Pirillo Angela, Tibolla Gianpaolo, Norata Giuseppe Danilo, Catapano Alberico Luigi
Center for the Study of Atherosclerosis, Ospedale Bassini, Cinisello Balsamo, Italy,
Curr Atheroscler Rep. 2014 Aug;16(8):429. doi: 10.1007/s11883-014-0429-x.
Several studies have shown an inverse relationship between HDL cholesterol (HDL-C) levels and the risk of cardiovascular disease. Low HDL-C levels are commonly present in subjects with diabetes, metabolic syndrome, or obesity. These observations have suggested that increasing HDL concentrations might help in decreasing the cardiovascular disease risk. However, despite initial positive results, some recent data from clinical trials with HDL-raising therapies failed to confirm this hypothesis; in addition, data from Mendelian randomization analyses showed that nucleotide polymorphisms associated with increased HDL-C levels did not decrease the risk of myocardial infarction, further challenging the concept that higher HDL-C levels will automatically translate into lower cardiovascular disease risk. Differences in the quality and distribution of HDL particles might partly explain these findings, and in agreement with this hypothesis, some observations have suggested that HDL subpopulation levels may be better predictors of cardiovascular disease than simple HDL-C levels. Thus, it is expected that increased HDL-C levels may be beneficial when associated with an improvement in HDL function, suggesting that pharmacological approaches able to correct or increase HDL functions might produce more reliable clinical benefits.
多项研究表明，高密度脂蛋白胆固醇（HDL-C）水平与心血管疾病风险呈负相关。糖尿病、代谢综合征或肥胖患者通常存在HDL-C水平较低的情况。这些观察结果表明，提高HDL浓度可能有助于降低心血管疾病风险。然而，尽管最初有积极结果，但近期一些关于升高HDL疗法的临床试验数据未能证实这一假设；此外，孟德尔随机化分析数据显示，与HDL-C水平升高相关的核苷酸多态性并未降低心肌梗死风险，这进一步挑战了HDL-C水平升高将自动转化为较低心血管疾病风险的概念。HDL颗粒质量和分布的差异可能部分解释了这些发现，与此假设一致，一些观察结果表明，HDL亚群水平可能比单纯的HDL-C水平更能预测心血管疾病。因此，预计当HDL-C水平升高与HDL功能改善相关时可能有益，这表明能够纠正或增强HDL功能的药理学方法可能会产生更可靠的临床益处。
