Dyslipidemia, Inflammation and Atherosclerosis Research Unit, UMR-S939, National Institute for Health and Medical Research (INSERM), Hôpital de la Pitié-Salpetriere, Paris, France.
Pharmacol Ther. 2010 Jun;126(3):314-45. doi: 10.1016/j.pharmthera.2010.01.008. Epub 2010 Feb 11.
Although statin therapy represents a cornerstone of cardiovascular disease (CVD) prevention, a major residual CVD risk (60-70% of total relative risk) remains, attributable to both modifiable and non-modifiable risk factors. Among the former, low levels of HDL-C together with elevated triglyceride (TG)-rich lipoproteins and their remnants represent major therapeutic targets. The current pandemic of obesity, metabolic syndrome, and type 2 diabetes is intimately associated with an atherogenic dyslipidemic phenotype featuring low HDL-C combined with elevated TG-rich lipoproteins and small dense LDL. In this context, there is renewed interest in pharmacotherapeutic strategies involving niacin and fibrates in monotherapy and in association with statins. This comprehensive, critical review of available data in dyslipidemic subjects indicates that niacin is more efficacious in raising HDL-C than fibrates, whereas niacin and fibrates reduce TG-rich lipoproteins and LDL comparably. Niacin is distinguished by its unique capacity to effectively lower Lp(a) levels. Several studies have demonstrated anti-atherosclerotic action for both niacin and fibrates. In contrast with statin therapy, the clinical benefit of fibrates appears limited to reduction of nonfatal myocardial infarction, whereas niacin (frequently associated with statins and/or other agents) exerts benefit across a wider range of cardiovascular endpoints in studies involving limited patient numbers. Clearly the future treatment of atherogenic dyslipidemias involving the lipid triad, as exemplified by the occurrence of the mixed dyslipidemic phenotype in metabolic syndrome, type 2 diabetes, renal, and auto-immune diseases, requires integrated pharmacotherapy targeted not only to proatherogenic particles, notably VLDL, IDL, LDL, and Lp(a), but also to atheroprotective HDL.
尽管他汀类药物治疗是心血管疾病（CVD）预防的基石，但仍存在主要的剩余 CVD 风险（总相对风险的 60-70%），这归因于可改变和不可改变的危险因素。在前者中，低水平的高密度脂蛋白胆固醇（HDL-C）与升高的甘油三酯（TG）丰富的脂蛋白及其残基一起是主要的治疗靶点。当前肥胖、代谢综合征和 2 型糖尿病的流行与致动脉粥样硬化的血脂异常表型密切相关，其特征是低 HDL-C 与升高的 TG 丰富的脂蛋白和小而密的 LDL 相结合。在这种情况下，人们对涉及烟酸和贝特类药物的单药治疗和与他汀类药物联合治疗的药物治疗策略重新产生了兴趣。对血脂异常患者的现有数据进行的全面、批判性综述表明，烟酸在升高 HDL-C 方面比贝特类药物更有效，而烟酸和贝特类药物可降低 TG 丰富的脂蛋白和 LDL 水平。烟酸的独特之处在于其有效降低脂蛋白（a）水平的能力。几项研究表明烟酸和贝特类药物具有抗动脉粥样硬化作用。与他汀类药物治疗不同，贝特类药物的临床益处似乎仅限于降低非致死性心肌梗死，而烟酸（通常与他汀类药物和/或其他药物联合使用）在涉及有限数量患者的研究中在更广泛的心血管终点方面发挥益处。显然，涉及脂质三联体的致动脉粥样血脂异常的未来治疗，如代谢综合征、2 型糖尿病、肾脏和自身免疫性疾病中混合血脂异常表型的发生，需要针对不仅针对致动脉粥样的颗粒，特别是 VLDL、IDL、LDL 和 Lp(a)，而且针对具有抗动脉粥样作用的 HDL 的综合药物治疗。
