Relationship between Sustained Reductions in Plasma Lipid and Lipoprotein Concentrations with Apheresis and Plasma Levels and mRNA Expression of PTX3 and Plasma Levels of hsCRP in Patients with HyperLp(a)lipoproteinemia

Abstract

The effect of lipoprotein apheresis (Direct Adsorption of Lipids, DALI) (LA) on plasma levels of pentraxin 3 (PTX3), an inflammatory marker that reflects coronary plaque vulnerability, and expression of PTX3 mRNA was evaluated in patients with hyperLp(a)lipoproteinemia and angiographically defined atherosclerosis/coronary artery disease. Eleven patients, aged 55 ± 9.3 years (mean ± SD), were enrolled in the study. PTX3 soluble protein levels in plasma were unchanged by 2 sessions of LA; however, a downregulation of mRNA expression for PTX3 was observed, starting with the first session of LA (p < 0.001). The observed reduction was progressively increased in the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session. A statistically significantly greater treatment-effect correlation was observed in patients undergoing weekly treatments, compared with those undergoing treatment every 15 days. A progressive reduction in plasma levels of C-reactive protein was also seen from the first session of LA, with a statistically significant linear correlation for treatment-effect in the change in plasma levels of this established inflammatory marker (R 2 = 0.99; p < 0.001). Our findings suggest that LA has anti-inflammatory and endothelium protective effects beyond its well-established efficacy in lowering apoB100-containing lipoproteins.

From lipoprotein apheresis to proprotein convertase subtilisin/kexin type 9 inhibitors: Impact on low-density lipoprotein cholesterol and C-reactive protein levels in cardiovascular disease patients

“…In addition to lipoprotein levels, the effects of apheresis and PCSK9 inhibitors on pro-inflammatory markers were investigated. As previously described, 38 In this study, apheresis treatment significantly reduced the hsCRP levels by 60.8% (1.55 ± 1.21 vs 0.61 ± 0.32 mg/l). Conversely, six-month treatment with PCSK9 inhibitors did not alter hsCRP levels (1.55 ± 1.21 vs 2.12 ± 1.92 mg/l).…”

“…45 The measurement of plasma levels of hsCRP levels highlighted a third relevant difference in switching from apheresis to PCSK9 inhibitors. As previously shown, we observed a significant reduction of hsCRP levels in response to apheresis, 38 while the inhibition of PCSK9 did not change its plasma concentrations. Furthermore, our results are in agreement with a meta-analysis showing that PCSK9 inhibitors do not exert a significant effect on hsCRP.…”

Toward an international consensus—Integrating lipoprotein apheresis and new lipid-lowering drugs

“…37 Significant downregulation of messenger RNA encoding the endothelial damage marker pentraxin-3 was seen after the first LA session, while soluble plasma pentraxin-3 levels did not change, but high-sensitivity C-reactive protein levels did. 38 Recently, it was demonstrated that LA therapy also removes PCSK9 in patients with severe FH. 35,39 This was confirmed in a study of 40 patients, and the effect was found to extend to a range of LA types.…”

Long-term lipoprotein apheresis in the treatment of severe familial hypercholesterolemia refractory to high intensity statin therapy: Three year experience at a lipoprotein apheresis centre

“…All LA techniques have been shown to effectively reduce LDL-C along with Lp(a) concentrations by more than 60%, while being well tolerated in long-term application. LDL-apheresis treatment also exerts a pleiotropic effect, improving rheological properties of the blood and reducing inflammatory markers [16,17]. Regular apheresis sessions have been proved to slow the progression of atherosclerosis and reduce the incidence of cardiovascular events [12,[18][19][20].…”