What is the significance of Very Low Density Lipoprotein (VLDL)?

From the Guidelines

Very Low Density Lipoprotein (VLDL) is a significant blood lipid particle that plays a crucial role in transporting triglycerides, cholesterol, and phospholipids from the liver to peripheral tissues throughout the body, and its elevated levels are associated with increased cardiovascular risk. VLDL is primarily produced in the liver and contains approximately 50-65% triglycerides, making it the main carrier of endogenous triglycerides in the bloodstream 1. Its significance lies in its metabolic pathway, as VLDL is eventually converted to Low Density Lipoprotein (LDL) through the action of lipoprotein lipase, which removes triglycerides from VLDL particles. Some key points to consider about VLDL include:

• Elevated VLDL levels (normal range typically 5-40 mg/dL) are associated with increased cardiovascular risk, as they contribute to atherosclerosis development 1.
• High VLDL levels often occur in conditions like obesity, diabetes, metabolic syndrome, and excessive alcohol consumption.
• Management of elevated VLDL typically involves lifestyle modifications including weight loss, regular exercise, reducing alcohol intake, and limiting simple carbohydrates.
• In some cases, medications such as fibrates (like fenofibrate 145mg daily or gemfibrozil 600mg twice daily), statins, or omega-3 fatty acids may be prescribed to help lower VLDL levels, particularly when lifestyle changes are insufficient. The relationship between VLDL and cardiovascular risk is further supported by studies showing that triglyceride-rich lipoproteins, including VLDL, can be taken up directly by macrophages, leading to the formation of foam cells and contributing to atherosclerosis development 1. Overall, VLDL plays a significant role in lipid metabolism and cardiovascular health, and its management is crucial for reducing the risk of cardiovascular disease.

From the Research

Significance of VLDL

The significance of Very Low Density Lipoprotein (VLDL) can be understood through its role in the body and its impact on health.

• VLDL is secreted by the liver and plays a crucial role in transporting cholesterol and other lipids to organs and cells for utilization 2, 3.
• VLDL is also known to contribute to the development of atherosclerotic cardiovascular disease, with large VLDL particles being significantly correlated with atherosclerosis, insulin resistance, and diabetes incidence 2.
• The most electronegative VLDL subclass is highly cytotoxic to endothelial cells and may contribute to coronary heart disease, as well as atrial remodeling in patients with metabolic syndrome 2.
• VLDL levels are affected by various endocrinological disorders and can be increased by therapeutic supplementation with certain hormones, such as cortisol, growth hormone, progesterone, and estrogen 3.
• Emerging evidence suggests that VLDL promotes atherosclerosis in metabolic syndrome, induces atrial myopathy, and promotes vulnerability to atrial fibrillation, as well as contributing to hypertension, neuroinflammation, and cognitive dysfunction 3.

VLDL and Cardiovascular Disease

The relationship between VLDL and cardiovascular disease is complex, with studies suggesting that:

• VLDL-cholesterol may mediate a substantial component of the effect of obesity on myocardial infarction risk, with cholesterol in large and small VLDLs combined explaining 40% of the excess risk of myocardial infarction associated with higher BMI 4.
• VLDL-C is not associated with risk of major adverse cardiovascular events (MACE) or all-cause mortality, but is associated with an increased risk of major adverse limb events (MALE) in patients with clinically manifest cardiovascular disease 5.
• Remnant lipoproteins, including IDL and smaller VLDL, may share with LDL the potential for promoting atherosclerosis, whereas very large VLDL and chylomicrons do not seem to have this effect 6.

VLDL Subclasses and Disease

Different subclasses of VLDL have been identified, with varying effects on health:

• Large VLDL particles are significantly correlated with atherosclerosis, insulin resistance, and diabetes incidence 2.
• The most electronegative VLDL subclass is highly cytotoxic to endothelial cells and may contribute to coronary heart disease, as well as atrial remodeling in patients with metabolic syndrome 2.
• VLDL isolated from subjects with metabolic syndrome exhibits cytotoxicity to atrial myocytes, induces atrial myopathy, and promotes vulnerability to atrial fibrillation 3.