Sign of heart disease seen in majority of adults with AAV: Study
Calcium buildup in blood vessels linked to increased risk for patients
A key sign of heart disease — calcium buildup in the blood vessels that supply the heart, known as coronary artery calcification — was found in a majority of adults with ANCA-associated vasculitis (AAV) in a study by U.S. researchers.
Such calcium deposits are associated with atherosclerosis, or the buildup of fatty deposits called plaques inside arteries, which increase the risk of cardiovascular events like heart attacks.
Further, among more than 100 patients found to be at risk, “only one-quarter of these individuals were on statins,” a treatment commonly used to reduce the risk of plaque formation, the researchers wrote.
According to the team, these results show “a high burden of [coronary artery calcium]” and highlight “a significant missed opportunity for early cardiovascular screening and implementation of primary prevention therapies in patients with AAV.”
The scientists added that “screening for atherosclerotic cardiovascular disease at [the] time of diagnosis of ANCA-associated vasculitis and intermittently throughout the treatment course is essential.”
Their study, “Burden of coronary artery calcification in ANCA-associated vasculitis,” was published in the journal RMD Open.
AAV patients face higher risk of cardiovascular diseases
AAV comprises a group of rare autoimmune diseases marked by inflammation and damage in small blood vessels. Most cases are associated with the production of self-reactive antibodies called ANCAs that ultimately result in the excessive activation of immune cells called neutrophils.
ANCAs typically target one of two neutrophil proteins — PR3 or MPO — with each leading to distinct disease manifestations.
Compared with the general population, people with AAV are at increased risk of cardiovascular diseases, including blood clots, heart failure, and coronary artery disease, the researchers noted.
Several factors are thought to contribute to this risk, including AAV-related blood vessel inflammation and the effects of immunosuppressive glucocorticoids used as a treatment for the disease.
“ANCA type is also an important consideration,” the scientists wrote, noting that individuals with anti-MPO ANCAs have been found to have a greater risk of cardiovascular problems than patients with anti-PR3-ANCAs.
Coronary artery disease is characterized by atherosclerosis in the coronary arteries, which supply the heart. Coronary artery calcification, in which calcium accumulates in these blood vessels, is a sign of plaque buildup because most of these plaques contain calcium. Over time, these plaques can grow large enough to slow or block blood flow to the heart.
As such, a CT scan to assess calcium levels in the coronary arteries, referred to as the coronary artery calcium or CAC test, has emerged as a valuable tool for estimating the risk of major cardiovascular events. CAC scores range from zero, meaning no plaques, to more than 300, reflecting extensive calcification and a high risk of coronary artery disease.
Most patients found to have sign of heart disease during screening
In this study, a team led by scientists at the Massachusetts General Hospital used CT scans to assess coronary artery calcification in 175 adults with AAV from the Mass General Brigham AAV cohort, which includes AAV patients diagnosed in a large multicenter healthcare system.
Nearly three-quarters of the participants (73%) tested positive for anti-MPO ANCAs; this was called the MPO-AAV group. The remaining 27% of patients had anti-PR3 ANCAs, and were known as the PR3-AAV group.
Compared with the PR3-AAV group, those with anti-MPO ANCAs were significantly older, with a median age of 70 versus 59. Those in PR3-AAV group also were significantly more likely (83% vs. 65%) to have at least one standard modifiable cardiovascular risk factor, such as high blood pressure, diabetes, high blood fats, or tobacco use.
Altogether, the patients’ median CAC score was 17, with 26% scoring above 300. Slightly more than 1 in 10 patients (11%) scored between 100 and 299, indicating moderate calcification. A total of 29% had scores between 1 and 99, denoting mild calcification.
About one-third of the patients (34%) scored zero.
The median CAC score was significantly higher in the MPO-AAV group than in the PR3-AAV group (24 vs. 1). Likewise, patients with anti-MPO ANCAs were significantly less likely to have a CAC score of zero (30% vs. 46%), and more likely to score at least 300 (32% vs. 10%).
Of the 116 patients with a CAC score higher than zero, 1 in 4 (25%) were being treated with statins to lower blood levels of cholesterol, a major component of plaques. Treatment with statins is known to reduce the risk of heart disease among patients.
The researchers also noted that, among patients with a CAC of 100 or higher, for whom statins are strongly recommended, 28% — “just 21” of 75 — were on statins at the time of the CT scan.
Just 25% of patients on statins when scanned for sign of heart disease
Statistical analyses showed several factors significantly associated with higher CAC scores. Key were markers of inflammation and estimated glomerular filtration rate, or eGFR — a standard measure of kidney function — at the study’s start, as well as eGFR at the time of scan.
About twice as many patients with anti-MPO ANCAs had CAC scores above the 75th percentile, or higher than 75% of the patient subgroup, than those with anti-PR3 ANCAs (32% vs. 15%), “indicating a high 10-year risk of a coronary artery event,” the researchers wrote.
Over a median follow-up of 2.2 years, 12 patients (7%) experienced a major heart-related adverse event, half of which were strokes and half heart attacks. Nine of these events occurred in patients with a CAC percentile of at least 50%, meaning those with scores higher than 50% of the patients.
These findings highlighted that most AAV patients have “coronary artery calcium on CT scans obtained for other purposes and thus would be recommended statin therapy by [current treatment] guidelines,” the researchers wrote. However, they noted that just 25% of these patients were taking statins at the time of the scan.
The team called for further research “to delineate relative contributions of proposed mechanisms of accelerated atherosclerosis in this population.” Additionally, the researchers said “guidelines should recommend cardiovascular disease screening and primary prevention therapies.”
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