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

Abstract

Homoarginine is associated with cardio- and cerebrovascular morbidity and mortality. However, the underlying pathomechanisms remain elusive. Here, we evaluated the association of homoarginine with adverse events (i.e., death, stroke, and myocardial infarction) and carotid intima-media thickness (cIMT) in stroke patients. In the prospective bioMARKers in STROKE (MARK-STROKE) cohort, patients with acute ischemic stroke or transient ischemic attack (TIA) were enrolled. Plasma homoarginine concentrations were analyzed and associated with clinical phenotypes in cross-sectional (374 patients) and prospective (273 patients) analyses. Adjustments for possible confounders were evaluated. A two-fold increase in homoarginine was inversely associated with the National Institutes of Health Stroke Scale (NIHSS) score at admission, cIMT, and prevalent atrial fibrillation (mean factor -0.68 [95% confidence interval (CI): -1.30, -0.07], -0.14 [95% CI: -0.22, -0.05]; and odds ratio 0.57 [95% CI: 0.33, 0.96], respectively). During the follow-up (median 284 [25th, 75th percentile: 198, 431] days), individuals with homoarginine levels in the highest tertile had fewer incident events compared with patients in the lowest homoarginine tertile independent of traditional risk factors (hazard ratio 0.22 [95% CI: 0.08, 0.63]). A lower prevalence of atrial fibrillation and a reduced cIMT pinpointed potential underlying pathomechanisms.

Keywords: acute stroke; atrial fibrillation; carotid intima-media thickness; homoarginine; transient ischemic attack.

Figure 1

Kaplan–Meier curves for homoarginine tertiles during a median follow-up time of 284 [25th, 75th percentile: 198, 431] days after stroke (lowest tertile: <1.0 µmol/L; second tertile: 1.0–1.5 µmol/L; highest tertile: >1.5 µmol/L). Univariate associations between homoarginine and events were compared using a Mantel–Cox log-rank test (n = 273). Abbreviations: hArg, homoarginine; MACE, major adverse cardiovascular event (i.e., death, nonfatal stroke, and myocardial infarction).