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

J Atheroscler Thromb. 2023 Oct 1;30(10):1364-1375. doi: 10.5551/jat.63779. Epub 2023 Feb 11.

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.

Keywords: Amino acid; Cardiovascular event; Mortality; Prognosis.

MeSH terms

  • Aged
  • Arginine*
  • Citrulline
  • Female
  • Humans
  • Hypertension*
  • Male
  • Middle Aged
  • Ornithine / metabolism
  • Prognosis

Substances

  • Arginine
  • Citrulline
  • Ornithine