Abstract
BackgroundL-Arginine and its dimethylated derivatives asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have been associated with cardiovascular (CV) and all-cause mortality in populations at risk. The present study aimed to investigate the prognostic value of L-arginine and its derivatives in the general population.Methods and ResultsWe evaluated 3,952 individuals (1,936 men and 2,016 women) aged 20–81 (median (IQR) 51 (37; 64) years) from the population-based Study of Health in Pomerania (SHIP). Associations of continuous [per standard deviation (SD) increase] and categorized (age- and sex-specific tertiles) serum L-arginine, ADMA, and SDMA concentrations with all-cause and cause-specific mortality were analysed. During a median (IQR) follow-up period of 10.1 (9.3; 10.8) years (38,476 person-years), 426 deaths (10.8%) were observed, including 139 CV deaths (3.5%), and 150 cancer deaths (3.8%). After multivariable adjustment, we revealed a positive association of SDMA with all-cause [hazard ratio (HR) per SD increase: 1.16, 95% confidence interval (CI): 1.07–1.25] and CV mortality [HR: 1.19, 95% CI: 1.05–1.35]. In contrast, we did not observe any association of SDMA with cancer mortality. Neither L-arginine nor ADMA were associated with all-cause or CV mortality.ConclusionSDMA, but not ADMA, is an independent predictor of all-cause and CV mortality in a large population-based cohort of European ancestry.
Highlights
L-Arginine is the precursor of the vasodilator nitric oxide (NO), which has been shown to have anti-aggregatory, anti-inflammatory, and anti-atherosclerotic effects [1]
Even though L-arginine is the main precursor of NO, regulation of NO production is not limited by circulating L-arginine,but by intracellular substrate and co-factor availability, NO synthase (NOS) activation by phosphorylation, and NOS inhibition by e.g., the endogenously methylated L-arginine derivate asymmetric dimethylarginine (ADMA), but not symmetric dimethylarginine (SDMA) [5]
General characteristics Serum L-arginine derivatives and phenotypes were available from 3,952 participants of the Study of Health in Pomerania (SHIP) cohort. 51% of the cohort represented females, characterized by a lower frequency of prevalent Cardiovascular disease (CVD) as well as lower ADMA and SDMA serum concentrations (Table 1)
Summary
L-Arginine is the precursor of the vasodilator nitric oxide (NO), which has been shown to have anti-aggregatory, anti-inflammatory, and anti-atherosclerotic effects [1]. L-Arginine and its methylated derivatives asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are constituents of human nutrition, with L-arginine as a proteinogenic amino acid being ubiquitous present whilst conspicuous amounts of ADMA and SDMA were found in some vegetables like soy beans [2]. Data of the Framingham Heart Study indicates that ADMA predicts all-cause mortality in a community-based cohort [9]. SDMA was identified as an independent predictor of all-cause and CV mortality in the multiethnic population-based cohort of the Dallas Heart Study. L-Arginine and its dimethylated derivatives asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have been associated with cardiovascular (CV) and all-cause mortality in populations at risk. The present study aimed to investigate the prognostic value of L-arginine and its derivatives in the general population
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