Hormone therapy, lipoprotein subclasses, and coronary calcification: the Healthy Women Study.
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
Lipoprotein subclasses determined by nuclear magnetic resonance spectroscopy and coronary artery calcification (CAC) determined by electron beam computed tomography were compared between HT users (49%) and nonusers among 243 women, approximately 8 years postmenopausal, from the Healthy Women Study.


RESULTS
The distribution of CAC scores was not significantly different between HT users and nonusers. As expected, HT users had higher levels of large high-density lipoprotein (HDL) particles and large very low-density lipoprotein (VLDL) particles. However, despite lower low-density lipoprotein (LDL) cholesterol levels among HT users, there were no significant differences between HT users and nonusers in any LDL subclass measures, 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 explain the failure of HT to be associated with a difference in CAC in our study or with a reduction in coronary heart disease risk in randomized clinical trials.
Mackey
Rachel H
RH
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 15261, USA. mackey@edc.pitt.edu
Kuller
Lewis H
LH
Sutton-Tyrrell
Kim
K
Evans
Rhobert W
RW
Holubkov
Richard
R
Matthews
Karen A
KA
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001795:Blood Pressure Determination; D015992:Body Mass Index; D002114:Calcinosis / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000032:analysis / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D015415:Biomarkers; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides