Lipid Biomarkers: Very Low-Density Lipoprotein (VLDL)

Optimal Takeaways

Very low-density lipoproteins (VLDLs) carry triglycerides and cholesterol through the blood. Once VLDL drops off triglycerides, it becomes intermediate-density lipoprotein and then low-density lipoprotein. The cholesterol remaining on VLDL is considered remnant cholesterol, which may increase the risk of CVD, stroke, and diabetes. Higher VLDL-C is associated with CVD, hypothyroidism, and liver disease.

Standard Range: 0.00 – 29.00 mg/dL (0.00 - 0.75 mmol/L)

The ODX Range: 0.00 - 15.00 mg/dL (0.00 - 0.39 mmol/L)

Low VLDL-C suggests a decreased risk of cardiovascular disease.

High VLDL-C may be associated with subclinical atherosclerosis (Prenner 2014, Gentile 2020), major adverse cardiovascular events, metabolic syndrome (Heidemann 2021), incident myocardial infarction (Balling 2020), and vitamin D insufficiency (Lupton 2016).

Overview

Very low-density lipoprotein (VLDL) is the lipoprotein that initially carries triglycerides primarily but also some cholesterol away from the liver. Approximately 10-15% of circulating cholesterol is carried on VLDL (Raymond 2021). VLDL becomes intermediate-density lipoprotein (IDL), then low-density lipoprotein (LDL) as triglycerides are cleaved away. VLDL and IDL can retain some cholesterol and become enriched with more cholesterol in the circulation, a form called “remnant” cholesterol considered highly atherogenic independent of LDL-cholesterol (Castaner 2020).

Increased remnant cholesterol/VLDL-C is associated with CVD, stroke, and new-onset type 2 diabetes (XIe 2021). Lipoproteins carrying remnant cholesterol are considered more atherogenic than LDL-C because they can be taken up by subendothelial macrophages without the need for oxidation (Schade 2020).

Increasing levels of VLDL-C are associated with cardiovascular disease and its related risk factors. In a prospective cohort study of 8,057 CVD patients in the UCC-SMART study, the highest quartile of VLDL-C at 35-155 mg/dL (0.91-4.01 mmol/L) was significantly associated with major adverse limb events, lipid-lowering medication use (statins and fibrates), metabolic syndrome, and higher total cholesterol, LDL-C, non-HDL-C, triglycerides, Apo B, and hs-CRP. These results were significant compared to the reference group with the lowest levels of VLDL-C at 3.47-17.4 mg/dL (0.09-0.45 mmol/L). In comparison, the highest quartile had a hazard ratio of 1.48 for major adverse cardiovascular events (MACEs) and 1.94 for myocardial infarction specifically (Heidemann 2021).

A follow-up of 25,480 individuals in the prospective Copenhagen General Population Study suggested that elevation in VLDL-C was associated with at least 50% of observed myocardial infarctions. Those having an MI during follow-up also had significantly increased systolic blood pressure, IDL-C, LDL-C, non-HDL-C, and Apo B, and were significantly more likely to be smokers (Balling 2020). Unfortunately, the study did not consider the oxidation of cholesterol in its design.

In the Penn Diabetes Heart Study, a study of cardiovascular risk in type 2 diabetics, increasing VLDL-C was associated with increased coronary artery calcification (CAC), a marker of subclinical atherosclerosis. The association was especially significant in women and subjects with serum triglycerides above 150 mg/dL (­­1.69 mmol/L) (Prenner 2014). Increasing VLDL-C was also significantly associated with subclinical atherosclerosis, identified as increased carotid intima-media thickness (IMT) in a cross-sectional cohort of postmenopausal women (Gentile 2020).

References

Balling, Mie et al. “VLDL Cholesterol Accounts for One-Half of the Risk of Myocardial Infarction Associated With apoB-Containing Lipoproteins.” Journal of the American College of Cardiology vol. 76,23 (2020): 2725-2735. doi:10.1016/j.jacc.2020.09.610

Castaner, Olga et al. “Remnant Cholesterol, Not LDL Cholesterol, Is Associated With Incident Cardiovascular Disease.” Journal of the American College of Cardiology vol. 76,23 (2020): 2712-2724. doi:10.1016/j.jacc.2020.10.008

Gentile, Marco et al. “Association between Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Carotid Intima-Media Thickness in Postmenopausal Women Without Overt Cardiovascular Disease and on LDL-C Target Levels.” Journal of clinical medicine vol. 9,5 1422. 11 May. 2020, doi:10.3390/jcm9051422

Heidemann, Britt E et al. “The relation between VLDL-cholesterol and risk of cardiovascular events in patients with manifest cardiovascular disease.” International journal of cardiology vol. 322 (2021): 251-257. doi:10.1016/j.ijcard.2020.08.030

Lupton, Joshua R et al. “Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study.” Journal of clinical lipidology vol. 10,1 (2016): 72-81.e1. doi:10.1016/j.jacl.2015.09.006

Prenner, Stuart B et al. “Very low density lipoprotein cholesterol associates with coronary artery calcification in type 2 diabetes beyond circulating levels of triglycerides.” Atherosclerosis vol. 236,2 (2014): 244-50. doi:10.1016/j.atherosclerosis.2014.07.008

Raymond, Janice L., et al. Krause and Mahan's Food & the Nutrition Care Process. Elsevier, 2021.

Schade, David S et al. “Cholesterol Review: A Metabolically Important Molecule.” Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists vol. 26,12 (2020): 1514-1523. doi:10.4158/EP-2020-0347

Xie, Guobo et al. “Remnant Cholesterol is an Independent Predictor of New-Onset Diabetes: A Single-Center Cohort Study.” Diabetes, metabolic syndrome and obesity : targets and therapy vol. 14 4735-4745. 3 Dec. 2021, doi:10.2147/DMSO.S341285