Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein...

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Medical Imaging

Background:

• Elevated lipoprotein(a) [Lp(a)] is linked to increased arterial inflammation and cardiovascular risk.
• Lipid-lowering therapies like statins and lipoprotein apheresis can reduce arterial inflammation in high-risk patients.
• The effect of lipid-lowering treatments on arterial inflammation in individuals with elevated Lp(a) remains unclear.

Purpose of the Study:

• To investigate if evolocumab, a drug that reduces both LDL-C and Lp(a), can attenuate arterial wall inflammation in patients with elevated Lp(a).

Main Methods:

• A multicentre, randomized, double-blind, placebo-controlled study involving 129 patients with elevated Lp(a).
• Patients received monthly subcutaneous evolocumab (420 mg) or placebo for 16 weeks.
• Arterial wall inflammation was assessed using 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) by measuring the most diseased segment target-to-background ratio (MDS TBR).

Main Results:

• Evolocumab significantly reduced LDL-C by 60.7% and Lp(a) by 13.9% compared to placebo.
• Despite treatment, mean LDL-C levels decreased from 3.7 to 1.6 mmol/L, and median Lp(a) levels remained elevated (baseline 200.0 nmol/L, Week 16: 188.0 nmol/L).
• No significant alteration in index vessel MDS TBR was observed between the evolocumab and placebo groups (P=0.18).

Conclusions:

• Evolocumab effectively lowers LDL-C and modestly reduces Lp(a) in patients with elevated Lp(a).
• The persistent elevation of Lp(a) levels post-treatment may have prevented a reduction in arterial wall inflammation.
• Further research is needed to understand the long-term impact of Lp(a) reduction on cardiovascular outcomes.