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

M. Iris Hermanns*, Vera Grossmann, Henri M. H. Spronk, Andreas Schulz, Claus Juenger, Dagmar Laubert-Reh, Johanna Mazur, Tommaso Gori, Tanja Zeller, Norbert Pfeiffer, Manfred Beutel, Stefan Blankenberg, Thomas Muenzel, Karl J. Lackner, Arina J. Hoek - ten Cate, Hugo ten Cate, Philipp S. Wild

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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. Methods: 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 (beta 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.
Original languageEnglish
Pages (from-to)166-174
JournalInternational Journal of Cardiology
Publication statusPublished - 6 May 2015


  • Venous thrombosis
  • Arterial thrombosis
  • Epidemiological studies
  • FVIII:c reference values


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