Diabetes and pre-diabetes in patients with heart failure and preserved ejection fraction

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  • Alice M. Jackson
  • Rasmus Rørth
  • Jiankang Liu
  • Søren Lund Kristensen
  • Inder S. Anand
  • Brian L. Claggett
  • John G.F. Cleland
  • Vijay K. Chopra
  • Akshay S. Desai
  • Junbo Ge
  • Jianjian Gong
  • Carolyn S.P. Lam
  • Martin P. Lefkowitz
  • Aldo P. Maggioni
  • Felipe Martinez
  • Milton Packer
  • Marc A. Pfeffer
  • Burkert Pieske
  • Margaret M. Redfield
  • Adel R. Rizkala
  • Jean L. Rouleau
  • Petar M. Seferović
  • Jasper Tromp
  • Dirk J. Van Veldhuisen
  • Mehmet B. Yilmaz
  • Faiez Zannad
  • Michael R. Zile
  • Køber, Lars Valeur
  • Mark C. Petrie
  • Pardeep S. Jhund
  • Scott D. Solomon
  • John J.V. McMurray
  • PARAGON-HF Committees and Investigators

Aim: There is an association between heart failure with preserved ejection fraction (HFpEF) and insulin resistance, but less is known about the diabetic continuum, and in particular about pre-diabetes, in HFpEF. We examined characteristics and outcomes of participants with diabetes or pre-diabetes in PARAGON-HF. Methods and results: Patients aged ≥50 years with left ventricular ejection fraction ≥45%, structural heart disease and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) were eligible. Patients were classified according to glycated haemoglobin (HbA1c): (i) normal HbA1c, <6.0%; (ii) pre-diabetes, 6.0%–6.4%; (iii) diabetes, ≥6.5% or history of diabetes. The primary outcome was a composite of cardiovascular (CV) death and total heart failure hospitalizations (HFH). Of 4796 patients, 50% had diabetes and 18% had pre-diabetes. Compared to patients with normal HbA1c, patients with pre-diabetes and diabetes more often were obese, had a history of myocardial infarction and had lower Kansas City Cardiomyopathy Questionnaire scores, while patients with diabetes had more clinical evidence of congestion, but similar NT-proBNP concentrations. The risks of the primary composite outcome (rate ratio [RR] 1.59, 95% confidence interval [CI] 1.35–1.88), total HFH (RR 1.67, 95% CI 1.39–2.02) and CV death (hazard ratio [HR] 1.35, 95% CI 1.07–1.71) were higher among patients with diabetes, compared to those with normal HbA1c. Patients with pre-diabetes had a higher risk (which was intermediate between that of patients with diabetes and those with normal HbA1c) of the primary outcome (HR 1.27, 95% CI 1.00–1.60) and HFH (HR 1.35, 95% CI 1.03–1.77), but not of CV death (HR 1.02, 95% CI 0.75–1.40). Patients with diabetes treated with insulin had worse outcomes than those not, and those with ‘lean diabetes’ had similar mortality rates to those with a higher body mass index, but lower rates of HFH. Conclusion: Pre-diabetes is common in patients with HFpEF and is associated with worse clinical status and greater risk of HFH. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT01920711.

Original languageEnglish
JournalEuropean Journal of Heart Failure
Volume24
Issue number3
Pages (from-to)497-509
ISSN1388-9842
DOIs
Publication statusPublished - 2022

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© 2021 European Society of Cardiology

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