高敏C反应蛋白对冠状动脉搭桥手术近期和中期预后的预测作用

【作者】 王健仰；

【导师】 胡盛寿；

【作者基本信息】 北京协和医学院 ， 临床医学， 2010， 博士

【摘要】 背景：人体血清C反应蛋白(C-reactive protein, CRP)升高是心血管事件的独立预测因子。高敏C反应蛋白(high sensitivity CRP, hsCRP)是使用高敏感的检测方法,对CRP的进行精确定量,从而更加准确的预测心血管事件。但是截至目前,还没有关于hsCRP与冠状动脉旁路移植手术中远期预后的相关性研究。本文将回顾性分析术前hsCRP对近期和中期预后的预测作用。方法：本研究入选了从2006年1月1日到2007年12月31日在阜外心血管病医院行单纯冠状动脉旁路移植手术(CABG)的冠心病患者,分析术前hsCRP水平与近期、中期预后的相关关系,并寻找合理的危险分层界值,最后采用多因素回归模型研究hsCRP升高对近期、中期预后的独立危险作用。近期预后终点为院内死亡、术后主要并发症。中期预后终点为(全因)死亡、主要不良心血管事件(MACE)和充血性心力衰竭(心衰)。结果：研究期间共有3236名患者接受CABG,其中373名患者术前未检测hsCRP而被排除,最终2863名患者入选本研究。住院期间,死亡患者为26名(0.9%),发生术后主要并发症患者288名(10.1%)。术后随访3.6年(平均1.7年),成功随访到2826名患者(随访率为99.6%),其中死亡患者56名(2.0%),发生MACE患者105名(3.7%),发生心衰患者70名(2.5%)。分析显示,术前hsCRP每升高1mg/L,发生院内死亡(OR=2.50,p=0.002)、术后主要并发症(OR=1.38,p=0.02)、中期死亡(HR=1.68,p=0.03)、主要不良心血管事件(MACE)(HR=1.48, p=0.04)和心衰(HR=1.88,p=0.01)的风险均显著增加。进一步分析表明hsCRP=2.5mg/L是本研究中CABG患者危险分层的理想界值。术前hsCRP升高患者(hsCRP>2.5mg/L, n=1070)的院内死亡、术后主要并发症、中期死亡、MACE和心衰发生率均显著高于术前hsCRP未升高的患者(hsCRP≤2.5mg/L,n=1793)。校正其他因素后,hsCRP>2.5mg/L是院内死亡(p=0.02,HR=2.55)、术后主要并发症(p=0.004,HR=1.46)、中期死亡p=0.02, HR=1.92)、MACE(p<0.001, HR=2.06)和心衰(p=0.03,HR=1.71)的独立危险因素。结论：术前hsCRP水平与冠状动脉旁路移植手术预后显著相关,hsCRP升高(hsCRP>2.5mg/L)是近期和中期预后的独立危险因素。hsCRP应该在冠状动脉旁路移植手术患者的危险分层中应用。背景：他汀类药物的抗炎作用在冠心的一级预防和二级预防中极为重要。在血脂水平正常的健康人群中,他汀类药物可以显著降低高炎症状态(CRP升高)患者的心血管事件发生率和死亡率,可是在低炎症状态人群中,这种保护作用并不明显。但目前还没有关于冠心病患者的类似报道。本研究将探索他汀类药物对于不同炎症状态冠状动脉旁路移植手术(CABG)患者的心血管事件保护作用是否存在差异。方法：本研究分析了从2006年1月1日到2007年12月31日在阜外心血管病医院行单纯冠状动脉旁路移植手术并存活出院的冠心病患者,按照本文第一部分获得的hsCRP界值(2.5mg/L)将其分为高、低炎症状态两组,再以术后是否长期服用他汀类药物进行亚组划分,分析他汀类药物对各亚组的中期预后保护作用。中期预后终点为(全因)死亡、主要不良心血管事件(MACE)和充血性心力衰竭(心衰)。结果：根据本文第一部分,共有2837名患者入选本研究。在高炎症状态组(n=1054),术后长期服用他汀类药物患者的死亡率(0.74%vs5.28%,p<0.001)、MACE发生率(3.31%vs7.05%,p=0.003)和心衰发生率(2.03%vs4.89%,p=0.01)均显著低于未长期服用他汀类药物组。但对于低炎症状态组(n=1783),死亡率(0.97%vs2.00%, p=0.10)、MACE发生率(3.29%vs2.27%,p=0.20)、心衰发生率(1.94%vs1.87%,p=0.98)没有差异。经过校正其他因素,术后长期服用他汀类药物可以降低高炎症状态患者的死亡风险64%(HR=0.36,p=0.002,95%CI=0.25-0.70),降低MACE风险54%(HR=0.46,p=0.01,95%CI=0.25-0.82),降低心衰风险69%(HR=0.31, p=0.003,95%CI=0.14-0.66)。但对于低炎症状态患者,术后长期服用他汀类药物对死亡(HR=0.53,p=0.12,95%CI=0.24-1.18)、MACE (HR=1.10, p=0.75,95%CI=0.60-2.04)、心衰(HR=1.35, p=0.42,95%CI=0.65-2.82)的作用无统计学意义。结论：术后长期服用他汀类药物对术前高炎症状态(hsCRP>2.5mg/L)患者的中期预后有保护作用,可以显著降低死亡、MACE和心衰的发生风险。而对于术前低炎症状态(hsCRP≤2.5mg/L)患者,术后长期服用他汀类药物对中期预后的影响并不明显。更多还原

【Abstract】 Background—Elevated C-reactive protein (CRP) is a powerful independent predictor of cardiovascular events in the healthy population and in patients with coronary artery disease. High-sensitive C-Reactive Protein (hsCRP) is precise and sensitive for quantification of CRP. But to date, there is no date on its impact on overall mid-term and late outcomes after coronary artery bypass grafting (CABG). The study objective was to evaluate the effect of hsCRP on early and mid-term outcome after CABGMethods—We have investigated the relationship of preoperative hsCRP with early and mid-term outcomes of all the patients who underwent isolated CABG between1st January2006and31st December2007in Fuwai Hospital. Then we tried to get an optimal cut off value of hsCRP for risk stratification and estimate the effect of elevated hsCRP on the early and mid-term outcomes by multivariable regression analysis. Early endpoints were in-hospital mortality and postoperative major morbidity. Mid-term endpoints were overall mortality, major adverse cardiovascular events (MACE) and new onset heart failure.Result—In2863of3236cases, the preoperative C-reactive protein level could be retrieved. During the in-hospital stay,26patients died (0.9%) and288patients suffered postoperative major morbidity (10.1%). Among operative survivors,11patients were unavailable for follow-up. At3.6year follow-up,56patients died (2.0%),105patients had MACE (3.7%) and70patients developed heart failure (2.5%). We found that every lmg/L uprising for hsCRP was associated with increased odds ratio (OR) for early mortality (OR=2.50, p=0.002), postoperative major morbidity (OR=1.38, p=0.02), and raised hazard ratio (HR) for mid-term mortality (HR=1.68, p=0.03), MACE (HR=1.48, p=0.04) and heart failure (HR=1.88,p=0.01). Further analysis showed that hsCRP=2.5mg/L was the best cutoff value for risk stratification in terms of both early and mid-term outcomes of CABG The patients whose preoperative hsCRP levels were elevated (>2.5mg/L, n=1070) suffered significantly increased early mortality (1.50%vs0.56%, p=0.01), major morbidity (12.71%vs8.48%, p<0.001), mid-term mortality (2.94%vs1.40%, p=0.01), MACE (5.12%vs2.86%,p=0.003) and heart failure (3.42%vs1.91%,p=0.02) than those whose preoperative hsCRP≤2.5mg/L (n=1793). Multivariate analysis revealed that preoperative hsCRP>2.5mg/L was an independent risk factor of both early (p=0.02, HR=2.55) and mid-term mortality (p=0.02, HR=1.92), postoperative major morbidity (p=0.004, HR=1.46), mid-term MACE (p<0.001, HR=2.06) and heart failure (p=0.03, HR=1.71).Conclusions—Preoperative hsCRP levels were significantly correlated with outcomes of CABG Elevated levels of hsCRP (>2.5mg/L) predict an increased risk of early and mid-term outcome after CABG. CRP levels should be taken into account for risk stratification in CABG. Background—Landmark clinical trials have demonstrated the prominent protective value of anti-inflammatory effect of statins on primary and secondary prevention of coronary artery diseases. In health people with average levels of total and LDL cholesterol, statins showed significant primary prevention effect for the group with elevated C reactive protein (CRP), but not for those without elevated CRP. However, no studies have addressed the issue that if patients with different inflammatory level might derive similar benefit from continuous statin treatment after coronary artery bypass grafting surgery (CABG). Therefore, we evaluated the effect of continuous statin treatment on late outcomes of patients with different CRP levels after CABG.Methods—This retrospective cohort study enrolled all the patients who underwent isolated CABG and survived to discharge between1st January2006and31st December2007in Fuwai Hospital, and was divided into two groups according to cut-off value of preoperative hsCRP (2.5mg/L) obtained in PART I. Then we evaluated the relations between postoperative continuous statin therapy and mid-term outcomes for both groups. Mid-term endpoints were overall mortality, major adverse cardiovascular events (MACE) and congestive heart failure.Result—According to PART I,2837patients were analyzed in this study. For the group of preoperative hsCRP>2.5mg/L, patients who took postoperative continuous statin therapy had remarkably reduced the mid-term incidences of death (0.74%vs5.28%,p<0.001), MACE (3.31%vs7.05%, p=0.003) and heart failure (2.03%vs4.89%, p=0.01) compared with those did not take persistent statins. For the group of preoperative hsCRP≤2.5mg/L, patients with postoperative continuous statin therapy had similar mid-term incidences of death (0.97%vs2.00%, p=0.10), MACE (3.29%vs2.27%, p=0.20) and heart failure (1.94%vs1.87%, p=0.98) compared with those did not take persistent statins. After adjusted for other variables, continuous statin therapy remarkably reduced risk of mid-term mortality by64%(HR=0.36,p=0.002,95%CI=0.25-0.70), MACE by54%(HR=0.46, p=0.01,95%CI=0.25-0.82) and heart failure by69%(HR=0.31,p=0.003, 95%CI=0.14-0.66) for patients with preoperative hsCRP>2.5mg/L. However, this protective effect was not statistically significant for mid-term mortality (HR=0.53,p=0.12,95%CI=0.24-1.18), MACE (HR=1.10, p=0.75,95%CI=0.60-2.04) and heart failure (HR=1.35,p=0.42,95%CI=0.65-2.82) among patients whose preoperative hsCRP≤2.5mg/L.Conclusions—Postoperative continuous statin therapy could significantly reduced the mid-term incidences of death, MACE, heart failure for patients with elevated preoperative levels of hsCRP(>2.5mg/L). Whereas, this protective effect was not statistically significant among patients whose preoperative levels of hsCRP≤2.5mg/L.更多还原