Dataset Information

The Effect of Mineralocorticoid Receptor 3 Antagonists on Anti-Inflammatory and Anti-Fatty Acid Transport Profile in Patients with Heart Failure.

ABSTRACT: Epicardial fat thickness is associated with cardiovascular disease. Mineralocorticoid receptor antagonist (MRA), a pharmaceutical treatment for CVD, was found to have an effect on adipose tissue. Our aim was to analyse the main epicardial fat genesis and inflammation-involved cell markers and their regulation by risk factors and MRA. We included blood and epicardial or subcutaneous fat (EAT or SAT) from 71 patients undergoing heart surgery and blood from 66 patients with heart failure. Cell types (transcripts or proteins) were analysed by real-time polymerase chain reaction or immunohistochemistry. Plasma proteins were analysed by Luminex technology or enzyme-linked immunoassay. Our results showed an upregulation of fatty acid transporter levels after aldosterone-induced genesis. The MRA intake was the main factor associated with lower levels in epicardial fat. On the contrary, MRA upregulated the levels and its secretion of the anti-inflammatory marker intelectin 1 and reduced the proliferation of epicardial fibroblasts. Our results have shown the local MRA intake effect on fatty acid transporters and anti-inflammatory marker levels and the proliferation rate on epicardial fat fibroblasts. They suggest the role of MRA on epicardial fat genesis and remodelling in patients with cardiovascular disease. Translational perspective: the knowledge of epicardial fat genesis and its modulation by drugs might be useful for improving the treatments of cardiovascular disease.

SUBMITTER: Fu X

PROVIDER: S-EPMC9027091 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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The Effect of Mineralocorticoid Receptor 3 Antagonists on Anti-Inflammatory and Anti-Fatty Acid Transport Profile in Patients with Heart Failure.

Fu Xiaoran X Almenglo Cristina C Fernandez Ángel Luis ÁL Martínez-Cereijo José Manuel JM Iglesias-Alvarez Diego D Duran-Muñoz Darío D García-Caballero Tomás T Gonzalez-Juanatey Jose Ramón JR Rodriguez-Mañero Moises M Eiras Sonia S

Cells 20220408 8

Epicardial fat thickness is associated with cardiovascular disease. Mineralocorticoid receptor antagonist (MRA), a pharmaceutical treatment for CVD, was found to have an effect on adipose tissue. Our aim was to analyse the main epicardial fat genesis and inflammation-involved cell markers and their regulation by risk factors and MRA. We included blood and epicardial or subcutaneous fat (EAT or SAT) from 71 patients undergoing heart surgery and blood from 66 patients with heart failure. Cell type ...[more]

PMID: 35455943

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Project description:AimsTo determine the incidence of hyperkalaemia in patients with heart failure with reduced ejection fraction (HFrEF) during up-titration of guideline-directed medical therapy (GDMT) in real-world settings.MethodsA retrospective review of medical records of all patients hospitalized for newly onset HFrEF at Sahlgrenska University Hospital, Sweden, between 1 January 2016 and 31 December 2019. Based on mineralocorticoid receptor antagonist (MRA) treatment within the first 6 months, patients were divided into four groups: (i) never received MRA, (ii) needed MRA dose reduction, (iii) needed discontinuation of MRA, and (iv) stable MRA treatment. Potassium levels were assessed at baseline and has the highest potassium level during the 6 months of up-titration.ResultsOf 3456 patients hospitalized for heart failure, 630 (18%) were eligible (68.4% men, 66.8 years, mean EF of 29.4%). After up-titration of GDMT 48.4% of patients received MRAs. Patients without MRA treatment were older (P < 0.0001), had lower EF (P = 0.022), had higher NTproBNP (P = 0.017), had lower eGFR (P = 0.001), and were more often treated with angiotensin receptor inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitors (all P < 0.0001). In overall study population, hyperkalaemia increased from 5.9 to 24.4% after 6 months of up-titration of GDMT (P < 0.0001). Among four groups, the incidence of hyperkalaemia throughout up-titration of GDMT increased from 6.8 to 54.5% in patients with dose reduction of MRA, from 8.8 to 50.9% in those with discontinuation of MRA, from 5 to 10% in patients with stable MRA treatment, and from 6 to 28% in patients who were MRA naive (all P < 0.0001). In the MRA-naive group, normokalaemia/hypokalaemia occurred in 87.5% at baseline, and after 6 months of up-titration of GDMT, normokalaemia/hypokalaemia remained in 47.8%, whereas mild, moderate, and severe hyperkalaemia occurred in 22.4%, 5.7%, and 0.9%, respectively.ConclusionsHyperkalaemia increased significantly during up-titration of GDMT but with varying magnitudes in different clinical phenotypes, which might explain why physicians refrain from prescribing MRAs to patients with HFrEF.

Project description:ObjectivesThe purpose of this study was to investigate the effects of mineralocorticoid receptor antagonists (MRAs) on systolic blood pressure (SBP) and outcomes according to baseline SBP in patients with heart failure with reduced ejection fraction (HFrEF).BackgroundMRAs are greatly underused in patients with HFrEF, often because of fear of adverse events. Concern about hypotension has been raised by the demonstration that MRAs are particularly effective treatment for resistant hypertension.MethodsThe effect of MRA therapy was studied in 4,396 patients with HFrEF randomized in the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials.ResultsMean SBP change from baseline to 6 months was +1.4 ± 18.1 mm Hg in the placebo group and -1.2 ± 17.9 mm Hg in the MRA group. The between-treatment difference was 2.6 mm Hg (95% confidence interval [CI]: 1.5 to 3.6; p < 0.001). All outcomes were reduced by MRA therapy overall, with consistent effects across SBP categories (e.g., all-cause mortality, overall hazard ratio [HR] of 0.72; 95% CI: 0.64 to 0.82; p < 0.001; SBP ≤105 mm Hg; HR: 0.72; 95% CI: 0.56 to 0.94; SBP >105 to ≤115 mm Hg; HR: 0.78; 95% CI: 0.60 to 1.02; SBP >115 to ≤125 mm Hg; HR: 0.71; 95% CI: 0.53 to 0.94; SBP >125 to ≤135 mm Hg; HR: 0.79; 95% CI: 0.57 to 1.10; and SBP > 135 mm Hg; HR: 0.67; 95% CI: 0.50 to 0.90; p for interaction = 0.95). Hypotension was infrequent and not more common with MRA therapy than with placebo, overall (4.6% vs. 3.9%; p = 0.25) or in any SBP category.ConclusionsMRA treatment had little effect on SBP in patients with HFrEF, and the clinical benefits were not modified by baseline SBP. MRA treatment infrequently caused hypotension, even when the baseline SBP was low. The treatment discontinuation rates between MRA and placebo therapy were similar. Low SBP is not a reason to withhold MRA therapy in patients with HFrEF.

Project description:AimsMineralocorticoid receptor antagonists (MRA) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but are underused. Point prevalent use has been described, but the kinetics of discontinuation and the extent of reinitiation have not been studied.Methods and resultsPatients with HFrEF enrolled in the Swedish Heart Failure Registry between 2006 and 2021 were linked to the Prescribed Drug Register. The rate of discontinuation during the first year of treatment and reinitiation the year after discontinuation were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to assess the predictors of discontinuation. Of 11 474 MRA new users, 71% remained on therapy at 1 year. Baseline characteristics independently associated with discontinuation were: estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.34-2.27), hyperkalaemia (HR 1.73, 95% CI 1.25-2.40), eGFR 30-60 ml/min/1.73 m2 (HR 1.51, 95% CI 1.37-1.66), age ≥80 years (HR 1.26, 95% CI 1.10-1.43), enrolment as inpatient (HR 1.25, 95% CI 1.14-1.38), a diagnosis of atrial fibrillation (HR 1.24, 95% CI 1.10-1.39), living alone (HR 1.23, 95% CI 1.13-1.34), ischaemic heart disease (HR 1.20, 95% CI 1.09-1.31), anaemia (HR 1.17, 95% CI 1.07-1.29), diabetes mellitus (HR 1.15, 95% CI 1.04-1.27) and New York Heart Association class III-IV (HR 1.13, 95% CI 1.02-1.24). Reinitiation within a year occurred in 46% of cases, mostly within 3 months after discontinuation.ConclusionAmong patients with HFrEF initiated on MRA, 71% remained on therapy at 1 year. Discontinuation occurred early and was more common in patients with advanced kidney disease, hyperkalaemia, lack of follow-up in specialty care, more severe heart failure, comorbidities, and markers of sociodemographic frailty. Among those who discontinued, almost half reinitiated treatment the year following discontinuation.

Dataset Information

The Effect of Mineralocorticoid Receptor 3 Antagonists on Anti-Inflammatory and Anti-Fatty Acid Transport Profile in Patients with Heart Failure.

Publications

The Effect of Mineralocorticoid Receptor 3 Antagonists on Anti-Inflammatory and Anti-Fatty Acid Transport Profile in Patients with Heart Failure.

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