D M Schulte1, K Paulsen2, K Türk2, B Brandt3, S Freitag-Wolf4, I Hagen2, R Zeuner2, J O Schröder1, W Lieb5, A Franke6, S Nikolaus1, U Mrowietz7, S Gerdes8, S Schreiber1, M Laudes9. 1. Department of Internal Medicine I, University of Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany; Cluster of Excellence Inflammation at Interfaces, University of Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany. 2. Department of Internal Medicine I, University of Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany. 3. Institute of Clinical Chemistry, University of Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany. 4. Institute of Medical Informatics and Statistics, University of Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany. 5. Institute of Epidemiology, University of Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany. 6. Cluster of Excellence Inflammation at Interfaces, University of Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany; Institute of Clinical Molecular Biology, University of Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany. 7. Cluster of Excellence Inflammation at Interfaces, University of Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany; Psoriasis-Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany. 8. Psoriasis-Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany. 9. Department of Internal Medicine I, University of Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany; Cluster of Excellence Inflammation at Interfaces, University of Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany. Electronic address: matthias.laudes@uksh.de.
Abstract
BACKGROUND AND AIMS: Chronic inflammatory diseases (CID) are associated with a profound increase in cardiovascular (CV) risk resulting in reduced life expectancy. However, LDL-cholesterol is reported to be low in CID patients which is referred to as the "LDL paradoxon". The aim of the present study was to investigate whether LDL-particles in CID exhibit an increased content of the highly atherogenic small-dense LDL subfraction (sdLDL). METHODS AND RESULTS: In this prospective, single center, observational study we enrolled 141 patients with CID (RA n = 59, inflammatory bowel disease (IBD) n = 35, ankylosing spondylitis (SpA) n = 25, Psoriasis n = 22) in 2011 through 2013 to evaluate sdLDL levels before as well as 6 and 26 weeks after initiation of different anti-cytokine therapies (anti-TNFα, anti-IL-6R antibodies). sdLDL levels were compared to 141 healthy individuals in a case control design. Compared to healthy controls, all CID patients displayed a significantly higher sdLDL content within the LDL cholesterol fraction: RA 35.0 ± 9.2% (p < 0.001), SpA 42.5 ± 10.5% (p < 0.001), IBD 37.5 ± 7.1% (p < 0.001), Psoriasis 33.6 ± 4.6% (p < 0.01). Furthermore, the sdLDL/LDL ratio was significantly higher in male compared to female RA subjects (p < 0.05). Neither anti-TNFα nor anti-IL6R medication altered sdLDL levels despite a significant improvement of disease activity. CONCLUSION: In several different chronic inflammatory disease entities, LDL-cholesterol is shifted toward a pro-atherogenic phenotype due to an increased sdLDL content which might in part explain the LDL paradoxon. Since premature CV disease is a major burden of affected patients, specifically targeting lipid metabolism should be considered routinely in clinical patient care. CLINICAL TRIALS: Registration at German Clinical Trial Register (DRKS): DRKS00005285.
BACKGROUND AND AIMS: Chronic inflammatory diseases (CID) are associated with a profound increase in cardiovascular (CV) risk resulting in reduced life expectancy. However, LDL-cholesterol is reported to be low in CID patients which is referred to as the "LDL paradoxon". The aim of the present study was to investigate whether LDL-particles in CID exhibit an increased content of the highly atherogenic small-dense LDL subfraction (sdLDL). METHODS AND RESULTS: In this prospective, single center, observational study we enrolled 141 patients with CID (RA n = 59, inflammatory bowel disease (IBD) n = 35, ankylosing spondylitis (SpA) n = 25, Psoriasis n = 22) in 2011 through 2013 to evaluate sdLDL levels before as well as 6 and 26 weeks after initiation of different anti-cytokine therapies (anti-TNFα, anti-IL-6R antibodies). sdLDL levels were compared to 141 healthy individuals in a case control design. Compared to healthy controls, all CID patients displayed a significantly higher sdLDL content within the LDL cholesterol fraction: RA 35.0 ± 9.2% (p < 0.001), SpA 42.5 ± 10.5% (p < 0.001), IBD 37.5 ± 7.1% (p < 0.001), Psoriasis 33.6 ± 4.6% (p < 0.01). Furthermore, the sdLDL/LDL ratio was significantly higher in male compared to female RA subjects (p < 0.05). Neither anti-TNFα nor anti-IL6R medication altered sdLDL levels despite a significant improvement of disease activity. CONCLUSION: In several different chronic inflammatory disease entities, LDL-cholesterol is shifted toward a pro-atherogenic phenotype due to an increased sdLDL content which might in part explain the LDL paradoxon. Since premature CV disease is a major burden of affected patients, specifically targeting lipid metabolism should be considered routinely in clinical patient care. CLINICAL TRIALS: Registration at German Clinical Trial Register (DRKS): DRKS00005285.
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