Improved RA Lipid Profile Associated with Decreased Inflammation

Patients with rheumatoid arthritis (RA) showed overall improvement in lipid profiles despite an increase in low-density lipoprotein (LDL) cholesterol levels when they experienced a decrease in inflammation, according to the results of a recent study [J Am Heart Assoc. 2015;4:e001588].

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“Heart disease is a leading cause of death in patients with [RA],” Katherine P. Liao, MD, MPH, Brigham and Women’s Hospital, said in an interview with First Report Managed Care. Compared with the general population, patients with RA have a 50% increased risk of cardiovascular disease. “While we know that inflammation plays an important role in the elevated risk for heart disease, the pathways linking inflammation with the development of heart disease remains unclear. [High-density lipoprotein cholesterol (HDL)] is also known as the ‘good cholesterol’ because it removes cholesterol from atherosclerotic plaques in blood vessels throughout the body. Previous studies have shown that this function of HDL, measured by HDL cholesterol efflux capacity, is an important predictor of heart disease and is impaired in RA patients.”   

Evidence thus far has indicated a reduction in inflammation in patients with RA is associated with a reduction in cardiovascular risk, despite increases in LDL cholesterol levels. Dr. Liao and colleagues conducted a prospective, observational, cohort study of 90 patients with RA who experienced a significant reduction in inflammation, as measured with high-sensitivity C-reactive protein (CRP).

The researchers ascertained changes in routine lipids, including total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B, apolipoprotein A1, and HDL cholesterol efflux capacity. They also sought to quantify the correlation between longitudinal changes in CRP with changes in those lipid parameters, hypothesizing that a reduction in CRP would equate to increases in LDL cholesterol and simultaneous improvements in HDL cholesterol efflux capacity.

Patients were eligible for study inclusion if they had a CRP reduction of ≥10 mg/L at 2 consecutive time points 1 year apart; patients were excluded if they received statins within 6 months of baseline blood collection and during the 1-year follow-up.

Patients had a median CRP at baseline of 28.6 mg/L and a mean disease activity score (DAS) 28 of 5, indicating moderate disease activity. All patients received at least 1 disease-modifying antirheumatic drug, with more than half (53%) receiving methotrexate or a tumor necrosis factor inhibitor (48%); 27% received a combination of the 2 at baseline.

Results at 1-year follow-up showed a median CRP of 4.3, which was an absolute reduction of 23.5 mg/L (P<.0001) and a mean reduction in DAS28-CRP of 1.6 (P<.0001). These results translated to an overall 85% reduction in CRP as well as a significant change in the DAS28-CRP (moderate-high to low disease activity).

The researchers also found a significant increase in LDL cholesterol by 7.2% (P=.02) and an improvement in HDL cholesterol efflux capacity of 5.7% (P=.002). Significant correlations between a reduction in CRP, increases in LDL cholesterol, HDL cholesterol, and apolipoprotein A1, and improvements in HDL cholesterol efflux capacity were observed. The associations observed in the study were not believed to be treatment related, as patients received a variety of RA therapies.

Limitations of the study included the measurement of lipids not being performed in a fasting state, although the variations between fasting and nonfasting states are not believed to be significant enough to affect the interpretation of cardiovascular risk, according to the authors.

“In our study, we found that HDL cholesterol efflux capacity improved significantly in RA patients who had a reduction in inflammation,” Dr. Liao concluded. “The greater the reduction in inflammation, the better the improvement in HDL function. This study highlights a potential pathway by which reducing inflammation can improve risk for heart disease in RA and potentially in non-RA patients.”—Mary Mihalovic