Department of Pathology & Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45215, USA.
Division of Endocrinology and Metabolism, Department of Medicine, Carbohydrate & Lipid Metabolism Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
Best Pract Res Clin Endocrinol Metab. 2014 Jun;28(3):309-24. doi: 10.1016/j.beem.2013.10.010. Epub 2013 Nov 5.
Low density lipoprotein cholesterol (LDL-C) is one of the most validated targets in clinical medicine. Large randomized, outcome trials have demonstrated a clear relationship between reducing LDL-C and cardiovascular disease (CVD) risk, which has been maintained to LDL-C levels of <1.8 mmol/L. To assess the benefit of even lower LDL-C it is important to recognize that CVD risk reduction is related to absolute reduction in LDL-C, not to percent change. Furthermore measurement of LDL-C is also critical as recent studies show the Friedewald calculation significantly underestimates true LDL-C values <1.8 mmol/L, distorting the relationship with CVD risk reduction. Discussion of potential harm from low, or lower, LDL-C has centered on cancer, hemorrhagic stroke, and violent death, but there is little evidence from outcome trials to show a relationship with low LDL-C. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors which will reduce LDL-C well below 1.3 mmol/L, will likely provide the clearest answer to both the question of efficacy and safety of low LDL-C within the next few years.
低密度脂蛋白胆固醇（LDL-C）是临床医学中最具验证性的靶点之一。大型随机、结局试验已经证明了降低 LDL-C 与心血管疾病（CVD）风险之间的明确关系，这种关系一直持续到 LDL-C 水平<1.8mmol/L。为了评估 LDL-C 更低水平的益处，重要的是要认识到 CVD 风险降低与 LDL-C 的绝对降低有关，而不是与百分比变化有关。此外，LDL-C 的测量也很关键，因为最近的研究表明，弗里德瓦尔德（Friedewald）计算法显著低估了<1.8mmol/L 的真实 LDL-C 值，从而扭曲了与 CVD 风险降低的关系。关于低或更低 LDL-C 潜在危害的讨论集中在癌症、出血性中风和暴力死亡上，但来自结局试验的证据很少表明 LDL-C 水平与低 LDL-C 之间存在关系。前蛋白转化酶枯草溶菌素 9（PCSK9）抑制剂可将 LDL-C 降低至<1.3mmol/L 以下，可能会在未来几年内为 LDL-C 水平低或更低的疗效和安全性问题提供最明确的答案。
