Combined hyperlipidemia

In medicine, combined hyperlipidemia (or -aemia) (also known as "Multiple-type hyperlipoproteinemia") is a commonly occurring form of hypercholesterolemia (elevated cholesterol levels) characterised by increased LDL and triglyceride concentrations, often accompanied by decreased HDL. On lipoprotein electrophoresis (a test now rarely performed) it shows as a hyperlipoproteinemia type IIB. It is the most common inherited lipid disorder, occurring in approximately one in two hundred persons. In fact, almost one in five individuals who develop coronary heart disease before the age of sixty will have this disorder.

The elevated triglyceride levels (>5 mmol/l) are generally due to an increase in VLDL (very low density lipoprotein), a class of lipoprotein that is prone to cause atherosclerosis.

Types
There are two forms of this lipid disorder:
 * Familial combined hyperlipidemia (FCH) is the familial occurrence of this disorder, probably caused by polymorphisms in molecules and enzymes that participate in lipoprotein metabolism, such as ApoCII and ApoCIII and CETP (cholesterylester transferring protein).
 * Acquired combined hyperlipidemia is extremely common in patients who suffer from other diseases from the metabolic syndrome ("syndrome X", incorporating diabetes mellitus type II, hypertension, central obesity and CH). Excessive free fatty acid production by various tissues leads to increased VLDL synthesis by the liver. Initially, most VLDL is converted into LDL until this mechanism is saturated, after which VLDL levels elevate.

Treatment
Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to decrease free fatty acid production.

Statin drugs, especially the synthetic statins (atorvastatin and rosuvastatin) can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression.