Thin-cap fibroatheroma and increased coronary intima-media thickness are associated with an altered balance of arginine metabolites.

INTRODUCTION

Arginase inhibition increases plasma citrulline and citrulline / ornithine (C/O) ratio, and reduces plasma ornithine and ornithine / arginine (O/A) ratio in an animal model of myocardial infarction (MI).

OBJECTIVES

We hypothesized that the presence of thin‑cap fibroatheroma (TCFA) in the culprit lesion and increased non‑culprit intima‑media thickness of an infarct‑related artery (IRA) are associated with an altered balance of arginine metabolites.

PATIENTS AND METHODS

Arginine and its metabolites were measured using liquid chromatography and tandem mass spectrometry in 100 consecutive MI patients upon admission and at 6‑month follow‑up. TCFA and adjacent to culprit lesion proximal and distal 10‑mm segments were assessed with optical coherence tomography in the acute phase. Twenty five patients without coronary lesions on angiography served as controls.

RESULTS

The C/O ratio increased 5.33 times (P <0.001), while the O/A ratio decreased 2.53 times (P <0.001) at the 6‑month follow‑up, as compared with the acute phase of MI. The patients with (n = 75) vs without (n = 25) TCFA had lower C/O ratio by 29% (P = 0.003), while the mean intima‑media diameter of adjacent non‑culprit region correlated with the follow‑up O/A ratio (R = 0.337; P = 0.003). In a multivariable analysis, a higher acute phase C/O ratio was associated with a lower risk of TCFA presence (odds ratio, 0.978; 95% CI, 0.962-0.994; P = 0.006), whereas a higher follow‑up O/A ratio correlated with larger intima‑media diameter of the adjacent segments (β coefficient, 0.227; 95% CI for β coefficient, 0.045-0.409; P = 0.018).

CONCLUSIONS

Enhanced arginase activity over nitric oxide synthase following ischemia was associated with the presence of TCFA in the culprit lesion, while a similar metabolic shift in the chronic phase correlated with a greater thickness of the intima‑media in the adjacent non‑culprit IRA segments.