Anemia Linked With Higher Risk of All-Cause, CVD-Related Mortality in Rheumatoid Arthritis

Having anemia puts patients with rheumatoid arthritis (RA) at higher risk of death, suggest findings of a new study. Published in Preventive Medicine Reports, the study revealed differences in all-cause mortality and cardiovascular disease (CVD)-related mortality, depending on the anemia subtype.1

The study, the researchers wrote, is the first to explore the mortality effects of different subtypes of anemia, a condition that has previously been shown to increase RA activity and structural joint damage.

The connection between anemia and mortality among patients with RA could likely be explained by inflammation, explained the researchers. | Image credit: Matthieu - stock.adobe.com

“Anemia is one of the most common extra-articular manifestations of rheumatoid arthritis, affecting approximately 30% to 70% of rheumatoid arthritis patients,” the researchers explained. “Anemia adversely impacts physical performance due to reduced oxygen transport capacity and diminished cellular oxidative metabolism, especially in the context of iron deficiency. Moreover, anemia has been shown to worsen outcomes in diseases such as heart failure and ischemic heart disease.”

The researchers used data from the National Health and Nutrition Examination Survey (NHANES)—an ongoing survey that collects health and nutritional information from people across the United States. The group analyzed data on patients with RA participating in the survey between 1999 to 2006 and 2017 to 2018. Due to the time gap in the 2 study periods, the researchers noted potential variability in findings due to changes in diagnostic criteria and treatment.

Among the more than 800 patients identified, those with iron deficiency anemia had a 2-fold risk of death from any cause (HR, 2.02; 95% CI, 1.37-2.96) while patients with non-iron deficiency anemia had a 2-fold risk of CVD-related death (HR, 2.07; 95% CI, 1.02-4.18).

Anemia overall was associated with an increased, albeit less pronounced, risk of death from any cause (HR, 1.64; 95% CI, 1.13-2.39) and from CVD-related death (HR, 1.76; 95% CI, 1.02-3.04). The researchers found no significant differences in mortality risk for patients with ferritin and transferrin saturation. However, the group noted that data on ferritin and transferrin saturation were limited in their data set.

The connection between anemia and mortality among patients with RA could likely be explained by inflammation, explained the researchers, noting that inflammation and anemia have been closely linked in patients with chronic conditions, as well as inflammation and comorbidities in RA.

“This persistent inflammatory state may exacerbate mortality risk patients with anemia, especially those with non–iron deficiency anemia, which is frequently induced by inflammation,” wrote the researchers, adding, “The interplay between inflammation, anemia, and comorbid conditions may exacerbate systemic burden and elevate mortality risk in this population.”

With inflammation as a key mediator in RA, research has explored approaches to reducing inflammation. In another analysis of data from NHANES, researchers found that hemoglobin had a protective effect against C-reactive protein, a marker of inflammation in the body. The findings suggest that regulating hemoglobin levels can help slow progression of RA.2

In the current study, overall, 37.91% of patients died throughout the study period and 12.79% died from CVD-related causes.1

"Subsequent studies are needed to investigate the underlying mechanisms by which different types of anemia influence mortality risk in patients with rheumatoid arthritis," the authors concluded.

References

1. Dong J, Yin X, Zhang X, Chen Z. Association between anemia and mortality in patients with rheumatoid arthritis: A retrospective cohort study of the National Health and nutrition examination survey (NHANES) database. Prev Med Rep. Published online April 12, 2025. doi:10.1016/j.pmedr.2025.103068

2. McCormick B. Hemoglobin may protect against inflammation from rheumatoid arthritis. AJMC®. March 20, 2025. Accessed May 29, 2025. https://www.ajmc.com/view/hemoglobin-may-protect-against-inflammation-from-rheumatoid-arthritis