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 markerfor atheromatous-plaque burden and is predictive of future riskof cardiovascular events. We examined the relationship betweenestrogen therapy and coronary-artery calcium in the contextof a randomized clinical trial.
Methods In our ancillary substudy of the Women's Health Initiativetrial of conjugated equine estrogens (0.625 mg per day) as comparedwith placebo in women who had undergone hysterectomy, we performedcomputed tomography of the heart in 1064 women aged 50 to 59years at randomization. Imaging was conducted at 28 of 40 centersafter a mean of 7.4 years of treatment and 1.3 years after thetrial was completed (8.7 years after randomization). Coronary-arterycalcium (or Agatston) scores were measured at a central readingcenter without knowledge of randomization status.
Results The mean coronary-artery calcium score after trial completionwas lower among women receiving estrogen (83.1) than among thosereceiving placebo (123.1) (P=0.02 by rank test). After adjustmentfor coronary risk factors, the multivariate odds ratios forcoronary-artery calcium scores of more than 0, 10 or more, and100 or more in the group receiving estrogen as compared withplacebo 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 correspondingodds ratios among women with at least 80% adherence to the studyestrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and0.46 (P=0.001). For coronary-artery calcium scores of more than300 (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 womenwith at least 80% adherence.
Conclusions Among women 50 to 59 years old at enrollment, thecalcified-plaque burden in the coronary arteries after trialcompletion was lower in women assigned to estrogen than in thoseassigned to placebo. However, estrogen has complex biologiceffects and may influence the risk of cardiovascular eventsand other outcomes through multiple pathways. (ClinicalTrials.govnumber, NCT00000611
[ClinicalTrials.gov]
.)
Source Information
From Brigham and Women's Hospital, Harvard Medical School, Boston (J.E.M.); the University of California, San Diego, San Diego (M.A.A.); the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (J.E.R., S.E.L.); Wake Forest University School of Medicine, Winston-Salem, NC (J.J.C.); Geisinger Health System, Danville, PA (R.D.L.); George Washington University, Washington, DC (J.H.); the University of Pittsburgh, Pittsburgh (L.H.K.); the University of Washington (B.B.C.) and Fred Hutchinson Cancer Research Center (J.R.H., M.B.P., R.L.P.) — both in Seattle; the University of Cincinnati, Cincinnati (M.G.); HealthPartners Research Foundation and the University of Minnesota — both in Minneapolis (K.L.M.); the University of California at Los Angeles, Los Angeles (L.N.); the University of Massachusetts Medical School, Worcester (J.K.O.); the University of California at Davis, Sacramento (J.R.); and Stanford University, Palo Alto, CA (M.L.S.).
Address reprint requests to Dr. Manson at the Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Ave. E., 3rd Fl., Boston, MA 02215, or at jmanson{at}rics.bwh.harvard.edu.
Estrogen Therapy and Coronary-Artery Calcification
Hodis H. N., Mack W. J., Brouwer M. A., Dieker H.-J., Verheugt F. W.A., Hofbauer L. C., Khosla S., Schoppet M., Manson J. E., Allison M. A., Rossouw J. E.
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N Engl J Med 2007;
357:1252-1254, Sep 20, 2007.
Correspondence
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