Abstract
The kallikrein/kinin system, an intravascular biochemical pathway that includes several
proteins involved in the contact activation system of coagulation, renin–angiotensin
activation and inflammation, may or may not play a role in venous thromboembolism
(VTE) occurrence. Within a large prospective population-based study in the United
States, we conducted a nested case–cohort study to test the hypothesis that higher
plasma levels of high molecular weight kininogen (HK) or prekallikrein are associated
with greater VTE incidence. We related baseline enzyme-linked immunosorbent assay
measures of HK and prekallikrein in 1993 to 1995 to incidence VTE of the lower extremity
(n = 612) through 2015 (mean follow-up = 18 years). We found no evidence that plasma
HK or prekallikrein was associated positively with incident VTE. HK, in fact, was
associated inversely and significantly with VTE in most proportional hazards regression
models. For example, the hazard ratio of VTE per standard deviation higher HK concentration
was 0.88 (95% confidence interval = 0.81, 0.97), after adjustment for several VTE
risk factors. Our findings suggest that plasma levels of these factors do not determine
the risk of VTE in the general population.
Keywords
high molecular weight kininogen - prekallikrein - prospective study - pulmonary embolus
- venous thrombosis
