Proteins & Nucleic Acids

NMR Delves into Details of Lipid Paradox Seen in Rheumatoid Arthritis

In recent years, the term lipid paradox has emerged for a phenomenon seen in rheumatoid arthritis (RA), where patients are at an increased risk of cardiovascular disease (CVD), despite often having healthy lipid profiles that would usually suggest a reduced CVD risk.

CVD is the leading cause of death in this patient group, yet the RA lipid profile is often characterized by reduced levels of total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol – the opposite of what’s expected when people are at a high CVD risk.

In attempts to understand this paradox, researchers have previously used nuclear magnetic resonance (NMR) to measure lipoprotein particles in RA. They have found that RA patients have reduced levels of small HDL and small LDL particles, compared with controls. In addition, NMR studies have demonstrated an inverse relationship between small HDL particles and increased disease activity in RA patients.

Researchers at Duke University set out to learn more and used NMR to augment traditional approaches. They examined which blood parameters of inflammation, disease activity and cardiometabolic risk had the biggest impact on the RA lipid profile.

Led by Kim Huffman at the Duke School of Medicine in North Carolina, the researchers used a traditional approach complemented by NMR profiling to study lipoproteins in blood samples from 50 RA patients and 39 BMI-matched controls. Using a Bruker 400 MHz NMR, the researchers analyzed the size of lipoprotein particles in the samples.

They found that their results broadly reflected previous findings, with RA patients having lower levels of total and smaller LDL particles, compared with controls, as well as larger LDL and HDL particle sizes. For both LDL and HDL, trends existed towards lower concentrations of small particles and/or higher concentrations of large particles.

The team then looked at whether any of these NMR-measured lipoprotein parameters correlated with factors relating to inflammation, physical activity and classic cardiometabolic risk factors.

As reported in Lipids, Health and Disease, the most interesting finding was that minimal physical activity and less time spent exercising were associated with lower levels of small LDL particles and total and small HDL particles.

Minimally active patients were more likely to have an unfavorable HDL profile, including fewer small HDL particles, fewer total HDL particles, more large HDL particles and an increased mean HDL size. More exercise time, on the other hand, was linked to trends towards a more favorable HDL profile, with increases in the level of small HDL particles, decreases in the level of large HDL particles and a decreased mean HDL size.

Huffman and team noted that, while HDL profiles were associated with pain and disability, they were not linked to the concentration of inflammatory cytokines, suggesting that the HDL profile seen in RA is not mediated by inflammation, but instead points to a role for exercise and physical activity.

Future RA research should investigate whether implementing physical activity interventions when disease activity increases could have a beneficial effect on lipid profiles and cardiometabolic health, the authors conclude.


AbouAssi H, Connelly MA, Bateman LA, et al. Does a lack of physical activity explain the rheumatoid arthritis lipid profile? Lipids in Health and Disease 2017; 16: 39.

Choy E, Ganeshalingam K, Grete Semb A, et al. Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment. Rheumatology 2014; 53: 2143-2154.

Liao KP, Liu J, Lu B, et al. Association between lipid levels and major adverse cardiovascular events in rheumatoid arthritis compared to non-rheumatoid arthritis patients. Arthritis & Rheumatology 2015; doi: 10.1002/art.39165.

Myasoedova E, Crowson CS, Maradit Kremers H, et al. Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Annals of Rheumatic Disease 2011; 70: 482-487.