Related Experiment Videos
Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular
Insights
High levels of lipoprotein(a) [Lp(a)] are a major genetic risk factor for cardiovascular disease. Further research is needed to standardize Lp(a) testing and develop targeted treatments to reduce associated health risks.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Biochemistry
Background:
- Lipoprotein(a) [Lp(a)] is a significant independent risk factor for atherosclerotic cardiovascular diseases.
- Elevated Lp(a) contributes to atherogenesis, inflammation, and thrombosis.
- Genetic factors determine a substantial portion (70-90%) of interindividual Lp(a) level variation.
Purpose of the Study:
- To provide a comprehensive overview of the current understanding of Lp(a).
- To highlight knowledge gaps and future research directions for Lp(a).
- To address the clinical need for standardized diagnostics and targeted therapies for Lp(a).
Main Methods:
- Review of existing scientific literature and clinical evidence on Lp(a).
- Expert consensus from a diverse basic science and clinical workgroup.
- Synthesis of historical, biological, and pathophysiological data.
Main Results:
- Lp(a) is a causal risk factor for cardiovascular disease, independent of LDL-C.
- Current diagnostic assays lack standardization and universal guidelines are absent.
- Effective Lp(a)-lowering treatments are still under development.
Conclusions:
- Standardization of Lp(a) assays and development of universal guidelines are critical.
- Understanding the genetic and biological basis of Lp(a) variation across ancestries is essential.
- Targeted therapies are needed to mitigate cardiovascular disease risk associated with elevated Lp(a).
Abstract:
High levels of lipoprotein(a) [Lp(a)], an apoB100-containing lipoprotein, are an independent and causal risk factor for atherosclerotic cardiovascular diseases through mechanisms associated with increased atherogenesis, inflammation, and thrombosis. Lp(a) is predominantly a monogenic cardiovascular risk determinant, with ≈70% to ≥90% of interindividual heterogeneity in levels being genetically determined. The 2 major protein components of Lp(a) particles are apoB100 and apolipoprotein(a). Lp(a) remains a risk factor for cardiovascular disease development even in the setting of effective reduction of plasma low-density lipoprotein cholesterol and apoB100. Despite its demonstrated contribution to atherosclerotic cardiovascular disease burden, we presently lack standardization and harmonization of assays, universal guidelines for diagnosing and providing risk assessment, and targeted treatments to lower Lp(a). There is a clinical need to understand the genetic and biological basis for variation in Lp(a) levels and its relationship to disease in different ancestry groups. This scientific statement capitalizes on the expertise of a diverse basic science and clinical workgroup to highlight the history, biology, pathophysiology, and emerging clinical evidence in the Lp(a) field. Herein, we address key knowledge gaps and future directions required to mitigate the atherosclerotic cardiovascular disease risk attributable to elevated Lp(a) levels.