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People With Coeliac Disease at Higher CVD Risk

People with coeliac disease have a heightened risk of cardiovascular disease (CVD) even though they have fewer known risk factors, according to a new study led by researchers from Oxford Population Health.

Coeliac disease affects around 1% of the UK population.There is mixed published evidence on whether or not coeliac disease is associated with a heightened risk of CVD, and previous studies have tended to not investigate the potential role of traditional cardiovascular risk factors, such as hypertension or elevated cholesterol.

The team conducted a prospective analysis of 469,095 people in the UK Biobank, all aged 40-69 years and without CVD at baseline between 2006 and 2010, and monitored their cardiovascular health using linked hospital records and death certificates.

Their study, published online in BMJ Medicine, compared the 2083 participants who had coeliac disease with those who didn't in terms of a composite primary outcome – the relative risk of CVD, ischaemic heart disease, myocardial infarction, and stroke.

Over a median follow-up of 12.4 years (interquartile range 11.5 to 13.1), 40,687 incident CVD events occurred in the whole cohort, of which 218 were among people with coeliac disease.

Raised CVD Incidence Despite Fewer Risk Factors

This gave an incidence rate of 9.0 CVD cases per 1000 person-years (95% CI 7.9 to 10.3) among coeliac disease patients, compared with 7.4 per 1000 person years (7.3 to 7.4) in people without coeliac disease.

This was despite the fact that the participants with coeliac disease had lower average body mass indices and systolic blood pressures, were less likely to smoke or have high cholesterol, less likely to have a poor cardiovascular risk score (5% vs 9%), and more likely to have an ideal risk score than those who did not have coeliac disease (23% vs 14%).

The researchers said that the hazard ratio (HR) of CVD among people with coeliac disease was 1.27 (95% CI 1.11 to 1.45), and this was not influenced by adjusting for lifestyle factors, but was strengthened by further adjusting for other cardiovascular risk factors (adjusted HR 1.44 [1.26 to 1.65]). The risk seemed to increase the longer a person had been living with coeliac disease – from around 30% among those who had had the condition for less than 10 years, to 34% among those who had had it for 10 or more years, a significant trend.

Similar associations were identified for ischaemic heart disease and myocardial infarction separately, but fewer stroke events were reported and there was no evidence of an association between coeliac disease and risk of stroke.

Reasons for Increased Risk Unclear

The researchers said that it was not clear what the reasons for the elevated CVD risk among people with coeliac disease might be, but noted that a number of autoimmune conditions are associated with a heightened CVD risk of as a result of systemic inflammation. Further research is needed to unearth the drivers behind the association, they said, and "this includes the role of a gluten free diet, which those affected are required to follow to ease symptoms".

Previous research on this has been conflicting, with some studies suggesting that a gluten free diet might reduce inflammation and, therefore, CVD risk, while others indicated that the diet might actually boost risk, either because gluten-free foods tend to be higher in saturated fats, sugar, and salt, or because a gluten-free diet limits consumption of complex whole grains.

'Clinicians Should Make Patients Aware of Risk'

The team noted that, as this was an observational study, it couldn't establish cause and effect, but said that in the light of their findings, it was possible that cardiovascular risk scores used in clinical practice might not adequately capture the excess risk. "Given the increased rates of CVD reported in people with coeliac disease who have an ideal and moderate CVD risk score, clinicians should make patients with coeliac disease aware of their elevated risk, and work with their patients to optimise their cardiovascular health.

"Consideration should be given to inclusion of coeliac disease as a risk factor in CVD risk prediction models, such as the QRISK model," which they noted currently includes other autoimmune conditions (i.e., systemic lupus erythematosus and rheumatoid arthritis) as recognised risk factors.

"In addition, an investigation is warranted into the extent to which any risk reduction is reported by adherence to a gluten-free diet in people with coeliac disease, or whether a gluten-free diet itself contributes to the increased risk identified."

Asked to comment by Medscape News UK, patient charity Coeliac UK issued a statement saying: "This observational study has identified a small increased risk of CVD with diagnosed coeliac disease, having adjusted for many typical CVD risk factors, i.e., if we looked at 1000 people for a period of 1 year, 1.6 more people with coeliac disease may experience a cardiovascular diagnosis than the general population.

"The researchers have not identified a cause, which could only be determined from further research. It is likely there are many other factors that could be contributing to this marginally higher incidence. We recommend that our community do not become concerned and continue to adhere to a strict healthy, nutritionally balanced gluten free diet. We will advise if and when any further findings are reported."

UK Biobank was established by Wellcome, Medical ResearchCouncil, Department of Health, Northwest Regional developmentAgency, and the Scottish Government. UK Biobank has also receivedfunding from the Welsh Assembly Government, British HeartFoundation, Cancer Research UK, and Diabetes UK. The salaries ofMCC, NEA and BL are funded in part by Wellcome. TJL and ES have no funding to declare.