Menopause Live (21 June, 2010) from IMS 

In a recently published study, Jeon and colleagues report on a retrospective analysis of coronary-artery calcium scores in 436 postmenopausal women who underwent computed tomography (CT) scanning in the hospital’s Health Promotion Center [1]. Serum estradiol, lipids and bone mineral densities were also obtained. In women not receiving hormonal therapy, the women were divided into those with serum estradiol levels < 20 pg/ml and those with estradiol levels ≥ 20 pg/ml; the women were also divided into those with coronary artery calcium scores < 100 and those with scores ≥ 100. Women with lower estradiol levels (< 20 pg/ml) had significantly higher calcium scores (p < 0.05). After adjusting for multiple variables by weighted logistic regression, women with higher estradiol levels had a reduced chance of having a higher coronary calcium score (adjusted odds ratio 0.25; 95% confidence interval 0.07–0.86; p = 0.03).

Comment
In this report from Korea by Jeon and colleagues [1], endogenous estradiol after menopause correlated negatively with the coronary calcium score. Coronary calcium has been found to be a good marker for the extent of coronary atherosclerosis and correlates with cardiac events. This finding is consistent with data from an ancillary study from the Women’s Health Initiative by Manson and colleagues in hysterectomized women using conjugated estrogens alone [2]. In this study, the multivariate odds ratio of having a calcium score > 100 was 0.41 in adherent women using estrogen (defined as taking at least 80% of the estrogen pills over 5 years). This is also consistent with an observational study by Barrett-Connor, where users of hormonal therapy had an odds ratio of 0.40 for having a severe score; in this study, there was also a duration-of-use effect in that long-term users (≥ 10 years) had better scores than short-term users [3]. 

Estrogen is one of the only therapies known to affect calcium coronary scores. As shown in Jeon’s study, even the use of statins did not influence the calcium score.

This observational study by Jeon and colleagues only assessed women not receiving hormones, and thus approximately 15% of women receiving CT scans for coronary calcium in their Health Promotion Center were eliminated. Apart from the effect of endogenous estrogen described above, coronary calcium scores of > 100 Agatston units were significantly related to age, time from menopause, and existence of hypertension as well as diabetes. In the ongoing KEEPS trial of women within 3 years of menopause, the calcium score at baseline was correlated with age and smoking, but not with blood pressure. In addition, approximately 14% of ‘healthy’ asymptomatic women in KEEPS had Agatston scores > 50 units and were eliminated from the trial, showing that there is a relatively high prevalence of some degree of coronary calcification in the US population [4].

One of the concerns in this study is that a relatively insensitive direct assay for estradiol was used, leading to 21% of the women not having exact measurements of estradiol. Accordingly, the data were broken down, fairly arbitrarily, into those with estradiol levels greater and those with estradiol levels less than 20 pg/ml. It would have been preferable to have more precise data and the demonstration, if possible, of a direct negative correlation with Agatston units. It would also be important to know if some of these women were smokers, and what the interaction of this was with the calcium score.
Nevertheless, this study adds more data to the notion of a beneficial interaction between estrogen and the inhibition of coronary calcification. Further, these data also remind us that time from menopause (a surrogate for the length of estrogen insufficiency) is a significant predictor of the extent of coronary calcification.

Roger Lobo
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, USA

References
1. Jeon G-H, Kim,SH, Yun S-C, Chae HD, Kim C-H, Kang BM. Association between serum estradiol level and coronary artery calcification in postmenopausal women. Menopause 2010; May 26. Epub ahead of print.
http://www.ncbi.nlm.nih.gov/pubmed/20512078
2. Manson JE, Allison MA, Rossouw JE, et al. Estrogen therapy and coronary-artery calcification. N Engl J Med 2007;356:2591-602.
http://www.ncbi.nlm.nih.gov/pubmed/17582069
3. Barrett-Connor E, Laughlin GA. Hormonal therapy and coronary calcification in asymptomatic postmenopausal women: the RanchoBernardo Study. Menopause 2005;12:40-8.
http://www.ncbi.nlm.nih.gov/pubmed/15668599
4. Miller VM, Black DM, Brinton EA, et al. Using basic science to design a clinical trial: baseline characteristics of women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). J Cardiovasc Trans Res 2009;2:228-39.
http://www.ncbi.nlm.nih.gov/pubmed/19668346