All-cause and cause-specific mortality in ANCA-associated vasculitis: overall and according to ANCA type

Abstract

Objective The objective of this study was to evaluate causes of death in a contemporary inception cohort of ANCA-associated vasculitis patients, stratifying the analysis according to ANCA type. Methods We identified a consecutive inception cohort of patients newly diagnosed with ANCA-associated vasculitis from 2002 to 2017 in the Partners HealthCare System and determined vital status through the National Death Index. We determined cumulative mortality incidence and standardized mortality ratios (SMRs) compared with the general population. We compared MPO- and PR3-ANCA+ cases using Cox regression models. Results The cohort included 484 patients with a mean diagnosis age of 58 years; 40% were male, 65% were MPO-ANCA+, and 65% had renal involvement. During 3385 person-years (PY) of follow-up, 130 patients died, yielding a mortality rate of 38.4/1000 PY and a SMR of 2.3 (95% CI: 1.9, 2.8). The most common causes of death were cardiovascular disease (CVD; cumulative incidence 7.1%), malignancy (5.9%) and infection (4.1%). The SMR for infection was greatest for both MPO- and PR3-ANCA+ patients (16.4 and 6.5). MPO-ANCA+ patients had an elevated SMR for CVD (3.0), respiratory disease (2.4) and renal disease (4.5). PR3- and MPO-ANCA+ patients had an elevated SMR for malignancy (3.7 and 2.7). Compared with PR3-ANCA+ patients, MPO-ANCA+ patients had a higher risk of CVD death [hazard ratio 5.0 (95% CI: 1.2, 21.2]; P = 0.03]. Conclusion Premature ANCA-associated vasculitis mortality is explained by CVD, infection, malignancy, and renal death. CVD is the most common cause of death, but the largest excess mortality risk in PR3- and MPO-ANCA+ patients is associated with infection. MPO-ANCA+ patients are at higher risk of CVD death than PR3-ANCA+ patients.

ANCA-Associated Vasculitis: An Update

“…Similarly, an increased risk of cardiovascular events (coronary artery disease and ischemic stroke) is also observed in patients with AAV [ 132 ]. Similar to VTE, most cardiovascular events occur in the first year after diagnosis [ 132 ]; both disease activity and ANCA type appear to be associated with cardiovascular risk [ 133 , 134 ]. Thus, aggressive cardiovascular risk factor assessment and modification should be integrated within the therapeutic approach of AAV patients.…”

Cardiovascular events and the role of accelerated atherosclerosis in systemic vasculitis

“…Despite tremendous improvements in prognosis, AAV is still associated with a significant increased risk of death, estimated about 2.7 times above that of the general population [73], with cardiac involvement being an important predictor of mortality [70,74]. Cardiovascular death is most common (7.1%), followed by death due to malignancy and infection [2]. MPO-ANCA-associated vasculitis patients carry a higher risk of CV death than PR3-ANCA-associated vasculitis patients [2], which may be a consequence of the more profound renal damage that typically occurs in MPA patients, or may be due to biochemical differences in these diseases, such as enhanced myeloperoxidase-mediated LDL oxidation, as has been identified in MPA patients [75].…”

“…Cardiovascular death is most common (7.1%), followed by death due to malignancy and infection [2]. MPO-ANCA-associated vasculitis patients carry a higher risk of CV death than PR3-ANCA-associated vasculitis patients [2], which may be a consequence of the more profound renal damage that typically occurs in MPA patients, or may be due to biochemical differences in these diseases, such as enhanced myeloperoxidase-mediated LDL oxidation, as has been identified in MPA patients [75].…”

“…Classified by size of blood vessel affected (see Table 1), these rare autoimmune diseases may result in lifethreatening organ ischemia and infarction [1]. Although early loss of life typically occurs as a consequence of either uncontrolled vasculitis or infection from immunosuppression, cardiovascular (CV) death is now the leading cause of mortality in these patients [2,3].…”

Immunopathogenesis of ANCA-Associated Vasculitis

“…Cases with double seropositivity for both PR3- and MPO-ANCA are rarely seen, and are mainly associated with secondary forms of ANCA-associated vasculitis (i.e., in cocaine-induced forms or drug-induced vasculitis) [ 8 , 9 ]. Recent research found that the ANCA serotype better discriminates between genetic associations, therapeutic response, relapse risk, prognosis and co-morbidities (venous thromboembolic events and cardiovascular death) than a classification based on the clinical phenotype [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. In addition, the respective ANCA serotype more closely relates to biomarkers of disease activity [ 17 ] and may help to identify novel therapeutic targets and predict response to current treatment regimens.…”