Hyperlipoproteinaemia (a)

Approximately one in people in five have an lipoprotein a plasma concentration greater than 0.3 g/l

Elevated levels of lipoprotein A is an independent risk factor for coronary artery disease

• 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. This includes up to 20% of the population
  
  
  • concentrations vary from almost undetectable to greater than 1 g/l; differing little with sex, body mass index and age in adults
    
    
  • 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)
    
    
  • 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
      
      
    • 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)
  
  

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.

Reference:

• 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
• 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
• 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
• 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
• O'Donoghue ML et al. Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk.Circulation. 2019 Mar 19;139(12):1483-1492
• 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.