Thyroid function and cardiovascular disease: the mediating role of coagulation factors.

Bano, Arjola; Chaker, Layal; de Maat, Moniek P M; Atiq, Ferdows; Kavousi, Maryam; Franco, Oscar H; Mattace-Raso, Francesco U S; Leebeek, Frank W G; Peeters, Robin P (2019). Thyroid function and cardiovascular disease: the mediating role of coagulation factors. The Journal of clinical endocrinology and metabolism, 104(8), pp. 3203-3212. The Endocrine Society 10.1210/jc.2019-00072

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CONTEXT Mechanisms linking high and high-normal thyroid function to an increased cardiovascular risk remain unclear. Hypothetically, coagulation can play a role. OBJECTIVE To investigate: (i) the association of thyroid function with coagulation factors, (ii) whether coagulation factors mediate the association of thyroid function with cardiovascular disease (CVD). DESIGN AND SETTING Rotterdam Study, a population-based, prospective study. PARTICIPANTS AND MAIN OUTCOME MEASUREMENTS In 5918 participants (mean age, 69.1 years), we measured thyrotropin, free thyroxine (FT4) and coagulation factors (von Willebrand factor antigen [VWF:Ag], ADAMTS13 activity, fibrinogen). Participants were followed for the occurrence of cardiovascular events and deaths. Associations of thyroid function with coagulation factors (standardized Z scores) and CVD were assessed through linear regression and Cox-proportional hazard models, adjusted for potential confounders. We performed causal mediation analyses to evaluate if the effect of thyroid function on CVD is mediated by coagulation. RESULTS Higher FT4 levels were associated with higher VWF:Ag (β=0.34; 95% confidence interval [95%CI]=0.22,0.47), lower ADAMTS13 activity (β=-0.22; 95%CI=-0.35,-0.09), and higher fibrinogen (β=0.26; 95%CI=0.13,0.39). 857 incident cardiovascular events and 690 cardiovascular deaths occurred. FT4 levels were positively associated with cardiovascular events and deaths. The effect of FT4 on incident cardiovascular events was minimally mediated by fibrinogen (1.6%), but not by VWF:Ag and ADAMTS13. VWF:Ag and fibrinogen together mediated 10.0% of the effect of FT4 on cardiovascular deaths. CONCLUSIONS Higher FT4 levels were associated with higher VWF:Ag, lower ADAMTS13 activity and higher fibrinogen, indicating a procoagulant state. VWF:Ag and fibrinogen explained up to 10% of the link between FT4 with CVD.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Bano, Arjola and Franco Duran, Oscar Horacio

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

1945-7197

Publisher:

The Endocrine Society

Language:

English

Submitter:

Beatrice Minder Wyssmann

Date Deposited:

18 Apr 2019 11:25

Last Modified:

23 Oct 2019 15:50

Publisher DOI:

10.1210/jc.2019-00072

PubMed ID:

30938758

BORIS DOI:

10.7892/boris.130185

URI:

https://boris.unibe.ch/id/eprint/130185

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