C 反应蛋白，但不是低密度脂蛋白胆固醇水平，与最大强度他汀类药物治疗后冠状动脉粥样斑块消退和心血管事件相关。
C-reactive protein, but not low-density lipoprotein cholesterol levels, associate with coronary atheroma regression and cardiovascular events after maximally intensive statin therapy.
机构信息
Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH (R.P., S.E.N., K.U., Y.K., S.J.N.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.L.); C5Research, Cleveland Clinic, Cleveland, OH (M.S.); Section of Cardiovascular Research, Baylor College of Medicine, and the Methodist DeBakey Heart and Vascular Center, Houston, TX (C.M.B.); Centre for Vascular Research, University of New South Wales, Sydney, Australia (P.J.B.); INSERM Dyslipidaemia and Atherosclerosis Research Unit, Hôpital de la Pitié, Paris, France (M.J.C.); West German Heart Center, Essen, Germany (R.E.); AstraZeneca, Wilmington, DE (J.S.R.); and South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia (S.J.N.).
出版信息
Circulation. 2013 Nov 26;128(22):2395-403. doi: 10.1161/CIRCULATIONAHA.113.004243. Epub 2013 Sep 16.
BACKGROUND
Baseline C-reactive protein (CRP) levels predict major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, coronary revascularization, and hospitalization for unstable angina). The association between changes in CRP levels with plaque progression and MACE in the setting of maximally intensive statin therapy is unknown.
METHODS AND RESULTS
The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. The treatment groups did not differ significantly in the change from baseline of percent atheroma volume on intravascular ultrasound, CRP-modulating effects, or MACE rates, thus allowing for a (prespecified) post hoc analysis to test associations between the changes in CRP levels with coronary disease progression and MACE. Patients with nonincreasing CRP levels (n=621) had higher baseline (2.3 [1.1-4.7] versus 1.1 [0.5-1.8] mg/L; P<0.001) and lower follow-up CRP levels (0.8 [0.5-1.7] versus 1.6 [0.7-4.1] mg/L; P<0.001) versus those with increasing CRP levels (n=364). Multivariable analysis revealed a nonincreasing CRP level to independently associate with greater percent atheroma volume regression (P=0.01). Although the (log) change in CRP did not associate with MACE (hazard ratio, 1.18; 95% confidence interval, 0.93-1.50; P=0.17), the (log) on-treatment CRP associated significantly with MACE (hazard ratio, 1.28; 95% confidence interval, 1.04-1.56; P=0.02). On-treatment low-density lipoprotein cholesterol levels did not correlate with MACE (hazard ratio, 1.09; 95% confidence interval, 0.88-1.35; P=0.45).
CONCLUSIONS
Following 24 months of potent statin therapy, on-treatment CRP levels associated with MACE. Inflammation may be an important driver of residual cardiovascular risk in patients with coronary artery disease despite aggressive statin therapy.
CLINICAL TRIAL REGISTRATION URL
http://clinicaltrials.gov. Unique identifier: NCT000620542.
背景
基线 C 反应蛋白（CRP）水平可预测主要不良心血管事件（MACE：死亡、心肌梗死、卒、冠状动脉血运重建和不稳定型心绞痛住院）。在最大程度强化他汀类药物治疗的情况下，CRP 水平变化与斑块进展和 MACE 之间的关系尚不清楚。
方法和结果
冠状动脉粥样硬化的研究：瑞舒伐他汀与阿托伐他汀的效果（SATURN）使用经导管血管内超声连续测量接受瑞舒伐他汀 40mg 或阿托伐他汀 80mg 治疗 24 个月的患者的冠状动脉粥样斑块体积百分比。两组在经导管血管内超声测量的动脉粥样斑块体积百分比的变化、CRP 调节作用或 MACE 发生率方面无显著差异，因此可以进行（预设的）事后分析，以检验 CRP 水平变化与冠状动脉疾病进展和 MACE 之间的关联。CRP 水平无升高的患者（n=621）基线 CRP 水平较高（2.3[1.1-4.7]与 1.1[0.5-1.8]mg/L；P<0.001），随访时 CRP 水平较低（0.8[0.5-1.7]与 1.6[0.7-4.1]mg/L；P<0.001），而 CRP 水平升高的患者（n=364）则不然。多变量分析显示，CRP 水平无升高与更大的动脉粥样斑块体积消退独立相关（P=0.01）。虽然 CRP（log）变化与 MACE 无相关性（风险比，1.18；95%置信区间，0.93-1.50；P=0.17），但治疗中 CRP（log）与 MACE 显著相关（风险比，1.28；95%置信区间，1.04-1.56；P=0.02）。治疗中的低密度脂蛋白胆固醇水平与 MACE 不相关（风险比，1.09；95%置信区间，0.88-1.35；P=0.45）。
结论
在接受 24 个月强化他汀类药物治疗后，治疗中的 CRP 水平与 MACE 相关。炎症可能是冠状动脉疾病患者在强化他汀类药物治疗后残余心血管风险的一个重要驱动因素。
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