Objective Antinuclear antibodies (ANA) at low titers of 1:40 may be present in up to 30% of healthy individuals and have been associated with increased cardiovascular mortality, but their role in atrial fibrillation (AF) remains unclear. This study assessed ANA prevalence and its association with outcomes in AF patients. Methods In a cohort of 240 AF patients on anticoagulant therapy (median age 69, median CHA2DS2-VASc = 4), without any ANA-related autoimmune diseases, we determined ANA (positive if > 20 ELISA units [EU]) along with antiphospholipid antibodies in accordance to ACR/EULAR (ACR/EULAR-aPL). During a median follow-up of 52 months, ischemic stroke (IS), transient ischemic attack (TIA), cardiovascular (CV) death, major bleeding, and a composite endpoint (defined as IS, TIA, or CV death) were recorded. Results 43 patients (17.9%) were positive for ANA (mean 22.9 EU), including 20 (46.5%) with positive ACR/EULAR-aPL. ANA-positive patients were older (by 9.9 years), predominantly female (65.1%), and had higher CHA2DS2-VASc scores (median 5 vs 4; all P < 0.001). IS or CV death occurred in 30 patients (12.5%, 3% per year) who were ANA positive. ANA positivity was associated with the composite endpoint occurrence (odds ratio [OR] = 2.84, 95% confidence interval [CI] 1.21–6.65). Furthermore, the presence of both ANA and ACR/EULAR-aPL positivity significantly increased the likelihood of the composite endpoint (OR = 4.85, 95%CI 1.75–13.43). Conclusions Positive ANA coexisting with ACR/EULAR-aPL may contribute to the failure of oral anticoagulation in AF patients, highlighting a potential role of autoimmune mechanisms in thromboembolism associated with this common arrhythmia.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> Key Points • The role of antinuclear antibodies (ANA) in atrial fibrillation (AF) remains underexplored, despite their known association all-cause mortality. • This study addresses the gap by evaluating coexistence of ANA and antiphospholipid antibodies in accordance to ACR/EULAR (ACR/EULAR-aPL) in anticoagulated AF patients without autoimmune disease. • ANA positivity, particularly when coexisting with ACR/EULAR-aPL, was associated with an increased risk of thromboembolic events despite anticoagulation. • ANA was more frequently detected in patients who experienced the composite endpoint of ischaemic stroke, transient ischaemic attack, or cardiovascular death. </entry> </row> </tbody> </tgroup> </Table> Graphical abstract

Antinuclear antibodies as a risk factor for ischemic stroke or death in elderly patients with atrial fibrillation despite anticoagulation

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2025年8月22日

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Maksymilian Hanarz,
Michał Ząbczyk,
Joanna Natorska,
Elżbieta Pociask,
Anetta Undas

摘要

Objective

Antinuclear antibodies (ANA) at low titers of 1:40 may be present in up to 30% of healthy individuals and have been associated with increased cardiovascular mortality, but their role in atrial fibrillation (AF) remains unclear. This study assessed ANA prevalence and its association with outcomes in AF patients.

Methods

In a cohort of 240 AF patients on anticoagulant therapy (median age 69, median CHA2DS2-VASc = 4), without any ANA-related autoimmune diseases, we determined ANA (positive if > 20 ELISA units [EU]) along with antiphospholipid antibodies in accordance to ACR/EULAR (ACR/EULAR-aPL). During a median follow-up of 52 months, ischemic stroke (IS), transient ischemic attack (TIA), cardiovascular (CV) death, major bleeding, and a composite endpoint (defined as IS, TIA, or CV death) were recorded.

Results

43 patients (17.9%) were positive for ANA (mean 22.9 EU), including 20 (46.5%) with positive ACR/EULAR-aPL. ANA-positive patients were older (by 9.9 years), predominantly female (65.1%), and had higher CHA2DS2-VASc scores (median 5 vs 4; all P < 0.001). IS or CV death occurred in 30 patients (12.5%, 3% per year) who were ANA positive. ANA positivity was associated with the composite endpoint occurrence (odds ratio [OR] = 2.84, 95% confidence interval [CI] 1.21–6.65). Furthermore, the presence of both ANA and ACR/EULAR-aPL positivity significantly increased the likelihood of the composite endpoint (OR = 4.85, 95%CI 1.75–13.43).

Conclusions

Positive ANA coexisting with ACR/EULAR-aPL may contribute to the failure of oral anticoagulation in AF patients, highlighting a potential role of autoimmune mechanisms in thromboembolism associated with this common arrhythmia.

Key Points

• The role of antinuclear antibodies (ANA) in atrial fibrillation (AF) remains underexplored, despite their known association all-cause mortality.

• This study addresses the gap by evaluating coexistence of ANA and antiphospholipid antibodies in accordance to ACR/EULAR (ACR/EULAR-aPL) in anticoagulated AF patients without autoimmune disease.

• ANA positivity, particularly when coexisting with ACR/EULAR-aPL, was associated with an increased risk of thromboembolic events despite anticoagulation.

• ANA was more frequently detected in patients who experienced the composite endpoint of ischaemic stroke, transient ischaemic attack, or cardiovascular death.

Graphical abstract