Lipoprotein (a), Inflammation, and Atherosclerosis

Abstract

Growing evidence has shown that high levels of lipoprotein (a) (Lp(a)) and chronic inflammation may be responsible for the residual risk of cardiovascular events in patients managed with an optimal evidence-based approach. Clinical studies have demonstrated a correlation between higher Lp(a) levels and several atherosclerotic diseases including ischemic heart disease, stroke, and degenerative calcific aortic stenosis. The threshold value of Lp(a) serum concentrations associated with a significantly increased cardiovascular risk is >125 nmol/L (50 mg/dL). Current available lipid-lowering drugs have modest-to-no impact on Lp(a) levels. Chronic inflammation is a further condition potentially implicated in residual cardiovascular risk. Consistent evidence has shown an increased risk of cardiovascular events in patients with high sensitivity C reactive protein (>2 mg/dL), an inflammation biomarker. A number of anti-inflammatory drugs have been investigated in patients with or at risk of cardiovascular disease. Of these, canakinumab and colchicine have been found to be associated with cardiovascular risk reduction. Ongoing research aimed at improving risk stratification on the basis of Lp(a) and vessel inflammation assessment may help refine patient management. Furthermore, the identification of these conditions as cardiovascular risk factors has led to increased investigation into diagnostic and therapeutic strategies targeting them in order to reduce atherosclerotic cardiovascular disease burden.

Keywords: cardiovascular prevention; colchicine; inflammation; lipoprotein (a); personalized medicine.

Figure 1

The potential impact of lipoprotein(a) (Lp(a)) on atherosclerotic and thrombotic processes. The figure represents the main hypothetic mechanisms involved in the pathogenesis of atherosclerosis and thrombosis in patients with higher Lp(a) serum concentrations. Apo(a): apolipoprotein(a); CD: cluster of differentiation; cGMP: guanosine 3′,5′-cyclic monophosphate; ICAM-1: intercellular adhesion molecule-1; KIV: kringle IV; KV: kringle V; LDL: low density lipoprotein; MCP-1: monocyte chemoattractant protein-1; NFkB: nuclear factor kB; OxPLs: oxidized phospholipids; PFKFB-3: 6-phophofructo-2-kinase/fructose-2,6-biphosphatase enzyme; SMC: smooth muscle cell; TFPI: tissue factor pathway inhibitor; TGF-β: transforming growth factor-beta; tPA: tissue plasminogen activator.

Figure 2

Impact of lipid-lowering treatments on Lp(a) serum concentrations.

Figure 3

Biomarkers and imaging techniques for estimation of residual inflammatory risk in patients with cardiovascular disease. CCTA: Coronary computed tomography angiography; CT: computed tomography; Lp(a): Lipoprotein(a); IL-6 Interleukin-6; IL-1b: Interleukin-1b; LDL: Low-density lipoprotein; MR, magnetic resonance; PET, positron emission tomography; VEGF: Vascular endothelial growth factor; PON-1: Paraoxonase-1.