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Learn how elevated Lp(a) impacts cardiovascular risk

Even in the absence of other cardiovascular risk factors, elevated Lp(a) may be a threat.3,4 Watch this video to see what may be hiding in your patients' routine blood work.

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The higher a patient’s Lp(a) level, the higher their risk for a lifetime cardiovascular event5

At normal levels, Lp(a) may help promote tissue repair and accelerate wound healing.6,7

At elevated levels of ≥50 mg/dL (≥125 nmol/L), Lp(a) can increase lifelong risk of cardiovascular disease, aortic valve stenosis, coronary artery disease, heart attack, and stroke via proatherogenic, proinflammatory, and prothrombotic mechanisms.5,8,9

Lp(a) is a unique and large prothrombotic glycoprotein called apo(a), bound to ApoB.

Lp(a) is a unique and large prothrombotic glycoprotein called apo(a), bound to ApoB. Lp(a) levels are determined by genetic variants: the number of copies in the kringle IV type 2 (KIV-2) domain of apo(a) is variable and correlates inversely with Lp(a) concentrations.9

Large-scale genetic studies have established that elevated Lp(a) is an independent and causal risk factor for cardiovascular disease, increasing the risk by 2- to 4-fold2,10,11

Icon of heart and blood vessel to show cardiovascular disease.

See the data for coronary artery disease (CAD) and ischemic heart disease (IHD)

People with elevated Lp(a) levels face a consistent and lifelong increased risk of premature cardiovascular events, even in the absence of other risk factors3-5,9,12

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Elevated Lp(a) levels are established by 5 years of age and remain relatively consistent over time.5,13 Endothelial dysfunction associated with high Lp(a) levels has been detected in children as young as 11 years of age.14

Elevated Lp(a) is the only known single genetic risk factor for calcific aortic valve stenosis2

Icon of patient with aortic valve stenosis

See the data for aortic valve calcification (AVC) and prevalence of calcific aortic valve stenosis (CAVS)15,16

Elevated Lp(a) was associated with an increased rate of CAVS progression in patients with mild to moderate calcific aortic valve stenosis17

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Elevated Lp(a) doubled the risk of a recurrent cerebrovascular event in a subgroup analysis of patients <60 years of age who had suffered an arterial ischemic stroke (AIS)18

Icon of patient suffering a stroke.

Important considerations

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Certain groups of individuals are at additional risk from elevated Lp(a)

For women after menopause:

  • Elevated Lp(a) is associated with the presence and severity of new-onset coronary artery disease (CAD) and obstructive CAD19,20

For people with diabetes or prediabetes:

  • Elevated Lp(a) was associated with a significant increase in ASCVD risk in Caucasian individuals with diabetes (HR=1.59; 95% CI 1.18–2.15) or prediabetes (HR=1.40; 95%CI 1.09–1.81)21

For people of African ancestry:

  • Lp(a) levels of >30 mg/dL are associated with an up to 2-fold increased risk of incident ischemic stroke. Median Lp(a) levels are also highest compared with other racial subgroups22,23

For people of South Asian ancestry:

  • Median Lp(a) levels are second highest after those of African ancestry and may account, in part, for their tendency to develop premature CAD2,24,25

Despite its clinical impact, <1% of people living with elevated Lp(a) have been identified.26

References: 1. Tsimikas S, Fazio S, Ferdinand KC, et al. NHLBI Working Group recommendations to reduce Lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis. J Am Coll Cardiol. 2018;71(2):177-192. 2. Tsimikas S. A test in context: Lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69(6):692-711. 3. Enas EA, Varkey B, Dharmarajan TS, Pare G, Bahl VK. Lipoprotein(a): An independent, genetic, and causal factor for cardiovascular disease and acute myocardial infarction. Indian Heart J. 2019;71(2):99-112. 4. Willeit P, Kiechl S, Kronenberg F, et al. Discrimination and net reclassification of cardiovascular risk with Lipoprotein(a): prospective 15-year outcomes in the Bruneck Study. J Am Coll Cardiol. 2014;64(9):851-860. 5. Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925-3946. 6. Orsó E, Schmitz G. Lipoprotein(a) and its role in inflammation, atherosclerosis and malignancies. Clin Res Cardiol. 2017;12(Suppl 1):31-37. 7. Safiullah ZN, Leucker T, Jones SR, et al. Physiological Roles and Functions of Lipoprotein(a). In: Lipoprotein(a). Contemporary Cardiology. Humana, Cham; 2023. 8. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;10;140(11):e596-e646. 9. Reyes-Soffer G, Ginsberg HN, Berglund L, et al; 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. Arterioscler Thromb Vasc Biol. 2022;42(1):e48-e60. 10. Clarke R, Peden JF, Hopewell JC, et al; PROCARDIS Consortium. Genetic variants associated with Lp(a) Lipoprotein level and coronary disease. N Engl J Med. 2009;361(26):2518-2528. 11. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated Lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301(22):2331-2339. 12. Virani SS, Koschinsky ML, Maher L, et al. Global think tank on the clinical considerations and management of Lipoprotein(a): The top questions and answers regarding what clinicians need to know. Prog Cardiovasc Dis. 2022;73:32-40. 13. Scheel P, Meyer J, Blumenthal RS, Martin SS. Lipoprotein(a) in clinical practice. A commentary based on Wilson DP, Jacobson TA, Jones PH, et al. Use of lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association. J Clin Lipidol. 2019;13(3)374-392. J Am Coll Cardiol. July 2, 2019. Accessed August 22, 2023. 14. Lapinleimu J, Raitakari OT, Lapinleimu H, et al. High Lipoprotein(a) concentrations are associated with impaired endothelial function in children. J Pediatr. 2015;166(4):947-952.e1-2. 15. Kaiser Y, Singh SS, Zheng KH, et al. Lipoprotein(a) is robustly associated with aortic valve calcium. Heart. 2021;107(17):1422-1428. 16. Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Elevated Lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol. 2014;63(5):470-477. 17. Capoulade R, Chan KL, Yeang C, et al. Oxidized phospholipids, Lipoprotein(a), and progression of calcific aortic valve stenosis. J Am Coll Cardiol. 2015;66(11):1236-1246. 18. Arnold M, Schweizer J, Nakas CT, et al. Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years: results from the BIOSIGNAL study. Eur Heart J. 2021;42(22):2186-2196. 19. Sposito AC, Mansur AP, Maranhão RC, Martinez TR, Aldrighi JM, Ramires JA. Triglyceride and lipoprotein (a) are markers of coronary artery disease severity among postmenopausal women. Maturitas. 2001;39(3):203-208. 20. Yan XN, Jin JL, Hong LF, et al. Lipoprotein(a) is associated with the presence and severity of new-onset coronary artery disease in postmenopausal women. J Womens Health (Larchmt). 2020;29(4):503-510. 21. Saeed A, Sun W, Agarwala A, et al. Lipoprotein(a) levels and risk of cardiovascular disease events in individuals with diabetes mellitus or prediabetes: The Atherosclerosis Risk in Communities study. Atherosclerosis. 2019;282:52-56. 22. Virani SS, Brautbar A, Davis BC, et al. Associations between Lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2012;125(2):241-249. 23. Reyes-Soffer G. The impact of race and ethnicity on Lipoprotein(a) levels and cardiovascular risk. Curr Opin Lipidol. 2021;32(3):163-166. 24. Enas EA, Varkey B, Dharmarajan TS, et al. Lipoprotein(a): An underrecognized genetic risk factor for malignant coronary artery disease in young Indians. Indian Heart J. 2019;71(3):184-198. 25. Mehta A, Jain V, Saeed A, et al. Lipoprotein(a) and ethnicities. Atherosclerosis. 2022;349:42-52. 26. McGowan M, Wilemon K, Ahmed C, et al. Characterization of Lipoprotein(a) measurement in a large US healthcare dataset. J Clin Lipidol. 2022;16(Suppl 3):e36-e37.