Effect of lipid-lowering medications on oxidized phospholipids in individuals with elevated LIPOPROTEIN(a)

Oxidized phospholipids (OxPLs) can bound to apolipoprotein B-100 (OxPL-apoB) and apolipoprotein(a) [OxPL-apo(a)] or be present freely within the phospholipid shell of apoB-containing lipoproteins. Oxidized phospholipids (OxPLs) are bound to apolipoprotein B-100 (OxPL-apoB) and apolipoprotein(a) [OxPL-apo(a)] and are present freely within the phospholipid shell of apoB-containing lipoproteins. OxPLs have been linked with the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPLs carried on plasminogen (OxPL-PLG) may extend the time to fibrinolysis. To evaluate the effect of lipid-lowering medications on OxPLs levels in individuals with elevated Lp(a) concentrations. In this prospective study, patients (n=70) with Lp(a) levels ≥75 nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n=28), ezetimibe added to high-intensity statin (n=31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n=11). Follow-up duration was 3 months. Patients had a mean age of 51±15 years, 40% were male, 39% were diagnosed with familial hypercholesterolemia, 16% had atherosclerotic cardiovascular disease, and 36%, 33% and 15% were at very high, high, and moderate cardiovascular risk, respectively. Lp(a) levels did not change significantly with high-intensity statin and add-on ezetimibe but significantly decreased with add-on PCSK9i treatment. OxPL-apoB and OxPL-apo(a) significantly increased, while OxPL-PLG significantly decreased with both high-intensity statin and add-on ezetimibe. Add-on PCSK9i treatment was associated with no significant changes in OxPL-apoB, OxPL-apo(a) and OxPL-PLG levels. Among patients with elevated Lp(a), both high-intensity statin and add-on ezetimibe significantly increased OxPL-apoB and OxPL-apo(a) levels, while significantly decreased OxPL-PLG levels. Add-on PCSK9i had no significant effect on OxPLs levels. The clinical implications of these findings should be further explored. A prospective study including 70 adult patients with Lp(a) levels ≥75 nmol/L and dyslipidemia. Patients were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n=28), ezetimibe added to high-intensity statin (n=31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n=11). Lipoprotein(a) [Lp(a)], oxidized phospholipids (OxPLs) associated with apolipoprotein B-100 (OxPL-apoB), OxPLs associated with apolipoprotein(a) [OxPL-apo(a)], plasminogen (PLG) and OxPLs associated with PLG (OxPL-PLG) were measured at baseline and 3 months after the intervention. Lp(a) levels did not significantly change with high-intensity statin and add-on ezetimibe but significantly decreased with PCSK9i treatment. OxPL-apoB and OxPL-apo(a) significantly increased, while OxPL-PLG significantly decreased with both high-intensity statin and add-on ezetimibe. PCSK9i treatment was associated with no significant change on OxPL-apoB, OxPL-apo(a) and OxPL-PLG levels. • Prospective study including patients with Lp(a) ≥75 nmol/L and dyslipidemia. • In naïve patients receiving high-intensity statins, OxPL-apoB and OxPL-apo(a) levels increased, while OxPL-PLG decreased. • The same observations were noted in patients receiving ezetimibe as add-on to high-intensity statins. • In patients receiving add-on PCSK9i to high-intensity statin plus ezetimibe, a significant decline was noted in Lp(a). • In patients receiving add-on PCSK9i to high-intensity statin plus ezetimibe, no significant changes were noted in any OxPL.