Arginine and homoarginine as predictors of cardiovascular mortality in chronic coronary syndrome

Background and aims Arginine (Arg) and homoarginine (hArg) are related to the nitric oxide pathway, which is important for vascular function. We investigated if serum concentrations of Arg and hArg predicted long-term cardiovascular disease (CVD) mortality in patients with chronic coronary syndrome (CCS), and whether associations differed between non-obstructive coronary artery disease (NOCAD) and obstructive coronary artery disease (OCAD). Methods and results We included 4164 patients undergoing invasive coronary angiography for suspected CCS. Associations with CVD mortality were assessed using multivariable Cox regression, reporting hazard ratios (HRs) per standard deviation increase in log-transformed concentrations. During a median follow-up of 14.1 years, 586 (14.1%) patients died from CVD. Serum hArg was inversely associated with CVD mortality [HR (95% CI): 0.81 (0.74–0.88)] as was serum Arg [HR (95% CI): 0.90 (0.83–0.98)]. However, in Fine–Gray competing risk analyses, the association of serum Arg with CVD mortality was no longer statistically significant, whereas the inverse association for serum hArg persisted. Addition of serum hArg to the clinical model increased the C-statistic from 0.771 to 0.776, indicating a modest improvement in discrimination. In exploratory subgroup analyses, the association between serum hArg and CVD mortality was stronger in NOCAD than OCAD [0.54 (0.40–0.73) vs. 0.84 (0.77–0.92); P for interaction = 0.037]. Conclusion Serum Arg and hArg were inversely associated with long-term CVD mortality in patients with CCS. However, the association of serum hArg was more robust than that of serum Arg. The stronger association observed in NOCAD requires independent validation.