Characterization of the Obese Phenotype of Heart Failure With Preserved Ejection Fraction

A RELAX Trial Ancillary Study

Yogesh N.V. Reddy, Gregory D. Lewis, Sanjiv J. Shah, Masaru Obokata, Omar F. Abou-Ezzedine, Marat Fudim, Jie Lena Sun, Hrishikesh Chakraborty, Steven McNulty, Martin M. LeWinter, Douglas L. Mann, Lynne W. Stevenson, Margaret May Redfield, Barry A Borlaug

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective: To characterize the obese heart failure with preserved ejection fraction (HFpEF) phenotype in a multicenter cohort. Patients and Methods: This was a secondary analysis of the randomized clinical trial RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) performed between October 1, 2008, and February 1, 2012. Patients with HFpEF were classified by body mass index (BMI) as obese (BMI≥35 kg/m2) and nonobese (BMI<30 kg/m2) for comparison. Results: Obese patients with HFpEF (n=81) were younger (median age, 64 [interquartile range (IQR), 67-79] years vs 73 [IQR, 56-70] years; P<.001) but had greater peripheral edema (31% [25] vs 9% [6]; P<.001), more orthopnea (76% [56] vs 53% [35]; P=.005), worse New York Heart Association class (P=.006), and more impaired quality of life (P<.001) as compared with nonobese patients with HFpEF (n=70). Despite more severe signs and symptoms, obese patients with HFpEF had lower N-terminal pro B-type natriuretic peptide level (median, 481 [IQR, 176-1183] pg/mL vs 825 [IQR, 380-1679] pg/mL [to convert to pmol/L, multiply by 0.118]; P=.007) and lower left atrial volume index (median, 38 [IQR, 31-47] mL/m2 vs 54 [IQR, 41-63] mL/m2; P<.001). Serum C-reactive protein (median, 5.0 [IQR, 2.4-9.9] mg/dL vs 2.7 [IQR, 1.6-5.4] mg/dL [to convert to mg/L, multiply by 10−3]; P<.001) and uric acid (median, 7.8 [IQR, 6.1-8.7] mg/dL vs 6.8 [IQR, 5.5-8.3] mg/dL; P=.03) levels were higher in obese HFpEF, indicating greater systemic inflammation, than in nonobese HFpEF. Peak oxygen consumption was impaired in obese HFpEF (median, 11.1 [IQR, 9.6-14.4] mL/kg per minute vs 13.1 [IQR, 11.3-14.7] mL/kg per minute; P=.008), as was submaximal exercise capacity (6-minute walk distance, 272 [IQR, 200-332] m vs 355 [IQR, 290-415] m; P<.0001). Conclusion: Obese HFpEF is associated with decreased quality of life, worse symptoms of heart failure, greater systemic inflammation, worse exercise capacity, and higher metabolic cost of exertion as compared with nonobese HFpEF. Further study is required to understand the pathophysiology and potential distinct treatments for patients with the obese phenotype of HFpEF. Trial Registration: clinicaltrials.gov Identifier: NCT00763867

Original languageEnglish (US)
Pages (from-to)1199-1209
Number of pages11
JournalMayo Clinic proceedings
Volume94
Issue number7
DOIs
StatePublished - Jul 1 2019

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Heart Failure
Phenotype
Exercise
Body Mass Index
Quality of Life
Type 5 Cyclic Nucleotide Phosphodiesterases
Inflammation
Brain Natriuretic Peptide
Uric Acid
Oxygen Consumption
C-Reactive Protein
Signs and Symptoms
Blood Proteins
Edema
Randomized Controlled Trials
Costs and Cost Analysis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Characterization of the Obese Phenotype of Heart Failure With Preserved Ejection Fraction : A RELAX Trial Ancillary Study. / Reddy, Yogesh N.V.; Lewis, Gregory D.; Shah, Sanjiv J.; Obokata, Masaru; Abou-Ezzedine, Omar F.; Fudim, Marat; Sun, Jie Lena; Chakraborty, Hrishikesh; McNulty, Steven; LeWinter, Martin M.; Mann, Douglas L.; Stevenson, Lynne W.; Redfield, Margaret May; Borlaug, Barry A.

In: Mayo Clinic proceedings, Vol. 94, No. 7, 01.07.2019, p. 1199-1209.

Research output: Contribution to journalArticle

Reddy, YNV, Lewis, GD, Shah, SJ, Obokata, M, Abou-Ezzedine, OF, Fudim, M, Sun, JL, Chakraborty, H, McNulty, S, LeWinter, MM, Mann, DL, Stevenson, LW, Redfield, MM & Borlaug, BA 2019, 'Characterization of the Obese Phenotype of Heart Failure With Preserved Ejection Fraction: A RELAX Trial Ancillary Study', Mayo Clinic proceedings, vol. 94, no. 7, pp. 1199-1209. https://doi.org/10.1016/j.mayocp.2018.11.037
Reddy, Yogesh N.V. ; Lewis, Gregory D. ; Shah, Sanjiv J. ; Obokata, Masaru ; Abou-Ezzedine, Omar F. ; Fudim, Marat ; Sun, Jie Lena ; Chakraborty, Hrishikesh ; McNulty, Steven ; LeWinter, Martin M. ; Mann, Douglas L. ; Stevenson, Lynne W. ; Redfield, Margaret May ; Borlaug, Barry A. / Characterization of the Obese Phenotype of Heart Failure With Preserved Ejection Fraction : A RELAX Trial Ancillary Study. In: Mayo Clinic proceedings. 2019 ; Vol. 94, No. 7. pp. 1199-1209.
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abstract = "Objective: To characterize the obese heart failure with preserved ejection fraction (HFpEF) phenotype in a multicenter cohort. Patients and Methods: This was a secondary analysis of the randomized clinical trial RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) performed between October 1, 2008, and February 1, 2012. Patients with HFpEF were classified by body mass index (BMI) as obese (BMI≥35 kg/m2) and nonobese (BMI<30 kg/m2) for comparison. Results: Obese patients with HFpEF (n=81) were younger (median age, 64 [interquartile range (IQR), 67-79] years vs 73 [IQR, 56-70] years; P<.001) but had greater peripheral edema (31{\%} [25] vs 9{\%} [6]; P<.001), more orthopnea (76{\%} [56] vs 53{\%} [35]; P=.005), worse New York Heart Association class (P=.006), and more impaired quality of life (P<.001) as compared with nonobese patients with HFpEF (n=70). Despite more severe signs and symptoms, obese patients with HFpEF had lower N-terminal pro B-type natriuretic peptide level (median, 481 [IQR, 176-1183] pg/mL vs 825 [IQR, 380-1679] pg/mL [to convert to pmol/L, multiply by 0.118]; P=.007) and lower left atrial volume index (median, 38 [IQR, 31-47] mL/m2 vs 54 [IQR, 41-63] mL/m2; P<.001). Serum C-reactive protein (median, 5.0 [IQR, 2.4-9.9] mg/dL vs 2.7 [IQR, 1.6-5.4] mg/dL [to convert to mg/L, multiply by 10−3]; P<.001) and uric acid (median, 7.8 [IQR, 6.1-8.7] mg/dL vs 6.8 [IQR, 5.5-8.3] mg/dL; P=.03) levels were higher in obese HFpEF, indicating greater systemic inflammation, than in nonobese HFpEF. Peak oxygen consumption was impaired in obese HFpEF (median, 11.1 [IQR, 9.6-14.4] mL/kg per minute vs 13.1 [IQR, 11.3-14.7] mL/kg per minute; P=.008), as was submaximal exercise capacity (6-minute walk distance, 272 [IQR, 200-332] m vs 355 [IQR, 290-415] m; P<.0001). Conclusion: Obese HFpEF is associated with decreased quality of life, worse symptoms of heart failure, greater systemic inflammation, worse exercise capacity, and higher metabolic cost of exertion as compared with nonobese HFpEF. Further study is required to understand the pathophysiology and potential distinct treatments for patients with the obese phenotype of HFpEF. Trial Registration: clinicaltrials.gov Identifier: NCT00763867",
author = "Reddy, {Yogesh N.V.} and Lewis, {Gregory D.} and Shah, {Sanjiv J.} and Masaru Obokata and Abou-Ezzedine, {Omar F.} and Marat Fudim and Sun, {Jie Lena} and Hrishikesh Chakraborty and Steven McNulty and LeWinter, {Martin M.} and Mann, {Douglas L.} and Stevenson, {Lynne W.} and Redfield, {Margaret May} and Borlaug, {Barry A}",
year = "2019",
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day = "1",
doi = "10.1016/j.mayocp.2018.11.037",
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TY - JOUR

T1 - Characterization of the Obese Phenotype of Heart Failure With Preserved Ejection Fraction

T2 - A RELAX Trial Ancillary Study

AU - Reddy, Yogesh N.V.

AU - Lewis, Gregory D.

AU - Shah, Sanjiv J.

AU - Obokata, Masaru

AU - Abou-Ezzedine, Omar F.

AU - Fudim, Marat

AU - Sun, Jie Lena

AU - Chakraborty, Hrishikesh

AU - McNulty, Steven

AU - LeWinter, Martin M.

AU - Mann, Douglas L.

AU - Stevenson, Lynne W.

AU - Redfield, Margaret May

AU - Borlaug, Barry A

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Objective: To characterize the obese heart failure with preserved ejection fraction (HFpEF) phenotype in a multicenter cohort. Patients and Methods: This was a secondary analysis of the randomized clinical trial RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) performed between October 1, 2008, and February 1, 2012. Patients with HFpEF were classified by body mass index (BMI) as obese (BMI≥35 kg/m2) and nonobese (BMI<30 kg/m2) for comparison. Results: Obese patients with HFpEF (n=81) were younger (median age, 64 [interquartile range (IQR), 67-79] years vs 73 [IQR, 56-70] years; P<.001) but had greater peripheral edema (31% [25] vs 9% [6]; P<.001), more orthopnea (76% [56] vs 53% [35]; P=.005), worse New York Heart Association class (P=.006), and more impaired quality of life (P<.001) as compared with nonobese patients with HFpEF (n=70). Despite more severe signs and symptoms, obese patients with HFpEF had lower N-terminal pro B-type natriuretic peptide level (median, 481 [IQR, 176-1183] pg/mL vs 825 [IQR, 380-1679] pg/mL [to convert to pmol/L, multiply by 0.118]; P=.007) and lower left atrial volume index (median, 38 [IQR, 31-47] mL/m2 vs 54 [IQR, 41-63] mL/m2; P<.001). Serum C-reactive protein (median, 5.0 [IQR, 2.4-9.9] mg/dL vs 2.7 [IQR, 1.6-5.4] mg/dL [to convert to mg/L, multiply by 10−3]; P<.001) and uric acid (median, 7.8 [IQR, 6.1-8.7] mg/dL vs 6.8 [IQR, 5.5-8.3] mg/dL; P=.03) levels were higher in obese HFpEF, indicating greater systemic inflammation, than in nonobese HFpEF. Peak oxygen consumption was impaired in obese HFpEF (median, 11.1 [IQR, 9.6-14.4] mL/kg per minute vs 13.1 [IQR, 11.3-14.7] mL/kg per minute; P=.008), as was submaximal exercise capacity (6-minute walk distance, 272 [IQR, 200-332] m vs 355 [IQR, 290-415] m; P<.0001). Conclusion: Obese HFpEF is associated with decreased quality of life, worse symptoms of heart failure, greater systemic inflammation, worse exercise capacity, and higher metabolic cost of exertion as compared with nonobese HFpEF. Further study is required to understand the pathophysiology and potential distinct treatments for patients with the obese phenotype of HFpEF. Trial Registration: clinicaltrials.gov Identifier: NCT00763867

AB - Objective: To characterize the obese heart failure with preserved ejection fraction (HFpEF) phenotype in a multicenter cohort. Patients and Methods: This was a secondary analysis of the randomized clinical trial RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) performed between October 1, 2008, and February 1, 2012. Patients with HFpEF were classified by body mass index (BMI) as obese (BMI≥35 kg/m2) and nonobese (BMI<30 kg/m2) for comparison. Results: Obese patients with HFpEF (n=81) were younger (median age, 64 [interquartile range (IQR), 67-79] years vs 73 [IQR, 56-70] years; P<.001) but had greater peripheral edema (31% [25] vs 9% [6]; P<.001), more orthopnea (76% [56] vs 53% [35]; P=.005), worse New York Heart Association class (P=.006), and more impaired quality of life (P<.001) as compared with nonobese patients with HFpEF (n=70). Despite more severe signs and symptoms, obese patients with HFpEF had lower N-terminal pro B-type natriuretic peptide level (median, 481 [IQR, 176-1183] pg/mL vs 825 [IQR, 380-1679] pg/mL [to convert to pmol/L, multiply by 0.118]; P=.007) and lower left atrial volume index (median, 38 [IQR, 31-47] mL/m2 vs 54 [IQR, 41-63] mL/m2; P<.001). Serum C-reactive protein (median, 5.0 [IQR, 2.4-9.9] mg/dL vs 2.7 [IQR, 1.6-5.4] mg/dL [to convert to mg/L, multiply by 10−3]; P<.001) and uric acid (median, 7.8 [IQR, 6.1-8.7] mg/dL vs 6.8 [IQR, 5.5-8.3] mg/dL; P=.03) levels were higher in obese HFpEF, indicating greater systemic inflammation, than in nonobese HFpEF. Peak oxygen consumption was impaired in obese HFpEF (median, 11.1 [IQR, 9.6-14.4] mL/kg per minute vs 13.1 [IQR, 11.3-14.7] mL/kg per minute; P=.008), as was submaximal exercise capacity (6-minute walk distance, 272 [IQR, 200-332] m vs 355 [IQR, 290-415] m; P<.0001). Conclusion: Obese HFpEF is associated with decreased quality of life, worse symptoms of heart failure, greater systemic inflammation, worse exercise capacity, and higher metabolic cost of exertion as compared with nonobese HFpEF. Further study is required to understand the pathophysiology and potential distinct treatments for patients with the obese phenotype of HFpEF. Trial Registration: clinicaltrials.gov Identifier: NCT00763867

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