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

TY - JOUR

T1 - Clinical and prognostic associations of autoantibodies recognizing adrenergic/muscarinic receptors in patients with heart failure

AU - Markousis-Mavrogenis, George

AU - Minich, Waldemar B.

AU - Al-Mubarak, Ali A.

AU - Anker, Stefan D.

AU - Cleland, John G. F.

AU - Dickstein, Kenneth

AU - Lang, Chim C.

AU - Ng, Leong L.

AU - Samani, Nilesh J.

AU - Zannad, Faiez

AU - Metra, Marco

AU - Seemann, Petra

AU - Hoeg, Antonia

AU - Lopez, Patricio

AU - van Veldhuisen, Dirk J.

AU - de Boer, Rudolf A.

AU - Voors, Adriaan A.

AU - van der Meer, Peter

AU - Schomburg, Lutz

AU - Bomer, Nils

N1 - Funding 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) and the European Social Fund (ESF); EXIST-Project ‘Bridge-ART’, FKZ: 03EFLBE114. Publisher Copyright: © 2023 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.

PY - 2023/6

Y1 - 2023/6

N2 - 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 analyzed 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, 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.

AB - 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 analyzed 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, 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.

KW - Autoimmunity

KW - Beta 1

KW - Beta 2

KW - Beta 3

KW - Immune system

KW - M2

UR - https://www.scopus.com/pages/publications/85164263763

U2 - 10.1093/cvr/cvad042

DO - 10.1093/cvr/cvad042

M3 - Article

C2 - 36883593

SN - 0008-6363

VL - 119

SP - 1690

EP - 1705

JO - Cardiovascular Research

JF - Cardiovascular Research

IS - 8

M1 - cvad042

ER -