Cardiovascular and cerebrovascular outcomes in anti-neutrophil cytoplasmic antibody-associated vasculitis: A systematic review with meta-analysis

To quantify the magnitude of the risk of total and type-specific cardiovascular and cerebrovascular diseases (CCVD) in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Searches of PubMed, Embase, and the Cochrane Library were conducted. Observational studies were included if they reported data on CCVD in AAV patients. Pooled risk ratios (RR) with 95% confidence intervals were calculated. Fourteen studies met the inclusion criteria, comprising 20,096 AAV patients (over 46,495 person-years) with 5757 CCVD events. Compared with non-vasculitis population, AAV patients showed an 83% increased risk of incident CCVD (1.83 [1.37–2.45]; n = 10), 48% for coronary artery disease (1.48 [1.26–1.75]; n = 9), and 56% for cerebrovascular accident (1.56 [1.22–1.99]; n = 9). For type-specific CCVD, the risks of myocardial infarction, stroke, heart failure were increased by 67% (1.67 [1.29–2.15]; n = 6), 97% (1.97 [1.19–3.25]; n = 8) and 72% (1.72 [1.28–2.32]; n = 4), whereas there was only a trend toward a higher risk of angina pectoris (1.46 [0.90–2.39]; n = 2), and ischemic stroke (1.88 [0.86–4.12]; n = 4). Subgroup analyses by AAV type found significantly increased CCVD risk in both granulomatosis with polyangiitis (1.87 [1.29–2.73]; n = 7) and microscopic polyangiitis (2.93 [1.58–5.43]; n = 3). In three studies reporting impact of follow-up period after AAV diagnosis, the CCVD risk was significantly higher in the first two years after diagnosis than the subsequent follow-up (2.23 [2.00–2.48] vs. 1.48 [1.40–1.56]; p < 0.01). Significant heterogeneity existed in the main analyses. This meta-analysis demonstrates that AAV is associated with increased risks of overall and type-specific CCVD, especially within two years after AAV diagnosis.