Cholesterol Lowering and SCD

Another important issue at a time when so many people are taking cholesterol-lowering drugs with the hope to improve their life expectancy is whether cholesterol lowering might reduce the risk of SCD. According to recent data standardized to the 2000 US population,2 of 719,456 cardiac deaths among adults aged >35 years, 63% were defined as sudden cardiac death (SCD). In that study, SCD was defined as death occurring out of the hospital or in the emergency room or as "dead on arrival" with an underlying cause of death reported as a cardiac disease. Among those aged 35 to 55, about 75% of cardiac deaths were SCD.2

Another question is: are we able to identify people at risk of SCD? In other words, are the traditional risk factors of CHD predictive of SCD? Several studies have recently tried to answer that question. For instance, in a prospective study in healthy men, investigators found that only C-reac-tive protein (CRP) was significantly associated with the risk of SCD whereas homocysteine and all lipid parameters, including total and LDL cholesterol levels, were not.15 In another study investigating the determinants of SCD in women, diabetes and smoking conferred markedly elevated risk of SCD whereas hypercholesterolemia did not increase the risk of SCD.16 Thus, it seems that high cholesterol level is not a risk factor for SCD while SCD appears to be the main cause of CHD death.

If these epidemiological data are true, the next obvious question is whether (or in which proportions) cholesterol lowering is able to reduce the risk of SCD and consequently the risk of CHD death. As the best cholesterol-lowering treatments are the statin drugs, it is important to look at the SCD data (and CHD mortality data) in the recently published statin trials. However, in most (recent as well as old) statin trials, there is curiously no data regarding the effect of statins on SCD. This suggests that, as expected from epi-demiological data, statins had no significant effect on SCD. Given the importance of SCD as a cause of death in CHD patients,we can therefore suspect that the effect of cholesterol lowering by statins on CHD death was, at best, small. In fact, when carefully looking at the published trials, it appears that the effect of statins on mortality was either small or non significant. For instance, in HPS, PROSPER, ALLHAT-LLT, ASCOT-LLA, and ALLIANCE, the death rate ratios were 0.87(indicating a risk reduction of 13%), 0.97

(nonsignificant), 0.99 (nonsignificant), 0.87 (nonsignificant), and 0.92 (nonsignificant), respectively.17-21 Furthermore, the effect of statins specifically in women has been recently analyzed using a meta-analysis of 13 studies retained in the Cochrane database.22 The authors conclude that in both primary and secondary prevention, statins had no significant effect on mortality in women. Finally, in the most recent statin trials focusing on patients with acute CHD syndromes and early and intensive lipid lowering (MIRACL, PROVE-IT,A to Z Trial), the effects on mortality were again small or nonsignificant despite the recruitment of several thousand patients in these trials.23,24 Thus, cholesterol lowering with statins does not appear to be a very effective way of reducing CHD mortality in our populations. This is not unexpected as the main cause of CHD death is SCD (up to 75% of cardiac deaths among people aged 35-55) and SCD is apparently not determined by lipid factors.

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