title: Distribution, genetic and cardiovascular determinants of FVIII:c - Data from the population-based Gutenberg Health Study.
abstract: BACKGROUND
  Elevated levels of
  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
  c and its cardiovascular determinants is available.
  
  
  METHODS
  
  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
  c were performed under adjustment for genetic determinants, cardiovascular risk factors and cardiovascular disease.
  
  
  CONCLUSIONS
  Females (126.6% (95% CI: 125.2/128)) showed higher
  c levels than males (121.2% (119.8/122.7)).
  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
  c were created.
  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
  c variation. In multivariable analysis,
  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
  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
  c might be useful to identify high-risk cohorts for thromboembolism. Additionally, the prospective evaluation of
  c as a risk predictor becomes feasible.
authors.affiliation: Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Germany. Electronic address: iris.hermanns@unimedizin-mainz.de.
authors.forename: M Iris
authors.initials: MI
authors.lastname: Hermanns
authors.affiliation: Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Grossmann
authors.affiliation: Laboratory for Clinical Thrombosis and Hemostasis, Dept. of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Henri M H
authors.initials: HM
authors.lastname: Spronk
authors.affiliation: Preventive Cardiology and Preventive Medicine, Dept. of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Preventive Cardiology and Preventive Medicine, Dept. of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Jünger
authors.affiliation: Preventive Cardiology and Preventive Medicine, Dept. of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Laubert-Reh
authors.affiliation: Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Mazur
authors.affiliation: Dept. of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Gori
authors.affiliation: Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.affiliation: Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Beutel
authors.affiliation: Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Dept. of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.affiliation: Laboratory for Clinical Thrombosis and Hemostasis, Dept. of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Arina J
authors.initials: AJ
authors.lastname: Ten Cate-Hoek
authors.affiliation: Laboratory for Clinical Thrombosis and Hemostasis, Dept. of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Ten Cate
authors.affiliation: Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Germany; Preventive Cardiology and Preventive Medicine, Dept. of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany.
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Wild
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D004247:DNA / Q000235:genetics*; D005169:Factor VIII / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011159:Population Surveillance / Q000379:methods*; D011446:Prospective Studies; D017678:Sex Distribution; D013923:Thromboembolism / Q000097:blood / Q000453:epidemiology* / Q000235:genetics
chemical_list: D005169:Factor VIII; D004247:DNA
keywords: Arterial thrombosis; Epidemiological studies; FVIII:c reference values; Venous thrombosis