Kinlay Scott, Schwartz Gregory G, Olsson Anders G, Rifai Nader, Leslie Sally J, Sasiela William J, Szarek Michael, Libby Peter, Ganz Peter
Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, Mass 02115, USA.
Circulation. 2003 Sep 30;108(13):1560-6. doi: 10.1161/01.CIR.0000091404.09558.AF. Epub 2003 Sep 15.
Inflammation promotes acute coronary syndromes and ensuing clinical complications. Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina, the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown.
We measured C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects with unstable angina or non-Q-wave myocardial infarction were randomized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks. The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome, country, and initial level of marker. All 3 markers were markedly elevated at randomization and declined over the 16 weeks in both treatment groups. Compared with placebo, atorvastatin significantly reduced CRP, -83% (95% CI, -84%, -81%) versus -74% (95% CI, -75%, -71%) (P<0.0001) and SAA, -80% (95% CI, -82%, -78%) versus -77% (-79%, -75%) (P=0.0006) but not IL-6, -55% (95% CI, -57%, -53%) versus -53% (95% CI, -55%, -51%) (P=0.3). Reductions in CRP and SAA were observed in patients with unstable angina and non-Q-wave myocardial infarction, with initial LDL cholesterol <3.2 or > or =3.2 mmol/L (125 mg/dL), age > or =65 or <65 years, and in men and women. By 16 weeks, CRP was 34% lower with atorvastatin than with placebo.
High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes. This supports the value of early statin therapy in these patients.
炎症会促发急性冠状动脉综合征及随后的临床并发症。虽然他汀类药物可降低无症状成年人或稳定型心绞痛患者的炎症标志物水平，但他汀类药物对急性冠状动脉综合征患者显著升高的炎症的影响尚不清楚。
我们在纳入强化降胆固醇治疗降低心肌缺血（MIRACL）研究的2402名受试者中测量了C反应蛋白（CRP）、血清淀粉样蛋白A（SAA）和白细胞介素6（IL-6）。不稳定型心绞痛或非Q波心肌梗死患者在入院24至96小时内被随机分为阿托伐他汀80mg/d组或安慰剂组，并治疗16周。在对所呈现的综合征、国家和标志物初始水平进行调整后，通过协方差分析评估治疗对炎症标志物的影响。所有3种标志物在随机分组时均显著升高，且在两个治疗组中均在16周内下降。与安慰剂相比，阿托伐他汀显著降低了CRP，分别为-83%（95%CI，-84%，-81%）和-74%（95%CI，-75%，-71%）（P<0.0001），以及SAA，分别为-80%（95%CI，-82%，-78%）和-77%（-79%，-75%）（P=0.0006），但未降低IL-6，分别为-55%（95%CI，-57%，-53%）和-53%（95%CI，-55%，-51%）（P=0.3）。在不稳定型心绞痛和非Q波心肌梗死患者中，无论初始低密度脂蛋白胆固醇<3.2或≥3.2mmol/L（125mg/dL）、年龄≥65岁或<65岁，以及男性和女性，均观察到CRP和SAA降低。到16周时，阿托伐他汀组的CRP比安慰剂组低34%。
大剂量阿托伐他汀可增强急性冠状动脉综合征患者炎症的下降。这支持了在这些患者中早期使用他汀类药物治疗的价值。
