Clinical Study On Relationship Of Plasma C-reactive Protein And Endothlin-1 With Atherosclerotic Lesion Progression In Patients With Stable Angina Pectoris After Coronary Stenting

Objective:Chronic stable angina pectoris (SAP) is the most frequent form of ischemic heart disease, and percutaneous coronary intervention (PCI) with stent implantation has been a common treatment in these patients. Despite the current practice of invasive and medical treatment, these patients are still at increased risk for progression of native coronary atherosclerotic lesion after coronary stent implantation. Further, restenosis remains a major clinical issue after coronary stenting in diabetes mellitus and morphologically complex coronary lesions. Accumulated data have demonstrated that almost all known mechanisms involving the atherosclerotic lesions development, progression, vulnerability, and disruption are associated with activating and perpetuating inflammatory processes. However, in the drug-eluting stent era and with the optimal medical treatments including statins in patients, the study on relationship between systemic inflammatory biomarkers and progression of coronary artery atherosclerotic lesion is largely absent or the role of inflammatory markers in atherosclerotic plaque progression remains controversial. Therefore, the present study evaluated a relatively big-size patient cohort who underwent drug-eluting stent implantation and standard medical treatments and tested the hypothesis that increased plasma inflammatory biomarkers including C-reactive protein (CRP) and endothelin-1 (ET-1) would indicate rapid progression of coronary artery atherosclerotic lesions in Chinese patients with SAP.Methods:We consecutively studied 311 Chinese patients with SAP (243 men; mean age,57±10 years) who underwent diagnostic coronary angiography and successful PCI with drug-eluting stent implantation on initial admission, and were scheduled to receive angiographic follow-up (6-9 months; mean interval,8.5±1.2 months) on re-admission. Two consecutive diagnostic coronary angiograms were used to quantitatively evaluate coronary artery atherosclerotic lesion progression. Rapid angiographic stenotic progression (RASP) of non-intervened native coronary artery atherosclerotic plaque and in-stent restenosis (ISR) of stented target coronary lesion were well defined. Plasma levels of CRP, ET-1 and other inflammatory indicators were measured on initial admission as the baseline and at angiographic follow-up in all eligible patients. The standard medications including statins were not discontinued throughout the study period.Results:RASP of non-intervened de novo atherosclerotic plaques occurred in 136 patients (43.7%) who were categorized into the progression group, and 175 patients were not found RASP at follow-up (the non-progression group). ISR of stented target lesions were seen in 51 patients (16.4%) by about 9 months who were categorized into the restenosis group, and other 260 patients were not observed ISR (the non-restenosis group). Baseline demographic and clinical data were similar in patients with and without RASP as well as with and without ISR. Compared with the non-progression group, the progression group had higher baseline plasma high-sensitive CRP (median,1.60 mg/L vs 0.96 mg/L, P<0.001) levels. There was no significant difference in baseline big ET-1, white blood cell count, or erythrocyte sedimentation levels between the 2 groups. Compared with the non-restenosis group, the restenosis group had higher baseline and follow-up high-sensitive CRP concentrations (median,2.98 mg/L vs 1.05 mg/L, P<0.001; median, 2.55 mg/L vs 0.72 mg/L, P<0.001). There were no significant differences in big ET-1 and other inflammatory indicators levels between the 2 groups. Multivariate regression analysis showed that baseline plasma high-sensitive CRP (P=0.001) and coronary multi-vessel disease (P=0.002) were independently predicted RASP. We used cutoff value (1.32 mg/L) to calculate the predictive value of baseline high-sensitive CRP for RASP (odds ratio,3.497; 95% confidence intervals, 2.045-5.980). The rate of RASP was significantly higher in patients with high-sensitive CRP levels>1.32 mg/L than in patients with high-sensitive CRP levels≤1.32 mg/L (54% vs 30%, P<0.001). In multivariate regression analysis model, we found that both plasma baseline and follow-up high-sensitive CRP (P=0·001 and P<0·001) and the number of implanted stents (P=0.015) were independent risk predictors of the occurrence of ISR. According to receiver operating characteristic curve assessment, the predictive value of follow-up CRP was more powerful than that of baseline CRP (the area under the curve, 0.796 vs 0.752).Conclusions:The present study indicated that increased plasma baseline levels of CRP might be independent predictors of RASP in patients with SAP after successful drug-eluting stents implantation and standard medical treatments, and that both baseline and follow-up CRP might independently predict ISR. Our data suggested that a systemic inflammatory response might be involved in the pathogenesis of coronary atherosclerotic disease progression Objective:Chronic stable angina pectoris (SAP) is the most frequent form of ischemic heart disease, and percutaneous coronary intervention (PCI) with stent implantation has been a common treatment in these patients. Despite the current practice of invasive and medical treatment, these patients are still at increased risk for progression of native coronary atherosclerotic lesion after coronary stent implantation. Further, restenosis remains a major clinical issue after coronary stenting in diabetes mellitus and morphologically complex coronary lesions. N-terminal pro-brain natriuretic peptide (NT-proBNP) has been a strong prognostic biomarker regarding cardiovascular mortality for patients with chronic SAP treated with coronary stent inplantation. However, in the drug-eluting stent era and with the optimal medical treatments including statins, its ability to predict angiographic progression of de novo coronary atherosclerotic plaque remains unclear or the role of NT-proBNP in restenosis of target atherosclerotic lesion remains controversial. Therefore, the present study evaluated a relatively big-size patient cohort who underwent drug-eluting stent implantation and standard medical treatments and tested the hypothesis that increased plasma NT-proBNP would predict rapid progression of coronary artery atherosclerotic lesions in Chinese patients with SAP preserved left ventricular (LV) function.Methods:We prospectively studied 303 consecutive patients with SAP (236 men; mean age,57±10 years) with preserved LV systolic function (ejection fraction>50%) who underwent diagnostic coronary angiography and successful PCI with drug-eluting stent implantation on initial admission, and were scheduled to receive angiographic follow-up by 9 months (mean interval,8.5±1.0 months) on re-admission. Two consecutive diagnostic coronary angiograms were used to quantitatively evaluate coronary artery atherosclerotic lesion progression. Rapid angiographic stenotic progression (RASP) of non-intervened native coronary artery atherosclerotic plaque and in-stent restenosis (ISR) of stented target coronary lesion were well defined. Peripheral blood samples for determination of NT-proBNP were drawn on initial admission as the baseline and at angiographic follow-up in all eligible patients.The standard medications including statins were not discontinued throughout the study period.Results:All 303 patients underwent follow-up CAG and had preserved LV function at follow-up. No patients had death or heart failure during clinical follow-up. RASP of non-intervened de novo atherosclerotic plaques occurred in 133 patients (43.8%) who were categorized into the progression group, and 170 patients were not found RASP at follow-up (the non-progression group). ISR of stented target lesions were seen in in 49 patients (16.2%) by about 9 months who were categorized into the restenosis group, and other 254 patients were not observed ISR (the non-restenosis group). Baseline demographic and clinical data were similar in patients with and without RASP as well as with and without ISR. Compared with the non-progression group, the progression group had higher baseline plasma NT-proBNP (mean,563 fmol/mL vs 463 fmol/mL, P<0.017) levels. There was no significant difference in follow-up NT-proBNP levels between the 2 groups (P=0.487). There were no significant differences in NT-proBNP levels between the restenosis and non-restenosis groups. The RASP rate in patients increased directly across quartiles of the baseline NT-proBNP levels (P=0.037). Multivariate regression analysis showed that baseline plasma NT-proBNP (P=0.035), and coronary multi-vessel disease (P=0.001) were independently predicted RASP. When cutoff value (515 fmol/mL) was used, we found that baseline NT-proBNP levels also had the predictive power for RASP (odds ratio,1.944; 95% confidence intervals, 1.047-3.608). However, NT-proBNP was not significantly associated with ISR in this population.Conclusions:The present study indicated that increased plasma baseline levels of NT-proBNP might be independent predictors of RASP in patients with SAP and normal cardiac function after successful drug-eluting stents implantation and standard medical treatments, and plasma NT-proBNP might not be associated with ISR of target lesion.