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. 2022 Aug;9(4):2367-2377.
doi: 10.1002/ehf2.13930. Epub 2022 May 20.

Relationship of diabetes, heart failure, and N-terminal pro-B-type natriuretic peptide with cardiovascular outcomes in patients with atrial fibrillation

Felix Hofer  1 , Ulrike Pailer  2 , Patrick Sulzgruber  1 , Christian Gerges  1 , Max-Paul Winter  1 , Robert P Giugliano  3 , Michael Gottsauner-Wolf  1 , Martin Hülsmann  1 , Niema Kazem  1 , Lorenz Koller  1 , Robert Schönbauer  1 , Alexander Niessner  1 , Christian Hengstenberg  1 , Thomas A Zelniker  1
Affiliations

Relationship of diabetes, heart failure, and N-terminal pro-B-type natriuretic peptide with cardiovascular outcomes in patients with atrial fibrillation

Felix Hofer et al. ESC Heart Fail. 2022 Aug.

Abstract

Aims: We aim to explore the relationship of heart failure (HF) and diabetes with cardiovascular (CV) death or hospitalization for HF (HHF) and to study the clinical utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an unselected patient population with atrial fibrillation (AF).

Methods and results: Patients with AF admitted to a tertiary academic center between January 2005 and July 2019 were identified through a search of electronic health records. We used Cox regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, HF, body mass index, prior myocardial infarction, coronary artery disease, hypertension, smoking, C-reactive protein, and low-density lipoprotein cholesterol. To select the most informative variables, we performed a least absolute shrinkage and selection operator Cox regression with 10-fold cross-validation. In total, 7412 patients (median age 70 years, 39.7% female) were included in this analysis and followed over a median of 4.5 years. Both diabetes [adjusted (Adj.) HR 1.87, 95% CI 1.55-2.25] and HF (Adj. HR 2.57, 95% CI 2.22-2.98) were significantly associated with CV death/HHF after multivariable adjustment. Compared with patients with diabetes, HF patients had a higher risk of HHF but a similar risk of CV and all-cause death. NT-proBNP showed good discriminatory performance (area under the curve 0.78, 95% CI 0.77-0.80) and the addition of NT-proBNP to the covariates used for adjustment resulted in a significant area under the curve improvement (Δ = 0.04, P < 0.001). With least absolute shrinkage and selection operator, the strongest associations for CV death/HHF were obtained for NT-proBNP [HR 1.91 per 1-SD in log-transformed biomarker], HF (HR 1.72), and diabetes (HR 1.56).

Conclusions: Diabetes and HF were independently associated with an increased risk of CV death/HHF in an unselected AF patient population, and NT-proBNP improved risk assessment. These findings suggest that AF patients with diabetes and/or HF should be managed not only for their risk of stroke and systemic embolic events but also for CV death/HHF.

Keywords: Atrial fibrillation; Diabetes mellitus; Heart failure; NT-proBNP.

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Conflict of interest statement

Dr. Hofer has no conflict of interest. Dipl. Ing. Pailer has no conflict of interest. Dr. Sulzgruber reports grants from Daiichi Sankyo, grants from AstraZeneca and grants from Boehringer‐Ingelheim outside the submitted work. Dr. Gerges has received compensation for scientific symposia from Actelion, AOPOrphan Pharmaceuticals, AstraZeneca, and GlaxoSmithKline. Dr. Winter has no conflict of interest. Dr. Giugliano reports grant support from Anthos. Amgen, and Daiichi Sankyo to his institution, and honoraria for CME lectures and/or consulting from Amgen, Boeheringer‐Ingelheim, Bristol Myers Squibb, CryoLife, Daiichi Sankyo, Janssen, Pfizer, SAJA, Servier, and St Lukes Hospital System of Kansas City. Dr. Gottsauner‐Wolf reports no conflicts of interest for this study. Dr. Hülsmann reports consultant, speaker, and research support by Roche Diagnostics, consultant and speaker fee, by Boehringer, Astra Zeneca, Vifor, Novartis, Pfizer, Merck and Bayer. Dr. Kazem reports no conflict of interest. Dr. Koller reports no conflict of interest. Dr. Schönbauer reports no conflict of interest. Dr. Niessner reports personal fees from Bayer, personal fees from BMS, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Daiichi Sankyo and personal fees from Pfizer outside the submitted work. Dr. Hengstenberg reports no conflicts of interest for this study. Dr. Zelniker reports research grants from the Austrian Science Funds and the German Research Foundation, honoraria for serving on advisory boards from Boehringer Ingelheim, personal fees from AstraZeneca, Boehringer Ingelheim, and Sun Pharmaceutical Industries, and educational grants from Eli Lilly and Company.

Figures

Figure 1
Figure 1
Kaplan–Meier curves and the corresponding 5‐year Kaplan–Meier event rates for (A) the composite of cardiovascular death or hospitalization for heart failure, (B) hospitalization for heart failure, and (C) cardiovascular death stratified by presence of diabetes and/or heart failure. CV, cardiovascular; HF, heart failure; HHF, hospitalization for heart failure.
Figure 2
Figure 2
Relationship between diabetes, heart failure, and NT‐proBNP and cardiovascular outcomes. Cox regression models were adjusted for age, sex, estimated glomerular filtration rate, diabetes, heart failure, body mass index, prior myocardial infarction, coronary artery disease, hypertension, low‐density lipoprotein cholesterol, C‐reactive protein, and smoking. CV, cardiovascular; HF, heart failure; HHF, hospitalization for heart failure.
Figure 3
Figure 3
Kaplan–Meier curves and the corresponding 5‐year Kaplan–Meier event rates for CV death/HHF stratified by quartiles of NT‐proBNP. CV, cardiovascular; HHF, hospitalization for heart failure; Q, quartile.
Figure 4
Figure 4
Kaplan–Meier curves and the corresponding 5‐year Kaplan–Meier event rates for CV death/HHF stratified by an NT‐proBNP cut‐off of 125 pg/mL.
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