title: Lower Apo A-I and lower HDL-C levels are associated with higher intermediate CD14++CD16+ monocyte counts that predict cardiovascular events in chronic kidney disease.
abstract: OBJECTIVE
  Patients with chronic kidney disease (CKD) display impaired cholesterol efflux capacity and elevated CD14(++)CD16(+) monocyte counts. In mice, dysfunctional cholesterol efflux causes monocytosis. It is unknown whether cholesterol efflux capacity and monocyte subsets are associated in CKD.
  
  
  RESULTS
  In 438 patients with CKD, mediators of cholesterol efflux capacity (high-density lipoprotein cholesterol/apolipoprotein A-I) and monocyte subsets were analyzed as predictors of cardiovascular events. Monocyte subset-specific intracellular lipid content, CD36, CD68, and ABCA1 were measured in a subgroup. Experimentally, we analyzed subset-specific cholesterol efflux capacity and response to oxidized low-density lipoprotein cholesterol stimulation in CKD. Epidemiologically, both low Apo-I and low high-density lipoprotein cholesterol were associated with high CD14(++)CD16(+) monocyte counts in linear regression analyses (apolipoprotein A-I: β=-0.171; P<0.001; high-density lipoprotein cholesterol: β=-0.138; P=0.005), but not with counts of other monocyte subsets. In contrast to apolipoprotein A-I or high-density lipoprotein cholesterol, higher CD14(++)CD16(+) monocyte counts independently predicted cardiovascular events (hazard ratio per increase of 1 cell/μL: 1.011 [1.003-1.020]; P=0.007). Experimentally, CD14(++)CD16(+) monocytes demonstrated preferential lipid accumulation, high CD36, CD68, and low ABCA1 expression and, consequently, displayed low cholesterol efflux capacity, avid oxidized low-density lipoprotein cholesterol uptake, and potent intracellular interleukin-6, interleukin-1β, and tumor necrosis factor-α production.
  
  
  CONCLUSIONS
  Taken together, mediators of cholesterol efflux are associated with CD14(++)CD16(+) monocyte counts, which independently predict adverse outcome in CKD.
authors: From the Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine (K.S.R., M.B) and Department of Internal Medicine IV, Nephrology and Hypertension (K.S.R., A.M.Z., I.E., S.S., D.F., G.H.H.), Saarland University Medical Center, Homburg, Germany; and Department of Medicine, Imperial College London, London, United Kingdom (K.J.W.). kyrill.rogacev@uks.eu gunnar.heine@uks.eu.
authors: Kyrill S
authors: KS
authors: Rogacev
authors: From the Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine (K.S.R., M.B) and Department of Internal Medicine IV, Nephrology and Hypertension (K.S.R., A.M.Z., I.E., S.S., D.F., G.H.H.), Saarland University Medical Center, Homburg, Germany; and Department of Medicine, Imperial College London, London, United Kingdom (K.J.W.).
authors: Adam M
authors: AM
authors: Zawada
authors: From the Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine (K.S.R., M.B) and Department of Internal Medicine IV, Nephrology and Hypertension (K.S.R., A.M.Z., I.E., S.S., D.F., G.H.H.), Saarland University Medical Center, Homburg, Germany; and Department of Medicine, Imperial College London, London, United Kingdom (K.J.W.).
authors: Insa
authors: I
authors: Emrich
authors: From the Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine (K.S.R., M.B) and Department of Internal Medicine IV, Nephrology and Hypertension (K.S.R., A.M.Z., I.E., S.S., D.F., G.H.H.), Saarland University Medical Center, Homburg, Germany; and Department of Medicine, Imperial College London, London, United Kingdom (K.J.W.).
authors: Sarah
authors: S
authors: Seiler
authors: From the Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine (K.S.R., M.B) and Department of Internal Medicine IV, Nephrology and Hypertension (K.S.R., A.M.Z., I.E., S.S., D.F., G.H.H.), Saarland University Medical Center, Homburg, Germany; and Department of Medicine, Imperial College London, London, United Kingdom (K.J.W.).
authors: Michael
authors: M
authors: Böhm
authors: From the Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine (K.S.R., M.B) and Department of Internal Medicine IV, Nephrology and Hypertension (K.S.R., A.M.Z., I.E., S.S., D.F., G.H.H.), Saarland University Medical Center, Homburg, Germany; and Department of Medicine, Imperial College London, London, United Kingdom (K.J.W.).
authors: Danilo
authors: D
authors: Fliser
authors: From the Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine (K.S.R., M.B) and Department of Internal Medicine IV, Nephrology and Hypertension (K.S.R., A.M.Z., I.E., S.S., D.F., G.H.H.), Saarland University Medical Center, Homburg, Germany; and Department of Medicine, Imperial College London, London, United Kingdom (K.J.W.).
authors: Kevin J
authors: KJ
authors: Woollard
authors: From the Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine (K.S.R., M.B) and Department of Internal Medicine IV, Nephrology and Hypertension (K.S.R., A.M.Z., I.E., S.S., D.F., G.H.H.), Saarland University Medical Center, Homburg, Germany; and Department of Medicine, Imperial College London, London, United Kingdom (K.J.W.).
authors: Gunnar H
authors: GH
authors: Heine
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000097:blood; D000368:Aged; D016632:Apolipoprotein A-I / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D007958:Leukocyte Count; D008055:Lipids / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification; D011446:Prospective Studies; D017452:Receptors, IgG / Q000032:analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications; D016037:Single-Blind Method; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D008055:Lipids; D018950:Lipopolysaccharide Receptors; D008077:Lipoproteins, LDL; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein
keywords: CD14; CD16; apolipoproteins; cardiorenal syndrome; cholesterol; monocytes