Increasing HDL-cholesterol and prevention of atherosclerosis: A critical perspective.

The relationship between atherosclerosis and HDL is more complex than between LDL and atherosclerosis. Low HDL-cholesterol is associated with atherosclerotic disease not in a causal way but because low HDL-cholesterol reflects an increased concentration of triglyceride-rich lipoproteins. At the same time the functionality of the HDL system plays an important role in atherosclerosis prevention (for example by mediating reverse cholesterol transport). However, these two observations are not directly linked to each other. Therefore therapeutic strategies must either aim at decreasing the concentration of triglyceride-rich lipoproteins (and thereby increase HDL-cholesterol concentration) or at improving HDL function (which may or may not affect HDL-cholesterol concentration). Simply increasing HDL-cholesterol concentration without improving function or decreasing triglyceride-rich lipoproteins will not be beneficial with respect to atherosclerosis prevention.