Cross-Sectional Associations between Homoarginine, Intermediate Phenotypes, and Atrial Fibrillation in the Community—The Gutenberg Health Study

Abstract

Homoarginine has come into the focus of interest as a biomarker for cardiovascular disease. Atrial fibrillation (AF) causes a substantial increase in morbidity and mortality. Whether circulating homoarginine is associated with occurrence or persistence of AF and may serve as a new predictive biomarker remains unknown. We measured plasma levels of homoarginine in the population-based Gutenberg health study (3761 patients included, of them 51.7% males), mean age 55.6 ± 10.9 years-old. Associations between homoarginine and intermediate electrocardiographic and echocardiographic phenotypes and manifest AF were examined. Patients with AF (124 patients, of them 73.4% males) had a mean age 64.8 ± 8.6 years-old compared to a mean age of 55.3 ± 10.9 in the population without AF (p-value < 0.001) and showed a less beneficial risk factor profile. The median homoarginine levels in individuals with and without AF were 1.9 μmol/L (interquartile range (IQR) 1.5–2.5) and 2.0 μmol/L (IQR 1.5–2.5), respectively, p = 0.56. In multivariable-adjusted regression analyses homoarginine was not statistically significantly related to electrocardiographic variables. Among echocardiographic variables beta per standard deviation increase was −0.12 (95% confidence interval (CI) −0.23–(−0.02); p = 0.024) for left atrial area and −0.01 (95% CI −0.02–(−0.003); p = 0.013) for E/A ratio. The odds ratio between homoarginine and AF was 0.91 (95% CI 0.70–1.16; p = 0.45). In our large, population-based cross-sectional study, we did not find statistically significant correlations between lower homoarginine levels and occurrence or persistence of AF or most standard electrocardiographic phenotypes, but some moderate inverse associations with echocardiographic left atrial size and E/A. Homoarginine may not represent a strong biomarker to identify individuals at increased risk for AF. Further investigations will be needed to elucidate the role of homoarginine and cardiac function.

Homoarginine Associates with Carotid Intima-Media Thickness and Atrial Fibrillation and Predicts Adverse Events after Stroke

“…Previously, we found that patients with persistent atrial fibrillation at the time of blood sampling had the lowest homoarginine concentrations compared to paroxysmal atrial fibrillation [22]. In contrast, homoarginine levels did not correlate with the occurrence or persistence of atrial fibrillation in a population-based study [32]. Therefore, it seems likely that the association of homoarginine with atrial fibrillation depends on the underlying pathology.…”

Association of Asymmetric Dimethylarginine and Diastolic Dysfunction in Patients with Hypertrophic Cardiomyopathy

“…However, in the community-based cohort of the Framingham Heart Study, ADMA and SDMA were not independently associated with the incidence of AF [23]. In the general population of the Gutenberg Health Study higher ADMA was associated with prevalent AF, whereas no association was seen for SDMA or hArg [24,25]. In CAD patients, lower hArg was associated with a higher prevalence of AF and an increased risk for incident fatal and non-fatal stroke or MI and all-cause mortality [26].…”

Homoarginine in health and disease

“…The biomarker and causal roles of hArg in the development of cardiometabolic diseases [42], and cross-sectional associations between hArg, intermediate phenotypes and atrial fibrillation in healthy humans [43] were recently investigated. The relationship between hArg and the methionine-homocysteine balance was investigated in patients with ischemic heart disease [44].…”