Study Identifies Risk Factors for Higher Cardiovascular Disease Rates in AAV Patients With GPA and EGPA

Study Identifies Risk Factors for Higher Cardiovascular Disease Rates in AAV Patients With GPA and EGPA
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A family history of cardiovascular disease and higher vasculitis disease activity are risk factors for fatal and non-fatal cardiac disease in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, a study suggests. 

The study, “Predictors of fatal and non-fatal cardiovascular events in ANCA-associated vasculitis: data from the Toronto CanVasc cohort,” was published in the journal Joint, Bone, Spine

ANCA-associated vasculitis (AAV) is an autoimmune disease characterized by the swelling and damage of blood vessels, and is categorized into several types. Each type is grouped according to the organs whose vessels have been damaged. Subtypes include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). 

MPA affects multiple tissues and organs including kidneys, skin, lungs, nerves, and joints. GPA has an impact on the lungs, kidneys, sinuses, nose, ears, and eyes, while EGPA is typically limited to the lungs and respiratory tract. 

Increasing evidence links AAV to cardiovascular disease. In particular, a recent study demonstrated the risk for CV disease in AAV patients is around 65% higher than in the general population. 

Studies assessing the risk of CV disease in people with AAV have been conducted in Europe and China; however, it is unknown whether the types of statistical models used in these studies can be applied to North American populations. 

Moreover, studies on CV disease risk factors included AAV patients with GPA and MPA, but not EGPA, which is a limitation given that the heart is frequently affected in patients with GPA and EGPA. 

In contrast, patients with GPA and EGPA whose ear, nose, and throat are affected are protected from CV disease, which suggests that CV risk may be due to unidentified factors in these subtypes of AAV. 

Thus, researchers based in Toronto, Canada, in collaboration with investigators in Amsterdam, the Netherlands, conducted a study to assess the rate of CV disease events in a large group of Canadian AAV patients with GPA and EGPA to help identify risk factors for CV disease. 

All patients included in the study were enrolled in the Canadian Vasculitis Research Network (CanVasc) cohort. CanVasc organizes a dedicated network of researchers from multiple disciplines to conduct and promote studies on vasculitis, while raising awareness for healthcare providers and acting as an advisory group to identify unmet needs in vasculitis research.  

The study recruited 336 patients and collected demographics and information on their disease characteristics, such as smoking status, obesity, diabetes, dyslipidemia (elevated blood fats), high blood pressure, ANCA status, and the first-degree relative history of CV disease events. 

Disease activity and affected organs were scored using the Birmingham Vasculitis Activity Score (BVAS) and the Vasculitis Damage Index (VDI). 

The occurrence of one or more CV events — such as heart attacks and strokes — following diagnosis were recorded, and during follow up, non-fatal CV events were identified by the VDI. 

Of the patients selected, 231 (69%) had GPA and 105 (31%) had EGPA, with an average age of 44 at diagnosis. Ears, nose, and throat were affected in the majority of patients (74%), with heart involvement in 23 patients. 

During an average follow-up time of eight years, which represented a cumulative total of 2,903 years in all patients studied, there were 20 non-fatal and three fatal CV events in 19 patients. Two of the non-fatal events were excluded from the analysis because the patients were found to have vasculitis-related cardiomyopathy without coronary artery disease or ischemia (blockage in brain blood vessels). The analysis ultimately included 18 non-fatal and three fatal events in 18 patients.

The calculated rate for CV events in these patients was 3.4 strokes per 1,000 patient-years and 3.8 heart attacks per 1,000 patient-years, totaling 7.2 CV events per 1,000 patient-years overall. In GPA patients, the overall CV event rate was 7.4 per 1,000 patient-years, while in those with EGPA, the rate was 6.8 per 1,000 patient-years. 

The authors pointed out that the CV event rate in the general population — between the ages of 40 and 79 — in the same geographic area was between 3.2 and 4.1 CV events per 1,000 patient-years. 

A statistical analysis found that a family history of CV events and a higher BVAS were predictive of these events in AAV patients. 

The analysis was repeated for the GPA and EGPA patients separately. In patients with GPA, a higher BVAS was predictive of CV disease events, while those who tested positive for ANCA were protected from these events. 

However, in patients with EGPA, CV risk factors or disease characteristics were not found to be associated with CV events. The authors noted a limited number of CV events in EGPA patients and recommended further research is needed to identify CV risk factors in this AAV subtype.

“In conclusion, in this large Canadian cohort of patients with GPA and EGPA, we found a high incidence of myocardial infarction [heart attack] and stroke,” the authors wrote.

“The relatively young age of subjects in our cohort emphasizes the importance of CV risk and CV risk management in all age categories in GPA and EGPA,” they said. 

Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone.
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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.
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Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone.
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