Increased risk of cardiovascular disease preceding diagnosis of incident ANCA-associated vasculitis: a danish nationwide study

ANCA-associated vasculitis (AAV) is associated with an increased risk of cardiovascular disease (CVD). The risk of CVD seems to be increased shortly after initial diagnosis as well as in the long-term setting. However, no studies have addressed the risk of CVD in the period preceding an AAV diagnosis. Since the diagnosis of AAV often is associated with a substantial diagnostic delay, we hypothesize that patients with AAV consistently are at an increased risk of developing CVD already before they even are diagnosed with AAV.Using a nested case-control framework, patients with AAV were identified through the Danish Nationwide Registries from 1996-2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV-diagnosis) as their corresponding case. Conditional logistic regression was used to compute age, sex and comorbidity adjusted Hazard Ratios (HRs) for major adverse cardiovascular events (MACE), ischemic heart disease, heart failure, venous thromboembolism, atrial fibrillation, ischemic stroke, pericarditis, and ventricular arrhythmias/ICD-implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before the index date.A total of 2371 patients with AAV (median age: 63 yrs, 53.7% male) were matched with 7113 controls. In patients with AAV, 10.33% had a cardiovascular outcome within 12 months preceding diagnosis as compared to 3.84% of controls (HR 3.05 [95% CI, 2.48-3.75]). The associated risk of cardiovascular outcomes was similarly increased in the temporal proximity of the diagnosis, with the highest HR at 1 month prior to index date (HR 10.73 [95% CI, 7.05-16.32], Fig. 1). In individual analysis, a significantly higher HR was observed for all outcomes (excluding VA/ICD/CA), Fig. 2.AAV disease is associated with an increased risk of CVD in the months preceding diagnosis, which underlines the importance of early clinical vigilance toward CVD starting in the diagnostic phase of AAV.Figure 1:Conditional logistic regression of the association between AAV and having any cardiovascular outcome in close proximity to AAV diagnosis. Any cardiovascular outcome was defined as having either ischemic heart disease, acute myocardial infarction/percutaneous coronary intervention/coronary-artery bypass graft surgery, coronary angiogram, heart failure, venous thromboembolism, atrial fibrillation, ischemic stroke, pericarditis, VA/ICD/CA, or any combination hereof. HRs were adjusted for age, sex, chronic kidney disease, hypertension, hyperlipidemia, peripheral artery disease, diabetes, chronic obstructive pulmonary disease, malignancies, chronic liver disease and a previous history of cardiovascular disease.Figure 2:Logarithmic radar chart of cardiovascular outcomes expressed as HRs of the association between AAV, and cardiovascular outcomes compared to age- and sex-matched controls preceding AAV diagnosis. HRs are adjusted for age, sex, and comorbidities. HRs of pericarditis and venous thromboembolism are not available at 1 month preceding index date, due to no events in the control group. MI, myocardial infarction, PCI, Percutaneous coronary intervention; CABG, Coronary artery bypass graft surgery, VA/ICD/CA, ventricular arrhythmia and/or implantable cardioverter-defibrillator and/or in-hospital cardiac arrest with subsequent recirculation.