| Objective:This study assessed the role of microRNAs and DNA methylation in progression of non-culprit coronary lesion (NCCL) atherosclerosis in patients who underwent coronary percutaneous coronary interventions (PCI).Methods:In the observational, retrospective, and single-center study,249 consecutive patients with coronary artery disease (CAD) who underwent successful percutaneous coronary intervention (PCI) with stents and follow-up (mean interval, (12.38 ±4.73)months) diagnostic coronary angiography (CAG) between August 1, 2010, and MAY 31,2013 were enrolled. The non-culprit coronary lesion (NCCL) was the de novo stenotic lesion that was not responsible for the ischemic symptom or positive functional ischemic test. When multiple NCCLs were present, the lesion had the biggest increase in diameter stenosis in the follow-up CAG was identified as the index lesion for each patient. The progression of non-culprit coronary lesion was assessed by using three-dimensional quantitative coronary angiography (3D QCA). The progression of NCCL was defined as≥10% diameter reduction of a preexisting stenosis≥50%,≥30% diameter reduction of a stenosis<50%, development of a new stenosis≥30% in a previously normal segment, or progression of any stenosis to total occlusion. The patients were classified into two groups according to whether the progression existed or not and the relation between a higher peak monocyte count and the progression of atherosclerosis was investigated. All patients gave written informed consent for participation in the study, and the study protocol was approved by the Ethic Committees of the Chinese PLA General Hospital and complies with the Declaration of Helsinki.Results: ① The plasma microRNA Let-7i (1.39±1.82 vs 3.09±5.03, P= 0.019) were significantly lower in NCCL progression group than in non-progression group. The methylation of promoter region of TLR4 gene(9.78± 3.38 vs12.95±5.23, P<0.001), the microRNA Let-7i target gene, was significantly lower in NCCL progression group than in non-progression group.Conclusions:The circulating microRNA Let-7i play an important role in the progression of NCCL. The methylation of promoter region of TLR4 gene may play an important role in the progression of NCCL.Objective:Coronary heart disease (CHD) occurs predominantly in elderly individuals, but also affects younger adults. It has been reported in recent studies that 5-10% of myocardial infarctions occur in people under 40 years of age and 7-10% under 45 years.Risk factors for CHD in young adults are the same as those in older individuals. Young patients usually have more than one traditional risk factor for CHD; smoking and dyslipidemia are the most strongly associated. Their angiographic profile differs from that of older patients, with a preponderance of single-vessel atherosclerotic disease compared with the multivessel disease that is more common in older patients.Many studies suggest that younger age is a significant independent indicator of a favorable prognosis after acute myocardial infarction and outcomes have been found to be more favorable in young CHD patients than any group of older patients for up to 7 years following hospitalization. However, a large study evaluated long term survival and predictors of elevated risk in young adults diagnosed with CHD and found that coronary disease in such patients can have a poor long term prognosis; overall mortality was 30% at 15 years and 45% in young patients with prior acute myocardial infarction (AMI). These conflicting results suggest that many questions remains regarding young patients with CHD.To the best of our knowledge, evidence on the progression of coronary lesions in young patients with CHD was limited as compared to the older population. In the present observational study, we investigated the difference in the progression of coronary lesions between young patients (< 45 years) and older patients (≥ 45 years).Methods:Eight hundred and forty-eight consecutive patients who underwent successful PCI with stents and second coronary angiography in a single center from January 7,2008 to May 7,2013 were enrolled. In patients with multiple NCCLs, the lesion that exhibited the greatest increase in stenosed diameter on second CAG was considered the index lesion.NCCL progression was assessed using three-dimensional quantitative coronary angiography and was defined as≥10% diameter reduction of preexisting stenoses of ≥50%,≥30% diameter reduction of <50% stenoses, development of a new stenosis of ≥30% in a previously normal segment, or progression to total occlusion. ①.A11 individuals are devided into NCCL progression group and NCCL no-progression group. Cox’s proportional hazards method was used to develop a multivariate model of NCCL progression rate, including the variables sex, STEMI, body mass index (BMI), SBP, DBP, serum lipids, fasting blood glucose, smoking, drinking, hypertension, family history of CHD, diabetes mellitus and NCCL characteristics.②Patients were divided into young patients(<45 years) and older patients(≥ 45 years) according to the age at the first catheterization.The differences of clinical risk factors and NCCL charactors between young patients and older patients was found to analyzed the reasons for higer NCCL progression rate of the former. Continuous variables were compared using Student’s t-test or one-way analysis of variance. If variables were not normally distributed, the Mann-Whitney U test was performed. Categorical variables were compared by chi-square analysis. The Kaplan-Meier method with a log-rank test was used for unadjusted analysis of the difference in the rate of atherosclerotic progression between young and older patients.Results: ①The mean time interval between two catheterization was 10.79 months; 136 (16.0%) patients exhibited progression of NCCLs. Patients with progression were more often males (88.2% vs.80.1%, respectively; p= 0.03), STEMI(39.0% vs.13.5%, respectively; p<0.001) and Young patients(19.9% vs.10%, respectively; p= 0.002). Patients with progression had lower Percent diameter obstruction (32.21±13.24% vs.35.03±13.01%, respectively; p= 0.021)and MLA (3.41±2.08 mm2 vs.3.99±2.75 mm2, respectively; p= 0.018). At baseline CAG, all lipid profile had no significantly difference between progression and non-progression of NCCL. Patients with progression had higer Low-density lipoprotein cholesterol levels (LDL) (2.24 ± 0.85 mmol/L vs 2.10 ± 0.75 mmol/L; P= 0.046) and lower high-density lipoprotein cholesterol (HDL-C) (1.01 ± 0.27 mmol/L vs 1.07 ± 0.30 mmol/L; P= 0.027) levels at second CAG. None of the other differences attained statistical significance. ②Multivariate Cox regression analysis (stepwise) showed young age to be an independent determinant of NCCL progression. Compared with the older patients(≥45 years), the crude hazard ratio (HR) for NCCL progression in the young patients(<45 years) was 2.17 (95% CI 1.42-3.30; P<0.001); the association remained significant after adjustment for sex, ST elevation myocardial infarction, body mass index, systolic and diastolic blood pressure, serum lipids, fasting blood glucose, smoking, drinking, hypertension, family history of CHD, diabetes mellitus, medication use and NCCL characteristics (adjusted HR 1.70,95% CI 1.06-2.72; P=0.029). Multivariate analysis identified STEMI as another independent predictors for NCCL progression. Diabetes associated with higher risks of NCCL progression in the reduce Cox proportional hazard model analysis but not in the full model analysis. ③ These young patients were more likely to be male (93.9% vs 79.7%; P< 0.001), to have STEMI (27.6% vs 16.3%; P= 0.01), to smoke (64.3% vs 39.5%; P< 0.001) and to drink (33.7% vs 22.7%; P= 0.023) and less likely to have hypertension (52.0% vs 65.5%; P= 0.01). The young patients had greater BMI (26.66 ± 3.39 kg/m2 vs 25.84 ± 3.04 kg/m2; P= 0.013), higher blood uric acid levels (357.70 ± 85.31 μmol/L vs 330.97 ± 86.55 μmol/L; P= 0.005) and DBP (75.92 ± 10.68 mmHg vs 73.37 ± 10.37 mm Hg; P= 0.023) and lower SBP (123.60 ± 14.56 mm Hg vs 127.31 ± 15.52 mm Hg; P= 0.026).Young patients had higher triglyceride (TG) levels (2.01 ±1.21 mmol/L vs 1.75 ± 1.12 mmol/L; P= 0.030) and lower high density lipoprotein cholesterol (HDL-C) (1.00 ± 0.35 mmol/L vs 1.07 ± 0.29 mmol/L; P= 0.025). Young patients usually have more than one traditional risk factor for CHD Conclusions: ① NCCLs in young patients (<45 years) with coronary artery disease have higher rates of atherosclerotic progression. STEMI as another independent predictors for NCCL progression; ②Young patients were more likely to be male,to have STEMI, to smoke and to drink and less likely to have hypertension. Young patients had higher triglyceride (TG) levelsand lower high density lipoprotein cholesterol. Young patients usually have more than one traditional risk factor for CHD... |
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