Abstract

Abstract Background and Aims Cardiovascular disease (CVD) is one of the leading causes of death in patients with ANCA-associated vasculitis (AAV). However, in current clinical guidelines, limited evidence is available to support the recommendation of AAV-specific screening for cardiovascular comorbidities. This study reported the prevalence of electrocardiogram (ECG) abnormalities and investigated associations between ECG abnormalities and fatal CVD in a validated cohort of patients with AAV compared to matched controls. Method Based on a retrospective matched cohort design, patients with granulomatosis with polyangiitis [ICD-10: DM31.3] or microscopic polyangiitis [ICD-10: DM3.17] and accessible ECGs were identified in nationwide Danish health care registers from 2000 to 2021. Patients with AAV were matched 1:3 on age, sex, and calendar year of ECG measurement with controls without AAV. Index date was defined as the date of ECG measurement. ECGs were hierarchically categorized as either no, minor, or major ECG abnormalities according to contemporary literature. The associations between ECG abnormalities and fatal CVD were assessed in multiple Cox regression models adjusted for age, sex, and comorbidities. Counterfactual G-estimation of hazard ratios (HRs) standardized to age and sex was performed to estimate the 5-year absolute risk (AR) of fatal CVD according to ECG-abnormalities. Results A total of 1431 patients with AAV were matched to 4293 controls. The median age of patients with AAV and matched controls was 69 (IQR 58-77) years, and 52.3% were males. Median study follow-up time was 4.8 (IQR, 2.7-7.8) years. AAV was associated with increased prevalence of left ventricular hypertrophy (17.5% vs. 12.5%, p < 0.001), ST-T deviations (10.1% vs. 7.1%, p < 0.001), atrial fibrillation (9.6% vs. 7.5%, p = 0.017) and corrected QT prolongation (5.9% vs. 3.6%, p < 0.001) compared to controls. When examining associations of fatal CVD across no, minor or major ECG abnormalities, only the patients with AAV and major ECG abnormalities had a higher risk of fatal CVD [HR 1.99 (95% CI, 1.49-2.65)], compared to matched controls. This corresponded to a significantly higher standardized 5-year AR of fatal CVD compared to controls: 19.14% (95% CI, 16-22%) vs. 9.41% (95% CI, 8-11%). Conclusion AAV was associated with a higher prevalence of major ECG abnormalities such as left ventricular hypertrophy, atrial fibrillation, and ST-T deviations compared to matched controls. Moreover, the patients with AAV demonstrating major ECG abnormalities had a particularly elevated risk of fatal CVD. This indicates that AAV patients with major ECG abnormalities are a distinct high-risk group within AAV patients prone to cardiovascular-related mortality.

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