Healthy male relatives of patients with premature CAD formed less permeable fibrin clots compared to controls (12.2 vs 15.2 x10^-9 cm2; P<0.001), with faster polymerization and thicker fibers.
Case-Control (n=200)
Do healthy male relatives of patients with premature CAD have altered ex vivo fibrin clot structure compared to age-matched controls?
Healthy male relatives of patients with premature CAD exhibit prothrombotic alterations in fibrin clot structure, including faster polymerization, thicker fibers, and reduced permeability, which may contribute to their increased cardiovascular risk.
Absolute Event Rate: 12.2% vs 15.2%
p-value: p=<0.001
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 ( micro ), and turbidity (lag phase and maximum absorbency max DeltaAbs). 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) x10(-9) cm(2) (P<0.001), associated with a smaller decrease in micro, 8.5 (7.7 to 9.2) versus 9.7 (8.9 to 10.5) x 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 DeltaAbs 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 Aalpha Thr312Ala and Bbeta -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.
Mills et al. (Mon,) conducted a case-control in Family history of premature coronary artery disease (n=200). Family history of premature CAD vs. Age-matched control subjects was evaluated on Fibrin clot permeability (K(s)) (p=<0.001). Healthy male relatives of patients with premature CAD formed less permeable fibrin clots compared to controls (12.2 vs 15.2 x10^-9 cm2; P<0.001), with faster polymerization and thicker fibers.