TY - JOUR
T1 - Diabetes and pre-diabetes in patients with heart failure and preserved ejection fraction
AU - PARAGON-HF Committees and Investigators
AU - Jackson, Alice M.
AU - Rørth, Rasmus
AU - Liu, Jiankang
AU - Kristensen, Søren Lund
AU - Anand, Inder S.
AU - Claggett, Brian L.
AU - Cleland, John G.F.
AU - Chopra, Vijay K.
AU - Desai, Akshay S.
AU - Ge, Junbo
AU - Gong, Jianjian
AU - Lam, Carolyn S.P.
AU - Lefkowitz, Martin P.
AU - Maggioni, Aldo P.
AU - Martinez, Felipe
AU - Packer, Milton
AU - Pfeffer, Marc A.
AU - Pieske, Burkert
AU - Redfield, Margaret M.
AU - Rizkala, Adel R.
AU - Rouleau, Jean L.
AU - Seferović, Petar M.
AU - Tromp, Jasper
AU - Van Veldhuisen, Dirk J.
AU - Yilmaz, Mehmet B.
AU - Zannad, Faiez
AU - Zile, Michael R.
AU - Køber, Lars
AU - Petrie, Mark C.
AU - Jhund, Pardeep S.
AU - Solomon, Scott D.
AU - McMurray, John J.V.
N1 - Funding Information:
PARAGON‐HF was funded by Novartis Pharmaceuticals. J.J.V.McM is supported by British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217. A.M.J. is supported by a British Heart Foundation Clinical Research Training Fellowship (FS/18/14/33330).
Funding Information:
: I.S.A. has received consulting fees from Amgen, ARCA Biopharma, AstraZeneca, Boston Scientific Corporation, Boehringer Ingelheim, LivaNova, Novartis, and Zensun. B.L.C. has been a consultant for Amgen, AO Biome, Biogen, Boehringer Ingelheim, Corvia, Gilead, Myokardia, and Novartis. J.G.F.C. has received research grants from Bayer, Bristol‐Myers Squibb, Pharmacosmos and Vifor and has received honoraria for advisory boards, lectures and or trial committees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol‐Myers Squibb, HeartFelt Technologies, Idorsia, Johnson & Johnson, Medtronic, Myokardia, Novartis, Pharmacosmos, Respicardia, Servier, Torrent, Vifor and Viscardia. A.S.D. reported receiving personal fees from Abbott, Biofourmis, Boston Scientific, Boehringer Ingelheim, Merck, Regeneron, and Relypsa and grants and personal fees from AstraZeneca, Alnylam, and Novartis, outside the submitted work. C.S.P.L. has received grant support and fees for serving on an advisory board from Boston Scientific and Roche Diagnostics; grant support, fees for serving on an advisory board, and fees for serving on steering committees from Bayer; grant support from Medtronic; grant support and fees for serving on a steering committee from Vifor pharma; fees for serving on an advisory board and for serving on steering committees from AstraZeneca and Novartis; fees for serving on an advisory board from Amgen, Boehringer Ingelheim, and Abbott Diagnostics; consulting fees from Merck and Stealth BioTherapeutics; fees for serving on a steering committee from Janssen Research and Development; lecture fees and consulting fees from Menarini; and fees for serving on a scientific committee from Corvia Medical. J.G., M.P.L. and A.R.R. are employees of Novartis and A.R.R. owns Novartis stock. A.P.M. reports receiving fees for serving on a study committee from Bayer and Fresenius. F.M. has received personal fees from Novartis. M.P. has received consulting fees from AbbVie, Akcea, Actavis, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiorentis, Daiichi Sankyo, Gilead, Johnson & Johnson, Novo Nordisk, Pfizer, Relypsa, Sanofi, Synthetic Biologics, and Theravance. M.A.P. has received grants paid to his institution for serving on the Steering Committee of PARAGON‐HF, and for serving as Study Chair of Prospective ARNI vs ACE Inhibitor Trial to DetermIne Superiority in Reducing Heart Failure Events After MI (PARADISE‐MI) from Novartis and personal fees for consulting from AstraZeneca, CinCor, Corvidia, DalCor, GlaxoSmithKline, Novartis, NovoNordisk, Pharmascience and Sanofi, and also owns Stock Options of DalCor. B.P. reports receiving fees for serving on a steering committee, fees for serving on an advisory board, and lecture fees from Bayer HealthCare Pharmaceuticals and MSD; lecture fees from AstraZeneca; fees for serving on an advisory board and lecture fees from Bristol‐Myers Squibb; fees for serving on an advisory board from Daiichi Sankyo; and lecture fees and honoraria from Medscape. M.M.R. reports being an unpaid consultant for Novartis. J.L.R. has received grants and consulting fees from Novartis and consulting fees from Abbott, AstraZeneca, MyoKardia, and Sanofi. P.M.S. has received honoraria for lectures from Medtronic, Abbott, Servier, AstraZeneca, Respicardia; consultancy agreement and honoraria for lecturer from Boehringer Ingelheim, Novartis; and consultancy agreement from Vifor Pharma. J.T. has received personal fees from Roche Diagnostics, Olink Proteomics, and Us2.ai, outside the submitted work, and has a patent 16/216929 licensed. D.J.vV. reports receiving fees for serving on a steering committee and travel support from ARCA biopharma and Corvia Medical. M.B.Y. reports grants from Amgen, Inc., Novartis, Bayer and Dalcor Pharmaceuticals. F.Z. has received personal fees from Novartis, Janssen, Bayer, Boston Scientific, Amgen, CVRx, Boehringer, Cardiorenal, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck and CardioVascular Clinical Trialists (CVCT). M.R.Z. has received research funding from Novartis and has been a consultant for Novartis, Abbott, Boston Scientific, CVRx, EBR, Endotronics, Ironwood, Merck, Medtronic, and Myokardia V Wave. L.K. has received honoraria from Novartis, Boehringer, Novo, and AstraZeneca. M.C.P. has received lecture fees from AstraZeneca and Eli Lilly, personal fees from NovoNordisk, AstraZeneca, NAPP Pharmaceuticals, Takeda Pharmaceutical, Alnylam, Bayer, Resverlogix, and Cardiorentis and grants and personal fees from Boehringer Ingelheim and Novartis. P.S.J. has received consulting fees, advisory board fees, and lecture fees from Novartis; advisory board fees from Cytokinetics; and grant support from Boehringer Ingelheim. S.D.S. has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and has consulted for Abbott, Action Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi‐Sankyo, Gilead, GSK, Ironwood, Lilly, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi‐Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent. J.J.V.McM. has received grants and his employer paid by AstraZeneca, Theracos, and GlaxoSmithKline during the conduct of the study and grants and his employer being paid by Novartis, Amgen, Bristol‐Myers Squibb, Bayer, Abbvie, Dal‐Cor, Kidney Research UK, and Cardurion and grants from British Heart Foundation. All other authors have nothing to disclose. Conflict of interest
Publisher Copyright:
© 2021 European Society of Cardiology
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
U2 - 10.1002/ejhf.2403
DO - 10.1002/ejhf.2403
M3 - Article
AN - SCOPUS:85122484097
SN - 1388-9842
VL - 24
SP - 497
EP - 509
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
IS - 3
ER -