Editorial
Current Status of Low-Density Lipoprotein Cholesterol and Cardiovascular Diseases in Japan
2023 Volume 30 Issue 5 Pages 432-433
Details
2023 Volume 30 Issue 5 Pages 432-433
See article vol. 30: 455-466
In this issue of Journal of Atherosclerosis and Thrombosis, Al-Shoaibi et al.1) reported the associations between low-density lipoprotein cholesterol (LDL-C) and the risk of coronary heart disease (CHD) and stroke subtypes among middle-aged Japanese workers. They revealed that LDL-C levels were significantly and positively associated with CHD and inversely associated with intracerebral hemorrhage. No such association was found with ischemic stroke. The study is based on the Japanese working population, and it examined the association of LDL-C with not only CHD but also stroke subtypes, which is worthy of specific comment.
The study was based on a large-scale cohort study (the Aichi Workers’ Cohort Study), which is an ongoing cohort study of noncommunicable diseases. The participants of this study are local government workers, including workers from both urban and suburban areas. Most of them were clerical workers. The mean age of the participants was approximately 45 years. A total of 8966 participants with no cardiovascular disease (CVD) history were enrolled in 2002, 2005, and 2008 and were followed-up for a median period of 12 years. It showed that among middle-aged Japanese workers, LDL-C was positively associated with risk of CHD in a dose-dependent manner (p for trend ＜0.001), and people with a high level of LDL-C (＞160 mg/dL) had a hazard ratio of 4.56 [95% confidence interval: 1.91–10.9] for developing CHD compared with those with a LDL-C level of 100–119 mg/dL. In contrast, LDL-C was inversely associated with the risk of intracerebral hemorrhage in a dose-dependent manner (p=0.009).
These findings were consistent with the U-shape theory that Komachi and his colleagues first observed in total cholesterol a half century ago2). The differential effects of cholesterol on intraparenchymal hemorrhage and ischemic heart disease could be explained by the pathology of atherosclerosis and arteriolosclerosis. High cholesterol level accelerates atherosclerosis in large vessels, leading to plaque and eventually blood clot, which causes ischemic heart disease and large artery occlusive ischemic stroke3, 4). In the meantime, low total or LDL-cholesterol levels may be linked to arteriolosclerosis in small vessels, which is characterized by the death of smooth muscle cells, and angionecrosis, which is characterized by the disappearance of medial smooth muscle cells and the infiltration of blood plasma into the intima, thereby weakening the vascular wall. When the fragility of the vascular walls progresses, they will subsequently rupture and cause intracerebral hemorrhage3).
In the late 20th century, Komachi’s U-shaped theory was discussed by researchers worldwide5). Many subsequent cohort studies6), as well as a pathological study3), supported Komachi’s U-shaped association between total cholesterol and risk of CVD. Noda et al 7) reported in a large cohort study involving 90000 residents of Ibaraki Prefecture an inverse association between LDL-cholesterol and intraparenchymal hemorrhage mortality, which revealed that LDL-cholesterol was likely a risk factor for hemorrhage instead of total cholesterol.
Although stroke mortality has been declining since the 1960s, stroke still accounted for 16.6% of the common cause of needing nursing care, whereas there is an increasing trend of the incidence of CHD among men who live in the urban areas of Japan8, 9). Therefore, preventing the development of CVD remains an important issue. The serum level of total cholesterol has gradually increased among Japanese10). The relatively young age of the subjects in this study compared with that in other previous studies in Japan suggests that LDL-C is useful in predicting CHD and intraparenchymal hemorrhage at midlife.
In summary, LDL-C plays an important role in the development of CVD. Al-Shoaibi et al ’s study revealed that the U-shape theory, established 50 years ago in Japan, could be applied to the contemporary relatively young urban and suburban workers.
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