Altered Fibrin Clot Structure in the Healthy Relatives of Patients With Premature Coronary Artery Disease

Abstract

Background— A family history of premature coronary artery disease (CAD) is an independent cardiovascular risk factor. Fibrin clots composed of dense fiber networks are found in young CAD patients and may occur in the relatives of such individuals. Methods and Results— The ex vivo fibrin structure of 100 healthy male relatives of patients with premature CAD and 100 age-matched control subjects was assessed by measurement of permeability ( K s ), fiber mass-length ratio (μ), and turbidity (lag phase and maximum absorbency [max ΔAbs]). Scanning electron microscopy was performed on selected samples. Relatives and controls shared similar levels of conventional cardiovascular risk factors. K s was lower in relatives than in controls, 12.2 (11.1 to 13.3) versus 15.2 (14.0 to 16.5) ×10 −9 cm 2 ( P <0.001), associated with a smaller decrease in μ, 8.5 (7.7 to 9.2) versus 9.7 (8.9 to 10.5) × 10 13 Da/cm ( P <0.05), respectively. Lag phase was shorter in relatives than in controls, 39 (37 to 41) versus 47 (44 to 50) seconds ( P <0.001), and max ΔAbs was higher in relatives, 0.78 (0.74 to 0.82) versus 0.71 (0.67 to 0.74) in controls ( P =0.02), which indicates the presence of thicker fibers in relatives. After adjustment for fibrinogen levels, lag phase and K s remained significantly different between relatives and control subjects. Scanning electron microscopy images confirmed increased fiber diameter in relatives, possibly of reduced density. Factor XIII Val34Leu and fibrinogen Aα Thr312Ala and Bβ -455 G/A showed no association with clot structure. Conclusions— The male relatives of patients with premature CAD form fibrin clots that begin polymerization more quickly, have thicker fibers, and are less permeable than those of control subjects.