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Coronary artery calcium and bone mineral density by serial CTA: Does menopausal hormone therapy modify the association?

      Highlights

      • Osteoporosis (ie, reduced bone mass and micro architectural deterioration) and coronary artery disease (CAD) are age related conditions associated with significantly high morbidity and mortality in post-menopausal women.
      • Women with osteoporosis and osteopenia are more prone to atherosclerotic cardiovascular disease compared with women without this condition.
      • Increased mortality rates due to cardiovascular disorders have been observed in postmenopausal women with low BMD.
      • Therefore, in postmenopausal women diagnosed with osteoporosis, it is critical to consider not only clinical management for fracture prevention, but also cardiovascular intervention to minimize the risk of adverse outcomes related to atherosclerotic vascular disease.
      • The KEEPS trial is an ideal setting to assess the correlation between progression of CAC and changes in volumetric BMD and the effect of early initiation of MHT on that association, as the inclusion criteria for KEEPS was a CAC score ≤ 50 Agatston Units.
      • Our current study demonstrated that, MHT (o-CEE and t-E2) decreases the bone loss among postmenopausal women with CAC progression and would encourage further research.

      Abstract

      Introduction

      Both osteoporosis and cardiovascular disease (CVD) increase in women after menopause. Estrogen deficiency is thought to be an underlying mechanism for both these conditions.

      Methods

      Healthy menopausal women (n = 374, age 42–58 years) underwent cardiac CT scans over four years as participants in the Kronos Early Estrogen Prevention Study (KEEPS), a randomized, controlled trial to Women randomized to either oral conjugated equine estrogens (o-CEE, n = 104), transdermal 17β-estradiol (t-E2, n = 119) or placebo (n-115). CAC (Agatston units, AU), and BMD (mg/cm3) were measured from thoracic vertebrae at baseline and at the 4 years of the study using validated software. ANOVA and multiple linear regression analyzed the association between incident CAC or progression of CAC and BMD among the treatment groups.

      Results

      At baseline 374 women, 40 participants with CAC >0 had greater decrements in BMD than the 334 participants with CAC = 0 at baseline, The average change in BMD in o-CEE group with CAC was −9.6 ± 13.3 versus −3.1 ± 19.5 in those with zero CAC, p = 0.0018. With t-E2, BMD changed by −11.7 ± 26.2 in those with CAC versus +5.7 ± 26.2 in the zero CAC group, p ≤ 0. 0001. Similarly in the 66 participants that showed progression of CAC >1, had more BMD loss, than those with stable CAC regardless of the treatment.

      Conclusion

      Progression of bone loss is reduced among women treated with o-CEE or t-E2. Progression of CAC is associated with greater BMD loss, a relationship that is differentially modified by t-E2 and o-CEE.

      Abbreviations:

      ANOVA (analysis of variance), BMI (body mass index), BMD (bone mineral density), CAC (coronary artery calcium), CAD (coronary artery disease), CT (computed tomography), CVD (cardiovascular disease), DXA (dual-energy X-ray absorptiometry), ECG (electrocardiogram), ERT (estrogen replacement therapy), IQR (interquartile range), KEEPS (Kronos Early Estrogen Prevention Study), LDL (low-density lipoprotein), MHT (menopausal hormonal therapy), NF-kB (nuclear factor kappa B), o-CEE (oral conjugated equine estrogens), PEPI (Postmenopausal Estrogen/Progestin Interventions), RANKL (receptor activator of NF-kB ligand), ROI (Region of Interest), SAS (Statistical Analysis System), SD (standard deviation), t-E2 (transdermal 17β-estradiol), WHI (Women's Health Initiative)

      Keywords

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