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Albumin Excretion a Prognostic Marker in Heart Failure

Excess urinary albumin excretion emerged as a significant predictor of mortality and other poor outcomes in a post analysis of about 2,300 heart-failure patients in a major clinical study. 


The results of the study showed that the risk of CV death or HF hospitalization climbed 40% to 75% with a finding of microalbuminuria or macroalbuminuria, respectively, as defined by the urinary-albumin-to-creatinine ratio (UACR). The risk increases were independent of major CV risk factors and comorbidities such as diabetes or hyperglycemia, renal dysfunction, and hypertension.

Dr. Colette E. Jackson,Glasgow Cardiovascular Research Center, Scotland, stated that the analysis was based on patients from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) trials. There were no signs in the analysis that the drug at the center of the trial (Atacand, AstraZeneca) had any effect on urinary albumin.
Because UACR is a simple, readily available, and widely used test, the group writes, it might be particularly useful for risk stratification in heart failure. “However, whether UACR adds incremental prognostic information to other new prognostic biomarkers, particularly natriuretic peptides, which are also increasingly and widely used in clinical practice, needs to be assessed.”
Macroalbuminuria was defined as UACR >25 mg/mmol and microalbuminuria as UACR 2.5–25.0 mg/mmol for men and 3.5–25.0 mg/mmol for women in the analysis, which included only North American patients from CHARM who had available UACR data.
NYHA class 3–4 heart failure was present in 60%, 64%, and 69% of the patients with UACR <2.5 mg/mmol (called normoalbuminuria), microalbuminuria, and macroalbuminuria, respectively. Systolic dysfunction was similarly prevalent in all three groups.
Over a 38-month average follow-up, the risks of CV death/HF hospitalization, all-cause mortality, and HF admission were consistently significantly increased when albuminuria was more pronounced than normal. The risk of the composite end point also went up moderately significantly (p=0.0414) for every 100-mg/mmol increment in UACR. The risks were independent of serum creatinine, glycosylated hemoglobin levels, demographic features, medical history, and heart-failure status.
Adjusted Hazard Ratios (95% CI) for Clinical Outcomes by Degree of Albuminuria (Defined by UACR with Cut Points and as Continuous Variable) in CHARM:

End point
Microalbuminuria, n=704*
Macroalbuminuria, n=257*
Per 100-mg/mmol UACR increment
CV death or HF hospitalization
1.43 (1.21–1.69)
1.75 (1.39–2.20)
1.07 (1.00–1.14)
All-cause mortality
1.62 (1.32–1.99)
1.76 (1.32–2·35)
1.08 (1.00–1.17)
HF hospitalization
1.31 (1.07–1.59)
1.67 (1.28–2·17)
1.07 (0.99–1.15)
UACR= urinary albumin to creatinine ratio
Macroalbuminuria=UACR >25 mg/mmol
Microalbuminuria=UACR 2.5–25.0 mg/mmol (men) or 3.5–25.0 mg/mmol (women).   
*compared with normoalbuminuria (UACR<2.5 mg/mmol), n=1349
Further adjustment for glomerular filtration rate (GFR) didn’t greatly affect the hazard ratios, according to the authors.
The findings suggest that, “Albuminuria in heart failure cannot be explained only by comorbid organ dysfunction such as diabetes or hypertension” and that other pathophysiologic factors related to heart failure may be involved, according to an accompanying editorial from Drs. Kevin Damman, and Hans L. Hillege, University Medical Centre Groningen, the Netherlands.
The CHARM trials didn’t look at treatment specifically aimed at albuminuria, they note, and it’s up to future trials to explore whether such treatment in heart failure might improve outcomes or renal function. However, “One can question whether therapy that successfully reduced albuminuria in other populations of patients (e.g., those with hypertension, diabetes, or renal disease) and which was associated with favorable outcome in these patients would also be beneficial in patients with heart failure.”
The Lancet, August 15, 2009
Jackson CE, Solomon SD, Gerstein HC, et al. Albuminuria in chronic heart failure: prevalence and prognostic importance. Lancet 2009; 374:543–550.
Damman K, Hillege HL, van Veldhuisen DJ. Albuminuria in heart failure: a CHARMing new risk factor? Lancet 2009; 374:506-508.