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

Abstract

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.

• Authors: 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, Lars Køber, Mark C Petrie, Pardeep S Jhund, Scott D Solomon, John J V McMurray, PARAGON-HF Committees and Investigators
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 24 Issue 3 Pg. 497-509 (03 2022) ISSN: 1879-0844 [Electronic] England
• PMID: 34918855 (Publication Type: Clinical Trial, Journal Article)
• Copyright: © 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Chemical References

• Peptide Fragments
• Natriuretic Peptide, Brain

Topics

• Diabetes Mellitus (epidemiology)
• Heart Failure (drug therapy)
• Humans
• Middle Aged
• Natriuretic Peptide, Brain (therapeutic use)
• Peptide Fragments (therapeutic use)
• Prediabetic State (epidemiology)
• Prognosis
• Stroke Volume
• Ventricular Function, Left