Influence of urine creatinine concentrations on the relation of albumin-creatinine ratio with cardiovascular disease events: the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Background: Higher urine albumin-creatinine ratio (ACR) is associated with cardiovascular disease (CVD) events, an association that is stronger than that between spot urine albumin on its own and CVD. Urine creatinine excretion is correlated with muscle mass, and low muscle mass also is associated with CVD. Whether low urine creatinine concentration in the denominator of the ACR contributes to the association of ACR with CVD is uncertain.

Study design: Prospective cohort study.

Setting & participants: 6,770 community-living individuals without CVD.

Predictors: Spot urine albumin concentration, the reciprocal of the urine creatinine concentration (1/UCr), and ACR.

Outcome: Incident CVD events.

Results: During a mean of 7.1 years of follow-up, 281 CVD events occurred. Geometric mean values for spot urine creatinine concentration, urine albumin concentration, and ACR were 95 ± 2 (SD) mg/dL, 0.7 ± 3.7 mg/dL, and 7.0 ± 3.1 mg/g. Urine creatinine concentration was lower in older, female, and low-weight individuals. Adjusted HRs per 2-fold higher increment in each urinary measure with CVD events were similar (1/UCr: 1.07 [95% CI, 0.94-1.22]; urine albumin concentration: 1.08 [95% CI, 1.01-1.14]; and ACR: 1.11 [95% CI, 1.04-1.18]). ACR ≥10 mg/g was associated more strongly with CVD events in individuals with low weight (HR for lowest vs highest tertile: 4.34 vs 1.97; P for interaction = 0.006). Low weight also modified the association of urine albumin concentration with CVD (P for interaction = 0.06), but 1/UCr did not (P for interaction = 0.9).

Limitations: We lacked 24-hour urine data.

Conclusions: Although ACR is associated more strongly with CVD events in persons with low body weight, this association is not driven by differences in spot urine creatinine concentration. Overall, the associations of ACR with CVD events appear to be driven primarily by urine albumin concentration and less by urine creatinine concentration.

Keywords: Urine creatinine concentration; cardiovascular disease events.

Figure 1

Unadjusted association, per 2-fold higher value, of spot urine albumin-creatinine ratio (ACR), spot urine albumin concentration (UAlb), and 1/spot urine creatinine concentration (1/UCr) with CVD events by sex-specific weight tertiles. P values for interaction between urinary variable and weight were 0.006 (ACR), 0.06 (UAlb), and 0.9 (1/UCr).