From the Guidelines
Lipoprotein(a) [Lp(a)] is a genetic risk factor for cardiovascular disease, composed of an apolipoprotein B (apoB)-containing low-density lipoprotein (LDL)-like particle covalently linked to the plasminogen-like glycoprotein apolipoprotein(a) (apo(a)) 1.
Definition and Composition
Lp(a) is a highly prevalent risk factor, with levels primarily determined by the LPA gene locus encoding apo(a), and influenced by the APOE locus and PCSK9 R46L loss of function mutations 1. The LPA gene is highly polymorphic, resulting in over 40 apo(a) isoforms that vary in distribution among individuals and populations.
Clinical Significance
High levels of Lp(a), typically above 30–50 mg/dL or 75–125 nmol/L, increase the risk of cardiovascular disease, including myocardial infarction, stroke, peripheral arterial disease, and heart failure, as well as calcific aortic valve disease (CAVD) 1. Elevated Lp(a) levels affect 20–30% of the global population, with a potentially higher incidence in patients with established cardiovascular disease and CAVD.
Mechanism of Action
Lp(a) promotes atherosclerosis through multiple mechanisms, including enhancing cholesterol deposition in arterial walls, promoting inflammation, and interfering with blood clot dissolution. The exact mechanisms are not fully understood, and significant knowledge gaps exist in Lp(a) biology and pathophysiology 1.
Management and Treatment
Currently, there are no FDA-approved medications specifically targeting Lp(a), although PCSK9 inhibitors and other therapies may modestly reduce levels 1. Emerging therapies, such as antisense oligonucleotides, show promise in clinical trials. For individuals with elevated Lp(a), the focus remains on aggressive management of other cardiovascular risk factors, including LDL cholesterol, blood pressure, diabetes, and smoking cessation, to mitigate overall cardiovascular risk. Aggressive management of cardiovascular risk factors is crucial for individuals with elevated Lp(a) to reduce the risk of cardiovascular disease and CAVD 1.
From the Research
Definition and Overview of Lipoprotein(a) [Lp(a)]
- Lipoprotein(a) [Lp(a)] is a variant of low-density lipoprotein (LDL) that is bound to apolipoprotein B100 2, 3, 4, 5.
- Elevated levels of Lp(a) are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), calcific aortic stenosis, and atrial fibrillation 2, 3, 4, 5.
- Lp(a) is considered the most prevalent inherited dyslipidemia and the strongest genetic ASCVD risk factor 2.
Risk Assessment and Management
- High levels of Lp(a) are causal for ASCVD, and this risk persists even in the presence of target LDL-C levels and adherence to lifestyle modifications 2.
- The measurement of Lp(a) levels is recommended for risk assessment, particularly in individuals with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, or recurrent cardiovascular events 2, 4.
- Current management strategies for elevated Lp(a) levels include lifestyle modifications, such as weight loss, dietary changes, and physical activity, as well as pharmacological interventions, such as statins and niacin 4, 5.
- Emerging therapies, such as antisense oligonucleotides (ASO) and small interfering RNAs (siRNAs), have shown promise in reducing Lp(a) levels and may contribute to the personalized prevention of ASCVD 3.
Lifestyle Factors and Lp(a) Levels
- Relevant body weight loss, a relatively high intake of saturated fatty acids, the consumption of red wine, and intense physical exercise may be associated with lower plasma Lp(a) levels 5.
- Foods rich in trans-unsaturated fatty acids are associated with increased Lp(a) levels, while dietary supplements such as coenzyme Q10, L-Carnitine, and flaxseed may have a mild lowering effect on plasma Lp(a) levels 5.
- However, the evidence on the effect of lifestyle changes on Lp(a) levels is limited, and further research is needed to determine the optimal management strategies for reducing CHD risk associated with elevated Lp(a) 2, 4.