FC059: Cardiovascular Outcomes in Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis in Denmark 1996–2018
Authors: Nygaard Pedersen Louis , Polcwiartek Christoffer , Nelveg-Kristensen Karl-Emil , Carlson Nicholas , Kristensen Salome , Torp-Pedersen Christian , Waarst Gregersen Jon 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Antineutrophil cytoplasmic antibody associated vasculitis (AAV) is a group of autoimmune systemic inflammatory diseases, with cardiovascular disease being the leading cause of death. However, large-scale real-world data on the risk of long-term cardiovascular outcomes associated with AAV are limited. Therefore, to understand, screen and optimize prevention of cardiovascular disease in AAV patients, we investigated the risk of long-term ischemic cardiovascular events, including ischemic heart disease, coronary angiogram (CAG), percutaneous coronary intervention (PCI) and ventricular arrhythmia/use of implantable cardioverter-defibrillator (ICD) devices. Secondary outcomes included heart failure (HF), atrial fibrillation (AF), stroke, venous thrombotic events and cardiac arrest.

METHOD
We included all incident patients with AAV diagnosed during 1996–2018. Patients were identified from the Danish nationwide healthcare registries by use of a recently validated method (positive predictive value of 97%) [1] comprising at least two consecutive hospital encounters registered as either polyangiitis with granulomatosis or microscopic polyangiitis (International Classification of Diseases, 10th Edition [ICD-10]: DM31.3 and DM31.7). Patients with AAV were matched 1:3 with controls from the general population on age and gender. We computed adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for each cardiovascular outcome, with all-cause mortality accounted for as a competing risk. G-computation of HRs was performed to estimate 5-year absolute risks standardized to the distribution of risk factors in the population.

RESULTS
A total of 2306 AAV patients [median age: 62.9 years (25th–75th percentile: 50.9–72.0 years), 52.6% male gender] were matched with 6918 controls. Median study follow-up was 9.5 years (25th–75th percentile: 5.3–15.8 years). Compared with controls, AAV patients had a higher rate of ischemic heart disease [HR 1.67 (95% CI 1.45–1.95)], myocardial infarction [HR 1.43 (95% CI 1.11–1.83)], CAG [HR 1.51 (95% CI 1.27–1.80)], PCI [HR 1.42 (95% CI 1.11–1.88)] and ventricular arrhythmia/ICD implantation [HR 2.03 (95% CI 1.17–3.55)]. Secondarily, AAV patients also had an increased rate of additional adverse cardiovascular events: HF [HR 1.77 (95% CI 1.48–2.11)], deep vein thrombosis [HR 2.89 (95% CI 2.24–3.72)], pulmonary embolism [HR 3.59 (95% CI 2.74–4.72)], AF [HR 1.73 (95% CI 1.51–1.98)], ischemic stroke [HR 1.34 (95% CI 1.12–1.61)] and in-hospital cardiac arrest [HR 1.97 (95% CI 1.29–2.99)]. AAV patients had a significantly increased standardized 5-year absolute risk of all outcomes except for MI, PCI and ventricular arrhythmia/ICD implantations compared with controls.

CONCLUSION
In this large nationwide registry-based follow-up study, AAV patients had a higher risk of ischemic cardiovascular events and were more likely to require revascularization therapy compared with matched control subjects. Moreover, AAV patients had a higher risk of HF, atrial- and ventricular arrhythmias as well as venous thrombotic events and ischemic stroke when compared with matched control subjects.