Cadiovascular Risk Factors in Metabolic Syndrome - Impact of Insulin Resistance on Lipids, Hypertension, and the Development of Diabetes and Cardiac Events

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To capture the risk of triglyceride remnants, the calculation of non-HDL cholesterol is helpful when triglycerides exceed 200mg/dl. Small dense LDL is associated with a three-fold increased CV risk compared with larger LDL particles. Optimization of glycemic control by insulin and thiazolidinediones (TZDs) improves LDL particle size, as does treatment with niacin. Statins markedly reduce total LDL concentrations, but generally do not alter particle size distribution. Fibrate therapy typically increases particle size, but clinical data is conflicting. Patients with established CVD and multiple risk factors of MS (especially elevated triglycerides, non-HDL cholesterol, and low HDL-C) are considered very high risk; this favors treatment to a lower LDL goal of <70mg/dl.

MS nearly doubles the CV risk associated with HTN, above and beyond the effects of traditional risk factors in both men and women. MS is also associated with over a two-fold increase risk of chronic renal disease and a 34% increase in microalbuminuria compared with controls. Microalbuminuria in itself is associated with a doubling of CV risk and mortality, independent of traditional CV risk factors.

HTN is associated with an incidence rate of approximately 2% per year of the development of new onset DM, which appears to be independently associated with CV events. Patients with new onset DM on hypertensive therapy had a CV event rate that was nearly three-fold higher than subjects who remained without diabetes throughout treatment. Treatment with angiotensin receptor antagonists/blockers (ARBs), angiotensin receptor inhibitors (ACE-Is), and calcium channel blockers (CCBs) is associated with a lower incidence of DM compared with beta blockers (BBs) and diuretics. Although BBs uniformly worsen insulin sensitivity, the addition of alpha blockade appears to improve insulin sensitivity. In the COMET trial, carvedilol was associated with a 22% lower incidence of new onset DM compared with metoprolol in heart failure patients. Although there are no official guidelines for the treatment of hypertensive subjects with MS, recent data would suggest the use of ACE-Is or ARBs for MS patients with impaired glucose metabolism or micro-albuminuria. There may also be rational for ARB/ACE-I combinations in hypertensive patients with glucose intolerance.

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