lipoprotein a ( lpa )

Last edited 03/2021 and last reviewed 01/2022

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 LPAgene, and levels of Lp(a) are almost entirely explained by genetics

Lp (a) is produced in the liver; its significance lying 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 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 have 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

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.