Stephen Zewinger1, Christiane Drechsler2, Marcus E Kleber3, Alexander Dressel3, Julia Riffel1, Sarah Triem1, Marlene Lehmann1, Chantal Kopecky4, Marcus D Säemann4, Philipp M Lepper5, Günther Silbernagel6, Hubert Scharnagl7, Andreas Ritsch8, Barbara Thorand9, Tonia de las Heras Gala9, Stefan Wagenpfeil10, Wolfgang Koenig11, Annette Peters9, Ulrich Laufs12, Christoph Wanner2, Danilo Fliser1, Thimoteus Speer1, Winfried März13. 1. Department of Internal Medicine IV, Saarland University Medical Centre, Homburg/Saar, Germany. 2. Division of Nephrology, Department of Medicine, University of Würzburg, Würzburg, Germany. 3. Mannheim Medical Faculty, Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany. 4. Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. 5. Department of Internal Medicine V, Saarland University Medical Centre, Homburg/Saar, Germany. 6. Department of Angiology, Swiss Cardiovascular Center, Inselspital Bern, Bern, Switzerland. 7. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. 8. Department of Internal Medicine I, Innsbruck Medical University, Innsbruck, Austria. 9. Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Epidemiology II, Munich, Germany. 10. Institute for Medical Biometry, Epidemiology, and Medical Informatics, Saarland University, Homburg/Saar, Germany. 11. Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany Deutsches Herzzentrum München, Technische Universität München, Munich, Germany DZHK (German Centre of Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany. 12. Department of Internal Medicine III, Saarland University Medical Centre, Homburg/Saar, Germany. 13. Mannheim Medical Faculty, Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria Synlab Academy, Mannheim, Germany winfried.maerz@medma.uni-heidelberg.de.
Abstract
AIMS: High-density lipoproteins (HDLs) are considered as anti-atherogenic. Recent experimental findings suggest that their biological properties can be modified in certain clinical conditions by accumulation of serum amyloid A (SAA). The effect of SAA on the association between HDL-cholesterol (HDL-C) and cardiovascular outcome remains unknown. METHODS AND RESULTS: We examined the association of SAA and HDL-C with mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, which included 3310 patients undergoing coronary angiography. To validate our findings, we analysed 1255 participants of the German Diabetes and Dialysis study (4D) and 4027 participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study. In LURIC, SAA concentrations predicted all-cause and cardiovascular mortality. In patients with low SAA, higher HDL-C was associated with lower all-cause and cardiovascular mortality. In contrast, in patients with high SAA, higher HDL-C was associated with increased all-cause and cardiovascular mortality, indicating that SAA indeed modifies the beneficial properties of HDL. We complemented these clinical observations by in vitro experiments, in which SAA impaired vascular functions of HDL. We further derived a formula for the simple calculation of the amount of biologically 'effective' HDL-C based on measured HDL-C and SAA from the LURIC study. In 4D and KORA S4 studies, we found that measured HDL-C was not associated with clinical outcomes, whereas calculated 'effective' HDL-C significantly predicted better outcome. CONCLUSION: The acute-phase protein SAA modifies the biological effects of HDL-C in several clinical conditions. The concomitant measurement of SAA is a simple, useful, and clinically applicable surrogate for the vascular functionality of HDL. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: High-density lipoproteins (HDLs) are considered as anti-atherogenic. Recent experimental findings suggest that their biological properties can be modified in certain clinical conditions by accumulation of serum amyloid A (SAA). The effect of SAA on the association between HDL-cholesterol (HDL-C) and cardiovascular outcome remains unknown. METHODS AND RESULTS: We examined the association of SAA and HDL-C with mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, which included 3310 patients undergoing coronary angiography. To validate our findings, we analysed 1255 participants of the German Diabetes and Dialysis study (4D) and 4027 participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study. In LURIC, SAA concentrations predicted all-cause and cardiovascular mortality. In patients with low SAA, higher HDL-C was associated with lower all-cause and cardiovascular mortality. In contrast, in patients with high SAA, higher HDL-C was associated with increased all-cause and cardiovascular mortality, indicating that SAA indeed modifies the beneficial properties of HDL. We complemented these clinical observations by in vitro experiments, in which SAA impaired vascular functions of HDL. We further derived a formula for the simple calculation of the amount of biologically 'effective' HDL-C based on measured HDL-C and SAA from the LURIC study. In 4D and KORA S4 studies, we found that measured HDL-C was not associated with clinical outcomes, whereas calculated 'effective' HDL-C significantly predicted better outcome. CONCLUSION: The acute-phase protein SAA modifies the biological effects of HDL-C in several clinical conditions. The concomitant measurement of SAA is a simple, useful, and clinically applicable surrogate for the vascular functionality of HDL. Published on behalf of the European Society of Cardiology. All rights reserved.
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