Could high-density lipoprotein cholesterol predict increased cardiovascular risk?

Serum high-density lipoprotein (HDL) is considered to be protective against cardiovascular disease. However, there is emerging evidence that under certain conditions the HDL molecule can become dysfunctional and proinflammatory, paradoxically leading to increased risk of cardiovascular disease. This review will provide a brief outline of the potential mechanisms by which HDL can become atherogenic and summarize some of the clinical evidence on this topic.

HDL metabolism, structure, and function in addition to its level can be profoundly altered under conditions of marked oxidative stress and chronic inflammation. These abnormalities, in turn, lead to impaired reverse cholesterol transport, increased systemic oxidative stress/inflammation, and endothelial dysfunction that subsequently may contribute to atherogenesis and progression of cardiovascular disease.

Association of serum HDL cholesterol level with outcomes is not only dependent on its serum concentration but also on the qualities/properties of this lipoprotein at a given point in time. Hence, it is essential that future studies examining association of HDL with risk of cardiovascular disease take into account the complexities of HDL metabolism and function and address the impact of the HDL particle as a whole (quantity as well as various properties) on atherosclerosis and cardiovascular outcomes.