Cholesterol Issues in Japan – Why Are the Goals of Cholesterol Levels Set So Low

Abstract

cholesterol levels and that low cholesterol levels were not the cause of death [5] . Without liver disease death, this would be no longer all-cause mortality. Besides, hepatitis C virus (HCV) enters hepatic cells via LDL receptors [7] , and low cholesterol levels are one of the major risk factors of HCV infection and chronic hepatitis. Hence, death from liver disease could be the result of low cholesterol levels [8] . Third, NIPPON DATA 80 apparently included a higher percentage of participants with familial hypercholesterolemia (FH) than the general Japanese population [9] , which exaggerated the risk of TC. With regard to Japanese women, no study has ever shown that TC or LDL-C is a risk factor of mortality from coronary heart disease (CHD) except for that flawed NIPPON DATA 80 [5] . Consequently, it is hard to understand why women for primary intervention comprise nearly two thirds of statin users in Japan [Ogushi, unpubl. data]. JASG 2012 has many flaws. It omitted many important pieces of information that the readers have to know. The strangest point is that the committee members of JASG 2012 did not disclose COI at all. How can one assess the reliability of medical guidelines without COI disclosure? In fact, most of the committee members are known to be recipients of huge amounts of research grants from the related industries. The following are some other unacceptable points of JASG 2012: This summary aims to elucidate the relationship between serum total cholesterol (TC) or LDL-cholesterol (LDL-C) levels and mortality from all and cardiovascular causes in Japan, and to criticize the recently revised ‘Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases, 2012’ [1] (JASG 2012). The hypothesis ‘the lower the cholesterol levels are, the better’ is absolutely wrong. The epidemiological studies in Japan with 1 10,000 participants over follow-ups of 1 10 years showed that allcause mortality in the groups of the highest TC or LDL-C levels was lower than most of the other groups [2–4] . The only exceptional study (NIPPON DATA 80, on which JASG 2012 depends almost exclusively) claimed that the group of the highest TC levels had the highest all-cause mortality [5] . However, this study had several important flaws. First, results were adjusted for sex and albumin levels. Without adjustment for sex, all-cause mortality in the groups of the highest TC levels ( 1 259 mg/dl) was not significantly higher than control groups (160–179 mg/dl) either in men or women. Serum albumin levels are positively associated with TC levels, especially in elderly people [6] . Thus, the adjustment for albumin (a negative risk factor for all-cause mortality) cancelled good aspects of TC. Second, the authors excluded liver disease deaths from all-cause mortality in one of their analyses claiming that liver disease caused both death and depression of Published online: December 4, 2012