Vitamin K-dependent clotting factors are elevated in young adults who have close relatives with ischemic heart disease

An increase in factor VII was found to be a risk factor for ischemic heart disease. The present study was designed to test the hypothesis that this increase in factor VII is part of a general increase in vitamin K-dependent clotting factors. Initially, a prospective analysis of factor VII antigen and prothrombin activity was performed in two groups of young subjects without symptoms who differed in their risk of ischemic heart disease based on a history (or lack thereof) of premature heart disease in a first-degree relative. A statistically significant increase in prothrombin activity and factor VII antigen was found in the high-risk group of subjects when compared with the low-risk group. In a second series of subjects, factor IX and X activity assays were also performed, and all four of the vitamin K-dependent clotting factors were found to be significantly higher in high-risk subjects when compared with low-risk subjects. A second goal of the study was to explore whether correlations between factor VII and cholesterol and triglycerides might be due to binding of factor VII with apolipoprotein B. Although a significant correlation of factor VII antigen with apolipoprotein B (rho = 0.523, p < 0.025) was found in our high-risk group of subjects, the correlation between factor VII and triglycerides (rho = 0.641, p < 0.005) was even stronger statistically, suggesting a probable interaction of factor VII with very-low-density lipoproteins in vivo. This study supports the hypothesis that a general increase in vitamin K-dependent clotting factors is part of the pathophysiology causing a familial risk of ischemic heart disease.