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ASC Methylation and Interleukin-1? Are Associated with Aerobic Capacity in Heart Failure.

ABSTRACT: Aerobic capacity, as measured by peak oxygen uptake (V?O2), is one of the most powerful predictors of prognosis in heart failure (HF). Inflammation is a key factor contributing to alterations in aerobic capacity, and interleukin (IL)-1 cytokines are implicated in this process. The adaptor protein ASC is necessary for inflammasome activation of IL-1? and IL-18. ASC expression is controlled through epigenetic modification; lower ASC methylation is associated with worse outcomes in HF. The purpose of this study is to examine the relationships between ASC methylation, IL-1?, and IL-18 with V?O2peak in persons with HF.This study examined the relationship between ASC methylation, IL-1?, and IL-18 with V?O2peak in 54 stable outpatients with HF. All participants were NYHA class II or III, not engaged in an exercise program, and physically able to complete an exercise treadmill test.Mean V?O2peak was 16.68 ± 4.7 mL·kg·min. V?O2peak was positively associated with mean percent ASC methylation (r = 0.47, P = 0.001) and negatively associated with IL-1? (r = -0.38, P = 0.007). Multiple linear regression models demonstrated that V?O2peak increased by 2.30 mL·kg·min for every 1% increase in ASC methylation and decreased by 1.91 mL·kg·min for every 1 pg·mL increase in plasma IL-1?.Mean percent ASC methylation and plasma IL-1? levels are associated with clinically meaningful differences in V?O2peak in persons with HF. Inflammasome activation may play a mechanistic role in determining aerobic capacity. ASC methylation is a potentially modifiable mechanism for reducing the inflammatory response, thereby improving aerobic capacity in HF.

SUBMITTER: Butts B

PROVIDER: S-EPMC5433894 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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ASC Methylation and Interleukin-1β Are Associated with Aerobic Capacity in Heart Failure.

Butts Brittany B Butler Javed J Dunbar Sandra B SB Corwin Elizabeth J EJ Gary Rebecca A RA

Medicine and science in sports and exercise 20170601 6

<h4>Background</h4>Aerobic capacity, as measured by peak oxygen uptake (V˙O2), is one of the most powerful predictors of prognosis in heart failure (HF). Inflammation is a key factor contributing to alterations in aerobic capacity, and interleukin (IL)-1 cytokines are implicated in this process. The adaptor protein ASC is necessary for inflammasome activation of IL-1β and IL-18. ASC expression is controlled through epigenetic modification; lower ASC methylation is associated with worse outcomes ...[more]

PMID: 28072632

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Project description:BackgroundHeart failure with preserved ejection fraction (HFpEF) often coexists with chronic kidney disease (CKD). Exercise intolerance is a major determinant of quality of life and morbidity in both scenarios. We aimed to evaluate the associations between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) with maximal aerobic capacity (peak VO2) in ambulatory HFpEF and whether these associations were influenced by kidney function.MethodsThis single-centre study prospectively enrolled 133 patients with HFpEF who performed maximal cardiopulmonary exercise testing. Patients were stratified across estimated glomerular filtration rate (eGFR) categories (<60 ml/min/1.73 m2 versus ≥60 ml/min/1.73 m2).ResultsThe mean age of the sample was 73.2 ± 10.5 years and 56.4% were female. The median of peak VO2 was 11.0 ml/kg/min (interquartile range 9.0-13.0). A total of 67 (50.4%) patients had an eGFR <60 ml/min/1.73 m2. Those patients had higher levels of NT-proBNP and lower peak VO2, without differences in CA125. In the whole sample, NT-proBNP and CA125 were inversely correlated with peak VO2 (r = -0.43, P < .001 and r = -0.22, P = .010, respectively). After multivariate analysis, we found a differential association between NT-proBNP and peak VO2 across eGFR strata (P for interaction = .045). In patients with an eGFR ≥60 ml/min/1.73 m2, higher NT-proBNP identified patients with poorer maximal functional capacity. In individuals with eGFR <60 ml/min/1.73 m2, NT-proBNP was not significantly associated with peak VO2 [β = 0.02 (95% confidence interval -0.19-0.23), P = .834]. Higher CA125 was linear and significantly associated with worse functional capacity without evidence of heterogeneity across eGFR strata (P for interaction = .620).ConclusionsIn patients with stable HFpEF, NT-proBNP was not associated with maximal functional capacity when CKD was present. CA125 emerged as a useful biomarker for estimating effort intolerance in HFpEF irrespective of the presence of CKD.

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Dataset Information

ASC Methylation and Interleukin-1? Are Associated with Aerobic Capacity in Heart Failure.

Publications

ASC Methylation and Interleukin-1β Are Associated with Aerobic Capacity in Heart Failure.

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