CV Death Rates in Autoimmune Disorders Waning, but Still Higher in Women

For people with some of the most common autoimmune diseases, cardiovascular disease-related mortality has declined over the last decade, but rates remain disproportionately higher among women than men, new data suggest.

In the analysis of 127,149 CVD-related deaths that occurred between 1999 and 2020, the sex disparities did show some narrowing, but women still had about a 50% higher risk. Looking strictly at those with rheumatoid arthritis, CV-related death rates were about three times higher in women compared with men.

According to senior author Heba S. Wassif, MD, MPH (Cleveland Clinic, OH), while there have been many epidemiologic and cohort studies assessing the CV impact of autoimmune diseases—which affect an estimated 27 million Americans—most have been limited to the rheumatology literature, and much of the evidence has been restricted to rheumatoid arthritis, specifically.

A seminal paper published in 1953 in the New England Journal of Medicine was among the first to bring recognition to the fact that patients with rheumatoid arthritis had different causes of death than patients without the disease, which included more valvular heart disease and pulmonary embolism, Wassif noted. At the time, study investigators called for further research into why these patients had different causes of death than the general population, but it has been slow to materialize.

“In the last 10 years or so, there’s been this evolution of cardio-rheumatology, which has brought more and broader interest to this area from cardiologists,” she said. “But when we talk about autoimmune disorders, it can become confusing. It’s a very vague term because it includes at least 80 different diseases.”

To TCTMD, Wassif said the declines in CV-related death in this paper should be seen as a positive trend that is likely the result of earlier diagnoses, advancements in biological therapies, and timely treatment of CV risk factors like hypertension and hyper­lipidemia.

Importance of Multidisciplinary Collaboration

For the study, published as a research letter this week in Circulation: Cardiovascular Quality and Outcomes, Wassif and colleagues, led by Issam Motairek, MD (Cleveland Clinic), used the CDC WONDER database to analyze CV death rates for three of the most common autoimmune diseases: rheumatoid arthritis, systemic lupus erythema­tosus, and systemic sclerosis.

Between 1999 and 2020, the CV-related death rate for patients with immune-mediated inflammatory diseases (IMIDs) declined from 3.9 to 2.1 per 100,000 in women and from 1.7 to 1.2 per 100,000 in men. Additionally, age-adjusted mortal­ity rates decreased from 3.3 to 1.4 per 100,000 in women and from 2.3 to 1.1 per 100,000 in men (P < 0.01 for all comparisons).

When the researchers looked at specific causes of CV-related death, the main contributors were ischemic heart disease and cerebrovascular dis­ease, both of which were higher in women. Women also had more than double the rate of death from arrhythmia and cardiac arrest than did men.

Of the three autoimmune diseases examined, rheumatoid arthritis was associated with the highest death rate, at 1.8 per 100,000 for women and 0.6 per 100,000 for men.

Wassif said the findings confirm suspicions about how these patients die and highlight the importance of primary care, rheumatology, and cardiology working together to intervene as early as possible in these patients.

“This tells us the importance of a multidisciplinary approach, and the rheumatology guidelines do recommend cardiovascular risk assessment,” she added. “The rheumatologist should start the ball rolling and make sure the patient gets to the cardiologist. I’ve seen patients who have had an event and they’ve said, ‘My rheumatologist didn’t think it was related to my autoimmune disease.’ That is not accurate. But the good thing is we are seeing more of these patients coming in where rheumatologists are asking that we do a cardiovascular risk assessment on them.”

While the study wasn’t designed to understand what is fueling the sex disparities with autoimmune disorders, Wassif and colleagues say the higher rate of arrhyth­mias and cardiac arrest in women may be related to systemic inflammation and sex hormones, though more research is needed.

“Estrogen prolongs the QT interval, predisposing to arrhythmias like torsades de pointes, while inflammatory cytokines exacer­bate myocardial electrical instability,” they write. “Addressing these risks requires increasing awareness of atypical cardiovascular symptoms in females with IMIDs, enhancing early detection through advanced imaging, and ensuring equitable access to therapies like biologics.”

To TCTMD, Wassif said highlighting the increased risk these patients have is half the battle.

“We need to look at these patients differently than we have in the past and try to fill some of these gaps in [understanding] who is at higher risk,” she added.