insights

Read Time: 3 minutes  |  Written: December 2023

Atherosclerosis is a lipid-driven inflammatory disease of the arteries and is a primary risk factor for atherosclerotic cardiovascular disease (CVD) development and events.¹ In addition, atherogenic dyslipidemia is frequently seen in patients with diabetes or metabolic syndrome and increases their risk of CVD.² Reports indicate a substantial global burden of carotid atherosclerosis with the prevalence of increased carotid intima-media thickness estimated at 27.6%, increased carotid plaque estimated at 21.1%, and carotid stenosis estimated at 1.5%.³ Further, diabetes and metabolic syndrome are highly prevalent worldwide,^4-6 and in the US, only an estimated 6.8% of adults have optimal cardiometabolic health.⁷

Understanding a patient’s cholesterol levels and overall lipid burden is an important component of health interventions for the prevention and treatment of atherosclerosis, metabolic disorders, and CVD. Appropriate laboratory testing of pertinent biomarkers helps clinicians evaluate a patient’s cardiometabolic risks and health and may highlight areas of concern, including genetic red flags. The information gleaned from standard and advanced laboratory tests may also help engage patients in health discussions and guide collaborative clinical decisions.

Beyond the Standard Lipid Profile

A standard lipid panel is often used as part of a cardiometabolic clinical evaluation and provides an overview of a patient’s baseline cardiometabolic biomarkers such as total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterols, and triglycerides. However, standard lipid profiles may not completely represent a patient’s cholesterol-related risk of myocardial infarction and stroke. Clinicians may consider advanced lipid testing to further assess a patient’s lipid burden, to better define their atherosclerosis risk, and to monitor any cholesterol-lowering treatments. This testing measures laboratory analytes such as lipoprotein (a) (Lp(a)) and apolipoprotein B (ApoB), as well as the number of LDL particles (LDL-P), LDL and HDL particle size, and pertinent inflammatory biomarkers like high-sensitivity C-reactive protein (hs-CRP).⁸

Among some patients, elevated levels of Lp(a) have been found to be associated with increased risk for atherosclerotic CVD,⁸ and plasma ApoB has been associated with risk of major adverse cardiovascular events such as myocardial infarction, stroke, and CVD mortality.⁹ Reports indicate that small and dense LDL-P is a significant predictor of cardiovascular risk and may be more accurate in this prediction than the standard LDL cholesterol measurements.¹⁰ Of note, the level of plasma ApoB is determined by levels of LDL-P;¹¹ therefore, ApoB may also offer a more precise measurement of heart health compared to LDL cholesterol levels for some patients.¹²

Lifestyle-Based Treatment Approaches

While laboratory analyte measurements highlight a patient’s risk and risk-enhancing factors for atherosclerosis and atherosclerotic CVD, they also inform functional medicine treatment approaches that consider potential underlying causes, from inflammation, lipid burden, and HDL function to endothelial function, metabolic dysfunction, and genetics. Modifiable lifestyle factors such as stress management, nutritious diet, and physical activity all have well-documented associations with heart health. Recent research emphasizes the benefit of lifestyle-based approaches specific to cholesterol-related CVD risks¹³ such as significant reduction in LDL-P¹⁴ and decreased levels of total cholesterol, LDL cholesterol, ApoB, and Lp(a).¹⁵

Lifestyle-based treatments such as dietary and exercise prescriptions are foundational in the functional medicine approach to optimal cardiometabolic health. In addition, more precise labs such as advanced lipid testing may also be appropriate for some patients to fully inform a personalized heart health intervention toward the prevention or reversal of dyslipidemias and atherosclerosis. At IFM’s Cardiometabolic Advanced Practice Module, learn more about cardiometabolic lab evaluations and how these biomarkers help inform functional medicine treatment approaches.

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References

1. Pahwa R, Jialal I. Atherosclerosis. StatPearls Publishing; August 8, 2023. https://www.ncbi.nlm.nih.gov/books/NBK507799/
2. Pirillo A, Casula M, Olmastroni E, Norata GD, Catapano AL. Global epidemiology of dyslipidaemias. Nat Rev Cardiol. 2021;18(10):689-700. doi:1038/s41569-021-00541-4
3. Song P, Fang Z, Wang H, et al. Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study. Lancet Glob Health. 2020;8(5):e721-e729. doi:1016/S2214-109X(20)30117-0
4. GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021 [published correction appears in Lancet. 2023;402(10408):1132]. Lancet. 2023;402(10397):203-234. doi:1016/S0140-6736(23)01301-6
5. Noubiap JJ, Nansseu JR, Lontchi-Yimagou E, et al. Geographic distribution of metabolic syndrome and its components in the general adult population: a meta-analysis of global data from 28 million individuals. Diabetes Res Clin Pract. 2022;188:109924. doi:1016/j.diabres.2022.109924
6. Liang X, Or B, Tsoi MF, Cheung CL, Cheung BMY. Prevalence of metabolic syndrome in the United States National Health and Nutrition Examination Survey 2011-18. Postgrad Med J. 2023;99(1175):985-992. doi:1093/postmj/qgad008
7. O’Hearn M, Lauren BN, Wong JB, Kim DD, Mozaffarian D. Trends and disparities in cardiometabolic health among U.S. adults, 1999-2018. J Am Coll Cardiol. 2022;80(2):138-151. doi:1016/j.jacc.2022.04.046
8. Sykes AV, Patel N, Lee D, Taub PR. Integrating advanced lipid testing and biomarkers in assessment and treatment. Curr Cardiol Rep. 2022;24(11):1647-1655. doi:1007/s11886-022-01775-5
9. Walldius G, de Faire U, Alfredsson L, et al. Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio—experience from the Swedish AMORIS cohort: a cohort study. PLoS Med. 2021;18(12):e1003853. doi:1371/journal.pmed.1003853
10.  Qiao YN, Zou YL, Guo SD. Low-density lipoprotein particles in atherosclerosis. Front Physiol. 2022;13:931931. doi:3389/fphys.2022.931931
11.  Glavinovic T, Thanassoulis G, de Graaf J, Couture P, Hegele RA, Sniderman AD. Physiological bases for the superiority of apolipoprotein B over low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol as a marker of cardiovascular risk. J Am Heart Assoc. 2022;11(20):e025858. doi:1161/JAHA.122.025858
12.  Marston NA, Giugliano RP, Melloni GEM, et al. Association of apolipoprotein B-containing lipoproteins and risk of myocardial infarction in individuals with and without atherosclerosis: distinguishing between particle concentration, type, and content. JAMA Cardiol. 2022;7(3):250-256. doi:1001/jamacardio.2021.5083
13.  Haslam DE, Chasman DI, Peloso GM, et al. Sugar-sweetened beverage consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations in US adults. J Nutr. 2022;152(11):2534-2545. doi:1093/jn/nxac166
14.  Falkenhain K, Roach LA, McCreary S, et al. Effect of carbohydrate-restricted dietary interventions on LDL particle size and number in adults in the context of weight loss or weight maintenance: a systematic review and meta-analysis. Am J Clin Nutr. 2021;114(4):1455-1466. doi:1093/ajcn/nqab212
15.  Xue T, Chiao B, Xu T, et al. The heart-brain axis: a proteomics study of meditation on the cardiovascular system of Tibetan monks. EBioMedicine. 2022;80:104026. doi:1016/j.ebiom.2022.104026