Abstract Number: PB2329
Meeting: ISTH 2020 Congress
Theme: Venous Thromboembolism and Cardioembolism » VTE Epidemiology
Background: Menopausal hormone therapy (MHT) increases venous thrombosis (VT) risk.
Aims: We aimed to further unravel the mechanism by which MHT leads to an increased risk of VT.
Methods: A case-control study of VT risk was conducted nested in two Women’s Health Initiative (WHI) trials where women were randomized to conjugated equine estrogen (CEE) alone and to CEE plus medroxyprogesterone (MPA) versus placebo. Activated Protein C resistance (APCsr, ratio) and tissue factor pathway inhibitor (TFPI, free:ng/ml, total:ng/ml, and activity:%) were measured at baseline and 1 year after follow-up.
We assessed whether MHT led to a more prothrombotic profile by measuring the change in biomarker levels from baseline to 1 year. We also assessed the VT risk by baseline biomarkers and MHT and whether a prothrombotic change in biomarker values (increase in APC resistance or a decrease in TFPI) after 1 year due to MHT was associated with VT risk.
Results: There were 217 VT cases and 817 controls in both trials. Those assigned to MHT showed more prothrombotic changes in biomarkers over time compared with placebo; +0.39 (SD=0.54) for APC resistance, -0.24 (SD=0.22) for TFPI activity, -0.21(SD=0.50) for free TFPI and -0.22(SD=0.20) for total TFPI.
Table 1 shows the VT risk by baseline biomarkers and MHT. The risk of VT due to MHT was not further increased in women with a prothrombotic profile at baseline. Women with a prothrombotic response to MHT did not have higher VT risk than women who did not show a prothrombotic response (Table 2).
Conclusions: Though MHT leads to a more prothrombotic profile, i.e. an increase in APC resistance and a decrease in TFPI levels over one year, these prothrombotic changes were not associated with an increased risk of VT.
| APCsr, ratio (>75th pctl)/MHT Use | OR (95% CI) | Free TFPI , ng/ml (<5th pctl)/MHT use | OR (95% CI) | Total TFPI, ng/ml (<5th pctl)/MHT use | OR (95% CI) | TFPI Activity, % (<5th pctl)/MHT use | OR (95% CI) |
| No/No | Ref | No/No | Ref | No/No | Ref | No/No | Ref |
| Yes/No | 1.05(0.53,2.06) | Yes/No | 2.27(0.82,6.24) | Yes/No | 1.58(0.54,4.64) | Yes/No | 1.60(0.59,4.35) |
| No/Yes | 2.13(1.40,3.25) | No/Yes | 2.42(1.70,3.45) | No/Yes | 2.43(1.71,3.46) | No/Yes | 2.40(1.69,3.42) |
| Yes/Yes | 2.89(1.69,4.95) | Yes/Yes | 3.19(1.21,8.43) | Yes/Yes | 2.22(0.85,5.77) | Yes/Yes | 2.60(0.89,7.58) |
| Adjusted for Age at baseline, BMI at baseline, Race/Ethnicity, History of VTE, Trial Randomization date, Hysterectomy status | |||||||
[Odds ratio (95% CI) of VT by baseline biomarkers and MHT]
| Biomarker change | OR (95% CI) | Biomarker change | OR (95% CI) | Biomarker change | OR (95% CI) | Biomarker change | OR (95% CI) |
| APC Sensitivity Ratio Change Tertiles | Free TFPI Change Tertiles | Total TFPI Change | TFPI Activity (%) Change Tertiles | ||||
| Low (-0.46) | 1.36(0.72,2.58) | Low (-0.59) | 1.06(0.61,1.85) | Increase (0.11) | Reference | Low (-0.38) | 1.30(0.73,2.29) |
| Medium (0.15) | Reference | Medium (-0.11) | Reference | Decrease (-0.21) | 0.69(0.41,1.13) | Medium (-0.11) | Reference |
| High (0.81) | 1.01(0.54,1.89) | High (0.34) | 1.46(0.86,2.49) | High (0.09) | 1.67(0.94,2.98) | ||
| Adjusted for Hysterectomy Status, Age at baseline, BMI at baseline, Race/Ethnicity, Previous History of VTE, Trial Randomization date | |||||||
[Odds ratio (95% CI) of VT after Year 1 by 1-year change in biomarkers]
To cite this abstract in AMA style:
Khialani D, Vasan S, Cushman M, Dahm A, Morten Sandset P, Rossouw J, van Hylckama Vlieg A. Tissue Factor Pathway Inhibitor, Activated Protein C Resistance and Risk of Venous Thrombosis Associated with Menopausal Hormone Therapy [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/tissue-factor-pathway-inhibitor-activated-protein-c-resistance-and-risk-of-venous-thrombosis-associated-with-menopausal-hormone-therapy/. Accessed October 1, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/tissue-factor-pathway-inhibitor-activated-protein-c-resistance-and-risk-of-venous-thrombosis-associated-with-menopausal-hormone-therapy/