High-Normal Albuminuria and Risk of Heart Failure in the Community

Background: Albuminuria has been associated with cardiovascular risk, but the relationship of high-normal albuminuria to subsequent heart failure has not been well established. Study Design: Prospective observational study, the Atherosclerosis Risk in Communities (ARIC) Study. Setting & Participants: 10,975 individuals free from heart failure were followed up from the fourth ARIC Study visit (1996-1998) through January 2006. Predictor: Urinary albumin-creatinine ratio (UACR), analyzed continuously and categorically as optimal (<5 mg/g), intermediate-normal (5-9 mg/g), high-normal (10-29 mg/g), microalbuminuria (30-299 mg/g), and macroalbuminuria (>= 300 mg/g). Outcomes & Measurements: Incident heart failure was defined as a heart failure-related hospitalization or death. Cox proportional hazard models were used to calculate the HR of heart failure after adjustment for age, race, sex, estimated glomerular filtration rate (eGFR), and other cardiovascular risk factors. Results: Individuals were followed up for a median of 8.3 years and experienced 344 heart failure events. Compared with normal UACR, albuminuria was associated with a progressively increased risk of heart failure from intermediate-normal (adjusted HR, 1.54; 95% CI, 1.12-2.11) and high-normal UACR (adjusted HR, 1.91; 95% CI, 1.38-2.66) to microalbuminuria (adjusted HR, 2.49; 95% CI, 1.77-3.50) and macroalbuminuria (adjusted HR, 3.47; 95% CI, 2.10-5.72). Results were similar in secondary analyses of participants censored at the time of coronary heart disease event and along a range of eGFRs. Limitations: UACR was measured as a single random sample. Conclusions: Albuminuria is associated with subsequent heart failure, even in individuals with few cardiovascular risk factors and UACR within the normal range. Our results suggest that the association between albuminuria and heart failure may not be mediated fully by ischemic heart disease or kidney disease, measured using eGFR. Am J Kidney Dis. 58(1):47-55. (C) 2011 by the National Kidney Foundation, Inc.