21 巻 (2012) 1 号 p. 67-75
Almost all Japanese epidemiological studies showed that all-cause mortality was lower in subjects with high serum total or LDL-cholesterol levels. Studies showing the disadvantage of high cholesterol levels included or were likely to include more participants with FH than in the general Japanese population. This also explains why epidemiological studies with elderly people are not able to detect any disadvantage of high cholesterol levels; groups of elderly subjects contain a smaller proportion of vulnerable FH patients who die earlier than those without FH. Meta-analyses of the effects of statins were used to indicate the favorable effects of these drugs, which might be considered as proof that cholesterol has unfavorable effects. However, the absolute effect size of statins on all-cause mortality is rather small, if any. Moreover, studies included in meta-analyses of statins were performed before the new clinical research regulation came into effect in 2005-2006 in the EU, which required clinical trial results to be published even if the data were not favorable for the tested drugs (BJOG 2007; 114: 917, http://www.bjog.org/view/0/index.html). Considering the fact that placebo-controlled clinical trials performed after the new regulation were mostly negative (J Lipid Nutr 2010; 19: 65, http://www.jstage.jst.go.jp/article/jln/19/1/65/_pdf/-char/ja/), the results published before the regulation were questionable and should not be used as the basis for recommendations for treatment with cholesterol-lowering medications. Because the relative risks of high cholesterol for CHD vary from <1 to >5, administering cholesterol-lowering medications to all Japanese individuals equally is not rational; at least women and elderly men need to be carefully re-examined because no or little positive associations between plasma cholesterol and CHD mortality rates have been reported in these groups.