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Subjects with familial hypercholesterolemia have lower aortic valve area and higher levels of inflammatory biomarkers
Authors:Anders Hovland  Ingunn Narverud  Linn Kristin Lie Øyri  Martin Prøven Bogsrud  Inger Aagnes  Thor Ueland  Monique Mulder  Frank Leijten  Gisle Langslet  Cecilie Wium  Arne Svilaas  Kjell Erik Arnesen  Jeanine Roeters van Lennep  Pål Aukrust  Bente Halvorsen  Kjetil Retterstøl  Kirsten B. Holven
Affiliation:1. Division of Internal Medicine, Nordland Hospital, Norway;2. Department of Clinical Medicine, University of Tromsø, Norway;3. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway;4. Norwegian National Advisory Unit on Familial Hypercholesterolemia, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Norway;5. Lipid Clinic, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Norway;6. Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital, Norway;7. Research Institute for Internal Medicine, Oslo University Hospital, Norway;8. Institute of Clinical Medicine, University of Oslo, Norway;9. K.G. Jebsen Thrombosis Research and Expertise Centre, University of Tromsø, Norway;10. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands;11. Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Norway
Abstract:BackgroundReduction of the aortic valve area (AVA) may lead to aortic valve stenosis with considerable impact on morbidity and mortality if not identified and treated. Lipoprotein (a) [Lp(a)] and also inflammatory biomarkers, including platelet derived biomarkers, have been considered risk factor for aortic stenosis; however, the association between Lp(a), inflammatory biomarkers and AVA among patients with familial hypercholesterolemia (FH) is not clear.ObjectiveWe aimed to investigate the relation between concentration of Lp(a), measurements of the aortic valve including velocities and valve area and circulating inflammatory biomarkers in adult FH subjects and controls.MethodsIn this cross-sectional study aortic valve measures were examined by cardiac ultrasound and inflammatory markers were analyzed in non-fasting blood samples. The study participants were 64 FH subjects with high (n = 29) or low (n = 35) Lp(a), and 14 healthy controls.ResultsAortic valve peak velocity was higher (p = 0.02), and AVA was lower (p = 0.04) in the FH patients compared to controls; however, when performing multivariable linear regression, there were no significant differences. Furthermore, there were no significant differences between the high and low FH Lp(a) groups regarding the aortic valve. FH subjects had higher levels of platelet-derived markers CD40L, PF4, NAP2 and RANTES compared to controls (0.003 ≤ P ≤ 0.03). This result persisted after multiple linear regression.ConclusionsMiddle-aged, intensively treated FH subjects have higher aortic valve velocity, lower AVA, and higher levels of the platelet-derived markers CD40L, PF4, NAP2 and RANTES compared to healthy control subjects. The aortic valve findings were not significant after multiple linear regression, whereas the higher levels of platelet-derived markers were maintained.
Keywords:Familial hypercholesterolemia  Lipoprotein(a)  Inflammation  Aortic valve  Aortic valve stenosis
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