Hormone Therapy, Lipoprotein Subclasses, and Coronary Calcification

Background: The Women’s Health Initiative (WHI) clinical trial found no reduction in coronary heart disease events among hormone therapy (HT) users despite an improvement in lipid levels. We hypothesized that a lack of benefit of HT on atherosclerosis would be better explained by the lipoprotein subclasses than by standard lipid levels. To test this hypothesis, we evaluated differences in coronary calcification, lipids, and lipoprotein subclasses among HT users and nonusers in a longitudinal study of the menopause. Methods:Lipoproteinsubclassesdeterminedbynuclear magneticresonancespectroscopyandcoronaryarterycalcification (CAC) determined by electron beam computed tomography were compared between HT users (49%) and nonusers among 243 women, approximately 8yearspostmenopausal,fromtheHealthyWomenStudy. Results: The distribution of CAC scores was not significantly different between HT users and nonusers. As expected, HT users had higher levels of large highdensity lipoprotein (HDL) particles and large very lowdensity lipoprotein (VLDL) particles. However, despite lower low-density lipoprotein (LDL) cholesterol levels among HT users, there were no significant differences betweenHTusersandnonusersinanyLDLsubclassmeasures, including particle size or concentration. Regardless of HT use, women with CAC had higher levels of large VLDL and small LDL particles, higher LDL particle concentration, and smaller mean LDL size compared with women with no detectable CAC. Conclusions: Compared with nonusers, HT users had higher levels of VLDL particles (triglycerides) and did not have a better LDL subclass distribution, which may explainthefailureofHTtobeassociatedwithadifferencein CAC in our study or with a reduction in coronary heart disease risk in randomized clinical trials. Arch Intern Med. 2005;165:510-515