Persistent Villous Atrophy of the Small Intestine Is Not Associated with Increased Risk of Atrial Fibrillation in Patients with Celiac Disease

Study results indicate that the extent of a patient’s physical recovery from celiac disease does not affect that patient’s long-term risk of developing atrial fibrillation.

Prior studies had already demonstrated that patients with celiac disease, as a whole, face a significantly elevated risk of both AF and ischemic heart disease long after they control the underlying condition by adopting a gluten-free diet. Questions remained, however, about whether patients with persistent villous atrophy of the small intestine face greater risks than patients who experience mucosal healing.

Researchers in New York and Sweden investigated by pulling records on 7,440 celiac disease patients who eventually underwent a follow-up biopsy that distinguished those with persistent atrophy from those with mucosal healing.

They then used follow-up data on atrial fibrillation and ischemic heart disease to see whether persistent villous atrophy predicted eventual heart problems, but — after adjusting for age, sex, duration of celiac disease, calendar period, and educational attainment — they found no significant relationship.

Overall, 139 patients were diagnosed with atrial fibrillation or heart disease during follow-up, and those with persistent atrophy actually accounted for very slightly less than their expected share of both atrial fibrillation (adjusted hazard ratio [HR], 0.98; 95% confidence interval [CI] 0.74—1.30) and heart disease (adjusted HR, 0.97; 95% CI 0.73–1.30).

“This null finding was present in both genders, across age strata, and persisted over time after follow-up biopsy,” the study authors wrote in Plos One.

“These negative findings suggest that follow-up histology does not risk-stratify patients for the development of ischemic heart disease or atrial fibrillation, with the caveat that a small positive association cannot be ruled out in certain subgroups due to limited statistical power.”

A better understanding of the link between celiac disease and atrial fibrillation could significantly improve treatment of the latter condition by helping to guide screening practices.

Indeed, the study team hoped its analysis might prove a step in that direction by uncovering a significant relationship between persistent atrophy and eventual heart problems.

Its members initially hypothesized that inflammation caused by celiac disease stresses the heart, that persistent atrophy might indicate persistent inflammation and that the long-term risks associated with celiac disease might apply mostly (or entirely) to a small subgroup of patients.

“Our null findings with regard to follow-up histology stand in contrast to this theoretical model,” they later wrote. “One potential explanation for these null findings is that [persistent atrophy] is not an adequate marker for immune activation in patients with celiac disease … Another possibility is that patients with persistent villous atrophy on a first follow-up biopsy may not reflect long-term mucosal healing rates.”

It is, in other words, still possible that greater ongoing inflammation puts some celiac disease patients at greater risk of atrial fibrillation than others, but the study team believes its analysis was large enough and strong enough to eliminate any practical hope of using existing biopsy results to predict risk levels for individual patients.

There were, of course, some potentially important limitations to their work, like the lack of data about factors such as alcohol use that affect the risk of heart problems. The study cohort, moreover, skewed very young. The median age at the follow-up biopsy was only 25.

But the sheer size of the cohort was likely enough to overcome any limitations, wrote the researchers, who noted that even with the low average age, more than 1,000 of the patients were more than 60 years old at biopsy.