Low Folate Levels Associated with Cardiovascular Death in RA

March 11, 2020

The risk of dying from a cardiovascular event can increase by 50 percent for rheumatoid arthritis patients with low serum folate levels, report researchers in JAMA Open Network.

The risk of dying from a cardiovascular event can increase by 50 percent for rheumatoid arthritis patients with low serum folate levels, report researchers in JAMA Open Network.

Conducted by a team at the University of Texas Health Science Center in Houston, researchers found that patients with serum folate levels less than 4.3 ng/mL, were at greater risk of dying from cardiovascular disease as compared to patients with levels of at least 4.3 ng/mL.

"It is unclear why higher folic acid concentrations would be associated with lower CV mortality risk among patients with RA. A possible explanation is that serum folate lowers CV risk through serum homocysteine reduction," wrote researchers who were led by Kalyani Sonawane, Ph.D., the University of Texas Health Science Center, Houston.

The findings confirm a series of published studies over the years that link a decrease in the protein amino acid homocysteine to cardiovascular disease.

Folate and homocysteine levels apparently have a mutual relationship. It has long been established that folate levels can decrease as homocysteine levels increase (largely due to an increase in meat consumption). In 2002, researchers writing in BMJ described strong evidence of a causal association between homocysteine and cardiovascular---a finding they described as "highly significant." They concluded that lowering homocysteine levels by 3 micromol/l by increasing folic acid intake, could reduce the risk of ischaemic heart disease by an average of 16 percent, deep vein thrombosis by an average of 25 percent, and stroke by an average of 24 percent in a general population of men and women.

The JAMA study is based on an analysis of the third National Health and Nutrition Examination Survey (1988-1994) and 2011 Linked Mortality File. The final analysis included 683 patients with RA (mean age, 55.9 uears, 30% men, 87% white). Of these, 239 (35%) had folate levels less than 4.3 ng/mL; 234 (34.3%) had folate level between 4.3-8.2 ng/mL; and, 210 (30.7%) had folate levels greater than 8.2 ng/mL. In this study, the average follow-up period was 17.4 years.

Patients with serum folate levels between 4.3 and 8.2 ng/mL had a 48 percent lower odds of dying from a cardiovascular event. Those with serum levels of greater than 8.2 ng/mL, had a 56 percent lower risk of dying from cardiovascular events. These findings were compared to those of patients with levels less than 4.3 ng/mL. Demographic characteristics, body mass index, C-reactive protein level, smoking, rheumatoid arthritis medication use, and comorbid conditions were accounted for in the calculations.