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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 12 5611-5614
Copyright © 2003 by The Endocrine Society

Special Feature

Hormone Replacement Therapy Is Associated with Less Coronary Atherosclerosis in Postmenopausal Women

Firas Akhrass, Arthur T. Evans, Yue Wang, Stuart Rich, C. R. Kannan, Leon Fogelfeld and Theodore Mazzone

Rush-Presbyterian-St. Luke’s Medical Center (F.A., A.T.E., S.R., C.R.K., L.F., T.M.), Chicago, Illinois 60612; and John H. Stroger, Jr., Hospital of Cook County (A.T.E., Y.W., L.F.), Chicago, Illinois 60612

Address all correspondence and requests for reprints to: Theodore Mazzone, M.D., University of Illinois, 1819 West Polk, M/C 797, Chicago, Illinois 60612. E-mail: tmazzone{at}uic.edu.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Most observational studies indicate that hormone replacement therapy (HRT) protects women from cardiovascular disease. Two recent randomized trials, however, showed no reduction in coronary events with HRT in postmenopausal women. A randomized study evaluating subclinical atherosclerosis showed a beneficial effect of estrogen. In the current study we evaluated the association between HRT and coronary artery atherosclerosis, as quantified by coronary artery calcium score. Current users of HRT were significantly more likely to have a coronary artery calcium score less than 100 and were less likely to have a score greater than 400 than non-HRT users. After adjustment for cardiac risk factors, current use of HRT was associated with a significant reduction of coronary artery calcium score (-28; 95% confidence interval, -48 to -10). The average age of users was 59 yr, the mean duration of use was 9 yr, and the duration of HRT use was significantly associated with a reduction in coronary artery calcium. These results suggest that HRT suppresses atherosclerosis in the coronary arteries. The failure to modify the cardiovascular event rate in clinical trials could result from the adverse effect of HRT on complicated lesions. Additional mechanistic studies may help identify therapeutic strategies that could maximize a potential benefit of HRT on early atherogenesis while minimizing adverse proinflammatory and procoagulant effects on complicated plaque lesions.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
CORONARY HEART DISEASE (CHD) is the most frequent cause of death among U.S. women (1). Most observational studies suggest that hormone replacement therapy (HRT) protects women from CHD (2, 3), and estrogen has been shown to have numerous beneficial effects on vascular wall cells and tissues (4). However, two recent randomized trials, the Women’s Health Initiative (WHI) and the Heart and Estrogen/Progestin Replacement Study (5, 6), showed no reduction in coronary events with HRT in postmenopausal women. There are several possible explanations, both methodological and biological, for these discrepant results (7). Further, a randomized, blinded, placebo-controlled trial recently provided strong evidence for a beneficial effect of estrogen therapy on subclinical atherosclerosis as measured by carotid artery intima-media thickness (8). In the current study we explore the physiological effects of HRT on the coronary arteries of postmenopausal women by assessing the association between current HRT use and coronary atherosclerosis measured by electron beam tomography (EBT), which quantifies coronary artery calcification.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
All women who underwent EBT scanning at Rush-Presbyterian-St. Luke’s Medical Center between March 1997 and August 2001 completed a self-administered questionnaire before the scan (9, 10). The questionnaire included questions regarding demographic information, cardiovascular risk factors, menopausal status, and current use of HRT. A total of 2213 women who were postmenopausal and who indicated whether they were currently using HRT comprised the study sample. These women were physician- or self-referred for EBT as a screening test, as more than 98% of women in each group denied a clinical history of CHD. The protocol was approved by the Medical Center’s institutional review board.

Measurement of coronary artery calcification scores

EBT was performed using an Imatron C100 scanner (Imatron, South San Francisco, CA) as previously described (9, 10). Briefly, 2 sets of 20 transverse 3-mm-thick slices were obtained in an axial fashion to image the entire heart. The coronary artery calcium (CAC) was measured with a densitometric program available on the Imatron scanner. Areas of increased density overlying coronary arteries were evaluated. Lesions were scored with calcium defined as present if found in at least 2 contiguous pixels where the attenuation was 130 Houndsfield units or more. An experienced reader who was blinded to the patients’ clinical data interpreted the scans.

Statistical analysis

The primary analytic goal was to compare CAC scores between women who were receiving hormone replacement therapy and those women who were not, controlling for possible confounders: age, diabetes, body mass index, hypertension, hypercholesterolemia, smoking (current, former, never), and family history of heart disease. As most women had the lowest possible calcium score (zero), the skewed distribution of scores precluded the use of parametric statistical techniques that assumed normality. We categorized the calcium score into three levels based on cut-points previously reported in the literature (11): less than 100, 100–399, and 400 and greater. We also used propensity scores to adjust for differences in risk factors and used bootstrap simulations to test for differences between groups (12, 13). After 2000 bootstrap samples, we estimated the 95% confidence interval for the difference in proportions between groups. We considered a difference statistically significant if the 95% confidence interval for the estimated parameter did not include the null value. We used multivariable logistic regression to estimate the effect of HRT on high risk calcium scores (>400), adjusting for cardiac risk factors using propensity scores and using bootstrap resampling to estimate confidence intervals for model parameters. We also assessed whether longer duration of HRT was associated with a lower calcium score (dose-response relationship) using a similar bootstrap strategy. Multivariable linear regression models were used to assess the independent effects of all risk factors on the CAC score. All statistical analyses were conducted using Stata Statistical software, version 7 (Stata Corp., College Station, TX).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Of 2213 postmenopausal women, 1172 (53%) were current users of HRT. The average duration of use in this group was 9 yr. HRT users were 2.7 yr younger and had a body mass index that was 1.2 kg/m2 lower than non-HRT users (Table 1Go). There was also a significant difference in smoking patterns between the 2 groups, with more former smokers in the HRT group, but more subjects who had never smoked in the nonuser group. The prevalence of all other risk factors was similar. The distribution of CAC scores was highly skewed. For both groups, the modal and median values of the unadjusted CAC score were zero, but the 75th and 90th percentile scores were lower in the HRT group (Table 1Go).


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  		TABLE 1. Demographic, clinical characteristics, and calcium scores by HRT use

 
After adjusting for cardiac risk factors, women using HRT were more likely to have low CAC scores (<100) and were less likely to have high CAC scores (>400; Table 2Go). HRT lessened the odds of having a CAC score greater than 400 by 50% (odds ratio, 0.5; P = 0.02) after adjusting for all measured risk factors in a logistic model.


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  		TABLE 2. Bootstrap-adjusted distribution of the coronary artery calcium score in HRT and non-HRT groups

 
The independent effects of the risk factors on the CAC score are described in Table 3Go. Current smoking was the most potent predictor of a high CAC score. As expected, other important predictors of a high CAC score were age, past history of smoking, hypertension, hypercholesterolemia, and family history of CHD. Current use of HRT significantly predicted a low CAC score, with a mean lowering of 28 (95% confidence interval, -48 to -10). In a subgroup analysis, women who had had their ovaries removed, regardless of whether they were currently using HRT, had lower CAC scores, similar in magnitude to the effect of current HRT use in women with ovaries. Thus, the effect of current HRT use was different for women with and without ovaries (test for interaction, P < 0.01).


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  		TABLE 3. The independent effect of each demographic and clinical characteristic on the CAC score

 
The duration of HRT (dose-response relationship) was a significant predictor of the CAC score after adjustment for age and other cardiac risk factors. In models that included quadratic terms for age and duration, the maximum benefit of HRT on the CAC score was observed after 23 yr of therapy.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The results of this study indicate that HRT use is associated with less coronary artery atherosclerosis as estimated by CAC. The significance of this association is preserved after correction for multiple cardiac risk factors. The use of HRT lowered the odds of having a very high CAC score (>400) by 50%, and HRT lowered the CAC score by an average of 28 points. There was also evidence of a dose-response relationship; longer duration of HRT was associated with a lower CAC score. All of the known risk factors for atherosclerosis (age, smoking, diabetes, hypertension, hypercholesterolemia, and positive family history) had the expected relationship with CAC score. Diabetes predicted an increased CAC score (63 points) consistent with previous reports (10, 14, 15). This increase, however, did not reach statistical significance, because of the small number of subjects with diabetes (6% of the cohort).

The CAC score determined by EBT has been shown to correlate with atherosclerosis in the coronary arteries at autopsy (16, 17, 18, 19). Even though EBT cannot identify plaques that are vulnerable to rupture, because of the strong association between CAC and coronary atherosclerosis, high calcium scores predict cardiovascular events in large observational studies (11, 20). In a recent report using coronary arteries obtained at autopsy from 46 postmenopausal women, it was found that coronary arteries from estrogen-treated women had lower calcium content, mean atherosclerotic plaque area, and calcium to plaque ratio than those from untreated menopausal women (21).

Recently, two randomized clinical trials showed no reduction in CHD events in postmenopausal women treated with continuous estrogen/progestin therapy (5, 6). Grodstein et al. (7) considered factors that could explain why results from these randomized clinical trials differed from the results of a large number of observational studies showing a reduction in CHD events in postmenopausal women who use HRT: healthy user bias, compliance bias, or incomplete capture of early clinical events in observational studies. However, healthy user bias or compliance bias should have also produced a beneficial association between HRT and stroke (7), which was not evident in observational studies. Unmeasured differences in socioeconomic status (7), a strong predictor of cardiovascular events, might also account for better outcomes among HRT users in observational studies. In our study socioeconomic status was not measured, but most women in our sample were well-insured, and many paid for the EBT heart scan themselves.

There are important biological differences between the randomized clinical trials and observational studies that could also contribute to divergent results: the type of HRT (formulation and dose) and the characteristics of the study population (7). Both the Heart and Estrogen/Progestin Replacement Study and WHI studied daily therapy with the combination of equine estrogen and progestin. In observational studies, most women probably used estrogen alone or periodic progestin therapy (7). We do not have specific information regarding the type of HRT used in our study. The effect of HRT could also be modified by a woman’s age and by the number of years from the onset of menopause to the initiation of HRT. In animal studies, hormone therapy generally has been shown to suppress the development of early lesions, and hormone therapy may have no benefit for advanced lesions (22, 23, 24). In nonhuman primates, conjugated estrogen had no effect on the extent of coronary artery plaque in monkeys assigned to estrogen alone or estrogen combined with progestin, when it was started 2 yr after oophorectomy. However, hormone therapy resulted in a 50% decrease in the extent of plaque when given to younger monkeys immediately after oophorectomy (7, 24). In our study, the average age in the HRT group was 59 yr, with an average duration of 9 yr, suggesting that HRT was started close to menopause. In WHI, the mean age of participants at randomization was 63 yr, well beyond menopause.

Several limitations of this study must be considered, besides the potential bias inherent in any cross-sectional study. First, cardiac risk factors were assessed by self-report. The crude categories (for example, hypertension vs. no hypertension) leave room for residual confounding despite adjustment in statistical models. A second limitation is that only current HRT use was identified, not past use. For example, it is likely that women who had an oophorectomy and were not currently using HRT had used HRT in the past. This would explain the unexpected observation that women without ovaries who were not currently using HRT were just as likely to have a low CAC score as women using HRT. This explanation is consistent with the evidence that early use of HRT is more beneficial than late use. In addition, our non-HRT group included women who had used HRT in the past; this would tend to underestimate the benefit of HRT on CAC score. Finally, it is possible that HRT modifies the calcium content of plaque without altering other important pathological characteristics of the plaque. However, a human autopsy study demonstrated that HRT use was associated with a lower calcium/plaque ratio as well as a lower plaque volume (21).

The results of our study are consistent with those of a recently reported randomized clinical trial evaluating the effect of estrogen therapy on subclinical atherosclerosis (8) and the established effect of HRT to suppress coronary artery atherosclerosis in animal models (7, 22, 23, 24). HRT could favorably affect events at the vessel wall during the early atherogenic process (i.e. directly suppress the development of vessel wall lesions), but adversely affect clinical events by activating clinically silent established lesions in the coronary arteries due to adverse effects on inflammatory or thrombotic processes (25, 26). This formulation of currently available evidence does not provide a basis for the current treatment of all postmenopausal women with HRT for prevention of CHD. It does, however, suggest further mechanistic studies to identify strategies that could maximize a potential benefit of hormone therapy on early atherosclerosis while minimizing adverse inflammatory and procoagulant effects on complicated lesions.


   Acknowledgments
 
We thank Stephanie Thompson for assistance with manuscript preparation.


   Footnotes
 
Abbreviations: CAC, Coronary artery calcium; CHD, coronary heart disease; EBT, electron beam tomography; HRT, hormone replacement therapy; WHI, Women’s Health Initiative.

Received June 10, 2003.

Accepted August 14, 2003.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. American Heart Association 2001 Heart and Stroke Statistical Update. Dallas: American Heart Association
  2. Grodstein F, Stampfer M 1995 The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. Prog Cardiovasc Dis 38:199–210[CrossRef][Medline]
  3. Grodstein F, Stampfer MJ 1998 Estrogen for women at varying risk of coronary disease. Matruitas 30:19–26
  4. Mendelsohn ME, Karas RH 1999 The protective effects of estrogen on the cardiovascular system. N Engl J Med 340:1801–1811[Free Full Text]
  5. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J 2002 Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative Randomized Controlled Trial. JAMA 288:321–333[Abstract/Free Full Text]
  6. Hulley S, Furberg C, Barrett-Connor E, Culey J, Grady D, Haskell W, Knopp R, Lowery M, Satterfield S, Schrott H, Vittinghoff E, Hunningbake D 2002 Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II). JAMA 288:58–66[Abstract/Free Full Text]
  7. Grodstein F, Clarkson TB, Manson JE 2003 Understanding the divergent data on postmenopausal hormone therapy. N Engl J Med 348:645–650[Free Full Text]
  8. Hodis HN, Mack WJ, Lobo RA, Shoupe D, Sevantan A, Mahrer PR, Selzer RH, Liu CR, Liu CH, Azen SP 2001 Estrogen in the prevention of atherosclerosis: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 135:939–953[Abstract/Free Full Text]
  9. McLaughlin VV, Hoff JA, Stuart R 1997 Relation between hormone replacement therapy in women and coronary artery disease estimated by electron beam tomography. Am Heart J 134:1115–1119[CrossRef][Medline]
  10. Schurgin S, Rich S, Mazzone T 2001 Increased prevalence of significant coronary artery calcification in patients with diabetes. Diabetes Care 24:335–338[Abstract/Free Full Text]
  11. Raggi P, Callister TQ, Cooil B, He Z-X, Lippolis NJ, Russo DJ, Zelinger A, Mahmarian JJ 2000 Identification of patients at increased risk of first unheralded acute myocardial infarction by electron-beam computed tomography. Circulation 101:850–855[Abstract/Free Full Text]
  12. Rosenbaum PR, Rubin DB 1994 Reducing bias in observational studies using subclassification on the propensity score. J Am Stat Assoc 79:516–524[CrossRef]
  13. Efron B, Tibshirani R 1993 An introduction to the bootstrap. New York: Chapman, Hall
  14. Meigs JB, Larson MG, D’Agostino RB, Levy D, Clouse ME, Nathan DM, Wilson PWF, O’Donnell CJ 2002 Coronary artery calcification in type 2 diabetes and insulin resistance. The Framingham Offspring Study. Diabetes Care 23:1313–1319
  15. Hoff JA, Quinn L, Sevrukov A, Lipton RB, Daviglus M, Garside DB, Ajmere ND, Gandhi S, Kondos GT 2001 The prevalence of coronary artery calcium among diabetic individuals without known coronary artery disease. J Am Coll Cardiol 41:1008–1012
  16. Simons DB, Schwartz RS, Edwards WD, Sheedy PF, Breen JF, Rumberger JA 1992 Noninvasive definition of anatomic coronary artery disease by ultrafast computed tomographic scanning: a quantitative pathologic comparison study. J Am Coll Cardiol 20:1118–1126[Abstract]
  17. Mautner SL, Mautner GC, Froehlich J, Feuerstein JM, Proschan MA, Roberts WC, Doppman JL 1994 Coronary artery calcification: assessment with electron beam CT and histomorphometric correlation. Radiology 192:619–623[Abstract/Free Full Text]
  18. Rumberger JA, Simons DR, Fitzpatrick JA, Sheedy PF, Schwartz RS 1995 Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area: a histopathologic correlative study. Circulation 15:2157–2162
  19. Sangiorgi G, Rumberger JA, Severson A, Edwards WD, Gregoire J, Fitzpatrick LA, Schwartz RS 1998 Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using non-decalcifying methodology: electron beam computed tomography and coronary artery disease: scanning for coronary artery calcification. J Am Coll Cardiol 31:126–133[Abstract/Free Full Text]
  20. Arad Y, Spadaro LA, Goodman K, Lledo-Perez A, Sherman S, Lerner G, Guerci AD 1996 Predictive value of electron beam computed tomography of the coronary arteries: 19-month follow-up of 1173 asymptomatic subjects. Circulation 93:1951–1953[Abstract/Free Full Text]
  21. Christian RC, Harrington S, Edwards WD, Oberg AL, Fitzpatrick LA 2002 Estrogen status correlates with the calcium content of coronary atherosclerotic plaques in women. J Clin Endocrinol Metab 87:1062–1067[Abstract/Free Full Text]
  22. Marsh MM, Walker VR, Curtiss LK, Banka CL 1999 Protection against atherosclerosis by estrogen is independent of plasma cholesterol levels in LDL receptor-deficient mice. J Lipid Res 40:893–900[Abstract/Free Full Text]
  23. Rosenfeld ME, Kauser K, Martin-McNulty B, Polinsky P, Schwartz SM, Rubanyi GM 2002 Estrogen inhibits the initiation of fatty streaks throughout the vasculature but does not inhibit intra-plaque hemorrhage and the progression of established lesions in apolipoprotein E deficient mice. Atherosclerosis 164:215–259
  24. Mikkola TS, Clarkson TB 2002 Estrogen replacement therapy, atherosclerosis, and vascular functions. Cardiovasc Res 53:605–619[Abstract/Free Full Text]
  25. Kah KK, Ahn JY, Kang MH, Kim DS, Jin DK, Sohn MS, Park S, Choi IS, Shin EK 2001 Effects of hormone replacement therapy on plaque stability, inflammation, and fibrinolysis in hypertensive or overweight postmenopausal women. Am J Cardiol 88:1423–1426[CrossRef][Medline]
  26. Pradhan AD, Manson JE, Rossouw JE, Siscovick DS, Mouton CP, Rifai N, Wallace RB, Jackson RD, Pettinger MB, Ridker PM 2002 Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women’s Health Initiative Observational Study. JAMA 288:980–987[Abstract/Free Full Text]



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