Cardiovascular mortality higher in women with rheumatoid arthritis and lupus

Women with the autoimmune diseases rheumatoid arthritis, lupus or systemic sclerosis may have a higher rate of death related to cardiovascular disease than men with the autoimmune diseases, according to new research published in the American Heart Association's journal Circulation: Cardiovascular Quality and Outcomes.

According to the National Institute of Allergy and Infectious Diseases, an estimated 8% of the U.S. population – approximately 27 million people – have an autoimmune disease. Immune-mediated inflammatory diseases, such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, asthma, multiple sclerosis and systemic lupus erythematosus, also called lupus, are a broad subset of autoimmune diseases that involve chronic inflammation, which can contribute to cardiovascular disease. Additionally, previous research has found that after a heart attack, people with the immune-mediated inflammatory diseases lupus, rheumatoid arthritis, systemic sclerosis, dermatomyositis or psoriasis were more likely to die, develop heart failure or have a second heart attack in comparison to people without one of these autoimmune diseases.

Rheumatoid arthritis, lupus and systemic sclerosis are among the most common immune-mediated inflammatory diseases, the authors said. Women are two to three times more likely than men to have rheumatoid arthritis and approximately nine times more likely than men to have lupus, according to the U.S. Centers for Disease Control and Prevention. Systemic sclerosis, also called scleroderma, is a group of rare autoimmune diseases distinct from multiple sclerosis that involves the tightening and hardening of the skin, potentially affecting the digestive tract, blood vessels and internal organs. It is also more common among women than men, according to the CDC. However, understanding the differences between men and women in the rate of cardiovascular disease-related death linked to immune-mediated inflammatory diseases such as these remains relatively unexplored, the study authors noted.

Our study highlights the significant burden of cardiovascular disease in patients with immune-mediated inflammatory diseases, which disproportionately affect women. It is critical to screen for and address cardiovascular risk factors early, at the time of diagnosis and periodically thereafter."

Heba S. Wassif, M.D., M.P.H., senior study author, assistant professor at Lerner College of Medicine of Case Western Reserve University and director of cardio-rheumatology at Cleveland Clinic, both in Cleveland

Researchers analyzed data from the CDC WONDER database for more than 127,000 deaths related to cardiovascular disease among more than 281,000 deaths associated with rheumatoid arthritis, lupus or systemic sclerosis. The researchers evaluated trends and differences in the rates of cardiovascular disease-related death for men and women with the most common auto-immune conditions between 1999 and 2020.

The analysis found:

• The overall cardiovascular disease-related death rate in individuals with immune-mediated inflammatory diseases declined from 3.9 to 2.1 per 100,000 in women and from 1.7 to 1.2 per 100,000 in men between 1999 and 2020, indicating women continue to be at a higher risk of dying from cardiovascular disease despite the overall decline in deaths.
• Stroke and coronary artery disease were the main causes of cardiovascular disease-related deaths in patients with immune-mediated inflammatory diseases. Women died from both stroke and coronary artery disease at a higher rate than men did.
• Women with immune-mediated inflammatory diseases were more than two times more likely to die from irregular heart rhythm or cardiac arrest than the male participants.
• The risk of cardiovascular disease-related death varied across common immune-mediated inflammatory diseases. People with rheumatoid arthritis had the highest death rate – 1.8 deaths per 100,000 among women compared to 0.6 deaths per 100,000 among men throughout the entire study period. In comparison, the cardiovascular disease-related death rate for people with lupus was 0.2 deaths per 100,000 among women and 0.1 deaths per 100,000 in men. The cardiovascular disease-related death rate among participants with systemic sclerosis was too low to compare to the rate in men v. women.

"There is a common perception that people with immune-mediated inflammatory diseases primarily die from infections or kidney disease. However, our study revealed that one-third of deaths in this population were due to cardiovascular disease, highlighting the significant burden of heart disease in these patients," said lead study author Issam Motairek, M.D., an internal medicine resident at Cleveland Clinic."This study reinforces the need to investigate drivers of these disparities between women and men and how to improve treatment for patients with immune-mediated inflammatory diseases."

Study details and background:

• Researchers analyzed data for 127,149 cardiovascular-related deaths out of 281,355 deaths among adults with underlying immune-mediated inflammatory diseases in the U.S. between 1999 and 2020.
• The data was from the Multiple Cause of Death files within the CDC WONDER database (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research).
• Multiple Cause of Death data details the causes of death listed on death certificates for adults in the U.S.

The study's limitations include that the findings may underestimate or overestimate death rates due to potential cause-of-death coding misclassifications in the CDC records in this analysis. Additionally, the contribution of immune-mediated inflammatory diseases to cardiovascular disease may be underestimated because less-common autoimmune diseases were not included in the study. The study also did not include information for individual patients about other health conditions and treatment because this data is not available in the CDC WONDER database and could not be considered in the analysis.

"As we gain a deeper understanding of inflammation's role in cardiovascular disease, we must translate this knowledge into targeted prevention strategies to reduce cardiovascular disease-related deaths in women with immune-mediated inflammatory diseases," Wassif said. "Key questions remain about the underlying causes of these disparities between women and men, about which therapies could be most effective in reducing risk, and about our understanding of the nature of coronary artery disease in patients with immune-mediated inflammatory diseases. Future research is needed to help address these gaps and improve outcomes for this high-risk population."