Coagulation, inflammation and cardiovascular risk in venous thromboembolism: risk factors, biomarkers and prevention

Abstract

Venous thromboembolism (VTE) carries increased long-term risk of arterial cardiovascular disease. Using the Dutch MEGA study and Singaporean COVID-19 cohorts, we examined how coagulation factors and inflammation relate to mortality and cardiovascular outcomes after VTE.

Elevated factor VIII (FVIII) predicted all-cause mortality in patients and controls. Genetically determined high FVIII (non-O blood group) did not, so FVIII marks underlying disease rather than causing death. Of six other coagulation factors, only X and XI predicted fatal myocardial infarction. Fibrinogen was the strongest predictor of arterial events after VTE and partly mediated the link between traditional risk factors and arterial disease. CRP was associated with VTE, particularly unprovoked VTE, but this association weakened substantially after adjustment for BMI, FVIII and chronic illness, suggesting a marker rather than a cause. Young VTE patients had no excess hypertension, diabetes or dyslipidaemia. They carried far more obesity, smoking and physical inactivity.

In our Asian COVID-19 cohorts VTE was rare, predicted by severity rather than variant. Arterial events and bleeding predominated in intensive care. Hypercoagulability persisted a year after mild infection. These findings support treating VTE as a cardiovascular warning sign, prioritising lifestyle modification in young patients, and caution against extrapolating Western thromboprophylaxis guidelines to Asia.