Estrogen therapy and coronary-artery calcification.

@article{citeulike:2205258, abstract = {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. (ClinicalTrials.gov number, NCT00000611.)}, address = {Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. jmanson@rics.bwh.harvard.edu}, author = {Manson, J. E. and Allison, M. A. and Rossouw, J. E. and Carr, J. J. and Langer, R. D. and Hsia, J. and Kuller, L. H. and Cochrane, B. B. and Hunt, J. R. and Ludlam, S. E. and Pettinger, M. B. and Gass, M. and Margolis, K. L. and Nathan, L. and Ockene, J. K. and Prentice, R. L. and Robbins, J. and Stefanick, M. L. and }, citeulike-article-id = {2205258}, comment = {Over the past 10 years physicians treating postmenopausal women have witnesses a sea change in the use of estrogen therapy as large randomized multicenter studies have determined that estrogen use is associated with a higher risk of thrombotic disease including CVAs and other blood clots and coronary artery disease and breast cancer. Therefore, estrogen is really only prescribed today for vasomotor instability in low doses and for as short of a treatment time as is possible. However, it has always been hypothesized that estrogen replacement therapy might delay the onset of atherosclerosis as it alters both systemic inflammation and lipid metabolism; few data recently have been able to support this hypothesis. This study evaluated calcified plaque in the coronary arteries as a marker for atheromatous plaque as part of the randomized trial of estrogen replacement therapy from the Women’s Health Initiative. They found significantly less plaque in subjects on estrogen compared to those not on estrogen and estrogen users had a lower proportion of subjects with high scores compared to the control group. These data are interesting but must be interpreted with caution, while it appears that estrogen does reduce coronary plaque in a number of women on therapy for 7.4 years, it is not appropriate to infer that estrogen therapy will reduce the number of cardiovascular events in women taking the medication. This study reminds us that estrogen has complex biologic effects and may be associated with cardiovascular events through other pathways such as thrombosis. The story of estrogen and heart disease is not over.--Nancy Lane, MD }, doi = {10.1056/NEJMoa071513}, issn = {1533-4406}, journal = {N Engl J Med}, keywords = {chd, estrogen, femalegonadal, therapy, vasculardisease}, month = {June}, number = {25}, pages = {2591--2602}, posted-at = {2008-01-07 22:29:36}, priority = {2}, title = {Estrogen therapy and coronary-artery calcification.}, url = {http://dx.doi.org/10.1056/NEJMoa071513}, volume = {356}, year = {2007} }

TY - JOUR ID - citeulike:2205258 L3 - citeulike-article-id:2205258 TI - Estrogen therapy and coronary-artery calcification. JF - N Engl J Med VL - 356 IS - 25 SP - 2591 EP - 2602 AD - Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. jmanson@rics.bwh.harvard.edu SN - 1533-4406 N2 - 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. (ClinicalTrials.gov number, NCT00000611.) KW - chd KW - estrogen KW - femalegonadal KW - therapy KW - vasculardisease N1 - Over the past 10 years physicians treating postmenopausal women have witnesses a sea change in the use of estrogen therapy as large randomized multicenter studies have determined that estrogen use is associated with a higher risk of thrombotic disease including CVAs and other blood clots and coronary artery disease and breast cancer. Therefore, estrogen is really only prescribed today for vasomotor instability in low doses and for as short of a treatment time as is possible. However, it has always been hypothesized that estrogen replacement therapy might delay the onset of atherosclerosis as it alters both systemic inflammation and lipid metabolism; few data recently have been able to support this hypothesis. This study evaluated calcified plaque in the coronary arteries as a marker for atheromatous plaque as part of the randomized trial of estrogen replacement therapy from the Women’s Health Initiative. They found significantly less plaque in subjects on estrogen compared to those not on estrogen and estrogen users had a lower proportion of subjects with high scores compared to the control group. These data are interesting but must be interpreted with caution, while it appears that estrogen does reduce coronary plaque in a number of women on therapy for 7.4 years, it is not appropriate to infer that estrogen therapy will reduce the number of cardiovascular events in women taking the medication. This study reminds us that estrogen has complex biologic effects and may be associated with cardiovascular events through other pathways such as thrombosis. The story of estrogen and heart disease is not over.--Nancy Lane, MD AU - Manson, JE AU - Allison, MA AU - Rossouw, JE AU - Carr, JJ AU - Langer, RD AU - Hsia, J AU - Kuller, LH AU - Cochrane, BB AU - Hunt, JR AU - Ludlam, SE AU - Pettinger, MB AU - Gass, M AU - Margolis, KL AU - Nathan, L AU - Ockene, JK AU - Prentice, RL AU - Robbins, J AU - Stefanick, ML PY - 2007/06/21/ UR - http://dx.doi.org/10.1056/NEJMoa071513 ER -