Is it Time to Revisit the Role of “Good” Cholesterol?
The role of Low Density Lipoproteins (LDL’s) in atherosclerosis was elaborated decades ago, both by observational and randomized controlled studies, hence these particles have been traditionally termed as “bad cholesterol”. The definitive evidence came from the fact that statins, which are so effective in reducing LDL levels have a beneficial effect in reducing mortality in patients with known Coronary Artery Disease (CAD). On the other hand, it was postulated that High Density Lipoproteins (HDL’s) by virtue of their property of transport of cholesterol from periphery back to the liver “reverse cholesterol transport” might be beneficial in improving outcomes in CAD patients. Several experts have advocated the necessity of raising the levels of “good” cholesterol, both by lifestyle changes and by pharmacological interventions. However, despite this notion, the evidence for such interventions till the recent past has been limited. We now have several studies which have challenged this traditional concept of raising HDL levels via pharmacological means.
The observational studies which lead to the hypothesis of potential benefits of HDL have been difficult to interpret because of the issues of confounding. It has been shown that the obese patients tend to have higher incidence of CAD and lower HDL levels, suggesting that the two conditions might be associated. On the other hand, obesity is also associated with insulin resistance and diabetes, both of which increase the incidence of CAD. Thus, it is difficult to decipher whether the increased CAD incidence is due to increased insulin resistance or decreased HDL levels?
To examine the potential cardio-protective role, scientists have investigated the effects of reconstituted HDL on atherosclerosis in coronary arteries (JAMA: April, 2007). Unfortunately, no significant effect on the atheroma volumes was noted by radiological means. After genome wide association studies identified several loci associated with increased HDL, it was postulated that these loci may provide protection to such population. Last month (April 2012), a Mendelian study was published in Lancet to test this hypothesis. The risk of MI was however shown to be similar in populations with or without such loci.
Thus so far the evidence both observational and in favor of pharmacological interventions is limited. The on-going large clinical trials are attempting to explore the relationship further and the till their results are available, the “goodness” of good cholesterol remains questionable.