8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV San Francisco, California - September 24 - 26, 2006

THE ‘METABOLIC SYNDROME’ AND CARDIOVASCULAR DISEASE: NEW INSIGHTS INTO MECHANISMS AND MANAGEMENT

Antiviral Therapy 2006; 11:Lx (abstract no. P5)

J Plutzky
Director, The Vascular Disease Prevention Program, Cardiovascular Disease, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Intense interest has focused on the concept of the metabolic syndrome – a variably defined, and also hotly debated, constellation of abnormalities that includes hypertension, dyslipidemia (increased triglycerides, low HDL, increased small dense LDL), insulin resistance/ glucose intolerance, and central obesity. Factors driving this attention include the wide and growing prevalence of the metabolic syndrome, its increasing incidence in ever younger individuals, the association between the metabolic syndrome and risk for future diabetes and/or cardiovascular disease, scientific interest in the mechanism( s) underlying the clustering of these cardio-metabolic components, and the prospect of modulating late stage morbid outcomes like diabetes, heart attack and stroke, through interventions that target the metabolic syndrome or its components. Evidence already documents a decrease in conversion to frank diabetes among metabolic syndrome patients through lifestyle changes. Similar data exists for certain drug therapies, including modulation of angiotensin system, orlistat, metformin and PPAR-γ activating thiazolidinediones. Presumably preventing diabetes in these individuals would also lower their cardiovascular risk, although this remains to be proven. Nevertheless, the potential impact of such therapies, as well as the size of the population eligible for such agents, has fostered interest in treating components of the metabolic syndrome, and more intriguingly, the syndrome itself. These efforts are closely coupled to better understanding the etiology and nature of the ‘metabolic syndrome’. Considerable data implicates fat and especially its abnormal distribution and/or accumulation in the genesis of these metabolic problems. Accordingly, novel weight loss agents are under study for their potential impact on the metabolic syndrome. Rimonabant, an endocannabinoid system modulator, induces weight loss and improves dyslipidemia. Similar prospects apply to other weight loss drugs in development. Alternatively, rather than modify a tissue driving insulin resistance, one might improve insulin sensitivity. The role PPARs play as ligand-activated nuclear receptors controlling the expression of multiple genes central to adipogenesis, lipid metabolism and glucose control system has combined with the insulin-sensitizing and anti-dyslipidemic effects of PPAR agonists in current clinical use to stimulate studies on novel PPAR modulators, including their effects on the metabolic syndrome and cardiovascular risk. Ultimately, greater scientific insight into the metabolic syndrome and its origins, including its induction in response to anti-retroviral therapy, is needed in order to provide the rationale and basis for considering therapeutic approaches to preventing or treating this increasingly common problem.

2006-09-24
P5

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