Study Examines Link Between Folate Levels and CV Risk in RA Patients

Maria Suarez-Almazor, MD, PhD

While mountains of data and research supports the notion that rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD) and mortality, new data from the University of Texas (UT) is revealing more about the potential underlying cause and how to address it.

A cohort study from an NHANES survey from 1998 and the 2011 Linked Mortality File examining serum folate levels in RA patients found those with serum folate levels greater than 4.3 ng/mL were at an increased risk of cardiovascular mortality than other RA patients—suggesting addressing levels might be a way to attenuate risk.

“Our findings suggest that serum folate level might be a useful indicator to assess cardiovascular mortality risk of a rheumatoid arthritis patient in clinical practice,” said study investigator Maria Suarez-Almazor, MD, PhD, Barnts Family Distinguished Professor at the UT MD Anderson Cancer Center, in a statement. “If future clinical studies validate a causal link, taking folate supplements could be an affordable way to reduce this risk in patients with rheumatoid arthritis.”

With RA patients 60% more likely to die from CVD and the knowledge that folic acid decreases levels of homocysteine, which is linked to an increase in developing CVD, investigators sought to assess how serum folate levels in patients might impact cardiovascular mortality risk. To do so, Suarez-Almazor and colleagues identified a cohort of 683 patients with RA from the National Health and Nutrition Examination Survey to examine possible associations using Cox proportional hazards models adjusted for characteristics including demographics, BMI, C-reactive protein level, smoking, RA, medication use, and comorbid conditions.

The mean age of the study cohort was 55.9 years, 225 of the 683 were men, and 87% were white. Individuals were divided into 3 tertiles based on folate levels—4.3 ng/mL (n=239), between 4.3-8.2 ng/mL (n=234), or greater than 8.2 ng/mL (n=210). During a follow-up period that lasted a mean of 17.4 years, a total of 392 all-cause and 258 cardiovascular deaths occurred.

When comparing tertile 1 (less than 4.3 ng/mL) to tertile 2, patients with increased serum folate levels had a lower all-cause mortality risk (HR 0.63; 95% CI, 0.47-0.85). The analyses also indicated the risk of cardiovascular morality among those in both tertile 2 (HR 0.52; 95% CI, 0.30-0.92) and tertile (HR, 0.44; 95% CI, 0.26-0.75)compared to individuals in tertile 1 (P for trend =.04).

Additionally, investigators noted findings for cardiovascular mortality were consistent in a sensitivity analysis aimed at estimating 10-year risk. Data from that analysis found patients in tertile 2 (HR 0.31; 95% CI, 0.17-0.57) and tertile 3 (HR 0.39; 95% CI, 0.22-0.69) had a lower cardiovascular mortality risk compared to individuals in tertile 1 (P for trend =.04).

“Our study is the first to show an association between serum folate and increased cardiovascular mortality in patients with rheumatoid arthritis,” said study investigator Kalyani Sonawane, PhD, an assistant professor at UTHealth School of Public Health. “It’s particularly important for patients taking disease-modifying anti-rheumatic drugs to understand this increased risk.”

This study, “Association of Serum Folate Levels With Cardiovascular Mortality Among Adults With Rheumatoid Arthritis,” was published in JAMA Network Open.