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APOA1
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APOA1

The need for an advanced understanding of lipidology structure and function in healthcare is growing.   Lipoprotein testing provides valuable insights into an individual's lipid profile, aiding in the assessment of cardiovascular risk and guiding interventions above and beyond the standard lipid panel.  

Apolipoprotein ApoA1 plays a pivotal role in lipid metabolism and cardiovascular health.  As a major component of high-density lipoprotein (HDL) particles, ApoA1 facilitates the reverse cholesterol transport pathway, removing excess cholesterol from peripheral tissues and transporting it back to the liver for excretion. 

Dysregulation of ApoA1 levels has been implicated in various cardiovascular diseases, including atherosclerosis, coronary artery disease, and myocardial infarction. 

In this article, we delve into the intricacies of ApoA1, exploring its function, clinical significance, testing options, interpretation of results, and natural strategies to optimize its levels through dietary, lifestyle, and supplement interventions. Additionally, we provide insights into the ApoA1 test, its procedures, and its importance in assessing cardiovascular risk.

Understanding ApoA1

What is ApoA1?

Lipoproteins are soluble proteins that can transport lipids throughout the body.

Apolipoprotein A1 (ApoA1) is a lipoprotein synthesized mainly in the liver and also in the small intestine. 

ApoA1 is the primary apolipoprotein component of high-density lipoprotein (HDL) particles, facilitating its formation and stability.  HDL molecules are composed of a shell of phospholipids and unesterified cholesterol along with ApoA1, and contain a center of cholesteryl esters and triglycerides.  

How are ApoA1 Lipoproteins and HDL Particles Related?

Understanding the relationship between ApoA1 and HDL particles begins with understanding the creation of HDL particles.  

HDL production begins when ApoA1 lipoproteins, secreted by the liver and intestines, bind with the ABCA1 transporter on peripheral cells.  This stimulates the extrusion of cholesterol and phospholipids from cells, forming what can be considered a “pre-HDL particle”. 

ApoA1 also activates the enzyme lecithin:cholesterol acyltransferase (LCAT) to esterify cholesterol, transforming pre-HDL particles into spherical HDL particles with a central core of cholesteryl esters.  

Subsequently, small spherical HDL particles accumulate additional free cholesterol from peripheral cells through ABCA1 and ABCG1-mediated efflux. The esterification of this newly acquired cholesterol by LCAT results in the formation of large HDL particles containing three or more apoA1 molecules per particle.

These HDL particles ultimately end up in the liver where they are degraded, or where much of their cholesterol is dropped off and the smaller HDL particle can then be released back into circulation.  [3.]

Function of ApoA1 in Lipid Metabolism and Cardiovascular Health

ApoA1 is integral to lipid metabolism and cardiovascular health, primarily through its involvement in the reverse cholesterol transport (RCT) pathway. This process involves the transport of excess cholesterol from peripheral tissues, including arterial walls, back to the liver for excretion.  

Additionally, ApoA1 exhibits anti-inflammatory, antioxidant, antithrombotic, and vasoprotective properties, contributing to the maintenance of vascular health and reducing the risk of atherosclerosis and cardiovascular disease. ApoA1 lipoproteins are responsible for much of HDL’s cardioprotective nature.  [4., 9.] 

ApoA1 exerts a variety of anti-inflammatory and vascular repair mechanisms on the endothelial tissue, while also stimulating cholesterol efflux from endothelial cells into HDL particles.   [4., 9.]  Also, the antioxidant enzyme paranoxase or PON1 is normally bound to ApoA1 lipoproteins, providing an additional levels of antioxidant benefit.  [10.]

Clinical Significance of ApoA1 Levels

Measurement of ApoA1 levels provides valuable information about an individual's cardiovascular risk profile. Higher levels of ApoA1 are associated with a lower risk of cardiovascular events, including heart attacks and strokes, due to its protective effects on lipid metabolism and vascular function. Conversely, lower ApoA1 levels are linked to an increased risk of atherosclerosis and coronary artery disease. 

ApoA1 specifically has demonstrated a high correlation with the amount of HDL in the bloodstream, therefore it is an effective marker of HDL presence in the bloodstream.   [9.]

One study of elderly Swedish men demonstrated that ApoA1 may be the strongest predictor of death from cardiovascular disease in men, more so than ApoB, ApoB/ApoA1 ratio, HDL-C, or LDL-C.  [7.]  For this reason ApoA1 assessment should be considered in all individuals with existing cardiovascular disease, or with increased risk of cardiovascular disease.  

While some markers of lipid status are genetic and therefore not very susceptible to lifestyle changes, ApoA1 levels can be influenced by diet and lifestyle; see below for specific therapies.  [5., 8., 12., 16.]

Therefore, understanding one’s ApoA1 levels can provide important clinical insight into effective diet and lifestyle therapies and potentially inform medication choices to reduce risk of fatal and nonfatal cardiovascular events.   

ApoA1 Testing Options

Overview of ApoA1 Testing

ApoA1 testing involves assessing the levels of apolipoprotein A1 (ApoA1) in the bloodstream, typically through blood serum or plasma samples.  Venipuncture is commonly required.

Preparation and Procedure for ApoA1 Testing

Preparation for ApoA1 testing typically involves fasting for 8 to 12 hours before blood collection to ensure accurate results. Blood samples are collected via venipuncture and processed to separate serum or plasma.  They are then sent to a lab for analysis.

Interpretation of ApoA1 Test Results

Normal Reference Range Values

Normal reference ranges for ApoA1 levels may vary depending on the laboratory and the specific assay used for testing.  Gender and age may also affect reference ranges.  

Reference ranges (mg/dL) are reported by one lab company as:  [1.]

Males

0-14 days: 62-91

15 days-11 months: 53-175

1-5 years: 80-164

6-12 years: 107-175

> 12 years: 101-178

Females

0-14 days: 71-97

15 days-11 months: 53-175 

1-5 years: 80-164

6-80 years: 116-209

> 80 years: 114-214

ApoA1 Levels Outside of the Reference Range

Abnormal ApoA1 levels can have significant clinical implications for cardiovascular health. Higher levels of ApoA1 are considered protective against heart disease, as they are associated with increased HDL cholesterol levels and enhanced reverse cholesterol transport.  

High alcohol use, pregnancy, and spring and summer seasons may also raise ApoA1 levels.  [2., 11.]  Otherwise, elevated ApoA1 levels are correlated with a decreased risk of cardiovascular disease and certain neurological diseases including ALS, Alzheimer’s disease, and neurodegeneration.  [6., 15.]

Conversely, lower levels of ApoA1 may indicate an increased risk of atherosclerosis, coronary artery disease, and other cardiovascular conditions. 

Monitoring ApoA1 levels can aid in risk assessment and guide preventive interventions to improve cardiovascular outcomes.

Natural Ways to Optimize ApoA1 Levels

Dietary Strategies

Diets Containing Fermented Dairy Products: diets containing fermented dairy products have been shown to increase ApoA1 levels.  [8., 12.]  

Foods Rich in Omega-3 Fatty Acids: Fatty fish (salmon, mackerel, sardines), flaxseeds, chia seeds, walnuts all have scientific evidence of efficacy in increasing ApoA1 levels and reducing cardiovascular disease risk.  [8., 12.]

Fiber-Rich Foods: Whole grains (oats, barley, quinoa), fruits (apples, berries, oranges), vegetables (broccoli, Brussels sprouts, carrots), legumes (beans, lentils) are all Mediterranean diet staples that have shown effectiveness in raising ApoA1 levels and reducing cardiovascular disease risk.  [12.]

Avoid excess sugar: diets high in sugar are highly negatively correlated with ApoA1 levels.  [8.]

Lifestyle Modifications

Regular Exercise: Aerobic activities (walking, jogging, swimming), strength training, yoga, tai chi may all benefit ApoA1 levels and promote cardiovascular health.  [8., 16.]

Smoking Cessation: Quitting smoking reduces oxidative stress and inflammation, contributing to improved lipid profiles including increases in ApoA1.  [8.]

Stress Management: Techniques such as meditation, deep breathing exercises, yoga, and mindfulness may help lower stress levels and improve overall cardiovascular health,and in some cases may also have a positive effect on lipid profiles.  [14.]

Niacin (Vitamin B3): Niacin supplementation has been shown to increase ApoA1 levels and improve HDL cholesterol levels.  [5.]

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See References

[1.] 016873: Apolipoprotein A-1 | Labcorp. www.labcorp.com. Accessed March 13, 2024. https://www.labcorp.com/tests/016873/apolipoprotein-a-1 

[2.] Apolipoprotein A-I: Reference Range, Interpretation, Collection and Panels. eMedicine. Published online January 24, 2022. Accessed March 13, 2024. https://emedicine.medscape.com/article/2087313-overview#a2 

[3.] Bailey A, Mohiuddin SS. Biochemistry, High Density Lipoprotein. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549802/ 

[4.] Bhale AS, Venkataraman K. Leveraging Knowledge of HDLs Major Protein ApoA1: Structure, function, mutations, and Potential Therapeutics. Biomedicine & Pharmacotherapy. 2022;154:113634. doi:https://doi.org/10.1016/j.biopha.2022.113634 

[5.] Brown WM, Chiacchia FS. Therapies to Increase ApoA-I and HDL-Cholesterol Levels. Drug Target Insights. 2008;3. doi:10.4137/DTI.S447

[6.] Endres K. Apolipoprotein A1, the neglected relative of Apolipoprotein E and its potential role in Alzheimer's disease. Neural Regen Res. 2021 Nov;16(11):2141-2148. doi: 10.4103/1673-5374.310669. PMID: 33818485; PMCID: PMC8354123. 

[7.] Florvall G, Basu S, Larsson A. Apolipoprotein A1 Is a Stronger Prognostic Marker Than Are HDL and LDL Cholesterol for Cardiovascular Disease and Mortality in Elderly Men. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2006;61(12):1262-1266. doi:https://doi.org/10.1093/gerona/61.12.1262 

[8.] Frondelius K, Borg M, Ericson U, Borné Y, Melander O, Sonestedt E. Lifestyle and Dietary Determinants of Serum Apolipoprotein A1 and Apolipoprotein B Concentrations: Cross-Sectional Analyses within a Swedish Cohort of 24,984 Individuals. Nutrients. 2017 Feb 28;9(3):211. doi: 10.3390/nu9030211. PMID: 28264492; PMCID: PMC5372874. 

[9.] Kuyl JM, Mendelsohn D. Observed relationship between ratios HDL-cholesterol/total cholesterol and apolipoprotein A1/apolipoprotein B. Clin Biochem. 1992 Oct;25(5):313-6. doi: 10.1016/0009-9120(92)80004-z. PMID: 1490290.

[10.] Morris G, Puri BK, Bortolasci CC, et al. The role of high-density lipoprotein cholesterol, apolipoprotein A and paraoxonase-1 in the pathophysiology of neuroprogressive disorders. Neuroscience & Biobehavioral Reviews. 2021;125:244-263. doi:https://doi.org/10.1016/j.neubiorev.2021.02.037 

[11.] Mustad V, Derr J, Reddy CC, Pearson TA, Kris-Etherton PM. Seasonal variation in parameters related to coronary heart disease risk in young men. Atherosclerosis. 1996 Sep 27. 126(1):117-29.

[12.] Nacarelli GS, Fasolino T, Davis S. Dietary, macronutrient, micronutrient, and nutrigenetic factors impacting cardiovascular risk markers apolipoprotein B and apolipoprotein A1: a narrative review. Nutrition Reviews. Published online August 23, 2023:nuad102. doi:https://doi.org/10.1093/nutrit/nuad102 

[13.] Nazir S, Jankowski V, Bender G, Zewinger S, Rye KA, van der Vorst EPC. Interaction between high-density lipoproteins and inflammation: Function matters more than concentration! Advanced Drug Delivery Reviews. 2020;159:94-119. doi:https://doi.org/10.1016/j.addr.2020.10.006

[14.] Papp ME, Lindfors P, Nygren-Bonnier M, Gullstrand L, Wändell PE. Effects of High-Intensity Hatha Yoga on Cardiovascular Fitness, Adipocytokines, and Apolipoproteins in Healthy Students: A Randomized Controlled Study. J Altern Complement Med. 2016 Jan;22(1):81-7. doi: 10.1089/acm.2015.0082. Epub 2015 Nov 13. Erratum in: J Altern Complement Med. 2017 May;23(5):396. PMID: 26565690; PMCID: PMC4739349.

[15.] Thompson AG, Talbot K, Turner MR. Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2022 Jan;93(1):75-81. doi: 10.1136/jnnp-2021-327133. Epub 2021 Sep 13. PMID: 34518331; PMCID: PMC8685635. 

[16.] Yazdani R, Marefati H, Shahesmaeili A, Nakhaei S, Bagheri A, Dastoorpoor M. Effect of Aerobic Exercises on Serum Levels of Apolipoprotein A1 and Apolipoprotein B, and Their Ratio in Patients with Chronic Obstructive Pulmonary Disease. Tanaffos. 2018 Feb;17(2):82-89. PMID: 30627178; PMCID: PMC6320561.

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