M Iris Hermanns1, Vera Grossmann2, Henri M H Spronk3, Andreas Schulz4, Claus Jünger4, Dagmar Laubert-Reh4, Johanna Mazur5, Tommaso Gori6, Tanja Zeller7, Norbert Pfeiffer8, Manfred Beutel9, Stefan Blankenberg7, Thomas Münzel10, Karl J Lackner11, Arina J Ten Cate-Hoek3, Hugo Ten Cate3, Philipp S Wild12. 1. Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Germany. Electronic address: iris.hermanns@unimedizin-mainz.de. 2. Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Germany. 3. Laboratory for Clinical Thrombosis and Hemostasis, Dept. of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands. 4. Preventive Cardiology and Preventive Medicine, Dept. of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Germany. 5. Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University Mainz, Germany. 6. Dept. of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Germany. 7. Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany. 8. Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Germany. 9. Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Germany. 10. 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. 11. Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Germany. 12. 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.
Abstract
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.
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.
Authors: Laura L Swystun; Kenichi Ogiwara; Jesse D Lai; Juha R M Ojala; Orla Rawley; Fanny Lassalle; Colleen Notley; Olle Rengby; Alison Michels; Kate Nesbitt; Karl Tryggvason; David Lillicrap Journal: J Thromb Haemost Date: 2019-06-20 Impact factor: 5.824
Authors: Pauline C S van Paridon; Marina Panova-Noeva; Rene van Oerle; Andreas Schulz; Jürgen H Prochaska; Natalie Arnold; Irene Schmidtmann; Manfred Beutel; Norbert Pfeiffer; Thomas Münzel; Karl J Lackner; Hugo Ten Cate; Philipp S Wild; Henri M H Spronk Journal: Thromb J Date: 2022-06-08