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Lipoprotein a (lpa)

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Lipoprotein A (Lp (a)) is an LDL-like particle that contains apolipoprotein (a) in addition to apo B

  • apo(a) component is encoded by the LPA gene, and levels of Lp(a) are almost entirely explained by genetics

Lp (a) is produced in the liver; its significance lies in the fact that numerous studies have found that concentrations of plasma Lp (a) above 0.3 g/l (note reference ranges may vary between laboratories) are associated with an increased risk of coronary heart disease.

Up to 20% of the population have an increased level of Lp (a)

  • 1 in 5 individuals affected in the United States [ie, based on Lp(a) > 0.5g/l or >120 nmol/L] (1)

Concentrations vary from almost undetectable to greater than 1 g/l; differing little with sex, body mass index and age in adults.

Epidemiological evidence has linked Lp(a) to several cardiovascular diseases (1)

  • including myocardial infarction (MI), stroke, and aortic valve stenosis
  • findings from a Mendelian randomization study suggest that elevated Lp(a) may directly contribute to CHD development
  • Lp(a) levels vary significantly across different ethnicities, with Africans having the highest Lp(a) levels (median 0.27 g/l ), whereas Chinese were observed to have the lowest (0.078 g/l) (3)
  • among patients with ACS, raised Lp(a) levels are associated with an increased atherosclerotic burden and it identifies a subset of patients with features of high-risk coronary atherosclerosis (2)
  • association between Lp(a) > 0.5g/l and MI, conferring an increased odds of MI of 48% (95% CI, 32%-67%) (3)
    • only ethnic groups that were heterogeneous were Africans and Arabs, in whom the association appeared null; however, these were the smallest subgroups and were affected by poor precision (3)
    • other evidence has revealed that Lp(a) > 0.5 g/l is a risk factor for cardiovascular disease in blacks (4)
  • evidence from FOURIER study revealed that raised Lp (a) was an independent marker of cardiovascular risk despite use of moderate or high-intensity statins (5)
    • in the well-treated FOURIER cohort, in which >99% of participants received moderate- or high-intensity statins and in which LDL cholesterol was <100 mg/dL (apoB <90 mg/dL), higher Lp(a) was associated with major adverse cardiovascular events (defined as a composite of coronary heart death, MI, or urgent coronary revascularization)
      • both the third and fourth upper quartiles of the Lp(a) distribution had an increased risk of major adverse cardiovascular events of 17% and 22%, respectively, compared with the lowest quartile
  • clinical benefit of lowering Lp(a) is likely to be proportional to the absolute reduction in Lp(a) concentration. Large absolute reductions in Lp(a) of approximately 100 mg/dL may be required to produce a clinically meaningful reduction in the risk of CHD similar in magnitude to what can be achieved by lowering LDL-C level by 38.67 mg/dL (ie, 1 mmol/L) (6)
  • PCSK9 inhibitors reduce Lp(a) concentrations (by approximately 20%-25%) in the circulation (7,8)
  • evidence of Lp(a) levels and stroke risk (9)
    • a study evaluated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events in acute ischaemic stroke patients
    • showed elevated Lp(a) was independently associated with LAA stroke aetiology and risk of recurrent cerebrovascular events among primarily Caucasian individuals aged <60 years or with evident arteriosclerotic disease
  • in comparison to hs-CRP (high sensitivity CRP) as an indicator of cardiovascular risk (10)
    • cohort study found in both a primary prevention population (UK Biobank) and secondary prevention populations (FOURIER [TIMI 59] and SAVOR-TIMI 53), higher Lp(a) was associated with increased risk of major adverse cardiovascular events, myocardial infarction, and peripheral artery disease regardless of baseline hs-CRP level

Levels may also be affected by:

  • hepatic disease and excessive alcohol decrease levels
  • diabetics with proteinuria and albuminuric renal disease have increased levels.

The pathway for clearance is uncertain.


  1. Erquo S et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality.JAMA. 2009 Jul 22;302(4):412-23
  2. Niccoli G et al. Lipoprotein (a) is related to coronary atherosclerotic burden and a vulnerable plaque phenotype in angiographically obstructive coronary artery disease. Atherosclerosis. 2016 Mar;246:214-20
  3. Pare G et al. Lipoprotein(a) Levels and the Risk of Myocardial Infarction Among 7 Ethnic Groups.Circulation. 2019 Mar 19;139(12):1472-1482
  4. Guan M et al. Race is a key variable in assigning lipoprotein(a) cutoff values for coronary heart disease risk assessment: the Multi-Ethnic Study of Atherosclerosis.Arterioscler Thromb Vasc Biol. 2015 Apr;35(4):996-1001
  5. O'Donoghue ML et al. Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk.Circulation. 2019 Mar 19;139(12):1483-1492
  6. Burgess S et al. Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies: A Mendelian Randomization Analysis.JAMA Cardiol. 2018 Jul 1; 3(7): 619-627.
  7. Malo, J, Parajuli, A, Walker, SW. PCSK9: from molecular biology to clinical applications. Ann Clin Biochem 2020; 57: 7-26
  8. Kasichayanula, S, Grover, A, Emery, MG, et al. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet 2018; 57: 769-779
  9. 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 Mar 8;ehab081. doi: 10.1093/eurheartj/ehab081.
  10. Small AM, Pournamdari A, Melloni GE, et al. Lipoprotein(a), C-Reactive Protein, and Cardiovascular Risk in Primary and Secondary Prevention Populations. JAMA Cardiol. Published online February 14, 2024. doi:10.1001/jamacardio.2023.5605

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