Lipoprotein (a): structure, pathophysiology and clinical implications

Area of Science:

• Cardiovascular Medicine
• Lipid Metabolism
• Atherosclerosis Research

Background:

• Lipoprotein (a) [Lp(a)] is structurally similar to LDL, with apolipoprotein (a) linked to apo B100.
• Elevated Lp(a) plasma concentrations (>20-30 mg/dL) are linked to a doubled risk of coronary artery disease (CAD).
• Lp(a) exhibits homology with plasminogen, suggesting interference with fibrinolysis and potential atherogenic mechanisms.

Purpose of the Study:

• To review the role of lipoprotein (a) in atherosclerosis.
• To discuss Lp(a) measurement, risk factors, and potential therapeutic interventions.
• To highlight the clinical implications of Lp(a) levels in cardiovascular disease prevention.

Main Methods:

• Literature review of prospective studies and clinical trials.
• Analysis of Lp(a) structure, synthesis, and catabolism.
• Examination of Lp(a) association with atherosclerosis and response to treatments like statins, niacin, and ezetimibe.

Main Results:

• Lp(a) levels vary significantly, with higher levels common in Black subjects, though the CAD association differs across ethnicities.
• Mechanisms of Lp(a)-induced atherosclerosis include fibrinolytic interference and direct arterial wall deposition, with Lp(a) being more prone to oxidation than LDL.
• Statin therapy does not reduce Lp(a) levels, whereas niacin and ezetimibe show potential, though ezetimibe's efficacy requires further confirmation.

Conclusions:

• Prospective studies confirm Lp(a) as a predisposing factor for atherosclerosis.
• Current evidence does not demonstrate that reducing Lp(a) concentrations lowers CAD risk.
• In cases of high Lp(a), intensified management of other CAD risk factors is recommended in the absence of proven therapies.