[in Japanese]

View full abstract

Background:The incidence of myocardial infarction among Japanese people appears to be far lower than that in Western countries. The efficacy of lowering the cholesterol level in a population with a low risk of coronary heart disease (CHD) is unclear.
Objective:We examined the risk and benefit of cholesterol lowering drugs to prevent CHD in Japanese patients with hypercholesterolemia.
Methods:Relevant publications (observational studies, randomized controlled trials and meta-analyses) were found using manual and computer-aided searches of the Cochrane Library and MEDLINE. The efficacy of cholesterol reduction has been quantified in the form of the number-needed-to-treat (NNT) to prevent a single incidence of myocardial infarction, according to the incidence of CHD in Japan and relative risk reduction (RRR) in a primary prevention trial. We examined the influence of cholesterol reduction on total mortality, and assessed the results of meta-analyses of interventional trials.
Resluts:In Japan, the average incidence of probable myocardial infarction is 0.99 per 1, 000 for males, and 0.24 per 1, 000 for females. In the United States and Northern European countries, the average incidence is 5.76 per 1, 000. If the RRR of CHD is 31%, the NNT to prevent a single incidence of myocardial infarction is 376 persons per 5 years in Japanese men with hypercholesterolemia (TC≥240mg/dl) and 1, 550 persons per 5 years in women. The relationship between mortality and the serum total cholesterol level was U-shaped. One metaanalysis indicated that intervention in a low risk population (CHD mortality <10/1, 000 person-years) increases the total mortality by 22%.
Conclusion:The effect of cholesterol lowering drugs for primary prevention of myocardial infarction is lower than in Western countries, and drug intervention may increase the total mortality in Japan.

View full abstract

Although many risk factors for atherosclerosis have been established, how these factors histopathologically modify the natural history of atherosclerosis is unknown. To investigate this issue, we performed histologic examinations of arterial tissue obtained from consecutive autopsies in Tokyo and forensic series from young subjects in a cooperative multicentric study in the U.S.A. (Pathobiological Determinants of Atherosclerosis in Youth, PDAY). The findings were compared with major antemortem risk factors, such as blood pressure and serum total cholesterol levels.
Aortas were collected from 573 male patients in Tokyo, aged 0 to 97 years. Intimal thickness was measured at 5 pre-determined sites at the thickest point, and atherosclerotic lesions at the same sites were classified into 4 categories;normal intima;fatty streak;preatheroma (characterized by microscopic extracellular lipid deposition);and atheroma. The density of foam cells was then microscopically graded. Elevated blood pressure accelerated the progression of intimal thickening, resulting in early appearance of advanced lesions, such as preatheroma and atheroma. Elevation of serum total cholesterol did not accelerate the progression of intimal thickening or advanced lesions until 50 years of age, although this factor increased the number of foam cells and frequency of fatty streaks in all older subjects. In subjects over 60 years of age, the proportions of advanced lesions and intimal thickening were greater in hypercholesterolemics than in the non-risk group.
A study using PDAY materials comprised aortas and left descending coronary arteries from 151 young male subjects, aged 15 to 34 years, that were observed by the same methods as the autopsy materials. The frequencies of fatty streaks and foam cells in the aorta were greater in hypercholesterolemics than in the non-risk group or hypertensives, as seen in the Tokyo series. There was a negative relationship between the HDL cholesterol level and the number of foam cells. Intimal thicknesses of both the aorta and coronary artery were significantly greater in hypertensives than in matched normotensives, but thickening was not correlated with the total cholesterol level.
Our studies suggest that the effects of risk factors such as hypertension and hypercholesterolemia vary according to the stage of atherosclerotic progression. Understanding the different influences and relationships of these risk factors may be important in constructing preventive medicine strategies.

View full abstract