ABSTRACT
Future prospects for coronary prevention Coronary prevention has been transformed by the availability of statin therapy that has proved to be safe and efficacious in long-term clinical trials. The cholesterol hypothesis is now accepted dogma and it appears as though clinical benefit from lipid lowering comes not from regression of atherosclerotic lesions but from stabilization of fragile, moderate-sized plaques. The precise details of how statins help prevent plaque rupture is as yet unclear (Fig. 3.7). Reduction in LDL is certain to play a major role since in the oxidized form this lipoprotein is known to promote endothelial damage and activation of macrophages. The removal of other atherogenic lipoproteins from the circulation (IDL, chylomicron and VLDL remnants) following receptor activation is also likely to contribute to reducing the cholesterol content of macrophages and smooth muscle cells in lesions. However, because statins inhibit a basic metabolic pathway which produces not only cholesterol but also important molecules such as geranyl and farnesyl derivatives that have roles in cell growth, the possibility exists that the drugs may have direct effects on the cells of the plaque. Evidence for such an action is emerging from clinical trial data30,52 and biochemical experiments.53 For example, in CARE a proinflammatory state as evidenced by elevated plasma C-reactive protein levels was associated with a 2-fold increase in CHD risk but this risk component was attenuated markedly by pravastatin treatment, apparently outside of any lipid changes generated by the drug.52
While all statins reduce LDL by a similar
