Research Blog

November 18, 2022

Lipoprotein Biomarkers: Lipoprotein(a)

Optimal Takeaways

Lipoprotein (a) represents a group of lipoproteins comprising a molecule of Apo(a) attached to a molecule of Apo B. It is considered highly atherogenic, damaging to the vascular endothelium, and may be an independent risk factor for atherosclerosis. Elevations in Lp(a) are closely associated with increased risk of major adverse cardiac and cerebrovascular events. Low levels can be seen with malnutrition, alcoholism, and liver disease.

Conventional Lab Range: 0.00 - 75.00 nmol/L

Optimal Dx’s Optimal Range: 0.00 - 18.00 nmol/L

Low lipoprotein(a) is associated with malnutrition, alcoholism, and chronic hepatocellular disease. Drugs that can decrease Lp(a) include niacin, stanozolol, neomycin, and estrogen (Pagana 2021).

High lipoprotein(a) is associated with premature coronary artery disease, cerebral artery stenosis, severe hypothyroidism, uncontrolled diabetes, familial hypercholesterolemia, estrogen depletion, and chronic renal failure (Pagana 2021).

Elevated Lp(a) has also been associated with major adverse cardiac and cerebrovascular events, (Mitsuda 2016), and specifically associated with increased risk of myocardial infarction, ischemic stroke (Lansted 2019), calcific aortic valve stenosis, peripheral artery disease (Tsimikas 2017), thin-cap fibroatheroma (Muramatsu 2019), heart failure, peripheral atherosclerotic stenosis, inflammation, endothelial dysfunction, and thrombosis (Madsen 2020).

Overview

Lipoprotein(a) is susceptible to oxidation inside the blood vessel wall where the oxidized molecule can become highly inflammatory and immunogenic. In general, Lp(a) is considered more atherogenic than LDL. Circulating Lp(a) levels are strongly influenced by genetic factors as well as variability in the size of its Apo(a) molecule. Statins have been known to increase Lp(a), and elevated levels can persist even in those with LDL-C below 70 mg/dL (1.81 mmol/L) (Tsimikas 2017). In a study of 220 subjects with aortic stenosis, progression of stenosis was found to be greater in those with the highest Lp(a) at 123 nmol/L or above (Capoulade 2015).

While elevated Lp(a) is a recognized risk factor for the development of CVD, research also demonstrates that it can be a factor in causing major adverse cardiovascular events (MACE) in those with established disease. Review of data from individuals with CVD participating in the Copenhagen General Population Study and the Copenhagen City Heart Study revealed increasingly greater risk of MACE in those with a lipoprotein(a) at or above 18 nmol/L, with the highest incidence occurring in those with Lp(a) of 214 nmol/L or higher (Madsen 2020).

Review of the same Copenhagen data revealed that an Lp(a) below 18 nmol/L had the lowest risk of ischemic stroke, whereas those with an Lp(a) above 199 nmol/L were at greatest risk. Interestingly, statin users tended to have higher Lp(a) (Langsted 2019).

Although genetic factors are believed to determine Lp(a) levels, a study of newly diagnosed CVD subjects found that levels significantly decreased upon following a defined plant-based diet for four weeks. Items excluded during the study included animal products, cooked foods, oils, soda, coffee, and alcohol. Lp(a) decreased from a mean of 200.7 nmol/L at baseline, to a mean of 168.8 nmol/L after 4 weeks. Levels of total cholesterol, LDL-C, small dense LDL-C, LDL particle number, triglycerides, Apo A-1, Apo B, and markers of inflammation including hs-CRP, IL-6, fibrinogen, and white blood cells decreased significantly as well (Najjar 2018).

References

Capoulade, Romain et al. “Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis.” Journal of the American College of Cardiology vol. 66,11 (2015): 1236-1246. doi:10.1016/j.jacc.2015.07.020

Langsted, Anne et al. “Elevated Lipoprotein(a) and Risk of Ischemic Stroke.” Journal of the American College of Cardiology vol. 74,1 (2019): 54-66. doi:10.1016/j.jacc.2019.03.524

Madsen, Christian M et al. “Lipoprotein(a)-Lowering by 50 mg/dL (105 nmol/L) May Be Needed to Reduce Cardiovascular Disease 20% in Secondary Prevention: A Population-Based Study.” Arteriosclerosis, thrombosis, and vascular biology vol. 40,1 (2020): 255-266. doi:10.1161/ATVBAHA.119.312951

Mitsuda, Takayuki et al. “Lipoprotein(a) levels predict adverse vascular events after acute myocardial infarction.” Heart and vessels vol. 31,12 (2016): 1923-1929. doi:10.1007/s00380-016-0823-0

Muramatsu, Yusuke et al. “Lipoprotein (a) level is associated with plaque vulnerability in patients with coronary artery disease: An optical coherence tomography study.” International journal of cardiology. Heart & vasculature vol. 24 100382. 13 Jun. 2019, doi:10.1016/j.ijcha.2019.100382

Najjar, Rami S et al. “Consumption of a defined, plant-based diet reduces lipoprotein(a), inflammation, and other atherogenic lipoproteins and particles within 4 weeks.” Clinical cardiology vol. 41,8 (2018): 1062-1068. doi:10.1002/clc.23027

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Tsimikas, Sotirios. “A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies.” Journal of the American College of Cardiology vol. 69,6 (2017): 692-711. doi:10.1016/j.jacc.2016.11.042

Tag(s): Biomarkers

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