Abstract 3683: Diminished Global Arginine Bioavailability is Associated with Increased Long-term Cardiovascular Risk and Independent of Endogenous Nitric Oxide Synthase Inhibition
Background: We hypothesize that assessment of diminished global arginine bioavailability (GABR), which measures the steady-state equilibrium of substrate (arginine) and its two main catabolic products (ornithine plus citrulline), may better predict cardiovascular risks than assessing arginine alone.
Methods: We measured plasma levels of free arginine, ornithine, citrulline and the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) using LC/MS/MS, and examined the relationship of GABR to both prevalent coronary artery diseases (CAD) and incident major adverse cardiovascular events (MACE, including death, myocardial infarction, stroke) over a 3-year follow-up in 1,010 subjects undergoing elective cardiac catheterization.
Results: Patients with CAD had significantly lower GABR (1.0±0.5 vs 1.4±0.8 respectively, p<0.001) and lower arginine levels (68.5±20 vs 74.1±24 respectively, p<0.001) than those with no CAD. After adjusting for Framingham risk score, C-reactive protein, and renal function, the lowest quartile of GABR remained significantly associated with CAD (odds ratio 3.93, 95%CI 2.55– 6.05, p<0.001) and 3-year risk for incident MACE (Hazard ratio 1.97, 95%CI 1.09 –3.59, p=0.025). When adjusted for ADMA levels, GABR remained independently predictive of incident MACE (Hazard ratio 2.93, 95%CI 1.66 –5.20, p<0.001). In contrast, plasma arginine levels were not predictive of incident MACE after adjustments.
Conclusions: Diminished global arginine bioavailability may lead to a relative nitric oxide deficiency state associated with vascular diseases and increased long-term cardiovascular risks.