An international research team led by KU Leuven published the results of an epidemiological investigation into possible links between 19 of the most common autoimmune disorders and cardiovascular disease. The results showed 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 study (“Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in the UK“), which appears in The Lancet, reportedly shows for the first time that cardiovascular risks affect autoimmune disease as a group of disorders, rather than selected disorders individually. The results were also discussed at the annual congress of the European Society of Cardiology.

“Some autoimmune diseases are associated with an increased risk of cardiovascular disease. We aimed to determine whether or not this is true, and to what extent, for a broad range of autoimmune conditions,” the investigators wrote.

Heart attack heart attack conceptual artwork-3d illustration
A recent study shows 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. [Peter Images]
“In this population-based study, we used linked primary and secondary care records from the Clinical Practice Research Datalink (CPRD), GOLD and Aurum datasets, to assemble a cohort of individuals across the U.K. who were newly diagnosed with any of 19 autoimmune diseases between Jan 1, 2000, and Dec 31, 2017, younger than 80 years at diagnosis, and free of cardiovascular diseases up to 12 months after diagnosis.

“We also assembled a matched cohort with up to five individuals matched on age, sex, socioeconomic status, region, and calendar year, who were free of autoimmune disease and free of cardiovascular diseases up to 12 months after study entry. Both cohorts were followed up until June 30, 2019. We investigated the incidence of 12 cardiovascular outcomes and used Cox proportional hazards models to examine differences in patients with and without autoimmune diseases.

“Of 22,009,375 individuals identified from the CPRD databases, we identified 446,449 eligible individuals with autoimmune diseases and 2,102,830 matched controls. In the autoimmune cohort, mean age at diagnosis was 46·2 years (SD 19·8), and 271 410 (60·8%) were women and 175 039 (39·2%) were men. 68 413 (15·3%) people with and 231 410 (11·0%) without autoimmune diseases developed incident cardiovascular disease during a median of 6·2 years (IQR 2·7–10·8) of follow-up.

“The incidence rate of cardiovascular disease was 23·3 events per 1000 patient-years among patients with autoimmune disease and 15·0 events per 1000 patient-years among those without an autoimmune disease (hazard ratio [HR] 1·56 [95% CI 1·52–1·59]).

“An increased risk of cardiovascular disease with autoimmune disease was seen for every individual cardiovascular disease and increased progressively with the number of autoimmune diseases present (one disease: HR 1·41 [95% CI 1·37–1·45]; two diseases: 2·63 [2·49–2·78]); three or more diseases: 3·79 [3·36–4·27]), and in younger age groups (age <45 years: 2·33 [2·16–2·51]; 55–64 years: 1·76 [1·67–1·85]; ≥75 years: 1·30 [1·24–1·36]). Among autoimmune diseases, systemic sclerosis (3·59 [2·81–4·59]), Addison’s disease (2·83 [1·96–4·09]), systemic lupus erythematosus (2·82 [2·38–3·33]), and type 1 diabetes (2·36 [2·21–2·52]) had the highest overall cardiovascular risk.”

“These findings warrant targeted cardiovascular prevention measures, in particular in younger patients with autoimmune diseases, and further research into pathophysiological mechanisms underlying these complications.”

Excess cardiovascular risk seen across cardiovascular disease spectrum

In the research paper, the authors showed that the group of nineteen autoimmune disorders they 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.

Also, 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 results showed that action is needed, pointed out Nathalie Conrad, PhD, lead author of the study and an epidemiologist at KU Leuven. “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,” she said.

Conrad mentions the European Society of Cardiology guidelines on the prevention of cardiovascular diseases, which don’t yet mention autoimmunity as a cardiovascular risk factor (the guidelines only mention some specific disorders, like lupus) nor do they list any specific prevention measures for patients with autoimmune disease.

Conrad hopes 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,” she continued. “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.”

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