title: Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study.
abstract: BACKGROUND
  The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels.
  
  
  METHODS
  Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC).
  
  
  RESULTS
  The mean age of women was 52.9 (± 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) μg/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients ≤0.06, P > 0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile). However, a squared RBP4 term in regression modeling was non-significant (P = 0.10).
  
  
  CONCLUSIONS
  In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis.
  
  
  BACKGROUND
  ClinicalTrials.gov number NCT00154180.
authors.forename: Gary
authors.initials: G
authors.lastname: Huang
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Unab I
authors.initials: UI
authors.lastname: Khan
authors.forename: Irfan
authors.initials: I
authors.lastname: Zeb
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Virginia
authors.initials: V
authors.lastname: Miller
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.forename: George R
authors.initials: GR
authors.lastname: Merriam
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Harman
authors.forename: Eliot A
authors.initials: EA
authors.lastname: Brinton
authors.forename: Marcelle I
authors.initials: MI
authors.lastname: Cedars
authors.forename: Yali
authors.initials: Y
authors.lastname: Su
authors.forename: Rogerio A
authors.initials: RA
authors.lastname: Lobo
authors.forename: Frederick
authors.initials: F
authors.lastname: Naftolin
authors.forename: Nanette
authors.initials: N
authors.lastname: Santoro
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
authors.forename: Rachel P
authors.initials: RP
authors.lastname: Wildman
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis; D015415:Biomarkers; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000032:analysis; D059168:Carotid Intima-Media Thickness; D003327:Coronary Disease / Q000000981:diagnostic imaging; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007328:Insulin / Q000097:blood; D008019:Life Style; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D017698:Postmenopause / Q000097:blood*; D011859:Radiography; D054839:Retinol-Binding Proteins, Plasma / Q000032:analysis*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D002097:C-Reactive Protein