State University of New York Health Science Center, New York, NY, USA.
Am J Cardiol. 2013 Apr 15;111(8):1221-9. doi: 10.1016/j.amjcard.2012.12.052. Epub 2013 Jan 30.
Based on the cardiovascular (CV) outcomes data derived predominantly from 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) trials, guidelines have set low-density lipoprotein (LDL) cholesterol targets at successively lower levels over time. Recent data have demonstrated that more-intensive statin therapy (and, consequently, lower LDL cholesterol level) is more effective at reducing CV events than less-intensive statin therapy. Although the average LDL cholesterol level for a United States adult is 119 mg/dl, within the "normal" range (90 to 130 mg/dl) per the United States National Cholesterol Education Program-Adult Treatment Panel III guidelines, data from fetal studies, diet studies, contemporary hunter-gatherer populations, and other mammals have suggested that the "normal" physiologic range for LDL cholesterol in humans is likely 50 to 70 mg/dl. Low LDL cholesterol levels have been sporadically associated with an increased risk of cancer, hemorrhagic stroke, and other complications in population studies and clinical trials. However, statin clinical trials have generally not demonstrated correlations between on-treatment LDL cholesterol levels and safety. Clinical data have suggested a linear relation between LDL cholesterol lowering and CV risk reduction, supporting a favorable risk/benefit ratio for attaining very low levels of LDL cholesterol to minimize the risk of CV events. In conclusion, clinical trial evidence demonstrating the efficacy and safety of LDL cholesterol lowering to a very low level is essential to ascertain the benefits and risks in reducing the residual risk of vascular disease.
基于主要源自 3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂（他汀类药物）试验的心血管（CV）结局数据，指南已设定 LDL 胆固醇目标，随着时间的推移逐渐降低。最近的数据表明，与较不强化的他汀类药物治疗相比，更强化的他汀类药物治疗（因此 LDL 胆固醇水平更低）在降低 CV 事件方面更有效。尽管美国成年人的平均 LDL 胆固醇水平为 119mg/dl，但根据美国国家胆固醇教育计划-成人治疗小组 III 指南，在“正常”范围内（90 至 130mg/dl），胎儿研究、饮食研究、当代狩猎采集人群和其他哺乳动物的数据表明，人类 LDL 胆固醇的“正常”生理范围可能在 50 至 70mg/dl 之间。在人群研究和临床试验中，低 LDL 胆固醇水平与癌症、出血性中风和其他并发症的风险增加偶尔相关。然而，他汀类药物临床试验通常未显示治疗期间 LDL 胆固醇水平与安全性之间的相关性。临床数据表明 LDL 胆固醇降低与 CV 风险降低之间存在线性关系，支持通过达到非常低的 LDL 胆固醇水平来降低 CV 事件风险的有利风险/获益比。总之，证明 LDL 胆固醇降低至非常低水平的疗效和安全性的临床试验证据对于确定降低血管疾病残余风险的益处和风险至关重要。
