Influence of Urine Creatinine on the Relationship between the Albumin-to-Creatinine Ratio and Cardiovascular Events

Background and objectives 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. Design, setting, participants, & 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 In-SD higher) and 1/spot urine creatinine concentration (HR, 1.16 per In-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 In-SD higher). Associations of spot-ACR >= 10 mg/g versus less (FIR, 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. Clin J Am Soc Nephrol 7: 595-603, 2012. doi: 10.2215/CJN.09300911