Top Things to Know: Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease
Published: October 14, 2021
Prepared by Prashant Nedungadi, PhD, Director - Stroke Guidelines
- High levels of lipoprotein(a) [Lp(a)], a unique apoB100 (apoB)-containing lipoprotein, are an independent and causal risk factor for atherosclerotic cardiovascular diseases (ASCVD) through mechanisms associated with increased atherogenesis, inflammation, and thrombosis.
- Despite its contribution to ASCVD, there is a lack of a) standardization and harmonization of assays, b) universal guidelines for diagnosing and providing risk assessment, and c) targeted treatments to lower Lp(a).
- This scientific statement highlights the established and emerging biology, pathophysiology, and clinical epidemiology of Lp(a). It also identifies key gaps in our understanding of the role of Lp(a) in ASCVD.
- Epidemiological, genome-wide association, and Mendelian randomization data provides clear support for a causal role for elevated Lp(a) in the development of ASCVD. Randomized cardiovascular outcome trial data will be needed to provide final proof of causality.
- Clinical use considerations for Lp(a) measurements are described in this scientific statement. These include a) why would a clinician measure Lp(a), b) how should Lp(a) be measured and c) How a clinician can gauge the proportion of apoB-containing lipoproteins that is actually Lp(a)
- Although Lp(a) is a common, and clinically important ASCVD risk factor that can be measured with a simple blood test, it is not measured in most patients. The scientific statement also provides guidance on how to use the Lp(a) levels, if measured, to update the 10-year ASCVD risk estimate.
- International standards for measurement of Lp(a) need to be established and codified to allow for consistent measurement, using assays expressing results in nmol/L, and a common protocol is needed for monitoring of assay performance to assure comparable results between laboratories.
- The Lp(a) concentration is heterogenous and to a major extent controlled by genetics, inversely related to the copy number variation in the apo(a) gene. Other factors such as ethnicity/race, medical and environmental conditions also play roles in Lp(a) regulation.
- Currently, the evidence in favor of screening for Lp(a) is strongest for those with a family or personal history of ASCVD, with consideration of cascade screening in appropriate individuals. The best approach to lower overall ASCVD risk in patients with high Lp(a) is to target LDL-cholesterol /apoB with statin and adjunctive medications as initial therapy.
- Novel therapies for Lp(a) lowering that target hepatic synthesis of apo(a) are in various phases of clinical trials. In addition, outcome studies using lipoprotein apheresis to remove Lp(a) and other apoB-containing lipoproteins from plasma are ongoing. The completion of these studies will provide critical insight into the cardiovascular benefits of lowering Lp(a) and provide further evidence supporting or refuting its role as a causal risk factor.
Citation
Reyes-Soffer G, Ginsberg HN, Berglund L, Duell PB, Heffron SP, Kamstrup PR, Lloyd-Jones DM, Marcovina SM, Yeang C, Koschinsky ML; on behalf of the American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; and Council on Peripheral Vascular Disease. Lipoprotein (a): a genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease: a scientific statement from the American Heart Association [published online ahead of print October 14, 2021]. Arterioscler Thromb Vasc Biol. doi: 10.1161/ATV.0000000000000147