Albuminuria was a powerful, independent predictor of poor prognosis in heart failure in a prospective study of more than 2,000 patients.
Because diagnosis of albuminuria using a patient's spot urinary albumin to creatinine ratio (UACR) is a “simple and readily available clinical test that is widely used in primary and secondary care, it might be of value in risk stratification of patients with heart failure,” Dr. Colette E. Jackson of the University of Glasgow, and her associates wrote in their report (Lancet 2009;374:543-50).
But the finding came with two important caveats: First, the new analysis did not establish whether reducing albumin excretion by treatment improves clinical outcomes. The study also did not establish whether calculating a patient's UACR adds incremental prognostic information to other new, prognostic biomarkers such as natriuretic peptides.
This uncertainty about the role of UACR in managing heart failure patients was echoed in a comment that accompanied the report, which asked whether albuminuria should be used as a (surrogate) treatment target in heart failure, and if so how it should it be treated. “Until a properly designed, adequately powered study is done, the question is open to debate,” Dr. Kevin Damman and his associates at the University Medical Centre in Groningen, the Netherlands, wrote in their comment (Lancet 2009;374:506-7).
The new analysis was a preplanned, investigator-originated substudy of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) study, which found that treatment with the angiotensin receptor blocker candesartan was significantly better than placebo for preventing cardiovascular death and heart failure hospitalization in patients with New York Heart Association class II-IV heart failure who were intolerant of an angiotensin-converting enzyme inhibitor (Lancet 2003;362:759-66).
The new analysis focused on 2,310 patients in CHARM who had their UACR measured. Overall, 58% of these patients had a normal UACR at baseline, 30% had microalbuminuria, and 11% had macroalbuminuria. Patients with high UACRs were older and had more cardiovascular comorbidity, worse renal function, and a higher prevalence of diabetes than did those with normal UACRs, but some patients had micro- or macroalbuminuria without having diabetes, hypertension, or renal dysfunction.
After adjustment for prognostic variables, including renal function, diabetes, and blood level of hemoglobin A1c, the hazard ratio for the incidence of cardiovascular death or hospitalization for heart failure was 43% higher in patients with microalbuminuria and 75% higher in patients with macroalbuminuria, compared with those with normal UACRs. These differences were statistically significant. For every 100 mg/mmol increase in the UACR the risk for cardiovascular death or heart failure hospitalization rose by 7%, a statistically significant effect.
Dr. Jackson said that she had no conflicts of interest, but several of her coauthors reported receiving research funding, and lecture and consulting fees, from AstraZeneca, the company that markets candesartan (Atacand). Dr. Damman and his coauthors said they had no conflicts.