Albuminuria in heart failure: what do we really know?

Dobre, Daniela; Nimade, Sandeep; Zeeuw, Dick de

doi:10.1097/hco.0b013e328323aa9a

Cited by 19 publications

(21 citation statements)

References 48 publications

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“…Albuminuria may be associated with activation of the renin-angiotensin-aldosterone system and subsequent cardiovascular effects. 3 Alternatively, the increased permeability of renal vessels in albuminuria may be a manifestation of general vascular endothelial dysfunction, 2,35 which has been associated with atherosclerosis. 36 Microalbuminuria has been associated with small-artery remodeling, 37 suggesting that impaired vascular function may represent a common link between albuminuria and cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

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“…3 Although albuminuria generally has been defined at albumin levels ≥30 mg/d (or urinary albumin-creatinine ratio [UACR] ≥30 mg/g), previous research suggests that more modest increases in albuminuria may be associated with poor clinical outcomes. 3–5 Albuminuria, even at levels considered to be high-normal, has been associated with increased rates of cardiovascular disease. 6–9 Although albuminuria has been associated with heart failure in high-risk individuals in clinical trials, 7,10–12 the association of lower levels of albuminuria and incident heart failure has been less well established in the community, particularly in a racially diverse sample.…”

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

Blecker

Matsushita

Köttgen

et al. 2011

American Journal of Kidney Diseases

109

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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.

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Section: Discussionmentioning

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

Blecker

Matsushita

Köttgen

et al. 2011

American Journal of Kidney Diseases

109

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“…Many, if not all, of these pathophysiological abnormalities also occur during heart failure 10,11. The prevalence of microalbuminuria in hypertensive and DM patients (10%–15% and 15%–20%, respectively) is higher than that in the general population (6%–8%) 12. Microalbuminuria is more frequent among patients with diastolic heart failure than in those with systolic heart failure (40% versus 24%) 13.…”

Section: Introductionmentioning

confidence: 99%

Adding thiazide to a rennin-angiotensin blocker regimen to improve left ventricular relaxation in diabetes and nondiabetes patients with hypertension

Takami¹,

Ito²,

Ishii³

et al. 2012

DDDT

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The urinary albumin to creatinine ratio (UACR) is an independent predictor of outcomes in patients with diastolic dysfunction. Thus, we investigated the relationship between diastolic dysfunction, UACR, and diabetes mellitus (DM) in the EDEN study. We investigated the effect of switching from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) to a combination of losartan and hydrochlorothiazide on left ventricular (LV) relaxation in patients with hypertension and diastolic dysfunction. We enrolled 106 patients with and 265 patients without DM. All patients had diastolic dysfunction and had not achieved their treatment goals with an ACEi or ARB. The measurements of e′ velocity and E/e′ ratio was performed with echocardiography as markers of LV diastolic function. We switched the ACEi or ARB to losartan/hydrochlorothiazide and followed these patients for 24 weeks. UACR was decreased in patients with DM (123.4 ± 288.4 to 66.5 ± 169.2 mg/g creatinine; P = 0.0024), but not in patients without DM (51.2 ± 181.8 to 39.2 ± 247.9 mg/g creatinine; P = 0.1051). Among DM patients, there was a significant relationship between changes in UACR and changes in e′ velocity (r = −0.144; P = 0.0257) and between changes in estimated glomerular filtration rate and changes in the E/e′ ratio (r = −0.130; P = 0.0436). Among patients without DM, there was a significant relationship between changes in high-sensitivity C-reactive protein (hs-CRP) and changes in E/e′ (r = 0.205; P = 0.0010). Multivariate analysis demonstrated changes in hemoglobin A1c levels as one of the determinants of change of e′ and E/e′ in patients with DM, whereas hs-CRP was the determinant of change of e′ among patients without DM. These data suggest that improvement in LV diastolic function is associated with an improvement of DM and a concomitant reduction in UACR among DM patients, and with a reduction of hs-CRP in patients without DM when thiazide is added to a renin–angiotensin blocker treatment regimen.

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“…Our observation in a cohort with IGT is consistent with previous population-based studies. Several possible mechanisms explaining the association have been postulated: albuminuria is most likely a marker of (1) activation of the renin-angiotensin aldosterone system, 25 (2) impaired vascular endothelial function with consequent increased renal vasculature permeability, 26 and (3) association with left ventricular hypertrophy. 27 A history of hypertension at baseline and systolic BP above 130 mm Hg were not found to be independent predictors of incident HF hospitalization in our study.…”

Section: Figurementioning

confidence: 99%

Predictors of Incident Heart Failure Hospitalizations Among Patients With Impaired Glucose Tolerance

Wong

Thomas

Sun

et al. 2013

Circ: Heart Failure

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Background— Impaired glucose tolerance and metabolic syndrome are associated with increased risk of heart failure (HF). However, predictors associated with the increased risk of incident HF have not been well characterized. We aimed to identify independent predictors of incident HF hospitalization among patients with impaired glucose tolerance. Methods and Results— In Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR), 9306 research participants with impaired glucose tolerance and ≥1 cardiovascular risk factors were randomized to valsartan versus placebo and nateglinide versus placebo in a 2×2 factorial manner, with a median follow-up of 6.5 years. Using a multivariable Cox proportional hazards model, we analyzed the relationships among baseline clinical factors and the outcome of incident HF hospitalization in patients without history of HF. Significant predictors were identified by forward selection. Increasing age, history of coronary heart disease, and atrial fibrillation or flutter were among several known independent predictors of incident HF hospitalization. Increased waist circumference (hazard ratio per 10 cm, 1.37; 95% confidence interval, 1.21–1.55; P <0.001) and increased urinary albumin–creatinine ratio ( P <0.001) were identified as novel predictors. The predictive model for incident HF hospitalization showed good discrimination, with an optimism-corrected C-index of 0.79. Conclusions— Among research participants with impaired glucose tolerance, there are several easily identifiable predictors of incident HF hospitalization, including traditional risk factors and novel indices of central adiposity and increased urinary albumin–creatinine ratio, which enable further risk stratification and help distinguish patients who could benefit from more aggressive risk factor management.

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Albuminuria in heart failure: what do we really know?

Abstract: Albuminuria is associated with increased heart failure risk. Lowering of albuminuria using RAAS inhibitors appears to lower the risk for heart failure.

Cited by 19 publications

References 48 publications

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

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

Adding thiazide to a rennin-angiotensin blocker regimen to improve left ventricular relaxation in diabetes and nondiabetes patients with hypertension

Predictors of Incident Heart Failure Hospitalizations Among Patients With Impaired Glucose Tolerance

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