TNF inhibitors exert a “hidden” beneficial effect in the cardiovascular lipoprotein profile of RA patients

Abstract

BACKGROUND: Higher cardiovascular risk has been largely described in rheumatoid arthritis as well as different effects of biologic agents in theses patients. The aim of present study is to analyze the effects of tumor necrosis factor inhibitors (TNFi) in the lipoprotein profile of rheumatoid arthritis (RA) patients using a broad laboratory assessment including a large number of no routine testsMETHODS: RA patients treated with and without TNFi were cross-sectionally compared regarding a broad spectrum of lipoprotein tests including serum levels of cholesterol, triglycerides, HDL, LDL and VLDL cholesterol, lipoprotein A (LpA), apolipoprotein A1 (Apo A) and B100 (Apo B), HDL, LDL and VLDL proteins, triglycerides and phospholipids, HDL Apo A, LDL and VLDL Apo B and paraoxonase 1 (PON 1), HDL, LDL and VLDL masses and number of particles of LDL and VLDL. Univariate and multivariate analyses of the different variables were performedRESULTS: Patients on treatment with TNFi showed a trend to be younger and had a longer disease duration. Regarding to the lipoprotein analyses, borderline significant higher levels of serum Apo A were detected and an independent association with lower HDL mass, LDL triglyceride, VLDL cholesterol, VLDL Apo B, VLDL mass, number of VLDL cholesterol molecules and number of particles of VLDL was clearly observed.CONCLUSIONS: TNFi treatment was associated with beneficial atherogenic effects at the lipoprotein level especially centered in VLDL related parameters consistent with a reduction of the remnant atherogenic risk.

Evaluation of dysfunctional high‐density lipoprotein levels with myeloperoxidase/paraoxonase‐1 ratio in rheumatoid arthritis

“…[24][25][26] HDL functions are also impaired as a result of cytokines such as TNFα increased in RA, causing HDL to become pro-atherogenic and proinflammatory. 22 As far as we know, in our study, dysfunctional HDL levels determined by measuring the MPO/PON1 ratio were shown in RA patients for the first time.…”

“…It has been reported that the levels of PON1 enzyme, which is the main antioxidant molecule of HDL, 22 can decrease in RA. 27 Similarly, in our study, it was observed that the PON1 activity was significantly lower in RA patients than the control group.…”

“…HDL, being the major antiatherogenic lipoprotein with its reverse cholesterol transport, 20 has anti‐inflammatory and antioxidative functions 21 . Antioxidant function of HDL molecules comes from the PON1 enzyme it contains 22 and HDL molecules protect LDL molecules from oxidation 23 . However, in the case of chronic inflammation, these protective functions of HDL deteriorate.…”