Clinical and prognostic associations of autoantibodies recognizing adrenergic/muscarinic receptors in patients with heart failure

Markousis-Mavrogenis, G. et al. (2023) Clinical and prognostic associations of autoantibodies recognizing adrenergic/muscarinic receptors in patients with heart failure. Cardiovascular Research, 119(8), pp. 1690-1705. (doi: 10.1093/cvr/cvad042) (PMID:36883593) (PMCID:PMC10325696)

Abstract

Aims: The importance of autoantibodies (AABs) against adrenergic/muscarinic receptors in heart failure (HF) is not well-understood. We investigated the prevalence and clinical/prognostic associations of four AABs recognizing the M2-muscarinic receptor or the β1-, β2-, or β3-adrenergic receptor in a large and well-characterized cohort of patients with HF. Methods and results: Serum samples from 2256 patients with HF from the BIOSTAT-CHF cohort and 299 healthy controls were analysed using newly established chemiluminescence immunoassays. The primary outcome was a composite of all-cause mortality and HF rehospitalization at 2-year follow-up, and each outcome was also separately investigated. Collectively, 382 (16.9%) patients and 37 (12.4%) controls were seropositive for ≥1 AAB (P = 0.045). Seropositivity occurred more frequently only for anti-M2 AABs (P = 0.025). Amongst patients with HF, seropositivity was associated with the presence of comorbidities (renal disease, chronic obstructive pulmonary disease, stroke, and atrial fibrillation) and with medication use. Only anti-β1 AAB seropositivity was associated with the primary outcome [hazard ratio (95% confidence interval): 1.37 (1.04–1.81), P = 0.024] and HF rehospitalization [1.57 (1.13–2.19), P = 0.010] in univariable analyses but remained associated only with HF rehospitalization after multivariable adjustment for the BIOSTAT-CHF risk model [1.47 (1.05–2.07), P = 0.030]. Principal component analyses showed considerable overlap in B-lymphocyte activity between seropositive and seronegative patients, based on 31 circulating biomarkers related to B-lymphocyte function. Conclusions: AAB seropositivity was not strongly associated with adverse outcomes in HF and was mostly related to the presence of comorbidities and medication use. Only anti-β1 AABs were independently associated with HF rehospitalization. The exact clinical value of AABs remains to be elucidated.

• Item Type: Articles
• Additional Information: BIOSTAT-CHF was funded by the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29]. The analytical work was supported by the German Federal Ministry for Economic Affairs and Energy (BMWi), EXIST-Project “Bridge-ART”, FKZ: 03EFLBE114.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cleland, Professor John
• Authors: Markousis-Mavrogenis, G., Minich, W. B., Al-Mubarak, A. A., Anker, S. D., Cleland, J. G.F., Dickstein, K., Lang, C. C., Ng, L. L., Samani, N. J., Zannad, F., Metra, M., Seemann, P., Hoeg, A., Lopez, P., van Veldhuisen, D. J., de Boer, R. A., Voors, A. A., van der Meer, P., Schomburg, L., Bomer, N., and The BIOSTAT-CHF Consortium,
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Cardiovascular Research
• Publisher: Oxford University Press
• ISSN: 0008-6363
• ISSN (Online): 1755-3245
• Published Online: 08 March 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Cardiovascular Research 119(8):1690-1705
• Publisher Policy: Reproduced under a Creative Commons License