XII^th International Symposium on Atherosclerosis, Stockholm, Sweden. (June 25-29, 2000)
Statins have multiple biological effects beyond lowering plasma cholesterol, which do contribute to the reduction in cardiovascular and total mortality observed in large-scale clinical trials.

Stockholm, Sweden -- Statins represent the most widely prescribed drugs worldwide for the reduction of plasma lipid levels, in particular plasma cholesterol. However, it has been recognized over the last few years that this class of drugs has multiple biological effects beyond lowering plasma cholesterol, which do contribute to the reduction in cardiovascular and total mortality observed in large-scale clinical trials. Some of these effects have been reviewed in the Workshop "New aspects of statin treatment", chaired by Dr M. Eriksson (Sweden) and Dr J. Kastelein (The Netherlands). Dr A.L. Catapano (Milan, Italy) reported on the ability of statins in cultured hepatic cells to decrease secretion of the major protein component of LDL, namely apoB-100. The implication of this finding is that statins may decrease not only cholesterol synthesis but also lipoprotein secretion by the liver, thus contributing to reduce LDL-cholesterol levels in plasma. Dr J. Davignon (Montreal, Canada) provided a comprehensive review of the many beneficial properties of statins beyond lipid lowering that could directly influence the formation of atherosclerotic lesion. For instance, statins have antioxidant effects that can be demonstrated both in vitro and in vivo. Macrophages, a cell population involved in lesion development, are affected by statins so as to reduce foam cell formation, a key feature of early atherosclerotic lesions. Indeed, formation of modified lipoproteins in the vessel wall and expression of cellular receptors responsible for the uptake of such modified, atherogenic lipoproteins is inhibited by statins. These drugs have also been shown to reduce vascular smooth muscle cell proliferation, a key feature of advanced atherosclerotic lesions. Even more intriguing is the observation that both short- and long-term statin treatment is associated with decreased levels of C-reactive protein, as reported by Dr T. Strandberg (Helsinki, Finland), which is not related to LDL-cholesterol reduction. C-reactive protein belongs to the so-called "acute phase proteins" whose concentration increases in the plasma of patients with ongoing inflammation. In addition, C-reactive protein concentration above 2 mg/l has been reported to predict future coronary disease events. This leads to the hypothesis that silent inflammation, either in the coronary arteries or elsewhere in the body, could play a role in the development of atherosclerosis. With this in mind, the ideal anti-atherosclerotic agent for the future should be endowed with anti-inflammatory properties, which seems to be the case for statins. Not all statins, however, display the same clinical effects. Dr J.R. Crouse (Winston-Salem, NC, USA) carried out a comparative study in 826 hypercholesterolemic patients randomised to increasing doses of simvastatin (40 to 80 mg) and atorvastatin (20 to 80 mg) for 36 weeks. Despite similar LDL-lowering activity (40-50% for both drugs), simvastatin was superior to atorvastatin at raising HDL-cholesterol at each dose comparison and had a better hepatic safety and tolerability profile than atorvastatin at the 80 mg dose. The effects of pravastatin on total and cardiovascular mortality were discussed by Dr J. Simes (Melbourne, Australia), who combined the results from three major recent clinical trials - WOSCOPS carried out in Europe, CARE in the US, and LIPID in Australia - yielding a data-base of some 20,000 patients. It was found that patients with or without coronary heart disease (CHD) taking pravastatin 40 mg/day for 5 years had significantly lower total mortality with a relative risk reduction of 20% as well as lower cardiovascular mortality with a relative risk reduction of 24%. The greatest reduction in absolute risk was found among patients at higher risk for vascular events. In other words, it was necessary to treat 150 patients without CHD history to avoid one major vascular event, whereas this number dropped to 50 in patients with CHD history. From these observation it becomes apparent that statins influence the atherogenic process at different levels.