Coronary Artery Calcification (CAC) and Post‐Trial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) Estrogen‐Alone Trial
Authors: Poornima Indu G. , Mackey Rachel H. , Allison Matthew A. , Manson JoAnn E. , Carr J. Jeffrey , LaMonte Michael J. , Chang Yuefang , Kuller Lewis H. , Rossouw J.E. , Ludlam S. , Cochrane B.B. , Hunt J.R. , Lund B. , Prentice R. , O'Rourke C. , Du L. , Pillsbury S. , Hightower C. , Ellison R. , Tan J. , Wassertheil‐Smoller S. , Magnani M. , Noble D.H. , Dellicarpini T. , Bueche M. , McGinnis A.D. , Rybicki F.J. , Assaf A.R. , Sloane G. , Phillips L.S. , Butler V. , Huber M. , Vitali J. , Hsia J. , LeBrun C. , Palm R. , Embersit D. , Whitlock E. , Arnold K. , Sidney S. , Cantrell V. , Kotchen J.M. , Feltz C. , Howard B.V. , Thomas‐Geevarghese A. , Boggs G. , Jelinick J.S. , Greenland P. , Neuman A. , Carlson‐Lund G. , Giovanazzi S.M. , Stefanick M.L. , Swope S. , Jackson R. , Toussant K. , Lewis C.E. , Pierce P. , Stallings C. , Wactawski‐Wende J. , Goel S. , Laughlin R. , Robbins J. , Zaragoza S. , Macias D. , Belisle D. , Nathan L. , Voigt B. , Goldin J. , Woo M. , Langer R.D. , Lien X. , Wright C.M. , Gass M. , Sheridan S. , Robinson J.G. , Feddersen D. , Kelly‐Brake K. , Carroll J. , Ockene J. , Churchill L. , Lasser N.L. , Miller B. , Maldjian P.D. , Pierre‐Louis J. , Fishman J. , O'Sullivan M.J. , Fernandez D. , Margolis K.L. , Bjerk C.L. , Truwit C. , Hearity J.A. , Hyslop W.B. , Darroch K. , Murphy C. , Heiss G. , Edmundowicz D. , Ives D. , Johnson K.C. , Satterfield S. , Connelly S.A. , Jones E.L. , Brzyski R. , Nashawati M.A. , Torchia S. , Rodriguez A. , Garza R. , Nentwich P. , Sarto G.E. , Broderick L. , Sweitzer N.K. , Rossouw Jacques , Ludlam Shari , McGowan Joan , Ford Leslie , Geller Nancy , Anderson Garnet , Prentice Ross , LaCroix Andrea , Manson JoAnn E. , Howard Barbara V. , Jackson Rebecca , Thomson Cynthia A. , Wactawski‐Wende Jean , Limacher Marian , Robinson Jennifer , Kuller Lewis , Shumaker Sally , Brunner Robert 
Published: October 2017

Background
Among women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) Estrogen‐Alone (E‐Alone) trial, randomization to conjugated equine estrogen‐alone versus placebo was associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHI‐CACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography ≈8.7 years after baseline randomization. We hypothesized that higher CAC would be related to post‐trial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors.

Methods and Results
WHI‐CACS participants (n=1020) were followed ≈8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low age‐adjusted rates/1000 person‐years of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were ≈2‐fold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogen–alone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality.

Conclusions
Among a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI E‐Alone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over ≈8 years, independent of baseline randomization to conjugated equine estrogen–alone versus placebo or CVD risk factors.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00000611.