A Low Arginine/Ornithine Ratio is Associated with Long-Term Cardiovascular Mortality

Abstract

Aims: The long-term prognostic value of the bioavailability of l-arginine, an important source of nitric oxide for the maintenance of vascular endothelial function, has not been investigated fully. We therefore investigated the relationship between amino acid profile and long-term prognosis in patients with a history of standby coronary angiography. Methods: We measured the serum concentrations of l-arginine, l-citrulline, and l-ornithine by high-speed liquid chromatography. We examined the relationship between the l-arginine/l-ornithine ratio and the incidence of all-cause death, cardiovascular death, and major adverse cardiovascular events (MACEs) in 262 patients (202 men and 60 women, age 65±13 years) who underwent coronary angiography over a period of ≤ 10 years. Results: During the observation period of 5.5±3.2 years, 31 (12%) patients died, including 20 (8%) of cardiovascular death, while 32 (12%) had MACEs. Cox regression analysis revealed that l-arginine/l-ornithine ratio was associated with an increased risk for all-cause death (unadjusted hazard ratio, 95% confidence interval) (0.940, 0.888–0.995) and cardiovascular death (0.895, 0.821–0.965) (p＜0.05 for all). In a model adjusted for age, sex, hypertension, hyperlipidemia, diabetes, current smoking, renal function, and log10-transformed brain natriuretic peptide level, cardiovascular death (0.911, 0.839–0.990, p=0.028) retained an association with a low l-arginine/ l-ornithine ratio. When the patients were grouped according to an l-arginine/l-ornithine ratio of 1.16, the lower l-arginine/l-ornithine ratio group had significantly higher incidence of all-cause death, cardiovascular death, and MACEs. Conclusion: A low l-arginine/l-ornithine ratio may be associated with increased 10-year cardiac mortality.