Hypothyroidism and the Risk of Venous Thromboembolism: A Nationwide Cohort StudyFunding This study was supported by a grant from Hualien Tzu Chi Hospital (TCRD108–21). The funder had no role in the design or conduct of the study or decision to submit for publication or approval of the manuscript for publication.
03 July 2019
25 November 2019
06 February 2020 (online)
Background Previous studies have shown that hypothyroidism may have an impact on blood coagulation. However, how hypothyroidism and thyroxine replacement therapy (TRT) affect the risk of venous thromboembolism (VTE) remains controversial. This study aimed to examine the associations of hypothyroidism and TRT with VTE risks.
Materials and Methods This nationwide population-based cohort study was conducted using Taiwan's National Health Insurance Research Database. We enrolled 10,818 hypothyroid patients (the exposed cohort) and 21,636 non-hypothyroid subjects (the unexposed cohort) between 2001 and 2014 after 1:2 exact matching according to age, sex, and index year. Hypothyroid patients were further divided into two groups depending on whether they received TRT or not. Adjusted hazard ratios (aHRs) for VTE were calculated using Fine and Gray competing risk models.
Results The mean follow-up period was 7.5 years. Hypothyroidism was significantly associated with a higher risk of VTE (aHR = 1.83 [95% confidence interval [CI]: 1.44–2.33, p < 0.001]). Among hypothyroid patients, the TRT subgroup had a non-significant trend of lower VTE risk than the non-TRT subgroup (aHR = 0.73 [95% CI: 0.52–1.01, p = 0.058]). The analysis for individual events revealed a significant association between TRT use and a lower risk of pulmonary embolism among hypothyroid patients (aHR = 0.34 [95% CI: 0.13–0.88, p = 0.026]).
Conclusion The data suggest that hypothyroidism was significantly associated with an increased risk of VTE. Among hypothyroid patients, a non-significant trend of lower VTE risk in patients treated with TRT was observed. Further prospective studies or clinical trials are necessary to confirm causality.
Keywordshypothyroidism - venous thromboembolism - deep vein thrombosis - pulmonary embolism - thyroxine
Wei-Ting Wei, Huei-Kai Huang, and Ching-Hui Loh were responsible for study conception and design. Peter Pin-Sung Liu and Huei-Kai Huang assumed responsibility for data acquisition, while the analysis and interpretation of data were undertaken by Wei-Ting Wei, Peter Pin-Sung Liu, and Huei-Kai Huang. Wei-Ting Wei, Huei-Kai Huang, and Ching-Hui Loh were in charge of manuscript preparation. Wei-Ting Wei, Peter Pin-Sung Liu, Shu-Man Lin, Carol Chiung-Hui Peng, Jen-Hung Wang, Huei-Kai Huang, and Ching-Hui Loh were all responsible for critical revision. All authors approved the final version of the manuscript for publication.
This study was approved by the Institutional Review Board of Hualien Tzu Chi Hospital.
* These authors contributed equally to this work.
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