The angiopoietin-like protein 4, apolipoprotein C3, and lipoprotein lipase axis is disrupted in patients with rheumatoid arthritis

Abstract

Background Modulators of triglyceride metabolism include lipoprotein lipase (LPL), angiopoietin-like protein 4 (ANGPTL4), and apolipoprotein C-3 (ApoC3). There is evidence on the influence of this triangle of molecules on an increased risk of atherosclerotic cardiovascular disease (CV) in the general population. Patients with rheumatoid arthritis (RA) present changes in lipid profiles and accelerated CV disease. In the present study, we set out to study whether the ANGPTL4, ApoC3, and LPL axis differs in subjects with RA compared to controls. In a further step, we investigated the relationship of this axis with subclinical atherosclerosis in patients with RA. Methods Cross-sectional study that included 569 individuals, 323 patients with RA and 246 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in RA patients. A multivariable analysis was performed to assess whether the ANGPTL4, ApoC3, and LPL axis was altered in RA and to study its relationship with RA dyslipidemia and subclinical carotid atherosclerosis. Results Most lipid profile molecules did not differ between patients and controls. Despite this, and after fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with RA showed higher serum levels of ANGPTL4 (beta coef. 295 [95% CI 213–376] ng/ml, p<0.001) and ApoC3 (beta coef. 2.9 [95% CI 1.7–4.0] mg/dl, p<0.001), but lower circulating LPL (beta coef. −174 [95% CI −213 to −135] ng/ml, p<0.001). ANGPTL4 serum levels were positively and independently associated with a higher cIMT in patients with RA after fully multivariable adjustment. Conclusion The axis consisting in ANGPTL4, ApoC3, and LPL is disrupted in patients with RA. ANGPTL4 serum levels are positively and independently associated with a higher cIMT in RA patients.

Tocilizumab‐related hypertriglyceridemia is independent of key molecules regulating lipid metabolism

“…In a previous work of our group, patients with RA showed higher serum levels of ANGPTL4 and ApoC3, but lower circulating LPL, compared with controls 12 . These differences in serum levels were of at least a 20% between populations.…”

“…In RA patients, increased triglyceride levels, as well as their relationships to atherosclerosis and cardiovascular events, have been reported 11 . Moreover, the axis consisting of ANGPTL4, ApoC‐III and LPL has been found to be disrupted in patients with RA 12 . In this report, patients with RA showed higher serum levels of ANGPTL4 and ApoC‐III, but lower circulating LPL, compared with controls.…”

Serum Levels of Lipoprotein Lipase Are Increased in Patients with Inflammatory Bowel Disease

“…We think that the disease, due to its inflammatory state, can lower the levels of apolipoprotein C-III and that, secondarily, in the absence of its inhibitor, it would increase LPL. In addition, we have previously studied LPL in RA [ 20 ]. In 323 patients with RA and 246 age-matched controls, after a multivariable analysis including cardiovascular risk factors, statin use, and lipid profile changes caused by the disease itself, RA patients showed lower circulating LPL levels [ 20 ].…”

“…In addition, we have previously studied LPL in RA [ 20 ]. In 323 patients with RA and 246 age-matched controls, after a multivariable analysis including cardiovascular risk factors, statin use, and lipid profile changes caused by the disease itself, RA patients showed lower circulating LPL levels [ 20 ]. This report supports the fact that LPL may be disrupted in inflammatory diseases.…”

Effect of Proinflammatory Cytokines and Adipokines on the Severity of Atherosclerotic Changes of the Brachiocephalic Arteries in Rheumatoid Arthritis Patients

“…de Armas-Rillo и соавт., у пациентов с РА АППБ4 может оказывать большее влияние именно на ТИМ, чем на развитие бляшек, представляющих собой более позднюю стадию атерогенеза [10].…”