The Atherogenic Dyslipidemia of Metabolic Syndrome- Are there New Effective Therapeutic Options Beyond Statins?

Abstract

The Metabolic Syndrome is commonly associated with an atherogenic dyslipidemia which accounts for a high risk of atherothrombosis and cardiovascular events. The fundamental defect of patients with the Metabolic Syndrome is the resistance to insulin action which is involved in the appearance of a combined dyslipidemia -i.e. hypertriglyceridemia, low HDL cholesterol, preponderance of small dense LDL particles and post-prandial lipidemia- owing to a reduced suppression of lipolysis in adipose tissue which leads to higher flux of free fatty acids to liver and increased synthesis and secretion of VLDL particles. Beyond the primary management which involves lifestyle intervention, patients with the Metabolic Syndrome could be treated with different therapeutic strategies to reduce cardiovascular risk. The main therapeutic option is statin therapy which provides effective decrease of LDL cholesterol levels and is shown effective in the prevention of coronary artery events, even though controlled studies are available only for few molecules. In turn, controlled trials -such as BIP, VA-HIT and FIELD- have proposed a possible benefit from fibrate administration in normalizing lipid profile and decrease insulin resistance in patients with the Metabolic Syndrome which exhibit low HDL cholesterol and hypertriglyceridemia. Other lipid modifying strategies based on nicotinic acid or ezetimibe have recently proposed as effective in the Metabolic Syndrome on the basis of preliminary results and could be future options. Finally, the simultaneous use of different drugs could provide benefits, avoiding inappropriate combinations due to the potential hazard of adverse drug interaction. The present review extensively examines the most recent results in the field of treatment of dyslipidemia in patients with the Metabolic Syndrome, starting from the trials with statin therapy. We consider also the role of drugs which regulate serum lipids by different mechanisms, such as fibrates, ezetimibe, nicotinic acid and omega3 fatty acids, on the basis of the evidences of effectiveness and safety. Finally, we take into account the therapeutic efficacy of new drugs, such as glitazones and rimonabant, whose main target is to improve the insulin sensitivity. Keywords: Atherogenic dyslipidemia, metabolic syndrome, statins, fibrates, ezetimibe, nicotinic acid