Lower serum folate level linked to increased CV mortality risk in RA
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Serum folate levels between 4.3 ng/mL and 8.2 ng/mL and greater were associated with a lower cardiovascular mortality risk among patients with rheumatoid arthritis, according to data published in JAMA Network Open.
“Folate deficiency is common among patients with autoimmune diseases, including RA, and it is also a well-documented adverse effect of the disease-modifying antirheumatic drug, methotrexate,” Kalyani Sonawane, PhD, of The University of Texas Health Science Center at Houston, and colleagues wrote. “To counteract reduced folate levels, folate supplements are recommended to patients with RA.”
“Among patients with RA, an inverse association between serum folate level and homocysteine has been reported,” they added. “However, to our knowledge, no published study has examined the association of serum folate levels with long-term CV outcomes.”
To examine the link between serum folate level and cardiovascular mortality risk among patients with RA, the researchers conducted a cohort study of the 1988-1994 National Health and Nutrition Examination Survey (NHANES III) and the 2011 Linked Mortality File. They reported that the NHANES III included data on 33,994 U.S. residents aged 2 months or older. The 2011 National Center for Health Statistics Linked Mortality File comprised NHANES III participants from the date of survey participation until death or Dec. 31, 2011, including information on cause of death.
The study included 683 adults with self-reported physician-diagnosed RA. Sonawane and colleagues grouped participants into tertiles based on serum folate levels, with tertile 1 defined as less than 4.3 ng/mL, tertile 2 as 4.3 ng/mL to 8.2 ng/mL, and tertile 3 as greater than 8.2 ng/mL. Tertile 1 consisted of 239 participants, tertile 2 had 234 participants and tertile 3 had 210 participants.
The researchers calculated all-cause and cardiovascular mortality risk using Cox proportional hazards models, adjusted for the complex survey design as well as demographic characteristics, BMI, C-reactive protein level, smoking, RA medication use and comorbid conditions.
The data showed there were 392 all-cause and 258 cardiovascular deaths during a median follow-up of 17.4 years. Compared with tertile 1, individuals in tertile 2 demonstrated lower all-cause mortality risk (HR = 0.63; 95% CI, 0.47-0.85). Additionally, risk for cardiovascular mortality was lower in tertile 2 (HR = 0.52; 95% CI, 0.3-0.92) and tertile 3 (HR = 0.44; 95% CI, 0.26-0.75) compared with tertile 1 (P =.01).
In a sensitivity analysis that estimated 10-year risk, findings for cardiovascular mortality were consistent. 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) demonstrated lower cardiovascular mortality risk compared with those in tertile 1 (P=.04).
“Our findings suggest that serum folate level is associated with CV mortality risk among patients with RA and might be a useful indicator for assessing patient risk in clinical practice,” Sonawane and colleagues wrote. “Additionally, if a causal link is validated in future clinical studies, folate supplementation can be an inexpensive strategy for reducing CV mortality risk in patients with RA.” – by Jason Laday
Disclosure: Sonawane reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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