Having rheumatoid arthritis (RA) is bad enough, what with the severe joint pain and swelling that it can bring.

But to make matters worse, having RA increases the risk of heart disease by 50 percent.

Scientists are trying to get to the bottom of this connection. One theory is that RA patients tend to have high levels of an amino acid known as homocysteine in their blood. Studies have linked high homocysteine levels to a higher risk of cardiovascular (CV) disease.

Now, a team of Spanish researchers has taken a deep look into the molecular profile of RA patients to see who carries the highest risk and why…

Drawing a molecular map

A first-of-its-kind study led by the University of Córdoba (UCO), the Maimonides Institute for Biomedical Research (IMIBIC) and the Rheumatology Department at the Reina Sofía University Hospital in Córdoba (HURS) has managed to establish the molecular profile of those patients with rheumatoid arthritis who have a higher risk of suffering cardiovascular (CV) events.

They analyzed 45 healthy donors and 387 RA patients (including 208 RA patients with established disease but without previous CV events). Their analysis established three different groups of patients with diverse inflammatory, oxidative and netotic profiles.

RA patients without CV events but highest CV risk showed inflammatory profiles akin to those with prior CV events. Those with the highest inflammatory profile were linked to a significant CV-risk score and a greater presence of atherosclerosis.

The authors suggest that CV risk in RA results from the activation of neutrophils, monocytes, and endothelial cells. Additionally, they stated that alterations in the composition and function of lipoproteins, increased oxidative stress and endothelial dysfunction play significant roles in connecting RA and CVD.

Interestingly treatment with either TNFi, IL6Ri, and JAKi for six months restores normal inflammatory biomolecule levels, cutting-RA-related CV-risk.

“We have been able to demonstrate that molecular analyses are able to stratify patients who have a particular clinical behavior, such as an increased cardiovascular risk,” says Carlos Pérez-Sánchez, Ramón y Cajal researcher and member of the Department of Cell Biology, Physiology and Immunology at the University of Córdoba.

“That we have been able to characterize this is an important result which, if validated, will allow the analysis of certain molecules to yield information about the likelihood of suffering a heart problem,” he adds.

Reducing the heart danger of RA

These results could lead to personalized medical treatments made possible in the future through blood tests to identify RA patients who have different characteristics and levels of risk.

However, the involvement of immune cells and inflammatory molecules is no surprise.

Not only are these two factors part of the RA disease profile, but activated immune cells and inflammation can contribute to heart attack even in people without RA.

RA is a serious condition that usually requires a specialist to help manage — one who is hopefully aware of the importance of avoiding low folate levels.

This B vitamin has a known homocysteine-lowering effect. One study found that RA patients with the lowest levels of folate (below 4.3 nanograms per milliliter) had a 50 percent higher risk of dying from heart or blood vessel disease than patients with higher folate levels.

Antirheumatic drugs used to treat RA, like methotrexate, can deplete folate levels.

Specific foods have also been recommended by some researchers for lowering inflammatory cytokines and reducing joint stiffness and pain in people with RA. Many of the fruits on their list, particularly berries and pomegranate, can combat oxidative stress.

Exercise may not be easy for those with RA, but one form that isn’t hard on the body is Tai Chi.

According to the authors of a study that featured elderly women with RA, “Tai Chi exercise in elderly women with RA significantly improves endothelial dysfunction and arterial stiffness, which are known atherosclerosis precursors, useful indexes for early detection of CVD, and predictors for increased cardiovascular mortality.”

Sources:

The molecular profile of Rheumatoid Arthritis patients at increased cardiovascular risk is identified — EurekAlert!

Molecular Profile for Cardiovascular Risk in Rheumatoid Arthritis — RheumNow

Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs — Biomedicine & Pharmacotherapy