medwireNews: Higher serum folate levels in patients with rheumatoid arthritis (RA) are associated with a reduced risk for cardiovascular (CV) mortality, researchers report.
They therefore believe that serum folate levels “might be a useful indicator for assessing patient risk in clinical practice.”
Kalyani Sonawane (The University of Texas Health Science Center at Houston, USA) and co-investigators propose that the association between elevated folate levels and a reduced risk for CV death may be partly explained by the homocysteine-lowering effects of folate. High levels of homocysteine – a known CV risk factor – can occur in RA patients as a result of chronic systemic inflammation, they note.
The cohort study included data from 683 individuals with self-reported diagnosis of RA, taken from the third National Health and Nutrition Examination Survey from 1988 to 1994 and the linked mortality data from 2011. Participants were divided into tertiles depending on whether their serum folate levels were below 4.3 ng/mL, between 4.3 and 8.2 ng/mL, or greater than 8.2 ng/mL.
The researchers caution, however, that “[t]he folate status of patients was based on a single serum folate concentration measurement that may not accurately represent long-term folate levels.”
Of the 650 deaths that occurred during the median 17.4 years of follow-up, 258 were CV-related with the lowest risk for CV mortality observed in the 444 patients with folate levels above 4.3 ng/mL.
Indeed, patients with the highest folate levels – greater than 8.2 ng/mL – had the lowest CV mortality risk and were 56% less likely to die from CV-related causes than those with folate levels below 4.3 ng/mL, while patients with folate levels between 4.3 and 8.2 ng/mL were 48% less likely.
Sensitivity analysis, restricting follow-up to 10 years, revealed consistent findings, with the CV mortality risk lowest among patients in the top two tertiles; however, the greatest reduction in risk, compared with patients in tertile 1, was seen among those with folate levels between 4.3 and 8.2 ng/mL rather than above 8.2 ng/mL.
Further subgroup analyses in patients with RA but no CV disease or diabetes at baseline similarly showed that patients with folate levels between 4.3 and 8.2 ng/mL had the lowest CV mortality risk, followed closely by those with levels exceeding 8.2 ng/mL.
Therefore, these “findings suggest that serum folate levels are associated with CV risk among patients with RA regardless of existing diabetes and CV [disease],” say Sonawane and team in JAMA Network Open.
They acknowledge, however, that “[t]he observational nature of the data precludes causal interference,” and add that “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.”
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