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- December 1, 2008 |
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| Presentation |
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"Management of the Metabolic Syndrome: The Evidence Base"Prof. Philip Barter (biography)
English - 2005-04-14 - 27 minutes
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 | (34 slides) |
Summary :
Features of the metabolic syndrome include central adiposity, insulin resistance, dyslipidaemia and mild hypertension. Each of these features contributes to an increased CV risk. Management includes lifestyle measures to promote weight reduction, anti-hypertensive therapy and the use of statins, fibrates and niacin to treat the dyslipidaemia. Insulin sensitizers such as PPAR-gamma agonists may reduce the overall CV risk associated with the condition, although trials to test this are not yet available. While it is therefore premature to support the use of that PPAR-gamma agonists, there is compelling circumstantial evidence that fibrates (PPAR-alpha agonists) reduce CV risk associated with the syndrome by actions beyond their effects on plasma lipids.
In the fibrate end-point trials, the extent of reduction in CV events is very large in people with features of the metabolic syndrome. In contrast, in people without features of the metabolic syndrome, the cardioprotective effect of fibrate therapy is small. This finding has been apparent in subgroup analyses of both the HHS and VA-HIT with gemfibrozil and the BIP study using bezafibrate and supports a view that fibrates should be considered as a first-line therapy to reduce the CV risk associated with the metabolic syndrome.
The fact that fibrates reduce CV risk in people with (but not in those without) the metabolic syndrome and that the benefits are achieved by a mechanism apparently independent of effects on plasma lipids is further circumstantial evidence metabolic syndrome is indeed an entity greater than the sum the individual feature used currently to define it.
Learning objectives :
After viewing this presentation, participants will be able to discuss:
• Which factors predict benefit (reduced cardiovascular risk) from fibrate therapy (Helsinki Heart Study, BIP Study, VA-HIT study)
• Which factors predict benefit from statin therapy (Heart Protection Study)
• What the evidence for fibrate therapy tells us about the metabolic syndrome as a disease entity
Bibliographic references :
Tenkanen L, Manttari M, Manninen V. Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil. Experience from the Helsinki Heart Study. Circulation. 1995 Oct 1;92(7):1779-85.
Manninen V, Tenkanen L, Koskinen P, Huttunen JK, Manttari M, Heinonen OP, Frick MH. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment. Circulation. 1992 Jan;85(1):37-45.
BIP Study Group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation. 2000 Jul 4;102(1):21-7.
Rubins HB, Robins SJ, Collins D, Nelson DB, Elam MB, Schaefer EJ, Faas FH, Anderson JW. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med. 2002 Dec 9-23;162(22):2597-604.
Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003 Jun 14;361(9374):2005-16.
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