Fig. 4. Association of coagulation system components with development of heart failure.

Diagram of protein interactions in the coagulation system based on a published review⁶⁰. The two activation pathways (red borders) lead to activation of factor X which further activates II (thrombin) and subsequently fibrin and XIII, which form the bloodclot. The bloodclot is digested into d-dimers by the plasmin system, and three additional systems (blue dashed borders) negatively regulate clotting (protein C, AT, TFPI). Directionality of nominally significant associations (p < 0.05) with incident heart failure (HF) from Cox proportional hazards regression models adjusting for age and sex (n = 583 population-representative controls, 185 cases) is indicated for each component with color codes, where red indicates higher concentration with incident HF, green lower concentrations, and yellow no significant association. Nominally significant associations (p < 0.10) are indicated in orange for higher (two components) and mint green for lower (one component) concentration. All associations were examined only after exclusion of subjects on oral anticoagulation therapy (warfarin). White color indicates that the component was not present on the aptamer-based proteomics platform. APC activated protein C, AT antithrombin III, Dd d-dimer, PC protein C, Pl plasmin, Plg plasminogen, PS protein S, Tbm thrombomodulin, TFPI tissue factor pathway inhibitor, TF tissue factor.