Nissen Steven E, Tuzcu E Murat, Schoenhagen Paul, Crowe Tim, Sasiela William J, Tsai John, Orazem John, Magorien Raymond D, O'Shaughnessy Charles, Ganz Peter
Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
N Engl J Med. 2005 Jan 6;352(1):29-38. doi: 10.1056/NEJMoa042000.
Recent trials have demonstrated better outcomes with intensive than with moderate statin treatment. Intensive treatment produced greater reductions in both low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP), suggesting a relationship between these two biomarkers and disease progression.
We performed intravascular ultrasonography in 502 patients with angiographically documented coronary disease. Patients were randomly assigned to receive moderate treatment (40 mg of pravastatin orally per day) or intensive treatment (80 mg of atorvastatin orally per day). Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis. Lipoprotein and CRP levels were measured at baseline and follow-up.
In the group as a whole, the mean LDL cholesterol level was reduced from 150.2 mg per deciliter (3.88 mmol per liter) at baseline to 94.5 mg per deciliter (2.44 mmol per liter) at 18 months (P<0.001), and the geometric mean CRP level decreased from 2.9 to 2.3 mg per liter (P<0.001). The correlation between the reduction in LDL cholesterol levels and that in CRP levels was weak but significant in the group as a whole (r=0.13, P=0.005), but not in either treatment group alone. In univariate analyses, the percent change in the levels of LDL cholesterol, CRP, apolipoprotein B-100, and non-high-density lipoprotein cholesterol were related to the rate of progression of atherosclerosis. After adjustment for the reduction in these lipid levels, the decrease in CRP levels was independently and significantly correlated with the rate of progression. Patients with reductions in both LDL cholesterol and CRP that were greater than the median had significantly slower rates of progression than patients with reductions in both biomarkers that were less than the median (P=0.001).
For patients with coronary artery disease, the reduced rate of progression of atherosclerosis associated with intensive statin treatment, as compared with moderate statin treatment, is significantly related to greater reductions in the levels of both atherogenic lipoproteins and CRP.
近期试验表明，强化他汀治疗比中等强度他汀治疗能带来更好的治疗效果。强化治疗使低密度脂蛋白（LDL）胆固醇和C反应蛋白（CRP）水平降低得更多，这表明这两种生物标志物与疾病进展之间存在关联。
我们对502例经血管造影证实患有冠心病的患者进行了血管内超声检查。患者被随机分配接受中等强度治疗（每天口服40毫克普伐他汀）或强化治疗（每天口服80毫克阿托伐他汀）。18个月后重复进行超声检查以测量动脉粥样硬化的进展情况。在基线和随访时测量脂蛋白和CRP水平。
在整个研究组中，平均LDL胆固醇水平从基线时的每分升150.2毫克（每升3.88毫摩尔）降至18个月时的每分升94.5毫克（每升2.44毫摩尔）（P<0.001），几何平均CRP水平从每升2.9毫克降至2.3毫克（P<0.001）。LDL胆固醇水平降低与CRP水平降低之间的相关性在整个研究组中较弱但具有统计学意义（r=0.13，P=0.005），但在单独的任何一个治疗组中均无此相关性。在单变量分析中，LDL胆固醇、CRP、载脂蛋白B-100和非高密度脂蛋白胆固醇水平的百分比变化与动脉粥样硬化的进展速度相关。在对这些血脂水平的降低进行校正后，CRP水平的降低与进展速度独立且显著相关。LDL胆固醇和CRP降低幅度均大于中位数的患者，其进展速度明显慢于两种生物标志物降低幅度均小于中位数的患者（P=0.001）。
对于冠心病患者，与中等强度他汀治疗相比，强化他汀治疗使动脉粥样硬化进展速度降低，这与致动脉粥样硬化脂蛋白和CRP水平更大幅度的降低显著相关。
