Swedish study links AAV to higher risk of heart attack, blood clots
Researchers call for early surveillance of heart and clot events in patients
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People with the two most common types of ANCA-associated vasculitis (AAV) face a substantially higher risk of cardiovascular disease and thromboembolism (blood clots) than the general population, according to a nationwide Swedish analysis.
The study, which compared over 4,000 patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) with more than 21,000 matched controls and more than 25,000 siblings, identified sex-based differences in such risk and showed the danger is highest in the months around diagnosis.
“Lack of increased risk among siblings emphasize the vasculitis per se as a risk factor for CVD-TE [cardiovascular disease and thromboembolism],” researchers wrote. “This study highlights the importance of timely diagnosis and increased surveillance of both cardiovascular and thromboembolic events in patients with AAV.”
The study, “Cardiovascular and thromboembolic risk in anti-neutrophil cytoplasmic antibody-associated vasculitis: a nationwide matched cohort study by disease, sex, and familial risk,” was published in the journal Rheumatology.
Study explores whether health risks vary by AAV type, sex
In AAV, the body’s immune system produces self-directed antibodies, called ANCAs, that attack small- to medium-sized blood vessels, causing inflammation that can damage nearly any organ.
People with AAV are also at risk for other health problems, including cardiovascular disease and thromboembolism (CVD-TE), a category that includes heart attacks, strokes, and blood clots.
However, it remains unclear whether these risks vary by sex or AAV type, or are influenced by familial factors.
To find out, a research team at Uppsala University in Sweden collected and examined data from the Swedish national patient registers covering 2005 to 2020.
The team identified 4,317 people with GPA or MPA, the two most common AAV types. Their median age at diagnosis was 67 years, and the group was evenly divided between men and women. Among them, 73% had GPA and the remaining 27% had MPA.
The researchers also retrieved data from 21,582 individuals in the Swedish population who did not have GPA/MPA and were matched by age, sex, and residence to patients (this group served as controls), as well as 25,568 first-degree siblings (brothers and sisters) of patients and controls.
Both AAV groups had uncreased risk of heart attacks, clots
The analysis showed that GPA and MPA patients were both significantly more likely, by about twofold, to have CVD-TE events compared with population controls. On average, both the GPA and MPA groups had more CVD-TE events than controls (1.6 vs. 0.91 per 10 patients).
Both AAV groups also had a significantly increased risk of myocardial infarction (heart attack), deep vein thrombosis (a blood clot in a deep vein), pulmonary embolism (a sudden blockage in a lung artery), and CVD-TE-related death compared with controls. The risk of ischemic stroke was increased in GPA patients (by 26%), but not in those with MPA.
Neither disease type was linked to an increased risk of hemorrhagic stroke, when a weakened blood vessel in the brain bursts.
When the researchers directly compared the GPA and MPA groups, they found no significant differences for any CVD-TE outcome.
When looking at potential sex differences, the team found that “both males and females with GPA or MPA had a significantly increased risk of composite CVD-TE events compared with population controls.”
However, in the GPA group, only men had a significantly increased risk of heart attack and only women had a significantly increased risk of CVD-TE-related death and ischemic stroke (a blockage of blood flow in the brain). In MPA patients, men had a significantly increased risk of heart attack and CVD-TE-related death.
“The increased risks of [heart attack] and ischemic stroke appeared to be sex-specific among patients with GPA and MPA,” the team wrote.
To explore whether shared family factors, such as genetics, might explain some of the higher risks seen in AAV patients, researchers compared AAV patients to their own siblings. They found that those with GPA and MPA had a significantly higher CVD-TE risk, by two to three times, relative to their own unaffected siblings.
Both GPA and MPA constitute strong and independent risk factors for CVD-TE, irrespective of pre-existing cardiovascular or kidney disease, with differences between the sexes.
When siblings of AAV patients were compared with siblings of population controls, researchers found no increased risk of any CVD-TE outcome.
“While our results do not support a substantial familial overlap in risk, a more subtle familial contribution cannot be excluded and additional studies addressing this issue are needed,” the researchers wrote.
A timing analysis showed that the higher CVD-TE risk in AAV patients centered around the time of diagnosis. Thromboembolic risks were markedly higher in the first 90 days after an AAV diagnosis than across the full follow-up period. Risk of heart attack, ischemic stroke, and CVD-TE-related death was also substantially elevated during this early window.
Notably, elevated CVD-TE risk was detectable even in the year preceding an AAV diagnosis, compared with controls, and in the 90 days before diagnosis.
“Both GPA and MPA constitute strong and independent risk factors for CVD-TE, irrespective of pre-existing cardiovascular or kidney disease, with differences between the sexes,” the researchers wrote. “Notably, the CVD-TE risk begins to increase already during the year preceding the clinical diagnosis of AAV.”
Jeff Butterfield
Did the patients in this study have active AAV or was AAV in remission?