The Lipid Paradox: Why Are RA Patients with Low Cholesterol at Risk for CVD?


Research from UNC may bring medicine closer to understanding the conundrum.

Rheumatoid Arthritis (RA) patients tend to have lower total cholesterol levels and a higher risk for heart disease. Known as the Lipid Paradox, the conundrum may be closer to a solution thanks to the work of North Carolina researchers. Their recent study suggested that a lack of physical exercise is the explanation for this contradiction to common wisdom about fat and the risks for heart disease.

“We identified intriguing associations for basal or minimal physical activity and exercise time with lipoprotein parameters suggestive that a large part of the RA lipid profile is mediated by a lack of physical of activity,” Kim M. Huffman MD, PhD and her colleagues wrote. Huffman (pictured) is an associate professor of medicine at Duke University School of Medicine’s Molecular Physiology Institute. Other co-authors were from Duke, the University of North Carolina at Chapel Hill and LabCorp-Raleigh.

The fewer total particles of HDL, the “good cholesterol”, and less small-particle HDL also was associated with RA patients with low amounts of exercise, the study said. “To our knowledge, this is the first report” suggesting such an association, the study added. “Further, fewer small HDL concentrations were associated with pain and disability.”

Patients who were more active were more likely to have less “typical inflammatory dyslipidemia than is observed in RA patients. These lipoprotein changes may be mediated by anti-inflammatory effects of exercise,” the study said. Positive changes in lipoproteins also were associated with treatment with RA medications such as TNF-alpha agents and IL-6 receptor antagonists. “Concomitant HDL function improvements suggest these shifts are atheroprotective,” the study added.

People with RA have a two to three times increased risk of heart disease, the study noted. Their risk factors included inflammation, overweight, metabolic syndrome and type2 diabetes. However, their lipid profile is the opposite of the one typically seen in people with an elevated risk, the study noted. The authors hypothesized that “the changes observed in the ‘lipid paradox’ are less related to metabolic syndrome risk factors and more related to a lack of physical activity as a result of increased disease activity pain and inflammation.”

The researchers reached these conclusions by measuring NMR lipoproteins in 50 RA patients and 39 matched controls along with 11 additional RA subjects. Relationships among RA patients and inactivity or exercise along with other variables, such as age and overweight, also were measured.

The study cautioned that because it was cross-sectional and small in size that it did not reach conclusions about causality. The results should be considered “preliminary and larger studies are needed to confirm these results,” the authors wrote. However, “These findings call for intervention studies in RA evaluating the impact of reduced sedentary time, in the setting of increased disability and pain, on lipoproteins and overall cardiometabolic health; they also call for research designed to understand the underlying mechanisms of these observed results.”

Does a lack of physical activity explain the rheumatoid arthritis lipid profile? was published in the February 10, 2017 issue of Lipids in Health and Disease.

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