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With the possible exception of atorvastatin, the statins are used to lower LDL cholesterol in familial or polygenic ( multifactorial) hypercholesterolemia (type Ila) and in combination with triglyceride-lowering drugs to treat combined hyperlipidemia (type lib) when both LDL and VLDL (very low density lipoproteins) are elevated (Table 23.2). However, the statins probably should not be given with the fibrates (triglyceride-lowering drugs, discussed later), since this combination may greatly increase statin toxicity. Atorvastatin, the most potent of the available statins (Fig. 23.3), has also been shown to lower blood triglycerides significantly.

This effect may be due to decreasing hepatic cholesterol and cholesterol ester levels to such an extent that hepatic formation of VLDL is impaired.The statins also have been claimed to reduce blood cholesterol levels modestly in some patients with homozygous familial hy-percholesterolemia, a condition often fatal in childhood or in early adulthood.

The statins may lower the risk of CHD by decreasing inflammation, an important component of atherogene-sis. Lovastatin decreased elevated plasma levels of C-reactive protein, a marker for cellular inflammation, and acute coronary events in patients with relatively low plasma cholesterol levels. Recent studies also suggest that use of statins may decrease the risk of stroke, dementia, and Alzheimer's disease and may improve bone density in postmenopausal women. These broad actions may be related to the hypocholesterolemic, antiprolifer-ative, antiinflammatory, or antioxidant properties of the statins or some combination of these properties.

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