAB AG, Mannheim, Germany.
⁸ European Center for Angioscience ECAS, Faculty of Medicine of the University of Heidelberg, Mannheim, Germany.
⁹ Department of Internal Medicine and Cardiology, Charitè Campus Virchow Klinikum, Berlin, Germany.
¹⁰ German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany.
¹¹ Medical University of Graz, Department of Internal Medicine, Division of Cardiology, Graz, Austria.
¹² Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany.
¹³ Health Centre Trofaiach, Trofaiach, Austria.

Abstract

Branched-chain amino acids (BCAAs) are effectors of metabolic diseases, but their impact on mortality is largely unknown. We investigated the association of BCAA with risk factors and mortality in 2,236 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study using linear and Cox regression. Adiponectin, hemoglobin, C-peptide, hemoglobin A_1c, and homoarginine showed the strongest association with BCAA concentration (all p < 0.001). During a median follow-up of 10.5 years, 715 participants died, including 450 cardiovascular-related deaths. BCAA concentrations were inversely associated with the risk of all-cause and cardiovascular mortality (HR [95% CI] per 1-SD increase in log-BCAA: 0.75 [0.69-0.82] and 0.72 [0.65-0.80], respectively) after adjustment for potential confounders. BCAAs are directly associated with metabolic risk but inversely with mortality in persons with intermediate-to-high cardiovascular risk. Further studies are warranted to evaluate the diagnostic and therapeutic utility of BCAA in the context of cardiovascular diseases.

Keywords: Association analysis; Cardiovascular medicine; Health sciences.