From the Guidelines
Elevated Very Low-Density Lipoprotein (VLDL) is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD).
Key Points
- VLDL is atherogenic, similar to LDL, and its elevation increases the risk of ASCVD 1.
- Elevated triglycerides, which are carried in VLDL, are associated with an increased risk of ASCVD, especially in individuals with moderate hypertriglyceridemia (fasting or nonfasting triglycerides 175–499 mg/dL) 1.
- Reducing VLDL levels can help reduce the risk of ASCVD, and treatment with certain medications, such as extended-release niacin and fibrates, may be beneficial in addition to statin therapy 1.
- However, it is essential to note that the cholesterol content of triglyceride-rich lipoproteins, including VLDL, varies, and estimating or measuring remnant cholesterol may be a more accurate indicator of ASCVD risk 1.
- Lifestyle modifications, such as regular aerobic exercise and resistance training, can also help improve the lipid profile and reduce the risk of ASCVD 1.
Mechanisms
- VLDL degradation and uptake into macrophage foam cells in the arterial intima contribute to the development of ASCVD 1.
- Exercise enhances the ability of skeletal muscles to utilize lipids, reducing plasma lipid levels, and increases lecithin-cholesterol acyltrans (LCAT) and lipoprotein lipase activity, which helps remove cholesterol from circulation 1.
Clinical Implications
- Clinicians should consider estimating or measuring remnant cholesterol to assess ASCVD risk in individuals with elevated triglycerides 1.
- Treatment strategies should focus on reducing VLDL levels and improving the overall lipid profile, using a combination of lifestyle modifications and medications, such as statins, niacin, and fibrates, as needed 1.
From the Research
Significance of Elevated Very Low-Density Lipoprotein (VLDL)
Elevated VLDL is associated with various cardiovascular risks and diseases. The key points related to the significance of elevated VLDL are:
- VLDL is involved in the development of atherosclerotic cardiovascular disease, with large VLDL particles 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
- Elevated VLDL levels are often found in obese subjects, who also have atherogenic dyslipidaemia, including elevated small, dense low-density lipoprotein (sdLDL) levels and decreased high-density lipoprotein cholesterol (HDL-C) levels 3
- VLDL cholesterol (VLDL-C) is a significant risk marker for coronary heart disease (CHD), along with non-high-density lipoprotein cholesterol (non-HDL-C) and intermediate-density lipoprotein (IDL) cholesterol (IDL-C) 4
- A low VLDL-C level but high VLDL receptor mRNA expression in peripheral white blood cells may be an atherogenic phenotype for atherosclerosis in a community-based population 5
- Elevated VLDL-C levels are associated with increased all-cause and cardiovascular mortality in peritoneal dialysis patients, even after adjusting for various covariates 6
Cardiovascular Risks Associated with Elevated VLDL
The cardiovascular risks associated with elevated VLDL include:
- Atherosclerotic cardiovascular disease
- Coronary heart disease
- Insulin resistance and diabetes incidence
- Atrial remodeling in patients with metabolic syndrome
- Increased all-cause and cardiovascular mortality in peritoneal dialysis patients
Lipoprotein Subclasses and VLDL
The lipoprotein subclasses associated with VLDL include:
- Large VLDL particles, which are correlated with atherosclerosis and insulin resistance
- The most electronegative VLDL subclass, which is highly cytotoxic to endothelial cells
- IDL-C, which is a significant risk marker for coronary heart disease (CHD)
- Non-HDL-C, which is also a significant risk marker for CHD