Role of HDL-C as a cardiovascular risk factor: clinical relevance of pitavastatin

Abstract

Atherogenic dyslipidemia is characterized by moderate to marked elevation of LDL-C levels, elevated levels of triglycerides and subnormal levels of HDL-C. It is further characterized by high apoB:apoA-I ratios. Current international recommendations for the treatment of dyslipidemia and prevention of coronary heart disease are primarily focused on reducing LDL-C levels in persons with, or at risk of, premature development of cardiovascular (CV) disease. In this regard, there is convincing evidence from prospective intervention trials that the statins are the drugs of choice for lowering LDL-C levels, and consequently, for reduction of morbid-mortality due to CV disease. This review is focused on recent findings relating to the role of HDL-C in CV medicine: the impact of low HDL-C levels as a major, independent risk factor for coronary heart disease events and, conversely, on the potential beneficial effects of supranormal HDL levels (>50% percentile). The effect of HDL-C on plaque formation is complex, since HDL particles are highly heterogeneous, and exist as a spectrum of small, intermediate and large particles that differ in lipid and protein content (lipidome and proteome, respectively). HDL particle size reflects the intravascular metabolism/recycling of apoA-I, which undergoes several lipidation and delipidation stages throughout its circulating lifecycle; such metabolism underlies the physicochemical, structural, metabolic and functional heterogeneity of HDL particles. It has recently been proposed that the protective role of HDL in atherosclerotic CV disease coincides with its ability to promote cholesterol efflux from macrophage foam cells, which initiates and drives the process of reverse cholesterol transport from the arterial wall to the liver. Current evidence suggests that for a lipid-modulating treatment to be fully effective, then it must target all key features of the atherogenic lipid profile that increase CV risk. In light of this, it is interesting to note that long-term treatment with pitavastatin progressively increases HDL-C and apoA-I levels, in addition to significantly reducing LDL-C; the former effect may reflect the long-term potential ability of this potent statin to progressively mobilize HDL-C from peripheral tissue stores, in which cholesterol turnover may be slow. The potential clinical significance of this new dimension of HDL-C metabolism in terms of CV outcomes remains to be clarified.

Key Words:

• atherosclerosis
• cardiovascular risk
• cholesterol
• dyslipidemia
• pitavastatin