Celiac Disease and CVD Link Bolstered in UK Biobank

Despite having a lower burden of cardiovascular risk factors, patients with versus without celiac disease carry a greater risk of incident CVD events over the long term, according to data from the UK Biobank.

During a median follow-up of 12.4 years, the rate of new CVD events (per 1,000 person-years) was 9.0 among patients with celiac disease and 7.4 among their counterparts without the diagnosis.

That worked out to a 27% greater relative risk of CVD among patients with celiac disease after accounting for potential confounders (HR 1.27; 95% CI 1.11-1.45), a relationship that grew stronger after further adjustment for traditional CV risk factors (HR 1.44; 95% CI 1.26-1.65).

The main takeaway from these data, published online this week in BMJ Medicine, is that clinicians managing patients with celiac disease “need to be aware that there’s a potential increased risk here, and monitor them in a way that they feel appropriate, and that’s going to vary patient to patient,” lead author Megan Conroy, MSc (Nuffield Department of Population Health, University of Oxford, England), told TCTMD.

She added, however, that the potential increased risk of CVD associated with celiac disease is not something that people should worry about too much, as the absolute difference—about two cases out of every 1,000 patients—was not that great. “It’s really more something for clinicians to be aware of as a potential complication of celiac disease,” said Conroy.

For Peter Green, MD director of the Celiac Disease Center at Columbia University Irving Medical Center (New York, NY), the paper is relevant because it underscores the importance of a condition that has not gotten the attention it deserves, which has resulted in a high rate of underdiagnosis, and places it in the category of other autoimmune conditions perceived to have negative health consequences, like rheumatoid arthritis and systemic lupus erythematosus.

“A study like this reinforces the deleterious effect and the significance of having a diagnosis of celiac disease,” Green commented to TCTMD.

Green said the purported mechanism linking celiac disease to CVD is inflammation, although he pointed to other issues that could be contributing. For instance, prior research from his group has shown that patients with celiac disease have lower levels of HDL cholesterol.

UK Biobank

Celiac disease is an autoimmune disorder stemming from the body’s reaction to gluten, and the primary treatment is adhering to a gluten-free diet. There’s evidence that celiac disease is associated with a greater risk of CVD, despite the fact that affected patients generally have a more-favorable cardiovascular risk profile compared with their peers, but prior studies have relied on data sources without detailed information on CV risk factors and have yielded mixed results.

The UK Biobank, which enrolled adults ages 40 to 69 living in England, Scotland, and Wales between 2006 and 2010, provided the opportunity to dig deeper into the potential link between celiac disease and CVD. The current analysis included 469,095 participants who were free from CVD at baseline, including 2,083 who had been diagnosed with celiac disease.

As observed previously, patients with celiac disease had a better cardiovascular risk profile compared with others, with lower body mass index, systolic blood pressure, total cholesterol, and C-reactive protein, less alcohol consumption, and lower rates of smoking and type 2 diabetes; they were also more likely to have an ideal CV risk score based on the American Heart Association’s Life Simple 7 construct (now Life’s Essential 8).

Even after accounting for those differences, however, patients with celiac disease maintained a higher risk of incident CVD events (incorporating ischemic heart disease, MI, and stroke) over the long term. The patterns were similar for ischemic heart disease and MI individually, although stroke events were less frequent and didn’t differ significantly based on the presence of celiac disease.

The data indicate that the longer a patient has celiac disease, the greater the risk of CVD (P < 0.001 for trend).

“Cardiovascular risk scores need to adequately account for the elevated risk among people with celiac disease; people with celiac disease and their clinicians need to be aware of their higher cardiovascular risk and to take relevant action; and further research is needed to understand the mechanisms underlying these associations,” Conroy et al write.

Seeking a Healthy Gluten-Free Diet

Another possibility with respect to understanding the celiac-CVD connection is the treatment for celiac disease—a gluten-free diet, Green said. In their quest to avoid gluten after being diagnosed with celiac disease, patients will often stick with what they know is safe, like rice, and restrict other foods that may have cardioprotective effects. That includes many naturally gluten-free sources of whole grains, like millet, sorghum, and quinoa.

Moreover, when patients search for gluten-free alternatives, they often find manufactured foods that are high in saturated fat, salt, and sugar, Green said, noting that many patients will gain weight after receiving a diagnosis of celiac disease.

For that reason, it’s critical to have them meet with a dietician “to make sure that they diversify their diet and eat a healthy diet,” he said. “You can have a healthy gluten-free diet, but it’s just that people don’t know how to do that and don’t think that it’s important.”

Conroy pointed out that the UK Biobank does not contain data specifically on adherence to gluten-free diets, making it difficult to tease out how that might be contributing to the findings. Future studies with more-detailed dietary information are needed, she said.