Extending the “Lower is Better” Principle to Japanese and Possibly Other Asian Populations
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Cardiovascular disease (CVD) is well known as a leading cause of death around the world, accounting for ≈30% of all deaths. Controlling hyperlipidemia, especially high low-density lipoprotein cholesterol (LDL-C), is widely recognized as an important countermeasure against CVD.
Notable progress in combating high LDL-C began with 2 ground-breaking events in the 1970s: the discovery of the LDL receptor by Brown and Goldstein,1 which provides a theoretical basis for understanding the mechanism of high LDL-C, and the discovery by Endo et al2 of statins, which increase the synthesis of LDL receptors and reduce LDL-C. From 2005, the Cholesterol Treatment Trialists’ Collaboration (CTTC) began to provide a focused meta-analysis of statin-driven inhibition of cardiovascular events. A CTT meta-analysis of large-scale randomized, controlled studies using statins in 2010 showed significant reductions in cardiovascular events with statin therapy (a decrease of 1 mmol/L in LDL-C was associated with a 22% reduction in cardiovascular events) and also demonstrated that high-dose statin therapy provided greater benefit than moderate-dose therapy.3 Based on these data, the 2013 American College of Cardiology/American Heart Association guidelines4 emphasized the importance of high-dose statin therapy in high-risk groups to reduce cardiovascular risk.
However, almost all of this evidence originated in Western countries, based primarily on data from white subjects. There is a possibility that the response to statin therapy differs among different regions or in different ethnicities. If we adhere strictly to the principles of evidence-based medicine, these data cannot be applied to non-white races or ethnic groups without supporting research. For example, Japan and South Korea have historically shown low levels of LDL-C, whereas hypertension is very common. As a result, these populations show a consistent trend toward high incidence of stroke, which is closely related to hypertension, and relatively low incidence of …