Estrogen therapy decreases coronary artery calcification

Estrogen therapy decreases coronary artery calcification

N Engl J Med 2007; 356: 2591-2602

MedWire News: Postmenopausal women receiving estrogen therapy have a lower build up of calcium plaque in their coronary arteries than women who do not take hormone replacement therapy (HRT), study findings show.

Calcified plaque in the coronary arteries is a marker for atheromatous plaque burden, and is predictive of future risk of cardiovascular events.

Results from the Women's Health Initiative (WHI) randomized trial of conjugated equine estrogens indicated a reduced need for coronary revascularization among women aged 50-59 years, but not older women, who were receiving estrogen compared with those on the placebo group.

JoAnn Manson (Harvard Medical School, Boston, Massachusetts, USA) and colleagues carried out a substudy shortly after the WHI trial ended to determine whether the coronary artery calcium burden differed according to group assignment among 1064 women, aged 50-59 years, after a mean of 7.4 years of treatment.

After trial completion, women receiving estrogen had lower mean coronary artery calcium scores than those receiving placebo, at 83.1 versus 123.1 (p=0.02).

Michael Mendelsohn and Richard Karas, from Tufts University School of Medicine, Boston, wrote in a related editorial that these findings support the "potentially beneficial cardiovascular effects of HRT in younger menopausal women receiving the therapy for symptoms."

They added, however, that "it remains important to continue to emphasize that HRT should not be considered as a strategy to prevent cardiovascular disease in women; there are proven therapies for cardiovascular disease that remain underused in women."

"Clear and striking" cardioprotective effect of estrogen in young women requires confirmation"



ABSTRACT

Estrogen Therapy and Coronary-Artery Calcification


JoAnn E. Manson, M.D., Dr.P.H., Matthew A. Allison, M.D., M.P.H., Jacques E. Rossouw, M.D., J. Jeffrey Carr, M.D., Robert D. Langer, M.D., M.P.H., Judith Hsia, M.D., Lewis H. Kuller, M.D., Dr.P.H., Barbara B. Cochrane, Ph.D., Julie R. Hunt, Ph.D., Shari E. Ludlam, M.P.H., Mary B. Pettinger, M.S., Margery Gass, M.D., Karen L. Margolis, M.D., M.P.H., Lauren Nathan, M.D., Judith K. Ockene, Ph.D., Ross L. Prentice, Ph.D., John Robbins, M.D., Marcia L. Stefanick, Ph.D., for the WHI and WHI-CACS Investigators

Background Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial.

Methods In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status.

Results The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and 0.46 (P=0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P=0.03) in an intention-to-treat analysis and 0.39 (P=0.004) among women with at least 80% adherence.

Conclusions Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways.