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

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

doi:10.1002/ejhf.2403

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

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 RizkalaJean 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

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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.

Originalsprog	Engelsk
Tidsskrift	European Journal of Heart Failure
Vol/bind	24
Udgave nummer	3
Sider (fra-til)	497-509
Antal sider	13
ISSN	1388-9842
DOI	https://doi.org/10.1002/ejhf.2403
Status	Udgivet - mar. 2022

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10.1002/ejhf.2403

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Jackson, A. M., Rørth, R., Liu, J., Kristensen, S. L., Anand, I. S., Claggett, B. L., Cleland, J. G. F., Chopra, V. K., Desai, A. S., Ge, J., Gong, J., Lam, C. S. P., Lefkowitz, M. P., Maggioni, A. P., Martinez, F., Packer, M., Pfeffer, M. A., Pieske, B., Redfield, M. M., ... PARAGON-HF Committees and Investigators (2022). Diabetes and pre-diabetes in patients with heart failure and preserved ejection fraction. European Journal of Heart Failure, 24(3), 497-509. https://doi.org/10.1002/ejhf.2403

Jackson, AM, Rørth, R, Liu, J, Kristensen, SL, Anand, IS, Claggett, BL, Cleland, JGF, Chopra, VK, Desai, AS, Ge, J, Gong, J, Lam, CSP, Lefkowitz, MP, Maggioni, AP, Martinez, F, Packer, M, Pfeffer, MA, Pieske, B, Redfield, MM, Rizkala, AR, Rouleau, JL, Seferović, PM, Tromp, J, Van Veldhuisen, DJ, Yilmaz, MB, Zannad, F, Zile, MR, Køber, L, Petrie, MC, Jhund, PS, Solomon, SD, McMurray, JJV & PARAGON-HF Committees and Investigators 2022, 'Diabetes and pre-diabetes in patients with heart failure and preserved ejection fraction', European Journal of Heart Failure, bind 24, nr. 3, s. 497-509. https://doi.org/10.1002/ejhf.2403

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title = "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.",

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

note = "{\textcopyright} 2021 European Society of Cardiology.",

year = "2022",

month = mar,

doi = "10.1002/ejhf.2403",

language = "English",

volume = "24",

pages = "497--509",

journal = "European Journal of Heart Failure",

issn = "1388-9842",

publisher = "John Wiley and Sons Ltd",

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TY - JOUR

T1 - Diabetes and pre-diabetes in patients with heart failure and preserved ejection fraction

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

AU - PARAGON-HF Committees and Investigators

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.

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U2 - 10.1002/ejhf.2403

DO - 10.1002/ejhf.2403

M3 - Journal article

C2 - 34918855

SN - 1388-9842

VL - 24

SP - 497

EP - 509

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 3

ER -

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

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