Clinlab Navigator

Lipoprotein a Cholesterol, Lp(a)

Lipoprotein (a) is a modified form of low-density lipoprotein (LDL) containing a large plasminogen-like glycoprotein and apolipoprotein (a) covalently bound to apolipoprotein B100 (apoB). The molecular mass can vary between 275 and 800 kDa due to inheritance of more than 40 different allelic LPA variants that encode different numbers of kringle IV type 2 repeat sequences. Plasma concentration of Lp(a) can vary as much as 1000-fold between individuals. Persons with lower molecular weight Lp(a) have higher plasma concentrations than those who synthesize higher molecular weight isoforms. Variation in Lp(a) concentration is predominantly determined by inheritance in an autosomal codominant manner. Approximately 1 in 5 individuals has elevated Lp(a) levels.

Although Lp(a) concentrations are predominantly under genetic control, some non-genetic factors are known to influence it. In chronic kidney disease, serum Lp(a) concentrations rise with decreasing glomerular filtration rate due to reduced catabolism of the larger isoforms. Renal transplantation returns Lp(a) concentration to baseline. Serum Lp(a) levels are fourfold higher in individuals with nephrotic range proteinuria due to increased rates of Lp(a) synthesis of all isoform sizes. L(a) levels are reduced in most types of liver disease. Serum Lp(a) levels are increased in patients with overt hypothyroidism and are reduced following levothyroxine replacement. Subclinical hypothyroidism does not affect levels.

Levels can increase dramatically after coronary ischemia and surgery because Lp(a) is an acute phase reactant. Lp(a) fluctuates during hormonal changes that occur in patients with diabetes mellitus, estrogen therapy, and pregnancy. Lower levels are seen in individuals with higher estrogen or androgen levels, cirrhosis, and alcoholism.  Exercise and low-fat diets do not significantly lower Lp(a). Serum Lp(a) levels are significantly reduced by hormone replacement in postmenopausal women.  

Lp(a) is an independent risk factor for both cardiovascular diseases, including both myocardial infarction and ischemic stroke, and calcific aortic valve stenosis. It contributes to atherogenesis through multiple mechanisms including inhibition of fibrinolysis, increased cholesterol deposition in the arterial wall, and enhanced oxidation of LDL cholesterol.

Lp(a) elevation is a frequent and independent risk factor for venous thromboembolism.  Furthermore, elevated Lp(a) levels may contribute to the thrombotic risk associated with factor V Leiden and other hereditary or acquired prothrombotic risk factors, compatible with the widely accepted concept that venous thrombosis is a multicausal disorder.

The most recent guidelines recommend that Lp(a) levels be measured in patients with a personal or family history of premature atherosclerotic CV disease, first degree relatives with Lp(a) levels >200 nmol/L, familial hypercholesterolemia, calcific aortic valve stenosis, and those with borderline increased (<15%) 10-year risk for a CV event.

Statins have no effect on Lp(a) concentration. The recommended management of patients with increased Lp(a) levels above >90 nmol/L includes reducing overall atherosclerotic risk and controlling hyperlipidemia (ie, not specifically targeting Lp[a] levels). In addition, lipoprotein apheresis should be considered in individuals who have progressive coronary disease, Lp(a) level >150 nmol/L (>60 mg/dL), and persistently high low-density lipoprotein level (>125 mg/dL) despite lipid-lowering treatment. PCSK9 monoclonal antibody therapy reduces Lp(a) level by approximately 25%. 

In Caucasians, 80% of the population have a serum Lp(a) <42 mg/dL (<90 nmol/L).  African Americans have Lp(a) levels that are twice as high as Caucasians. Lipoprotein(a) levels are not affected by age or gender. The association between Lp(a) levels and cardiovascular risk is summarized below:

Lp(a) Concentration (nmol/L) Cardiovascular Risk
32-90 Minor
90-200 Moderate
200-400 High
>400 Very High


Serum Lp(a) levels remain relatively stable over a lifespan because they are predominantly genetically determined. Clinicians need only measure Lp(a) once, unless a secondary cause is suspected or Lp(a)-lowering treatment has been initiated.

Conventional LDL assays are unable to measure Lp(a). The immunoassay used to measure Lp(a) should minimize the effect of isoform size and use antibodies and calibrators that are traceable to to World Health Organization (WHO)/International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference material. Assays using Denka reagents are the most reliable commercial assays available.

Lp(a) concentration can be expressed as either the mass of the entire Lp(a) particle in mg/dL or as a particle number of apo(a) in nmol/L. Lp(a) expressed in mass units (mg/dl) encompasses the mass of the entire particle; this comprises apo(a), apoB-100, cholesterol, cholesteryl esters, phospholipids, and triglycerides. Because patient samples contain a mixture of isoforms of Lp(a) it is impossible to convert mass units to molar units without detailed knowledge of the isoform composition.

Specimen requirement is one SST tube of blood.


Cegla J, Neely RDG, France M, et al. HEART UK consensus statement on lipoprotein(a): a call to action [published online October 14, 2019]. Atherosclerosis. doi:10.1016/j.atherosclerosis.2019.10.011

Miksenas H et al. Lipoprotein(a) and Cardiovascular Diseases, JAMA published online July 8, 2021.

Kamstrup PR, Lipoprotein(a) and cardiovascular disease, Clin Chem 2021;154-66.

AddThis Social Bookmark Button