Cardiovascular and thromboembolic risk in ANCA-associated vasculitis: a nationwide matched cohort study by disease, sex and familial risk.

objectivesTo 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 ANCA-associated vasculitis (AAV).

methodsAdults 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), ischaemic or haemorrhagic stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), CVD-TE-related death and a composite CVD-TE end point. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazards models.

resultsA total of 4317 AAV patients, 21 582 controls and 25 568 siblings were included. Both GPA and MPA were associated with increased CVD-TE risk compared with the 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 ischaemic 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 3 months of diagnosis (HR 7.69 [5.93, 9.99]).

conclusionGPA and MPA were associated with comparable increased risks of CVD-TE, with the highest risk within 3 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.