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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 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.
Original language | English |
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Article number | cvad042 |
Pages (from-to) | 1690–1705 |
Number of pages | 16 |
Journal | Cardiovascular Research |
Volume | 119 |
Issue number | 8 |
Early online date | 8 Mar 2023 |
DOIs | |
Publication status | Published - Jun 2023 |
Keywords
- Autoimmunity
- Beta 1
- Beta 2
- Beta 3
- Immune system
- M2
ASJC Scopus subject areas
- General Medicine
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- 1 Finished
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Aref#d: 21596. BIOSTAT-CHF: A Systems Biology Study to Tailored Treatment in Chronic Heart Failure
Doney, A. (Investigator), Guthrie, B. (Investigator), Lang, C. (Investigator), Morris, A. (Investigator), Palmer, C. (Investigator) & Struthers, A. (Investigator)
COMMISSION OF THE EUROPEAN COMMUNITIES
1/04/10 → 31/03/15
Project: Research