Cardiovascular and thromboembolic risk in anti-neutrophil cytoplasmic antibody-associated vasculitis: a nationwide matched cohort study by disease, sex, and familial risk

OBJECTIVES: To investigate influence of sex, diagnosis (granulomatosis with polyangiitis (GPA) vs. microscopic polyangiitis (MPA)), and familial factors on cardiovascular disease and thromboembolism (CVD-TE) risk in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides (AAV). METHODS: Adults with a diagnosis of GPA or MPA were identified from National Patient Registers (2005-2020) with five age- and sex-matched population controls randomly selected per patient. First-degree siblings of patients and matched controls were included. Outcomes were defined using ICD codes and included myocardial infarction (MI), ischemic or haemorrhagic stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), CVD-TE-related death, and a composite CVD-TE endpoint. Hazard ratios (HRs) with 95% confidence intervals were estimated using Cox proportional hazards models. RESULTS: 4,317 AAV patients, 21,582 controls, and 25,568 siblings were included. Both GPA and MPA were associated with increased CVD-TE risk compared with controls (HR 2.04 [1.83,2.38] and HR 2.45 [2.00,2.99]), with no differences between GPA and MPA for individual outcomes. Both sexes had increased DVT and PE risks. In GPA, only males had increased MI risk (HR 2.25 [1.74,2.92]), whereas only females had increased ischemic stroke risk (HR 1.64 [1.25,2.17]). Siblings of AAV patients had no excess CVD-TE risk. The highest CVD-TE risk occurred within three months of diagnosis (HR 7.69 [5.93,9.99]). CONCLUSION: GPA and MPA were associated with comparable increased risks of CVD-TE, with the highest risk within three months following AAV diagnosis and with sex-specific differences in GPA. Lack of increased risk among siblings emphasize the vasculitis per se as a risk factor for CVD-TE.