Changes in albuminuria predict mortality and morbidity in patients with vascular disease

Abstract

The degree of albuminuria predicts cardiovascular and renal outcomes, but it is not known whether changes in albuminuria also predict similar outcomes. In two multicenter, multinational, prospective observational studies, a central laboratory measured albuminuria in 23,480 patients with vascular disease or high-risk diabetes. We quantified the association between a greater than or equal to twofold change in albuminuria in spot urine from baseline to 2 years and the incidence of cardiovascular and renal outcomes and all-cause mortality during the subsequent 32 months. A greater than or equal to twofold increase in albuminuria from baseline to 2 years, observed in 28%, associated with nearly 50% higher mortality (HR 1.48; 95% CI 1.32 to 1.66), and a greater than or equal to twofold decrease in albuminuria, observed in 21%, associated with 15% lower mortality (HR 0.85; 95% CI 0.74 to 0.98) compared with those with lesser changes in albuminuria, after adjustment for baseline albuminuria, BP, and other potential confounders. Increases in albuminuria also significantly associated with cardiovascular death, composite cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure), and renal outcomes including dialysis or doubling of serum creatinine (adjusted HR 1.40; 95% CI 1.11 to 1.78). In conclusion, in patients with vascular disease, changes in albuminuria predict mortality and cardiovascular and renal outcomes, independent of baseline albuminuria. This suggests that monitoring albuminuria is a useful strategy to help predict cardiovascular risk.

Figure 1.

Adjusted HR (95 CI %) [x axis] of changes in UACR from baseline to 2-year visit for (A) all-cause mortality, (B) cardiovascular death, (C) composite cardiovascular outcome, and (D) composite renal outcome after the 2-year visit with mean follow-up of 32 months in the whole study group. Increase refers to at least doubling and decrease to at least halving of albuminuria. Minor change of albuminuria was taken as reference group (HR = 1.0) and P values of the adjusted HR are given in the figure next to the circles. (Hazard ratios were adjusted for age, sex, body mass index, smoking, alcohol consumption, eGFR, plasma glucose, systolic and diastolic BP and HR at baseline, BP change and eGFR change within 2-year study (ONTARGET, TRANSCEND), treatment, and diagnosis at study entry such as coronary artery disease, peripheral artery disease, previous stroke, transient ischemic attack, and high-risk diabetes.)

Figure 2.

Adjusted HR (95 CI%) for all-cause mortality in patients with a mean follow-up of 32 months: decrease of ≥50% or more (upper part); increase of ≥100% in all patients (lower part) in whole study group (N = 23,480) and in the five treatment groups. No heterogeneity between treatments has been observed (P = 0.12). Likewise, no heterogeneity between treatments were observed for cardiovascular death (P = 0.32) and composite cardiovascular outcome (P = 0.70). Minor change of albuminuria was taken as reference group (HR = 1.0) increase refers to at least doubling and decrease to at least halving of albuminuria. (P values of the adjusted HR are given in the figure, % numbers add to 100% per treatment group.) (Hazard ratios were adjusted for age, sex, body mass index, smoking, alcohol consumption, eGFR, plasma glucose, systolic and diastolic BP and HR at baseline, BP change and eGFR change within 2-year study (ONTARGET, TRANSCEND), treatment, and diagnosis at study entry such as coronary artery disease, peripheral artery disease, previous stroke, transient ischemic attack, and high-risk diabetes.)