Longitudinal increases in blood biomarkers of inflammation or cardiovascular disease and the incidence of venous thromboembolism

Essentials Inflammatory and cardiac diseases are associated with increased venous thromboembolism (VTE) risk. Our prospective study assessed rise in inflammatory or cardiac biomarkers and VTE risk. A greater 6-year rise in N-terminal natriuretic peptide is associated with increased VTE incidence. Volume overload or impending cardiac disease may contribute to VTE occurrence. Summary: Background We previously showed that participants in the population-based Atherosclerosis Risk in Communities (ARIC) cohort with elevated levels of blood biomarkers of inflammation or cardiac disease were at increased risk of venous thromboembolism (VTE). Objective We hypothesized that ARIC participants with larger 6-year increases in the levels of three biomarkers – C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and troponin T – would also have an increased subsequent risk of VTE. Methods We measured changes in the levels of these biomarkers in 9844 participants from 1990–1992 to 1996–1998, and then identified VTEs through 2015. Results A greater 6-year rise in the level of NT-proBNP, but not in that of CRP or troponin T, was significantly associated with increased VTE incidence over a median of 17.6 years of follow-up. After adjustment for other VTE risk factors, those whose NT-proBNP level rose from < 100 pg mL⁻¹ to ≥ 100 pg mL⁻¹ had a hazard ratio for VTE of 1.44 (95% confidence interval [CI] 1.15–1.80), as compared with the reference group with an NT-proBNP level of < 100 pg mL⁻¹ at both times. This hazard ratio was slightly higher (1.66, 95% CI 1.19–2.31) during the first 10 years of follow-up, but was attenuated (1.24, 95% CI 0.99–1.56) after adjustment for prevalent and incident coronary heart disease, heart failure, and atrial fibrillation. Conclusions The two most likely explanations for our results are that: (i) an increasing NT-proBNP level reflects increasing subclinical volume overload and potentially increased venous stasis or subclinical PE that had gone unrecognized over time; or (ii) an increasing NT-proBNP level is a risk marker for impending cardiac disease that places patients at risk of VTE.