Function of HDL Cholesterol is More Important than Quantity

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Keeping levels of bad LDL cholesterol down and good HDL cholesterol up have been the goal of patients to prevent atherosclerosis that can lead to heart disease. However, new research suggests that it may not be the amount of HDL cholesterol that you have, but whether or not you have the kind that functions more effectively.

Cholesterol Efflux Capacity a Measure of HDL Effectiveness

HDL cholesterol, or high-density lipoproteins, help decrease the risk of heart disease because these substances help scavenge excess LDL cholesterol from the blood and carries it back to the liver where it is broken down. Desirable levels for HDL are 60 mg/dL or above.

There are two major forms of HDL in the bloodstream. One is called AI-HDL or LpA-I because it contains the protein apoplipoprotein A-I. The second form is called AI/AII-ADL or LpA-1, A-II because it contains both apoA-I and apolipoprotein A-II. In a study conducted in the early 1990’s, mice that had AI-HDL had 15 times fewer atherosclerotic lesions than those that carried AI/AII-ADL.

Read: Low HDL Cholesterol Levels Linked to Abdominal Aortic Aneurysm

Dr. Daniel J. Rader, director of Preventive Cardiology at the University of Pennsylvania School of Medicine, further expanded on this research by drawing blood and measuring HDL levels of 203 healthy people without heart problems, 442 patients with coronary artery disease who were undergoing cardiac catheterization, and 351 control patients who were having the procedure but who didn’t have coronary heart disease. HDL cholesterol was isolated and tested for its ability to extract cholesterol from cells, called cholesterol efflux capacity.

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There were significant correlations between cholesterol efflux capacity and levels of both HDL cholesterol and apolipoprotein A-I in all participants.

As cholesterol efflux capacity increased, the odds of coronary artery disease dropped independently of the level of HDL cholesterol present in the blood. Compared with patients with the lowest efflux capacity, those with the highest had a 52% reduced risk of having coronary disease.

Read: Boosting HDL Levels May Not Benefit Patients On Statins

The study participants also had the artery walls tested for thickness using ultrasound – the thicker the arterial wall, the greater the risk of heart disease. Cholesterol efflux capacity was also inversely associated with carotid intima-media thickness (IMT), even after adjustment for HDL and apoA-I levels.

While the test is too labor-intensive to be used clinically for risk screening at this point in time, the researchers are optimistic that they will be able to use the results for future studies on the effectiveness of cardiovascular drugs.

For example, the researchers performed a separate study on 39 patients with metabolic syndrome given pioglitazone (Actos) and 99 patients with hypercholesterolemia who were given a statin to see if either medication could effectively enhance HDL efflux capacity. Pioglitazone appeared to be effective, but not the statins, which "is consistent with the concept that statins most likely exert therapeutic benefit by means of a mechanism that is distinct from the promotion of cholesterol efflux," according to the researchers.

Source references:
Khera A, et al "Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis" N Engl J Med 2011; 364: 127-135.
Heinecke J "HDL and cardiovascular disease risk -- Time for a new approach?" N Engl J Med 2011; 364: 170-171.

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