Shepherd James, Betteridge John, Van Gaal Luc
Department of Vascular Biochemistry, Glasgow Royal Infirmary, Glasgow, UK.
Curr Med Res Opin. 2005 May;21(5):665-82. doi: 10.1185/030079905x43677.
Individuals with type 2 diabetes and metabolic syndrome are at markedly increased risk of cardiovascular morbidity and mortality. The increasing prevalence of both conditions poses a major challenge for clinicians in the 21st century. Both diabetes and metabolic syndrome are associated with a clustering of cardiovascular risk factors. In particular, dyslipidaemia characterised by low plasma levels of high-density lipoprotein cholesterol (HDL-C), elevated triglycerides and an increase in small, dense low-density lipoprotein (LDL) particles (the lipid triad), has been established as the most important modifiable risk factor for coronary heart disease (CHD). Current treatment guidelines recognise the increased CHD risk associated with diabetes and metabolic syndrome and focus on LDL-C lowering with statin treatment, in addition to dietary and lifestyle modification, as the primary lipid-modifying therapy. However, while there is no doubt that statin therapy significantly reduces CHD risk in these patients, their residual absolute risk remains higher than in individuals without diabetes or metabolic syndrome. Thus, there is a clear need to target other aspects of lipoprotein metabolism, notably low HDL-C and hypertriglyceridaemia, to further reduce CHD risk. Combining statin therapy (targeting LDL-C) with interventions that also modify low HDL-C and elevated triglycerides could be a useful strategy to optimise CHD risk reduction. Cautious combination of a fibrate or nicotinic acid with a statin is useful for the management of combined dyslipidaemia. Nicotinic acid is the more potent agent for raising HDL-C (by up to 29% at clinically recommended doses). It also substantially reduces triglycerides and LDL-C, and promotes a shift from small, dense LDL to larger, more buoyant LDL particles. Preliminary clinical data suggest that combining nicotinic acid with a statin will produce a greater reduction in cardiovascular risk in patients with diabetes and metabolic syndrome than statin monotherapy alone. Nicotinic acid is also safe for use in patients with diabetes, with no evidence of clinically relevant deterioration in glycaemic control at recommended doses (< or = 2 g/day). On review of the available evidence, this European Consensus Panel recommends the combination of nicotinic acid and a statin, together with lifestyle modification, as a useful strategy to lower CHD risk in patients with diabetes and metabolic syndrome. Prolonged-release nicotinic acid with improved tolerability compared with previous formulations may have obvious advantages for use in this setting.
2型糖尿病和代谢综合征患者发生心血管疾病和死亡的风险显著增加。这两种疾病患病率的不断上升给21世纪的临床医生带来了重大挑战。糖尿病和代谢综合征均与心血管危险因素的聚集有关。特别是，以血浆高密度脂蛋白胆固醇（HDL-C）水平降低、甘油三酯升高以及小而密的低密度脂蛋白（LDL）颗粒增加（脂质三联征）为特征的血脂异常，已被确认为冠心病（CHD）最重要的可改变危险因素。当前的治疗指南认识到糖尿病和代谢综合征与CHD风险增加相关，并将除饮食和生活方式改变外，使用他汀类药物治疗降低LDL-C作为主要的血脂调节疗法。然而，虽然毫无疑问他汀类药物治疗可显著降低这些患者的CHD风险，但他们的残余绝对风险仍高于无糖尿病或代谢综合征的个体。因此，显然需要针对脂蛋白代谢的其他方面，特别是低HDL-C和高甘油三酯血症，以进一步降低CHD风险。将他汀类药物治疗（针对LDL-C）与同时改善低HDL-C和升高甘油三酯的干预措施相结合，可能是优化降低CHD风险的有用策略。谨慎地将贝特类药物或烟酸与他汀类药物联合使用，对混合型血脂异常的管理是有用的。烟酸是升高HDL-C更有效的药物（在临床推荐剂量下可升高多达29%）。它还能显著降低甘油三酯和LDL-C，并促使小而密的LDL向更大、更有浮力的LDL颗粒转变。初步临床数据表明，与单独使用他汀类药物单药治疗相比，将烟酸与他汀类药物联合使用可使糖尿病和代谢综合征患者的心血管风险降低更多。烟酸用于糖尿病患者也是安全的，在推荐剂量（≤2克/天）下没有血糖控制出现临床相关恶化的证据。在审查现有证据后，本欧洲共识小组建议将烟酸和他汀类药物联合使用，并结合生活方式改变，作为降低糖尿病和代谢综合征患者CHD风险的有用策略（与以前的制剂相比，耐受性有所改善的缓释烟酸在这种情况下使用可能具有明显优势）。 （括号内内容为使译文更通顺添加，原文括号内为注释内容，按要求不添加注释，此括号内容仅为译文通顺考虑，供参考）
