lipoprotein a (elevated)
Last edited 11/2020 and last reviewed 11/2023
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
- 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)
- including myocardial infarction (MI), stroke, and aortic valve stenosis
- concentrations vary from almost undetectable to greater than 1 g/l;
differing little with sex, body mass index and age in adults
- 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.