Lipoprotein(a) and Atrial Fibrillation: Mechanistic Insights and Therapeutic Approaches

Figures

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  Figure 1. Common risk factors for AF. Sex, age, genetics, history of underlying heart disease, particularly congestive HF and valvular disease, hypertension, obesity, diabetes, obstructive sleep apnea, smoking, vigorous exercise, sedentary lifestyle, smoking and alcohol have all been linked to the incidence of AF. AF, atrial fibrillation; HF, heart failure.

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  Figure 2. Adjusted models examining the associations between Lp(a) levels and AF in recent studies. Model a: Adjusted for age, sex, and ethnic groupings. Model b: Model a was extended by adding smoking status, systolic and diastolic blood pressure, hypertension therapy, heart rate, height, BMI, ECG left ventricular hypertrophy, PR interval, prevalent HF, CAD, and diabetes mellitus. Model c: Model b was further extended by adding LDL cholesterol, HDL cholesterol, triglycerides, lipid-lowering medication, and a log-transformed N-terminal pro-B-type natriuretic peptide. Model A: Adjusted for age, race, sex, education, income, and location. Model B: Model A was extended by adding height, BMI, smoking status, diabetes mellitus status, SBP, DBP, antihypertensive medication, physical activity, and alcohol intake. Model C further extended Model B by adding total cholesterol, HDL cholesterol, triglycerides, and lipid-lowering treatment. AF, atrial fibrillation; BMI, body mass index; CAD, coronary artery disease; DBP, diastolic blood pressure; ECG, electrocardiogram; HDL, high-density lipoprotein; HF, heart failure; LDL, low-density lipoprotein; Lp(a), lipoprotein(a); SBP, systolic blood pressure.

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  Figure 3. Comparison of Lp(a) levels and AF risk in European and Asian populations. The results from several independent studies investigating the relationship between Lp(a) levels and the risk of AF. The findings illustrate notable disparities in AF risk associated with Lp(a) levels between European and Asian populations. AF, atrial fibrillation; Lp(a), lipoprotein(a).

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  Figure 4. The proatherogenic, prothrombotic, and proinflammatory mechanisms of Lp(a). Lp(a) enters the endothelium and is readily oxidized, damaging endothelial cells and smooth muscle cells. The damaged endothelium secretes cytokines or growth factors to induce inflammatory cells such as macrophages and monocytes to enter the endothelium to phagocytose lipids and form foam cells. The damaged endothelium secretes growth factors that activate smooth muscle cells to proliferate and migrate, producing an extracellular matrix that increases the thickness and stiffness of the intima. The foam cells in the intima become necrotic and disintegrate to form atheromatous plaques. The inflammatory response occurs throughout the process of atherosclerosis, and OxPLs in Lp(a) are potent proinflammatory mediators. Lp(a) promotes thrombosis by exacerbating endothelial damage and activating platelet-associated responses, and high concentrations of Lp(a) may inhibit fibrinolytic responses by inhibiting fibrinogen activation. Lp(a), lipoprotein(a); OxPL, oxidized phospholipid.

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  Figure 5. Atherosclerosis, thrombosis, and stroke in patients with AF. AF increases the risk of thrombosis in the left atrium due to weak atrial contractility, stagnant blood flow, and a potential prethrombotic state. Thromboembolism, where a clot formed in the heart moves to other parts of the body, is a dangerous complication of AF, with ischemic stroke being the most serious outcome. Furthermore, AF and CAD are synergistic conditions. AF can exacerbate CAD through thrombosis, inadequate blood supply, and the promotion of atherosclerosis. AF, atrial fibrillation; CAD, coronary artery disease.