In his article, Grundy1 concludes that low-density lipoproteins (LDLs) play a pivotal role in the pathogenesis of coronary artery disease (CAD) and that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (releasing factors) are central to the observed reduction of cardiac events. The evidence may not justify this conclusion.
First, the majority of cases of CAD occur in the presence of normal levels of LDL.2 Second, cardiac events are infrequent when elevation of LDL levels is the only factor.3 Third, beneficial results from treatment with releasing factors appear to be unrelated to preexisting LDL levels.4 Fourth, therapy with releasing factors can inhibit intimal thickening with doses inadequate to alter LDL levels.5 Finally, reduction of LDL levels by means other than therapy with releasing factors yields less impressive changes in morbidity.6
Serjeant ME. The Key to Atherogenicity—Reply. Arch Intern Med. 1998;158(10):1157-1158. doi: