Friday, October 19, 2007


We have seen the pendulum swing back and forth on this issue of HDL-Cholesterol. It was the standard teaching when I was doing my membership exams that HDL-Cholesterol is a "good " cholesterol. That high levels of HDL-C will be protective of CAD. This was well supported by the all the major epidermiological data of the day, including the Framingham Study, MRFIT, etc. High HDL-C was associated with low incidence of CAD. We then when on to finding ways of increasing HDL-C, including the use of fibrates, nicotinic acids etc. Of course, the subjects were also advised to drink some wine and to exercise regularly. Giving them HRT or eostrogen was considered too drastic. Then Pfizer came out with this "torcetrapid ", a drug that, in animal experiment, increase HDL-C very well. This studies also followed early reports of the people from Limone sul Grada in north Italy, who had low HDL-C but a variant gene of the apo A1 Milano, who had low levels of CAD. This apo A1 Milano was manufactured by recombinant gene technique and given as infusion with good effect. The trial was carried out by non-other then the world reknown, media-philic Dr Steve Nissen. However, when torcetrapid was studied, in large randomised controlled trial, no less then three, two of which were led by Dt Steve Nissen again, the HDL-C levels went up but the incidence of cardiac events and cardiac death when up too. This led to Pfizer suffering a huge financial loss, loss of face and also for cardiologist, thorough confusion. Torcetrapid, Pfizer's block-buster drug after lipitor, was quickly withdrawn. The pendulum swung away from the HDL-C, the good cholesterol theory. We learned from the torcetrapid trials, that there maybe various kinds of HDL-C, some types of which may increase the risk of plaque rupture and cardiac events. Now, some Australian workers had done posthoc analysis of the TNT ( Treat to New Target ) study, and found that, in the 9,000 odd patients who had very low LDL-C levels, the levels of HDL-C predicted cardiac disease and events. These findings was published in the Sept 27th issue of NEJM. This findings seemed again to support the theory that there are actually good HDL-C molecules that can protect us. So the pendulum is swinging back again. One wonders what kind of HDL-C was measured in the TNT study. Anyway, I do not think that we have heard the end of the HDL-C story yet. There is surely more to come. For the moment, I must say that I still tell my patients to achieve as high a HDL-C level as they can with good wine and exercise. Perhaps, when the nicotinic acid derivatives are more patient friendly, I will use some nicotinic acid derivatives. The pendulum swings on.

No comments: