Association between asymmetric dimethylarginine and in-stent restenosis tissue characteristics assessed by optical coherence tomography.

Background: Impaired bioavailability of endothelium-derived nitric oxide (NO) and endothelial dysfunction may play a pivotal role in the pathogenesis of in-stent restenosis (ISR) after coronary stenting. We aimed to investigate the relation between asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, and the ISR lesions tissue characteristics assessed by optical coherence tomography (OCT).

Methods And Results: Forty-five patients with symptomatic ISR lesions (17 bare metal stents, 28 drug-eluting stents, medium implantation duration: 58.0 months) were evaluated by OCT for in-stent tissue characteristics and calcification. We defined neoatherosclerosis as the presence of lipid or calcified neointima in ISR lesions, and 12 (26.7%), 33 (73.3%) ISR lesions were classified as with homogenous neointima and neoatherosclerosis respectively. The patients with neoatherosclerosis have significantly higher plasma ADMA levels compared to those of patients with homogenous neointima (1.12 ± 0.21 μmol/l versus 0.83 ± 0.08 μmol/l, p < 0.001). Furthermore, the plasma ADMA level of ISR lesions with intra-stent calcification (n = 24, 53.3%) was also significantly higher than those of ISR lesions without (n = 21, 46.7%; p < 0.001). There was a highly significant association between plasma ADMA level and intra-stent relative calcium index (mean calcium arc × calcium length)/(360 × analyzed length) (p < 0.001, r = 0.702). In multivariate analyses adjusted for age, sex, diabetes, eGFR, plasma ADMA level remained the only significant predictor for the presence of neoatherosclerosis (p = 0.008) and intra-stent calcification (p < 0.001). In contrast, plasma ADMA level correlated with intra-stent relative lipid core index (mean lipid core arc × lipid core length)/(360 × analyzed length) only in subgroup without intra-stent calcification (p = 0.004, r = 0.596, multivariate-adjusted p = 0.022).

Conclusions: Increased plasma ADMA levels were associated with the development of in-stent neoatherosclerosis and calcification.