Abstract

Abstract Background and Aims ANCA associated vasculitis (AAV) is closely correlated to elevated cardiovascular disease (CVD) rates, positioning it a one of the leading causes of death among these patients. The impact of AAV on the risk of CVD has not been described in large prospective cohorts with a long-term follow up. The aim of our study was to evaluate the occurrence of cardiovascular events, encompassing major adverse cardiovascular events (MACE), to delineate associated risk factors, and to draw comparisons with other cohorts of patients diagnosed with CKD. Method We included 848 patients with a diagnosis of AAV who participated in 7 EUVAS RCTs (NORAM, CYCAZAREM, CYCLOPS, MEPEX, IMPROVE, RITUXVAS, and MYCYC), recruited from 74 centers in 17 European countries. The three-point MACE outcome was defined as acute myocardial infarction (AMI), stroke, or death from cardiovascular event. We used multivariate logistic regression analysis to assess the risk factors of MACE. Patients from our cohort were compared to the patients from the Chronic Renal Insufficiency Cohort (CRIC), which is a multicenter, prospective observational cohort study of participants with CKD. Results During the median follow up of 8 years (range 0-24.5, IQR: 2.9-13.6), 100 (11.8%) patients developed diabetes, 98 (13.4%) coronary heart disease (CHD), 90 (12.1%) hypertension, 70 (9.6%) deep vein thrombosis (DVT), 43 patients (5.9%) had a stroke and 28 (3.8%) an AMI. The number of MACE during FU was 144 (17%). MACE was more frequent among patients older than 65 years (n = 62 (43.1%); p-value: 0.013). CVD was the primary cause of death in 43 patients (14%). During the first 5 years after randomization, there was a significant increase in the number of cardiovascular events compared to the period 6 years- end of follow up (CHD: n = 55 vs n = 23, p ≤ 0.001; DVT: n = 55 vs n = 29; p < 0.001; stroke: n = 35 vs n = 24, p-value < 0.001). The prognostic factors for MACE in our cohort were hemodialysis dependency during RCT, age, male sex, previous history of CHD and stroke, and occurrence of diabetes during follow up. Within the subset of patients who underwent kidney biopsy, those in the crescentic class (n = 16) followed by the mixed class (n = 15) exhibited a significant higher incidence of MACE (p = 0.02). When compared to the cohort of patients with CKD from the CRIC study, the risk for CHD was higher (13.4% (95% CI: 11.16-16.11) vs 5.4% (95% CI 4.5-6.5); respectively; RR: 2.49 (95% CI 1.91-3.24); p-value<0.01). Additionally, there was a higher risk for stroke (5.6% (95% CI 4.2-7.4) vs 2.8% (95% CI 2.2- 3.7); RR 1.97 (95% CI: 1.33- 2.91) p-value: 0.0006). Conclusion Patients with AAV had an increased risk of stroke and CHD compared to patients with CKD from other etiologies. During the first years after diagnosis, there is an increased risk for CVD occurrence. The prognostic factors for MACE in our cohort were hemodialysis dependency, age, male sex, previous story of CHD and stroke, and diabetes during follow up. Patients with AAV should be considered at high cardiovascular risk; therefore, the therapeutic approach should include the management of traditional cardiovascular risk factors and lifestyle modification. Efforts should be made to meet strict therapeutic targets and to implement early CVD detection programs.

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