Pathogenesis and Management of the Dyslipidemia of the Metabolic Syndrome

The metabolic syndrome is a multiplex risk factor for atherosclerotic cardiovascular disease. The core components of the dyslipidemia of the metabolic syndrome, which most likely initiate atherosclerosis, are the lipid triad of high plasma triglycerides, low levels of high-density lipoprotein cholesterol (HDL-C), and a preponderance of small, dense low-density lipoprotein (LDL) particles. Postprandial lipemia is also recognized as an important component. Dysregulation of fat metabolism in the liver with overproduction of very-low-density lipoprotein 1 (VLDL1) particles is considered the hallmark of the dyslipidemia of the metabolic syndrome. The cornerstone of therapy is therapeutic lifestyle change. If this does not correct the dyslipidemia, drug therapy may be required. LDL-C lowering with statins is the first-line treatment; however, there is ongoing debate as to whether further aggressive LDL-lowering therapy with higher-dose statins as opposed to comprehensive lipid management is the optimal therapy to reduce cardiovascular risk in subjects with the metabolic syndrome. Combination of a statin with a fibrate and/or nicotinic acid can improve all components of the dyslipidemia. However, there are, as yet, no large cardiovascular outcome studies that show a reduction in cardiovascular morbidity or mortality using combination therapy. The current LDL-C goal in high-risk patients with the metabolic syndrome is below 100 mg/dL, with a non-HDL goal of below 130 mg/dL. However, in very high-risk patients, such as those with established cardiovascular disease, an LDL-C goal of below 70 mg/dL is recommended.