Low HDL: Not Bad?
Frikke-Schmidt R, Nordestgaard BG, Stene MCA, et al. Association of Loss-of-Function Mutations in the ABCA1 Gene With High-Density Lipoprotein Cholesterol Levels and Risk of Ischemic Heart Disease. JAMA 2008; 299:2524-32.
I'm afraid this paper is going to get misinterpreted. In this study they looked at a population of 56,886 people, in which they found 148 heterozygotes (0.26%) for the particular HDL mutation they were studying that is associated with normal triglyceride levels and a relatively low risk of heart disease. Thus the likelihood of a given patient with a low HDL having this particular pattern is very low. On the other hand, I believe that the point of the paper was not so much to suggest that low HDL is not a risk marker, but rather to add to the body of information trying to sort out the risk of high triglycerides. It has always been evident that there is a very strong inverse relationship between HDL levels and triglycerides, and partly as a consequence of this for decades it was thought that high triglycerides were not an independent risk factor but simply reflected the risk of low HDL levels. This paper attempts to turn that logic on its head and suggests that possibly low HDL levels are simply a marker for other metabolic abnormalities including high triglycerides. In any case, certainly if your patient with low HDL has high triglycerides it is a risk factor, but if they do not it probably does not carry the same impact. And of course, in any given individual it is the total concatenation of risk factors, including insulin resistance, hypertension, and so on, that determines overall risk. And finally, in addition to all of the usual risk factors, there is good karma!