Postprandial response of activated factor VII in elderly women depends on the R353Q polymorphism

Background: Activated factor VII (FVIIa) is a very potent coagulant and may be a key determinant of the outcome of a cardiovascular event. The main determinants of FVIIa are the R353Q polymorphism and dietary fat intake, which may have an interactive effect. Objective: The objective was to investigate whether the response of FVIIa to a fat-rich breakfast varies across genotypes of the R353Q polymorphism. Design: Ninety-one apparently healthy elderly women (>60 y of age), 56 with the RR genotype and 35 with the RQ or QQ genotype, participated in a randomized, controlled crossover study. Subjects received 5 breakfasts, each on a separate day: 1 low-fat control breakfast and 4 high-fat test breakfasts. Blood samples were taken for measurement of FVIIa at 0800 before each breakfast (fasting) and at 1300 and 1500. Results: The mean (±SD) fasting FVIIa concentration was 93.3 ± 26.7 U/L in women with the RR genotype, 49.3 ± 19.1 U/L in those with the RQ genotype and 39.5 ± 17.2 U/L in those with the QQ genotype. The mean absolute, response to all 4 test breakfasts was 37.0 U/L in those with the RR genotype and 16.1 U/L in those carrying the Q allele (P < 0.001 for difference). Likewise, the FvIIa response relative to fasting FVIIa was significantly higher in women homozygous for the R allele. Conclusion: This observation may indicate a considerable difference in cardiovascular risk between genotype groups as a result of an increase in FVIIa after a fat-rich diet.