Distribution, genetic and cardiovascular determinants of FVIII:c - Data from the population-based Gutenberg Health Study
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Distribution, genetic and cardiovascular determinants of FVIII:c - Data from the population-based Gutenberg Health Study. / Hermanns, M Iris; Grossmann, Vera; Spronk, Henri M H; Schulz, Andreas; Jünger, Claus; Laubert-Reh, Dagmar; Mazur, Johanna; Gori, Tommaso; Zeller, Tanja; Pfeiffer, Norbert; Beutel, Manfred; Blankenberg, Stefan; Münzel, Thomas; Lackner, Karl J; Ten Cate-Hoek, Arina J; Ten Cate, Hugo; Wild, Philipp S.
In: INT J CARDIOL, Vol. 187, 2015, p. 166-174.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Distribution, genetic and cardiovascular determinants of FVIII:c - Data from the population-based Gutenberg Health Study
AU - Hermanns, M Iris
AU - Grossmann, Vera
AU - Spronk, Henri M H
AU - Schulz, Andreas
AU - Jünger, Claus
AU - Laubert-Reh, Dagmar
AU - Mazur, Johanna
AU - Gori, Tommaso
AU - Zeller, Tanja
AU - Pfeiffer, Norbert
AU - Beutel, Manfred
AU - Blankenberg, Stefan
AU - Münzel, Thomas
AU - Lackner, Karl J
AU - Ten Cate-Hoek, Arina J
AU - Ten Cate, Hugo
AU - Wild, Philipp S
N1 - Copyright © 2015. Published by Elsevier Ireland Ltd.
PY - 2015
Y1 - 2015
N2 - BACKGROUND: Elevated levels ofFVIII: 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 plasmaFVIII: 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 forFVIII: 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 higherFVIII: 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 forFVIII: 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% ofFVIII: 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 elevatedFVIII: 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 ofFVIII: c might be useful to identify high-risk cohorts for thromboembolism. Additionally, the prospective evaluation ofFVIII: c as a risk predictor becomes feasible.
AB - BACKGROUND: Elevated levels ofFVIII: 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 plasmaFVIII: 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 forFVIII: 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 higherFVIII: 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 forFVIII: 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% ofFVIII: 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 elevatedFVIII: 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 ofFVIII: c might be useful to identify high-risk cohorts for thromboembolism. Additionally, the prospective evaluation ofFVIII: c as a risk predictor becomes feasible.
KW - Adult
KW - Age Distribution
KW - Aged
KW - DNA/genetics
KW - Factor VIII/genetics
KW - Female
KW - Follow-Up Studies
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Germany/epidemiology
KW - Humans
KW - Incidence
KW - Male
KW - Middle Aged
KW - Polymorphism, Genetic
KW - Population Surveillance/methods
KW - Prospective Studies
KW - Sex Distribution
KW - Thromboembolism/blood
U2 - 10.1016/j.ijcard.2015.03.330
DO - 10.1016/j.ijcard.2015.03.330
M3 - SCORING: Journal article
C2 - 25828346
VL - 187
SP - 166
EP - 174
JO - INT J CARDIOL
JF - INT J CARDIOL
SN - 0167-5273
ER -