Cardiometabolic Biomarkers: Lp-PLA2

Optimal Takeaways

The lipoprotein-associated phospholipase A2 (Lp-PLA2) enzyme is considered an inflammatory biomarker that is activated in the presence of oxidized lipoprotein compounds and is associated with atherosclerotic plaque. Its presence and increasing abundance suggest a severe degree of cardiovascular disease and may be associated with obesity, metabolic syndrome, and diabetes as well.

Standard Range: 0-200 ng/mL

The ODX Range: 0-165 ng/mL

Low levels of Lp-PLA2 suggest a reduced risk of oxidized lipoproteins and cardiometabolic disease.

High levels of Lp-PLA2 are seen with cardiometabolic disease, vascular inflammation, the increased presence of oxidized lipoproteins, advanced atherosclerotic plaque, atherosclerotic events, and carotid stenosis (Liu 2018, Pagana 2019). Increased levels may predict impending CVD events in those with heart failure or ischemic disease (Charniot 2013). High levels are also associated with metabolic syndrome, diabetes (De Stefano 2019), and stroke (Hu 2019).

Overview

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that hydrolyzes platelet-activating factors and oxidized lipoprotein phospholipids, releasing pro-inflammatory mediators. It is produced by monocytes/macrophages and T-lymphocytes, activated in the presence of oxidized lipoproteins, and is associated with necrotic atherosclerotic plaque (Bonnefont-Rousselot 2016, Silva 2011).

Lp-PLA2 is considered a vascular-specific marker of inflammation and increased levels are associated with blood clots and the rupture of atherosclerotic plaque. It is also associated with obesity, metabolic syndrome, and diabetes and warrants further evaluation in these metabolic disorders. Adipose tissue is a significant source of Lp-PLA2 in obesity and diabetes (De Stefano 2019).

Elevated levels of Lp-PLA2 combined with elevated hs-CRP are associated with carotid stenosis, coronary heart disease, atherosclerosis, and stroke (Liu 2018).

In one study of 494 subjects undergoing diagnostic coronary angiography versus controls without known CVD risk factors, Lp-PLA2 levels reflected the degree of atherosclerotic disease. Healthy individuals maintained mean Lp-PLA2 levels below 166 ng/mL while patients with coronary artery disease, heart failure, aortic aneurysm, and sepsis maintained levels above 200 ng/mL. Lp-PLA2 increased significantly and proportionally with the severity of atherosclerosis. Mean levels were 215.2 ng/mL in those with single-vessel disease; 222 ng/mL with two vessel involvement; and 251.9 ug/mL in those with the 3-vessel disease. Lp-PLA2 was also significantly higher in those with mild or severe carotid artery stenosis (Charniot 2013).

A meta-analysis of 22 studies comprising 157,693 subjects found a significantly increased risk of stroke in those with elevated Lp-PLA2 as well (Hu 2019).

A Western-style diet high in processed foods, fast foods, organ meats, and carbonated beverages can markedly increase Lp-PLA2, while a vegetarian diet with an abundance of fruits and vegetables can decrease it (Seyedi 2020).

Though circulating levels of Lp-PLA2 can be quantified, measurement of Lp-PLA2 activity may provide the most valuable information for cardiometabolic risk assessment.

References

Bonnefont-Rousselot, D. “La Lp-PLA2, marqueur d'inflammation vasculaire et de vulnérabilité de la plaque d'athérosclérose” [Lp-PLA2, a biomarker of vascular inflammation and vulnerability of atherosclerosis plaques]. Annales pharmaceutiques francaises vol. 74,3 (2016): 190-7. doi:10.1016/j.pharma.2015.09.002

Charniot, J C et al. “Interpretation of lipoprotein-associated phospholipase A2 levels is influenced by cardiac disease, comorbidities, extension of atherosclerosis and treatments.” International journal of cardiology vol. 168,1 (2013): 132-8. doi:10.1016/j.ijcard.2012.09.054

Cushman, M., et al. "Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and coronary heart disease risk in a biracial cohort: The reasons for geographic and racial differences in stroke (regards) cohort." Atherosclerosis 241.1 (2015): e9.

De Stefano, Alessandro et al. “Lp-PLA2, a new biomarker of vascular disorders in metabolic diseases.” International journal of immunopathology and pharmacology vol. 33 (2019): 2058738419827154. doi:10.1177/2058738419827154

Hu, Gaifeng et al. “Lipoprotein-Associated Phospholipase A2 Activity and Mass as Independent Risk Factor of Stroke: A Meta-Analysis.” BioMed research international vol. 2019 8642784. 20 May. 2019, doi:10.1155/2019/8642784

Liu, Huamin et al. “Association between high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2 and carotid atherosclerosis: A cross-sectional study.” Journal of cellular and molecular medicine vol. 22,10 (2018): 5145-5150. doi:10.1111/jcmm.13803

Seyedi, Seyed Hashem Sezavar et al. “The relationship between dietary patterns and lipoprotein-associated phospholipase A2 levels in adults with cardiovascular risk factors: Tehran Lipid and Glucose Study.” Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences vol. 25 3. 20 Jan. 2020, doi:10.4103/jrms.JRMS_256_19

Silva, Isis T et al. “Antioxidant and inflammatory aspects of lipoprotein-associated phospholipase A₂ (Lp-PLA₂): a review.” Lipids in health and disease vol. 10 170. 28 Sep. 2011, doi:10.1186/1476-511X-10-170