What is the significance of Apolipoprotein B (Apo B)?

From the Guidelines

Apolipoprotein B (ApoB) is a crucial biomarker for cardiovascular risk assessment, providing a direct measure of the number of atherogenic particles in the circulation, and its levels should be targeted below 80 mg/dL for high-risk patients and below 65 mg/dL for very high-risk patients with established cardiovascular disease. ApoB represents the total number of potentially harmful lipoprotein particles in the bloodstream, including LDL, VLDL, and lipoprotein(a), with each atherogenic particle containing exactly one ApoB molecule 1. This makes ApoB superior to LDL cholesterol measurements, especially in patients with metabolic syndrome, diabetes, or hypertriglyceridemia, where LDL levels may appear normal despite an elevated number of small, dense LDL particles.

The significance of ApoB can be understood by its role in atherogenesis, as it is contained within all potentially atherogenic lipoproteins, including lipoprotein(a), LDL, IDL, VLDL, and TRL remnants 1. The concentration of ApoB is a good estimate of the number of these particles in plasma, which might be of special importance in the case of high concentrations of small dense LDL 1.

Key points to consider when evaluating ApoB include:

• ApoB levels should be targeted below 80 mg/dL for high-risk patients and below 65 mg/dL for very high-risk patients with established cardiovascular disease 1
• Clinicians should consider measuring ApoB when standard lipid panels show discordance between LDL and non-HDL cholesterol, when triglycerides are elevated, or when patients have diabetes or metabolic syndrome
• Treatment to lower ApoB typically includes statins as first-line therapy, potentially combined with ezetimibe, PCSK9 inhibitors, or bempedoic acid for additional reduction
• Lifestyle modifications including Mediterranean or DASH diets, regular exercise, and weight management also help reduce ApoB levels and cardiovascular risk 1

In terms of clinical decision-making, targeting ApoB levels is a valuable strategy for reducing cardiovascular risk, particularly in high-risk patients. By prioritizing ApoB measurement and treatment, clinicians can better assess and manage cardiovascular risk, ultimately improving patient outcomes in terms of morbidity, mortality, and quality of life 1.

From the FDA Drug Label

Rosuvastatin reduces Total-C, LDL-C, ApoB, non-HDL-C, and TG, and increases HDL-C, in adult patients with hyperlipidemia and mixed dyslipidemia Rosuvastatin significantly reduced LDL-C, total cholesterol, ApoB, and non-HDL-C compared to placebo

The significance of Apolipoprotein B (Apo B) is that it is a primary target for reduction in the treatment of hyperlipidemia and mixed dyslipidemia, as it is a key component of low-density lipoprotein (LDL) cholesterol. Reducing Apo B levels is associated with a decrease in the risk of cardiovascular events. Rosuvastatin has been shown to significantly reduce Apo B levels in adult and pediatric patients with hyperlipidemia, including those with homozygous familial hypercholesterolemia (HoFH) and heterozygous familial hypercholesterolemia (HeFH) 2, 2.

• Key points:
  • Apo B is a primary target for reduction in the treatment of hyperlipidemia and mixed dyslipidemia
  • Reducing Apo B levels is associated with a decrease in the risk of cardiovascular events
  • Rosuvastatin significantly reduces Apo B levels in adult and pediatric patients with hyperlipidemia 2, 2

From the Research

Significance of Apolipoprotein B (Apo B)

• Apolipoprotein B (Apo B) is a more accurate measure of cardiovascular risk and a better guide to the adequacy of lipid lowering than low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (HDL-C) 3.
• The apoB/apoA-I ratio is a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy, with a lower ratio indicating lower risk 4.
• Apo B is a direct measure of the number of circulating atherogenic lipoproteins, making it a single atherogenic lipid marker present in all lipids sub-fractions except HDL-C 5.

Physiological Mechanisms

• The physiological mechanisms responsible for the superiority of Apo B as a marker of cardiovascular risk include the nature and relative numbers of atherogenic Apo B lipoprotein particles, such as chylomicron remnants, very low-density lipoprotein, and low-density lipoprotein particles 6.
• The total number of Apo B particles determines cardiovascular risk, except for dysbetalipoproteinemia, and the mechanisms that govern the number of very low-density lipoprotein and low-density lipoprotein particles are important in understanding the relationship between Apo B and cardiovascular risk 6.

Clinical Implications

• Apo B levels predict ischemic cardiovascular events in both genders and are better than LDL cholesterol in this respect 7.
• The association of mutations and polymorphisms in APOB with plasma Apo B levels and risk of ischemic cardiovascular disease is complex, with most polymorphisms needing to be evaluated separately in association studies 7.
• Apo B should be the primary metric to guide statin/ezetimibe/PCSK9 therapy, as using LDL-C to guide the adequacy of lipid lowering therapy represents an interpretive error of the results of the statin/ezetimibe/PCSK9 inhibitor randomized clinical trials 3.