Departments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL (K.M.A.W.); Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France (P.A.); Global Pharmaceuticals Pfizer, New York, NY (D.A.D.); Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia (A.M.T.); Department of Biochemistry and Lipid Clinic, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia (D.R.S.); NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia (A.K.); Medical Research Institute, University of Dundee, Dundee, United Kingdom (H.M.C.); Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom (G.A.H.); Department of Medicine, Royal Free and University College Medical School, London, United Kingdom (D.J.B.); School of Biomedicine, University of Manchester, Manchester, United Kingdom (P.N.D.); Touro University, Mare Island, CA (M.B.C.); Department of Medicine, University of Texas Health Science Center, and VERDICT, South Texas Veterans Health Care System, San Antonio, TX (J.R.D.); and Weill Cornell Medical College, New York, NY (A.M.G.).
Circulation. 2013 Oct 1;128(14):1504-12. doi: 10.1161/CIRCULATIONAHA.113.002670. Epub 2013 Aug 21.
It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk.
We performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38,153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels <50 mg/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97).
Among patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction.
在接受他汀类药物治疗使低密度脂蛋白胆固醇（LDL-C）水平非常低的患者中，高密度脂蛋白胆固醇（HDL-C）或载脂蛋白 A-I（apoA-I）水平是否仍然与心血管风险呈负相关尚不清楚。此外，他汀类药物治疗开始后 HDL-C 或 apoA-I 的升高是否与心血管风险降低相关也不得而知。
我们对 8 项他汀类药物试验进行了荟萃分析，所有研究参与者在基线和 1 年随访时均测定了血脂和载脂蛋白。从接受他汀类药物治疗的 38153 名试验参与者中获得了个体患者数据，其中 5387 人发生了主要心血管事件。HDL-C 水平与主要心血管事件风险降低相关（校正后的危险比 [HR]，0.83；95%置信区间 [CI]，每增加 1 个标准差的 0.81-0.86），载脂蛋白 A-I 水平也是如此（HR，0.79；95%CI，0.72-0.82）。这种相关性在 LDL-C 水平达到他汀类药物治疗目标<50mg/dL 的患者中也存在。HDL-C 升高与心血管风险降低无关（HR，每增加 1 个标准差 0.98；95%CI，0.94-1.01），而 apoA-I 升高与心血管风险降低相关（HR，0.93；95%CI，0.90-0.97）。
在接受他汀类药物治疗的患者中，HDL-C 和 apoA-I 水平与心血管风险降低密切相关，即使在 LDL-C 水平非常低的患者中也是如此。apoA-I 升高与主要心血管事件风险降低相关，而 HDL-C 则不然。这些发现表明，增加 apoA-I 浓度的治疗方法需要进一步探索，以降低心血管风险。
