Mediterranean Approach to Improving High-Density Lipoprotein Function
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Article, see p 633
The complex interrelationships among diet, high-density lipoprotein (HDL), and cardiovascular risk have been a topic of great interest for decades.1 HDL cholesterol (HDL-C) levels are strongly inversely associated with cardiovascular disease (CVD). Diets high in saturated fat are strongly positively associated with CVD. Yet, diets high in saturated fat increase HDL-C levels, and low-fat diets reduce HDL-C levels,1 a paradox that has never been fully reconciled. However, the past several years have provided insights into the relationship between HDL-C and CVD that may help to reconcile these disparate findings. Specifically, the “HDL hypothesis” that HDL-C is causally related to CVD and that intervention to increase HDL-C will reduce CVD risk has been largely disproven.2 Genetic studies in humans have shown that certain genetic variants that increase HDL-C are not associated with protection from CVD.3,4 Furthermore, pharmacological interventions that raise HDL-C levels such as niacin and cholesteryl ester transfer protein (CETP) inhibitors have failed to reduce CVD events in large randomized clinical trials.2,5 In this context, the fact that low-fat diets reduce HDL-C levels but do not increase risk of CVD can be reasonably interpreted: The reduction of HDL-C does not causally increase the risk of CVD.
However, studies in the last several years have given rise to an alternative hypothesis, namely the “HDL flux” or “HDL function” hypothesis.5 This concept is based on the idea that HDL has a number of putative antiatherogenic functions that may causally affect CVD risk but that are not directly related to simple measures of HDL mass such as HDL-C levels. The best established of the measures of HDL function is HDL cholesterol efflux capacity (CEC), an ex vivo measure of the ability of an individual’s HDL to promote cholesterol efflux …