Antibody type may influence cardiovascular risk timing in AAV
Study finds heart attacks and strokes happened earlier in MPO cases
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Adults with ANCA-associated vasculitis (AAV) who test positive for antibodies against the myeloperoxidase (MPO) protein may face cardiovascular events sooner than those with antibodies against the proteinase-3 (PR3) protein, according to a new study.
The French study analyzed data from 402 adults with AAV. While the overall proportion of major cardiovascular events was similar between the groups, events occurred earlier and at a higher rate over time among patients with anti-MPO antibodies. Heart attacks and strokes tended to happen sooner after diagnosis in this group, the data showed.
“Patients presenting anti-MPO [antibodies] could benefit from a more rigorous screening and management of cardiovascular risk factors,” the scientists wrote.
The study, “Impact of ANCA specificity on risk of cardiovascular events and death in ANCA-associated vasculitis,” was published in RMD Open.
How ANCA antibodies shape AAV
In AAV, self-targeting antibodies called ANCAs mistakenly attack and abnormally activate neutrophils, a type of immune cell. This leads to inflammation in small blood vessels, which can damage organs such as the kidneys and lungs. ANCAs usually target one of two proteins inside these cells — MPO or PR3.
Anti-MPO ANCAs are often linked to microscopic polyangitis (MPA), one of the most common types of AAV. In contrast, ANCAs against PR3 are commonly found in people with granulomatosis with polyangiitis (GPA), which tends to relapse more often than other forms of the disease.
Some experts suggest classifying AAV by ANCA type instead of traditional categories such as MPA or GPA, because antibody type has been linked to differences in genetics, symptoms, treatment response, and risk of relapse.
In fact, a recent study found that a gene variant linked to increased PR3 production is more common in people with anti-PR3 ANCAs, which may help explain why PR3-related AAV is associated with a higher relapse risk.
With this in mind, a team of researchers in France examined whether ANCA type is linked to cardiovascular risk. Heart attacks and strokes are known to occur more often in people with AAV, particularly in the years following diagnosis.
Study examines cardiovascular risk by antibody type
The team retrospectively analyzed clinical data from 402 adults with AAV (55% men) who were treated and followed for at least one year at two hospitals in France.
Among them, 214 were diagnosed with GPA, 159 with MPA, and 29 with eosinophilic granulomatosis with polyangiitis (EGPA), the rarest AAV type. They were followed for a mean of 7.5 years.
Of the 402 patients, 236 tested positive for anti-MPO ANCAs and 166 tested positive for anti-PR3 ANCAs.
Many participants also had traditional risk factors for cardiovascular disease, including high blood pressure (35%), smoking history (27%), abnormal blood fat levels (12%), or diabetes (7%). A few had experienced a heart attack (3%) or stroke (2%) before their AAV diagnosis.
The researchers found no significant differences in these cardiovascular risk factors between the MPO and PR3 groups.
These results suggest that tailored follow-up strategies could be considered for a more targeted management of individual patients based on ANCA specificity.
Patients in the MPO group were older at diagnosis and were more likely to be taking medications for high blood pressure. In contrast, the PR3 group had a longer follow-up period, a higher average body mass index, and a higher risk of relapse.
Researchers assessed the occurrence of major adverse cardiovascular events, or MACE, defined as heart attack, stroke, or death from any cause.
Over a mean follow-up of 7.5 years, the overall proportion of patients who experienced MACE was similar between the two groups (20% in MPO vs. 18% in PR3). However, there were significant differences in timing, with these events occurring sooner after diagnosis in the MPO group than in the PR3 group, on average 6.1 years vs. 7.6 years.
When researchers accounted for follow-up time, they found that cardiovascular events occurred at a higher rate over time in the MPO group. However, after adjusting for age, sex, and cardiovascular risk factors, the overall association between MPO antibodies and major cardiovascular events did not reach statistical significance. Patients with anti-PR3 antibodies were more likely to remain free of major cardiovascular events at five years (92.9% vs. 86.4%) and 10 years after diagnosis (83% vs. 73%).
“These results suggest that tailored follow-up strategies could be considered for a more targeted management of individual patients based on ANCA specificity,” the researchers wrote.
Heart attacks and strokes analyzed separately
When the team specifically examined heart attacks, they found similar overall rates (4%) in both groups. However, heart attacks occurred significantly sooner after an AAV diagnosis in the MPO group than in the PR3 group, on average 2.2 years vs. 4.2 years.
A similar pattern was observed with strokes, which occurred at roughly the same rate in both groups but significantly earlier in the MPO group than in the PR3 group, on average 4.4 years vs. 7.7 years.
At five and 10 years after diagnosis, heart attacks and strokes were slightly more common among patients with anti-MPO ANCAs, but these differences were not statistically significant.
After accounting for age, sex, and cardiovascular risk factors, researchers found that patients with anti-PR3 antibodies had a significantly lower risk of stroke than those with anti-MPO antibodies, by about 39%. No other significant associations were detected.
“Our findings support the existence of a difference in cardiovascular risk in AAV based on ANCA specificity, reinforcing the idea of the utility of a classification of AAV based on ANCA specificity for clinical practice,” the team concluded.
