Stewart Ralph A H, White Harvey D, Kirby Adrienne C, Heritier Stephane R, Simes R John, Nestel Paul J, West Malcolm J, Colquhoun David M, Tonkin Andrew M
Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
Circulation. 2005 Apr 12;111(14):1756-62. doi: 10.1161/01.CIR.0000160924.73417.26. Epub 2005 Apr 4.
Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment.
We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1x10(9)/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P=0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2x10(9)/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (P=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased (by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively).
These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.
血清炎症标志物水平升高与心血管事件的长期风险增加相关。由于3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）可能具有抗炎作用，因此有人提出，炎症标志物水平升高的患者接受他汀类药物治疗后心血管风险的降低幅度可能更大。
在缺血性疾病普伐他汀长期干预研究（LIPID研究）中，我们评估了白细胞计数（WBC）与冠心病死亡率之间的关联。该临床试验将9014例有心肌梗死病史或不稳定型心绞痛的稳定患者随机分为普伐他汀组（40mg/d）和安慰剂组，平均随访6.0年。基线白细胞计数升高与随机分配至安慰剂组的患者冠心病死亡率增加相关（白细胞计数每增加1×10⁹/L的风险比为1.18；95%可信区间为1.12至1.25；P<0.001），但与普伐他汀组无关（风险比为1.02；95%可信区间为`0.96至1.09；P=0.56；交互作用P=0.004）。对于基线白细胞计数四分位数分别为<5.9、6.0至6.9、7.0至8.1和>8.2×10⁹/L的患者，每1000例接受普伐他汀治疗的患者预防的冠心病死亡人数分别为0、9、30和38。白细胞计数比总胆固醇与高密度脂蛋白胆固醇之比以及心脏风险的综合指标更能预测这种治疗益处。随着基线白细胞计数升高（按四分位数），普伐他汀治疗使心血管死亡率、非致命性心肌梗死和中风的联合发生率也有更大幅度的降低（分别为每1000例接受治疗的患者预防3、41、61和60例事件；P=0.052）。
这些数据支持以下假设，即有炎症证据的个体可能从他汀类药物治疗中获得更大益处。
