Abstract

Introduction: Drug-eluting stents (DESs) are replacing bare-metal stents (BMSs), but in-stent restenosis (ISR) remains a problem. Impaired endothelial function is a key event in the atherosclerosis process and a predictor of future cardiovascular events. Reactive hyperemia index (RHI) assessed by peripheral arterial tonometry (PAT) evaluates endothelial function noninvasively. Hypothesis: We prospectively assessed the prognostic value of RHI in predicting ISR after percutaneous coronary intervention (PCI). Methods: RHI was measured using Endo-PAT 2000 before PCI (initial RHI) and at follow-up angiography (F/U RHI) in 249 consecutive patients who had successful PCI. F/U angiography was performed at six and nine months after PCI with BMS and DES, respectively. ISR was defined as percent diameter stenosis >50% at F/U angiography assessed by quantitative coronary angiography. Results: At F/U, ISR was seen in 68 patients (27.3%). F/U ln(RHI) was significantly lower in patients with ISR than in those without (0.52 ± 0.23 vs. 0.65 ± 0.27, p < 0.01); no between-group difference in initial ln(RHI) was seen (0.60 ± 0.26 vs. 0.62 ± 0.25, p = 0.56). By multivariate logistic regression analysis, even after adjusting for other significant parameters in univariate analysis (BMS use, total stent length, HDL-Cholesterol, HbA1c, calcium antagonist use, and post-PCI minimum lumen diameter), F/U ln(RHI) independently predicted ISR (odds ratio: 0.13; 95% confidence interval [CI]: 0.04-0.48; p = 0.002). In receiver operating-characteristic analysis, F/U RHI was the strongest predictor of ISR (area under the curve [AUC]: 0.67; 95% CI: 0.60-0.75; p < 0.01; RHI < 1.73 had 67.6% sensitivity, 64.1% specificity); AUC significantly improved from 0.62 to 0.70 when RHI was added to traditional ISR risk factors (diabetes mellitus, total stent length, minimum stent diameter) (p = 0.02). Net reclassification index was significant after addition of RHI (26.5%, p = 0.002). Conclusions: To our knowledge, this is the first study indicating that impaired RHI at F/U angiography independently predicts occurrence of ISR. The simple and noninvasive assessment of endothelial function by RH-PAT adds incremental prognostic value to ISR-risk stratification following PCI.

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