Albuminuria and Heart Failure: Key Points

Khan MS, Shahid I, Anker SD, et al.
Albuminuria and Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol 2023;81:270-282.

The following are key points to remember from this state-of-the-art review about albuminuria and heart failure (HF):

  1. Albuminuria (>300 mg/d) and estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m2) are independent predictors of HF exacerbation and increased risk of mortality. Albuminuria is a marker of early kidney disease that may be present even in the setting of a normal GFR.
  2. The pathophysiology between albuminuria and HF is multifactorial and stems from the combination of endothelial damage, tubular damage, and comorbid conditions (e.g., hypertension, obesity, diabetes mellitus) that ultimately result in an inflammatory state and volume overload due to activation of the renin-angiotensin-aldosterone system.
  3. Additionally, the relationship between albuminuria and cardiovascular disease is related to microvascular endothelial dysfunction resulting from an inflammatory state and accelerated atherosclerosis due to increased hepatic lipoprotein production. Resulting inflammation and neurohormonal activation promote oxidative stress and additional systemic vascular injury, increasing the risk of development or progression of HF.
  4. Albuminuria is measured using the urinary albumin-creatinine ratio (UACR) from a spot-urine sample and then classified as normal (<10 mg/g), normal to mildly increased (<30 mg/g), moderately increased (30-300 mg/g), or severely increased (>300 mg/g). Urinary albumin is utilized in lieu of urinary total protein, as it is a more sensitive and specific early marker of a change in glomerular permeability.
  5. Albuminuria in high-risk individuals has been found to increase the risk of incident HF by 1.7-2.7 times. Incorporating albuminuria in HF risk prediction models improves prediction of 10-year risk of developing HF in patients without HF. Notably, albuminuria may be present in patients with and without concomitant type 2 diabetes mellitus (T2DM), although the combination of kidney dysfunction, T2DM, and albuminuria is associated with the highest cardiorenal risk.
  6. Albuminuria is also a risk factor for disease progression in HF, though the prognostic utility in HF subtypes (i.e., HF with reduced ejection fraction [HFrEF] and HF with preserved EF [HFpEF]) requires further examination. Various trials have reported that increased albuminuria is associated with an increased risk of HF hospitalizations and mortality irrespective of comorbidities such as T2DM or hypertension.
  7. Urinary albuminuria presents a continuous risk factor for HF with the risk persisting even at low levels of albuminuria (e.g., 0.6 mg/mmol). Every 0.4 mg/mmol increase in UACR increases the risk of HF hospitalization by 11% (HOPE study).
  8. Screening for baseline albuminuria to estimate the risk of developing HF or HF progression is likely cost-effective; however, the optimal screening interval still needs to be determined. In other patient populations, screening for albuminuria is currently recommended biannually (T2DM) and at 5-year intervals (hypertension).
  9. Targeting decreased albuminuria by utilizing drug therapies has been associated with decreased risk of HF, hospitalizations for HF, and reduced risk of cardiovascular death. These findings suggest that reducing albuminuria may decrease the risk of developing HF and improve HF outcomes in patients with HF.
  10. Moderately increased albuminuria is a better predictor of the risk of incident HF, whereas severely increased albuminuria is a better predictor of kidney disease progression and end-stage kidney disease (which can exacerbate HF). Early identification and reduction of albuminuria may prove beneficial in patients with chronic kidney disease and/or HF.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Acute Heart Failure, Hypertension, Stress

Keywords: Albumins, Albuminuria, Atherosclerosis, Creatinine, Diabetes Mellitus, Type 2, Glomerular Filtration Rate, Heart Failure, Hypertension, Inflammation, Kidney Diseases, Kidney Failure, Chronic, Lipoproteins, Oxidative Stress, Renin-Angiotensin System, Secondary Prevention

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