What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Chronic heart failure (n=28820). Intervention: Higher BUN/creatinine ratio (≥median) vs. Lower BUN/creatinine ratio (<median). Primary outcome: Composite time to first HF hospitalization or cardiovascular death.

December 21, 2023Open Access

Independent Prognostic Importance of Blood Urea Nitrogen to Creatinine Ratio in Heart Failure

Q: What are the key findings of this study?

A higher BUN/creatinine ratio (median 20.1 in HFpEF, 18.7 in HFrEF) was independently associated with a significantly higher risk of first HF hospitalization or cardiovascular death.

Key Result

A higher BUN/creatinine ratio (median 20.1 in HFpEF, 18.7 in HFrEF) was independently associated with a significantly higher risk of first HF hospitalization or cardiovascular death.

Study Design

Type

Meta-Analysis (n=28,820)

Multicenter

Yes

Structured PICO

Does a higher BUN/creatinine ratio increase the risk of cardiovascular death or HF hospitalization in patients with chronic heart failure?

Population

28,820 patients with chronic heart failure (HFrEF and HFpEF) pooled from 5 clinical trials (PARADIGM-HF, ATMOSPHERE, DAPA-HF, PARAGON-HF, and I-PRESERVE)

Intervention

Higher BUN/creatinine ratio (≥median)

Comparator

Lower BUN/creatinine ratio (<median)

Outcome

Composite time to first HF hospitalization or cardiovascular deathcomposite

Higher BUN/creatinine ratio is independently associated with worse outcomes in patients with chronic heart failure across the spectrum of left ventricular ejection fraction.

Abstract

AIM: Blood urea nitrogen (BUN) to creatinine ratio is associated with worse outcomes in acute heart failure (HF) but little is known about its importance in chronic HF. METHODS AND RESULTS: We combined individual patient data from clinical trials (HF with reduced ejection fraction HFrEF: PARADIGM-HF, ATMOSPHERE and DAPA-HF, and HF with preserved ejection fraction HFpEF: PARAGON-HF and I-PRESERVE). The primary outcome examined was a composite time to first HF hospitalization or cardiovascular death; its components and all-cause death were also examined. Each HF phenotype was categorized according to median BUN/creatinine ratio, generating four groups that is, HFpEF ≤ and >median BUN/creatinine ratio and HFrEF ≤ and >median BUN/creatinine ratio. The association between BUN/creatinine ratio and outcomes was evaluated using the Kaplan-Meier estimator and Cox proportional hazard models. Overall, 28 820 patients were analysed. The median (IQR) BUN/creatinine ratio was 20.1 (Q1-Q3 16.7-24.7) in HFpEF and 18.7 (15.2-22.8) in HFrEF. In both HFpEF and HFrEF, higher BUN/creatinine ratio was associated with older age, female sex, and diabetes, but similar estimated glomerular filtration rate (eGFR). The risk of each outcome examined was significantly higher in patients with BUN/creatinine ratio ≥median, compared to <median, even after adjustment for other prognostic variables, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and eGFR. CONCLUSION: Higher BUN/creatinine ratio was associated with worse outcomes in patients with chronic HF across the spectrum of left ventricular ejection fraction, independently of eGFR and NT-proBNP. BUN/creatinine ratio may reflect neurohumoral activation (especially increased arginine vasopressin), altered renal blood flow or other pathophysiologic mechanisms not incorporated in conventional prognostic variables.