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Autoimmune disorders are associated with a substantially higher risk of developing cardiovascular disease than individuals without autoimmune disease, according to a new, large epidemiological study.

The research – led by KU Leuven in collaboration with colleagues in the UK, including the University of Glasgow, and published today in The Lancet – shows for the first time that cardiovascular risks affect autoimmune disorders as a group of diseases, with implications across a broad range of cardiovascular outcomes.

The excess risk is particularly high among younger patients, and suggests that autoimmune disorders are particularly important in causing premature cardiovascular disease, with the potential to result in a disproportionate loss of life years and disability.

Around ten percent of the population in high income regions like Europe and the United States has been diagnosed with one or multiple autoimmune disorders. Examples are rheumatoid arthritis, psoriasis, systemic sclerosis, lupus erythematosus and type I diabetes.

Although earlier research has suggested associations between some of these disorders and a higher risk of cardiovascular disease, these studies were often small and limited to selected autoimmune or selected cardiovascular conditions.

The findings are being announced this weekend at the annual congress of the European Society of Cardiology in Barcelona, where an international research team led by the KU Leuven will present the outcome of a thorough epidemiological investigation into possible links between 19 of the most common autoimmune disorders and cardiovascular disease.

The results of the study show that patients with autoimmune disease have a substantially higher risk (between 1.4 and 3.6 times depending on which autoimmune condition) of developing cardiovascular disease than people without an autoimmune disorder.

This excess risk is comparable to that of type 2 diabetes, a well-known risk factor for cardiovascular disease. The research shows for the first time that cardiovascular risks affect autoimmune disease as a group of disorders, rather than selected disorders individually.

In The Lancet paper, the authors show that the group of nineteen autoimmune disorders they have studied accounts for about 6% of cardiovascular events. Importantly, excess cardiovascular risk was visible across the whole cardiovascular disease spectrum, beyond classical coronary heart disease, including infection-related heart disorders, heart inflammation, as well as thromboembolic and degenerative heart disorders, suggesting the implications of autoimmunity on cardiovascular health are likely to be much broader than originally thought.

Furthermore, the excess risk was not explained by traditional cardiovascular risk factors such as age, sex, socioeconomic status, blood pressure, BMI, smoking, cholesterol and type 2 diabetes. Another noteworthy finding: the excess risk is particularly high among patients with autoimmune disorders under 55 years and suggests that autoimmune disease is particularly important in causing premature cardiovascular disease, with the potential to result in a disproportionate loss of life years and disability.

The study was based on electronic health records from the UK’s Clinical Practice Research Datalink (CPRD), a very large database of anonymised patient data from about one-fifth of the current UK population. Among 22 million patient records, the researchers assembled a cohort of patients newly diagnosed with any of the nineteen autoimmune disorders.

They then looked at the incidence of 12 cardiovascular outcomes – an unprecedented granularity that was made possible by the very large size of the dataset – in the following years, and they compared it to a matched control group.

The risk of developing cardiovascular disease for patients with one or more autoimmune disorders was on average 1.56 times higher than in those without autoimmune disease. They also found that the excess risk rose with the number of different autoimmune disorders in individual patients. Among the disorders with the highest excess risk were systemic sclerosis, Addison’s disease, lupus and type I diabetes.

Nathalie Conrad, lead author of the study from KU Leuven, said: “The results show that action is needed. We see that the excess risk is comparable to that of type 2 diabetes. But although we have specific measures targeted at diabetes patients to lower their risk of developing cardiovascular disease – in terms of prevention and follow-up – we don’t have any similar measures for patients with autoimmune disorders.”

The European Society of Cardiology guidelines on the prevention of cardiovascular diseases currently don’t mention autoimmunity as a cardiovascular risk factor, nor do they list any specific prevention measures for patients with autoimmune disease.

Prof John McMurray, Professor Cardiology at the University of Glasgow’s School of Cardiovascular and Metabolic Heath, said: “This important population-based study suggests that a much broader range of autoimmune disorders than previously recognised are associated with a variety of different cardiovascular problems.

“Some of these problems are potentially preventable using readily available treatments such as statins. The scale of this enormous new study and the breadth of findings across the full spectrum of autoimmune diseases suggest the contribution of this conditions to the burden or cardiovascular diseases in the community may be considerable and the value of a preventive approach substantial.”

Prof Conrad added: “We hope the study will raise awareness among patients with autoimmune disease and clinicians involved in the care of these patients, which will include many different specialties such as cardiologists, rheumatologists, or general practitioners.

“We need to develop targeted prevention measures for these patients. And we need to do further research that helps us understand why patients with an autoimmune disorder develop more cardiovascular diseases than others, and how we can prevent this from happening.”

The paper, ‘Autoimmune disorders and cardiovascular risk: A population-based study on 19 autoimmune disorders and 12 cardiovascular diseases in 22 million individuals’ is published in The Lancet. The study was funded by the European Union’s Horizon 2020, European Society of Cardiology, Wellcome Trust, National Institute for Health and Care Research (NIHR), British Heart Foundation, and UKRI’s Global Challenge Research Fund.

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Enquiries: ali.howard@glasgow.ac.uk or elizabeth.mcmeekin@glasgow.ac.uk / 0141 330 6557 or 0141 330 4831

First published: 27 August 2022