People with chronic immune-mediated inflammatory diseases (IMIDs) like rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus are also at a higher risk of cardiovascular disease (CVD). A new study from the European League Against Rheumatism is dedicated to uncovering the genetic mechanisms for this connection.
IMIDs like rheumatoid arthritis develop when the immune system mistakenly attacks healthy cells as if they were foreign invaders like bacteria or viruses. This “accidental” inflammatory response worsens existing cases of atherosclerosis, a precursor to heart disease that involves an aggregation of compounds like immune cells in the blood vessels that block blood flow. The new study, published in Annals of Rheumatic Diseases, is for researchers to explain further why people with IMIDs are more likely to experience adverse cardiac events.
"At this stage, our results are of significance to better understanding the disease process. However, they could also have clinical implications, since some of the associated biological pathways are targeted by current IMID therapies,” explained lead author Dr. Antonio Julia. “Gaining a better understanding of the genetic mechanisms underlying CVD risk in these patients could be fundamental to the development of more efficient preventive and treatment strategies."
Julia and a team of researchers conducted an experiment called “cross-phenotype genome-wide meta-analysis” to explore a wide variety of genetic patterns connected to CVD risk in people with different chronic IMIDs. Specific places on chromosomes, called loci, have already been linked to CVD risk in the context of IMID, 17 to be exact. The recent experiment zeroed in on four distinct loci especially connected to multiple types of chronic IMID.
Of the four loci, researchers looked even closer and identified ten genetic patterns significantly associated with CVD and chronic IMID. Of those ten patterns, two were found to have a highly significant association with CVD in chronic IMIDs, specifically rheumatoid arthritis (RA), psoriatic arthritis (PA), and systemic lupus erythematosus (SLE).
Further functional analyses uncovered vital cytokine pathways associated with the loci of interest as a mechanism of RA development. Researchers also completed gene profiling on over six thousand people with one of six chronic IMIDs: RA, PA, SLE, psoriasis, Crohn’s disease, and ulcerative colitis.
"Our research findings help explain the higher prevalence of cardiovascular events observed in chronic IMID patients compared to the general population,” Julia concluded.