title: Serum amyloid A: high-density lipoproteins interaction and cardiovascular risk.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Stephen
authors.initials: S
authors.lastname: Zewinger
authors.affiliation: Division of Nephrology, Department of Medicine, University of Würzburg, Würzburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Drechsler
authors.affiliation: Mannheim Medical Faculty, Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Mannheim Medical Faculty, Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dressel
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Riffel
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Triem
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Marlene
authors.initials: M
authors.lastname: Lehmann
authors.affiliation: Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Chantal
authors.initials: C
authors.lastname: Kopecky
authors.affiliation: Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Säemann
authors.affiliation: Department of Internal Medicine V, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Lepper
authors.affiliation: Department of Angiology, Swiss Cardiovascular Center, Inselspital Bern, Bern, Switzerland.
authors.forename: Günther
authors.initials: G
authors.lastname: Silbernagel
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: Department of Internal Medicine I, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ritsch
authors.affiliation: Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Epidemiology II, Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.affiliation: Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Epidemiology II, Munich, Germany.
authors.forename: Tonia
authors.initials: T
authors.lastname: de las Heras Gala
authors.affiliation: Institute for Medical Biometry, Epidemiology, and Medical Informatics, Saarland University, Homburg/Saar, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagenpfeil
authors.affiliation: 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.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.affiliation: Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Epidemiology II, Munich, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.affiliation: Department of Internal Medicine III, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
authors.affiliation: Division of Nephrology, Department of Medicine, University of Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Centre, Homburg/Saar, Germany.
authors.forename: Thimoteus
authors.initials: T
authors.lastname: Speer
authors.affiliation: 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.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
mesh_terms: D054058:Acute Coronary Syndrome / Q000401:mortality; D000328:Adult; D000368:Aged; D001011:Aorta / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D002423:Cause of Death; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000401:mortality; D003928:Diabetic Nephropathies / Q000401:mortality; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D011379:Prognosis; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000378:metabolism; D006435:Renal Dialysis / Q000401:mortality; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000378:metabolism* / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D017382:Reactive Oxygen Species; D000685:Serum Amyloid A Protein; D019010:Vascular Cell Adhesion Molecule-1; D009569:Nitric Oxide
keywords: Cardiovascular risk; Dysfunctional HDL; High-density lipoprotein; Mortality; Serum amyloid A