Distribution, genetic and cardiovascular determinants of FVIII:c - Data from the population-based Gutenberg Health Study

Background: Elevated levels of

Fviii: c are associated with risk for both venous and arterial thromboembolism. However, no population-based study on the sex-specific distribution and reference ranges of plasma

Fviii: c and its cardiovascular determinants is available.

Fviii: c was analyzed in a randomly selected sample of 2533 males and 2440 females from the Gutenberg Health Study in Germany. Multivariable regression analyses for

Fviii: c were performed under adjustment for genetic determinants, cardiovascular risk factors and cardiovascular disease.

Results and conclusions: Females (126.6% (95% CI: 125.2/128)) showed higher

Fviii: c levels than males (121.2% (119.8/122.7)).

Fviii: c levels increased with age in both sexes (ß per decade: 5.67% (4.22/7.13) male, 6.15% (4.72/7.57) female; p<0.001). Sex-specific reference limits and categories indicating the grade of deviation from the reference were calculated, and nomograms for

Fviii: c were created.

Fviii: c was approximately 25% higher in individuals with non-O blood type. Adjusted for sex and age, ABO-blood group accounted for 18.3% of

Fviii: c variation. In multivariable analysis,

Fviii: c was notably positively associated with diabetes mellitus, obesity, hypertension and dyslipidemia and negatively with current smoking. In a fully adjusted multivariable model, the strongest associations observed were of elevated

Fviii: c with diabetes and peripheral artery disease in both sexes and with obesity in males. Effects of SNPs in the vWF, STAB2 and SCARA5 gene were stronger in females than in males. The use of nomograms for valuation of

Fviii: c might be useful to identify high-risk cohorts for thromboembolism. Additionally, the prospective evaluation of

Fviii: c as a risk predictor becomes feasible.