High-normal albuminuria and risk of heart failure in the community

Abstract

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.

Figure 1

Incidence of heart failure by albuminuria category in 10,975 Atherosclerosis Risk in Communities (ARIC) Study participants. Albuminuria categories were based on urinary albumin-creatinine ratios (UACRs) as macroalbuminuria (UACR ≥300 mg/g), microalbuminuria (UACR <300 to ≥30 mg/g), high-normal (<30 to ≥10 mg/g), intermediate-normal (<10 to ≥5 mg/g), and optimal (<5 mg/g). P < 0.01 for differences among curves using the log-rank test.

Figure 2

Adjusted relative hazard of heart failure by continuous level of urinary albumin-creatinine ratio (UACR) in 10,975 Atherosclerosis Risk in Communities (ARIC) Study participants. Reference point is UACR of 1 mg/g. Graph represents a linear spline model, with spline terms at UACRs of 10, 300, and 300 mg/g. Shading represents the 95% confidence interval. Hazard ratio (HR) adjusted for age, sex, race, education attainment, smoking status, drinking status, coronary heart disease, hypertension, diabetes, systolic blood pressure, pulse pressure, use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, use of diuretic, use of statin therapy, body mass index, low- and high-density lipoprotein cholesterol level, and estimated glomerular filtration rate.