1.
Nicotinic acid in the management of dyslipidaemia associated with diabetes and metabolic syndrome: a position paper developed by a European Consensus Panel.
Shepherd, J, Betteridge, J, Van Gaal, L, ,
Current medical research and opinion. 2005;(5):665-82
Abstract
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.
Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid--a position paper developed by the European Consensus Panel on HDL-C.
Chapman, MJ, Assmann, G, Fruchart, JC, Shepherd, J, Sirtori, C, ,
Current medical research and opinion. 2004;(8):1253-68
Abstract
Reduction of low-density lipoprotein cholesterol (LDL-C) is presently the primary focus of lipid-lowering therapy for prevention and treatment of coronary heart disease (CHD). However, the high level of residual risk among statin-treated patients in recent coronary prevention studies indicates the need for modification of other major components of the atherogenic lipid profile. There is overwhelming evidence that a low plasma level of high-density lipoprotein cholesterol (HDL-C) is an important independent risk factor for CHD. Moreover, a substantial proportion of patients with or at risk of developing premature CHD typically exhibit distinct lipid abnormalities, including low HDL-C levels. Thus, therapeutic intervention aimed at raising HDL-C, within the context of reducing global cardiovascular risk, would benefit such patients, a viewpoint increasingly adopted by international treatment guidelines. Therapeutic options for patients with low HDL-C include treatment with statins, fibrates and nicotinic acid, either as monotherapy or in combination. Of these options, nicotinic acid is not only the most potent agent for raising HDL-C but is also effective in reducing key atherogenic lipid components including triglyceride-rich lipoproteins (mainly very low-density lipoproteins [VLDL] and VLDL remnants), LDL-C, and lipoprotein(a). The principal features of the atherogenic lipid profile in type 2 diabetes and the metabolic syndrome make them logical targets for nicotinic acid therapy, either alone or in combination with a statin. The lack of comprehensive European data on the prevalence of low HDL-C levels highlights a critical need for education on the importance of raising HDL-C in CHD prevention and treatment. The development of a reliable and accurate assay for HDL-C, as well as clarification of criteria for low and optimal levels of HDL-C in both men and women, constitute critical factors in the reliable identification and treatment of patients at elevated risk of CHD due to low HDL-C. Based on the available evidence, the European Consensus Panel recommends that the minimum target for HDL-C should be 40 mg/dL (1.03 mmol/L) in patients with CHD or with a high level of risk for CHD, including patients at high global risk with type 2 diabetes or the metabolic syndrome.