Coronary Artery Calcification (CAC) and Post-Trial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) Estrogen-Alone Trial

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

Abstract

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.

Keywords: cardiovascular disease; coronary artery calcification; hormonal therapy; mortality; women.

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
WHI‐CACS study timeline. CAC indicates coronary artery calcium; CACS, Coronary Artery Calcification study; CT, clinical trial; E‐Alone, estrogen‐alone; WHI, Women's Health Initiative.
Figure 2
Figure 2
Age‐adjusted CVD rates per 1000 PYs, by CAC categories. Results are among women without CVD before scan, n=931. Results for CVD and angina are for first events only. Results for CHD, stroke, and coronary revascularization include first and subsequent events. CAC categories defined as 0, 1 to 100, >100. Error bars show 95% confidence intervals for rates. CAC indicates coronary artery calcium; CHD, coronary heart disease; CVD, cardiovascular disease; PYs, person‐years.
Figure 3
Figure 3
Age‐adjusted mortality rates per 1000 PYs, by CAC categories. Results are among 1020 women. CAC categories defined as 0, 1 to 100, >100. Error bars show 95% confidence intervals for rates. CAC indicates coronary artery calcium; CVD, cardiovascular disease; PYs, person‐years.

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Source: PubMed

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