Celiac disease and cardiovascular risk: greater attention needed
Greater attention needs to be paid to the pre-clinical signs of atherosclerosis in celiac patients to prevent cardiovascular disease. These are the findings which have emerged from a recent review (December 2017) carried out by a team of Italian researchers, detailing the latest evidence on the link between celiac disease, atherosclerotic process acceleration, and cardiovascular risk.
Published in the European Review for Medical and Pharmacological Sciences, the study was conducted by L. Santoro and colleagues of the departments of Internal and Emergency Medicine, and of Geriatrics, Neurosciences and Orthopaedics at the Catholic University of the Sacred Heart in Rome.
The authors conducted a systematic literature review using the main specialist search engines, identifying various studies in which certain clinical parameters with the potential to cause atherosclerotic process acceleration (such as an increase in the carotid intima-media thickness, endothelial dysfunction, and an increase in arterial rigidity) were found in celiac patients. The research also highlighted recent studies which report an increase in the prevalence of cardiovascular disease (angina pectoris, acute myocardial infarction) in patients with celiac disease (CD) compared to controls. The incidence of mortality for ischemic heart disease was also greater. Other non-ischemic cardiovascular diseases associated with celiac disease are dilatative cardiomyopathy, atrial fibrillation, and myocarditis.
Among the studies taken into consideration was a cohort study based on the Swedish population, published by Ludvigsson et al. in 2011, who found a 19% increase in risk for ischemic heart disease (IHD) in patients with celiac disease. This study also found a 28% increase in the risk of IHD in individuals with intestinal inflammation, but without villous atrophy, and a 14% increase in the risk of IHD in subjects with normal mucosa but positive serology for celiac disease. In patients with latent celiac disease, however, the study showed only an association with angina pectoris, not with myocardial infarction or death due to IHD.
The authors of the review stress that the association between celiac disease and cardiovascular disease seems to be linked principally to the presence of a systemic pattern of inflammation and a diffuse immune activation. The concomitant presence of traditional cardiovascular risk factors, such as dyslipidemia and hypertension, could explain an increase in the risk of cardiovascular disease in these subjects. Additionally, the presence of other known cardiovascular risk factors, such as psychological stress and deficiencies of vitamin B12 and folic acid leading to high homocysteine levels, may explain an increase in the risk of ischemic disease.
Another factor to be considered, as the authors point out, is that the malabsorption typical of celiac disease may reduce the bioavailability of the drugs used for the prevention of cardiovascular risk, as well as of essential nutrients. One surprising aspect, reported in some of the studies, is that the rates of myocardial infarction and stroke among celiac patients who follow a gluten-free diet, despite the presence of factors with the potential to protect against ischaemic disease (low levels of cholesterol, lowering of blood pressure, and potentially fewer smokers), are not substantially different from those of the general population.
One of the most important reports of the link between celiac disease and other non-ischemic cardiovascular diseases is the national database study conducted by Emilsson et al., who found a positive link between celiac disease and atrial fibrillation, showing that the celiac patients had a 30% increased risk of developing atrial fibrillation compared to the general population. The study suggests that the inflammation and immune-mediated disturbances associated with celiac disease could increase the risk of atrial fibrillation. Finally, Frustaci et al. demonstrated the presence of intestinal inflammatory disease in 4.4% of a broad population of patients with myocarditis, with a prevalence 14 times higher than in the control subjects. A combination of villous atrophy and lymphocytic infiltration into the small bowel mucosa was documented in nine patients, and the clinical manifestation of myocarditis in these patients (in the form of heart failure) significantly improved following the adoption of a gluten-free diet and administration of immunosuppressive treatment.
The authors conclude that “the recommendations as to the management of patients with celiac disease should include a more detailed assessment of cardiovascular risk than that performed in current practice, in order to analyze and treat the modifiable cardiovascular risk factors in these patients. We suggest using diagnostic tests to detect atherosclerosis at the sub-clinical stage, using parameters such as carotid intima-media thickness, endothelial dysfunction, and increased arterial rigidity to prevent the development of atherosclerotic cardiovascular diseases in these patients. We would also like to stress once more the importance of a gluten-free diet, which seems to eliminate the alterations observed, also in terms of cardiovascular risk reduction.”
The authors conducted a systematic literature review using the main specialist search engines, identifying various studies in which certain clinical parameters with the potential to cause atherosclerotic process acceleration (such as an increase in the carotid intima-media thickness, endothelial dysfunction, and an increase in arterial rigidity) were found in celiac patients. The research also highlighted recent studies which report an increase in the prevalence of cardiovascular disease (angina pectoris, acute myocardial infarction) in patients with celiac disease (CD) compared to controls. The incidence of mortality for ischemic heart disease was also greater. Other non-ischemic cardiovascular diseases associated with celiac disease are dilatative cardiomyopathy, atrial fibrillation, and myocarditis.
Among the studies taken into consideration was a cohort study based on the Swedish population, published by Ludvigsson et al. in 2011, who found a 19% increase in risk for ischemic heart disease (IHD) in patients with celiac disease. This study also found a 28% increase in the risk of IHD in individuals with intestinal inflammation, but without villous atrophy, and a 14% increase in the risk of IHD in subjects with normal mucosa but positive serology for celiac disease. In patients with latent celiac disease, however, the study showed only an association with angina pectoris, not with myocardial infarction or death due to IHD.
The authors of the review stress that the association between celiac disease and cardiovascular disease seems to be linked principally to the presence of a systemic pattern of inflammation and a diffuse immune activation. The concomitant presence of traditional cardiovascular risk factors, such as dyslipidemia and hypertension, could explain an increase in the risk of cardiovascular disease in these subjects. Additionally, the presence of other known cardiovascular risk factors, such as psychological stress and deficiencies of vitamin B12 and folic acid leading to high homocysteine levels, may explain an increase in the risk of ischemic disease.
Another factor to be considered, as the authors point out, is that the malabsorption typical of celiac disease may reduce the bioavailability of the drugs used for the prevention of cardiovascular risk, as well as of essential nutrients. One surprising aspect, reported in some of the studies, is that the rates of myocardial infarction and stroke among celiac patients who follow a gluten-free diet, despite the presence of factors with the potential to protect against ischaemic disease (low levels of cholesterol, lowering of blood pressure, and potentially fewer smokers), are not substantially different from those of the general population.
One of the most important reports of the link between celiac disease and other non-ischemic cardiovascular diseases is the national database study conducted by Emilsson et al., who found a positive link between celiac disease and atrial fibrillation, showing that the celiac patients had a 30% increased risk of developing atrial fibrillation compared to the general population. The study suggests that the inflammation and immune-mediated disturbances associated with celiac disease could increase the risk of atrial fibrillation. Finally, Frustaci et al. demonstrated the presence of intestinal inflammatory disease in 4.4% of a broad population of patients with myocarditis, with a prevalence 14 times higher than in the control subjects. A combination of villous atrophy and lymphocytic infiltration into the small bowel mucosa was documented in nine patients, and the clinical manifestation of myocarditis in these patients (in the form of heart failure) significantly improved following the adoption of a gluten-free diet and administration of immunosuppressive treatment.
The authors conclude that “the recommendations as to the management of patients with celiac disease should include a more detailed assessment of cardiovascular risk than that performed in current practice, in order to analyze and treat the modifiable cardiovascular risk factors in these patients. We suggest using diagnostic tests to detect atherosclerosis at the sub-clinical stage, using parameters such as carotid intima-media thickness, endothelial dysfunction, and increased arterial rigidity to prevent the development of atherosclerotic cardiovascular diseases in these patients. We would also like to stress once more the importance of a gluten-free diet, which seems to eliminate the alterations observed, also in terms of cardiovascular risk reduction.”
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