Paradigm Shift in Lipid Nutrition for the Prevention of Ischemic Stroke

Ischemic stroke and coronary heart disease (CHD) share common mechanisms through blood circulation, but their relationships with cholesterol levels are different. In the case of CHD, “the lower, the better” hypothesis with regards to cholesterol has prevailed so far in clinical fields, setting upper limits of cholesterol levels and advising maintenance of the levels below the limits. However, the mortality ratio of the highest to lowest cholesterol levels (relative risk, RR) varies much among selected populations. We interpreted that the RR value is a surrogate marker of the proportion of familial hypercholesterolemia (FH) cases in the population or subpopulation selected [1]. As the CHD mortality of the FH cases is >10 times greater than that of the non-FH cases, and the survival of FH cases is generally shorter, the proportion of FH is expected to decrease along with ageing, and so does the RR value [1]. Because of genetically impaired LDL receptor functions, the FH cases develop hypercholesterolemia from young ages. However, high plasma cholesterol levels per se are unlikely to be the major causative factor for CHD, because 1 a high cholesterol level does not necessarily lead to CHD among general populations over 40-50 years of age, when atherogenesis is rapidly in progress, 2 in the FH cases, no significant difference is observed in average cholesterol levels between those who died of CHD and those still alive, 3 in CHD patients, tissue damage precedes plaque formation in the artery [2], and 4 statins lower LDL-C levels significantly but they are ineffective in preventing CHD. In the FH cases, a persistently restricted supply of energy (triacylglycerol) carried by LDL would damage coronary artery cells leading to CHD just as in non-FH cases with thrombosis at the coronary artery.