High triglycerides and low high-density lipoprotein cholesterol lipid profile in rheumatoid arthritis: A potential link among inflammation, oxidative status, and dysfunctional high-density lipoprotein

BACKGROUND: The interactions between inflammation and lipid profile in rheumatoid arthritis (RA) are poorly understood. The lipid profile study in RA has been biased toward lipoprotein levels, whereas those of triglycerides (TGs) and lipoprotein functionality have been underestimated. OBJECTIVES: Since recent findings suggest a role for TG and TG-rich lipoproteins (TRL) on inflammation, we aimed to evaluate a combined lipid profile characterized by high TG and low high-density lipoprotein cholesterol levels (TG(high)HDL(low)) in RA. METHODS: Lipid profiles were analyzed in 113 RA patients, 113 healthy controls, and 27 dyslipemic subjects. Levels of inflammatory mediators, paraoxonase-1 (PON1) activity, and total antioxidant capacity were quantified in serum. PON1-rs662 status was evaluated by real-time polymerase chain reaction. RESULTS: The TG(high)HDL(low) profile was detected in 29/113 RA patients. Although no differences in prevalence compared with healthy controls or dyslipemic subjects were observed, this profile was associated with increased tumor necrosis factor alpha (P = .004), monocyte chemotactic protein (P = .004), interferongamma inducible protein-10 (P = .018), and leptin (P < .001) serum levels in RA, where decreased PON1 activity and total antioxidant capacity were found. TG(high)HDL(low)' prevalence was lower among anti-TNF alpha treated patients (P =.004). When RA patients were stratified by PON1-rs662 status, these associations remained in the low-activity genotype (QQ). Finally, a poor clinical response on TNF alpha blockade was related to an increasing prevalence of the TGIughHDLI' profile over treatment (P = .021) and higher TRL levels at baseline (P = .042). CONCLUSIONS: The TGI(high)HDL(low) profile is associated with systemic inflammation, decreased PON1 activity, and poor clinical outcome on TNFa blockade in RA, suggesting a role of TRL and HDL dysfunction as the missing link between inflammation and lipid profile. (C) 2017 National Lipid Association. All rights reserved.