動脈硬化と高脂血症

It is well known that four major risk factors for atherosclerosis include diabetes mellitus, hypertension, hyperlipidemia and smoking. Among these risk factors, management of hyperlipidemia, especially hyper-LDL cholesterolemia, has become to be strictly achieved by the appearance of statins. Many randomized control trials using statins have been performed, and the effectiveness in reduction of cardiovascular events is clearly established. Under these circumstances, we planed and performed the Shikoku Hyperlipidemia Study（SHS）to reveal how do we treat and what degree do we strictly manage patients with hyperlipidemia.
Evidence obtained by The SHS study were 1）unmeasurement rates of serum cholesterol levels in categories B and C were 28.1% and 18.2%, respectively, 2）among patients in categories B and C who need to be treated by drugs, only 35.5% and 35.9% of patients in categories B and C were treated, respectively, 3）drugs medicated in such patients were mostly statins and a single kind of statin was administered, and 4）rate of successfully treated patients in category B was 40～50% and that in category C was 20～30%. When this analysis, which was performed based upon guideline published in 1997, was re-analyzed by new guideline published in 2002, rates of successfully treated patients in categories A, B1, B2, B3, B4, and C were 91.7%, 66.1%, 77.6%, 42.9%, 60.7%, and 32.6%, respectively.
Pleiotropic effects of statins have been postulated, however, a couple of issues are still elusive ; that is, 1）can statins suppress the progression of atherosclerosis by the mechanism other than cholesterol lowering in humans? and 2）should statins be administered to patients for secondary and primary preventions against cardiovascular events to anticipate pleiotropic effects of statins?. Evidence obtained so far suggest that statins exert its pleiotropic effects via 1）enhancement of NO production by phosphorylation of eNOS, Akt and PI 3 kinase, 2） inhibition of Ras activation by reduction of farnesyl-pyrophosphate, and 3）inhibition of Rho family activation by reduction of geranylgeranyl-pyrophosphate, and that Heart Protection Study and ASCOT-LLA study revealed that additive benefits can be elicited when hyperlipidemic patients bearing many risk factors including diabetes mellitus were treated with statins.
In conclusion, we need to treat patients with hyperlipidemia in consideration of the quality and quantity of risk factors for cardiovascular diseases.

四国医学雑誌 : http://www.tokushima-u.ac.jp/med/research/shikoku_acta_medica.html