title: Influence of urine creatinine on the relationship between the albumin-to-creatinine ratio and cardiovascular events.
abstract: OBJECTIVE
  In the albumin-to-creatinine ratio (spot-ACR), urine creatinine corrects for tonicity but also reflects muscle mass. Low muscle mass is associated with cardiovascular disease (CVD). We hypothesized that the spot-ACR would be higher in women, lower-weight persons, and older individuals, independent of timed urine albumin excretion (24hr-UAE), and accordingly, that spot-ACR would be more strongly associated with CVD events than 24hr-UAE in these subgroups.
  
  
  METHODS
  2627 PREVEND (Prevention of Renal and Vascular End-stage Disease) participants with 24hr-UAE <30 mg/d were followed for CVD events for 11 years. Cox regression evaluated associations of spot-ACR and 24hr-UAE with CVD events by sex, weight, and age.
  
  
  RESULTS
  Female sex (26%), lower weight (2% per 5 kg), and older age (4% per 5 years) were associated with higher spot-ACR independent of 24hr-UAE (P<0.001). Spot urine albumin concentration (hazard ratio [HR], 1.26 per ln-SD higher) and 1/spot urine creatinine concentration (HR, 1.16 per ln-SD higher) were associated with CVD events. Spot-ACR was more strongly associated with CVD events than either component of the ratio (HR, 1.41 per ln-SD higher). Associations of spot-ACR ≥10 mg/g versus less (HR, 2.33) and 24hr-UAE ≥10 mg/d versus less (HR, 2.09) with CVD events were similar, and there were no significant differences across subgroups (P for interactions >0.06).
  
  
  CONCLUSIONS
  In community-living individuals with 24hr-UAE <30 mg/d, spot-ACR is higher in women, older persons, and lower-weight persons, independent of 24hr-UAE. Low spot urine creatinine is associated with CVD risk, but high urine albumin is a stronger determinant of the association of spot-ACR with CVD than is low urine creatinine.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, USA.
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Carter
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Gansevoort
authors.forename: Lieneke
authors.initials: L
authors.lastname: Scheven
authors.forename: Hiddo J Lambers
authors.initials: HJ
authors.lastname: Heerspink
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.forename: Paul E
authors.initials: PE
authors.lastname: de Jong
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000419:Albuminuria / Q000175:diagnosis / Q000453:epidemiology* / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000652:urine; D016009:Chi-Square Distribution; D003404:Creatinine / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000652:urine*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009426:Netherlands / Q000453:epidemiology; D009929:Organ Size; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; D003404:Creatinine