What are the implications of elevated Apolipoprotein B (ApoB) levels?

From the Guidelines

Apolipoprotein B (ApoB) levels above 130 mg/dL are considered a risk-enhancing factor for atherosclerotic cardiovascular disease (ASCVD), and individuals with elevated ApoB levels should be considered for statin therapy. To manage high ApoB levels, lifestyle modifications are essential, including a heart-healthy diet low in saturated fats and trans fats, regular exercise (aim for 150 minutes of moderate activity weekly), weight management, and avoiding tobacco.

Key Recommendations

• Medications that can effectively reduce ApoB include statins (like atorvastatin 10-80mg daily or rosuvastatin 5-40mg daily), which are typically first-line therapy 1.
• For those who don't respond adequately to statins, ezetimibe (10mg daily) may be added.
• In cases of very high levels or genetic disorders, PCSK9 inhibitors (evolocumab or alirocumab) might be prescribed.

Importance of ApoB Measurement

ApoB provides a more accurate assessment of cardiovascular risk than LDL cholesterol alone because it counts the actual number of atherogenic particles in the bloodstream.

Monitoring and Follow-Up

Regular monitoring through lipid panel testing is important to assess treatment effectiveness, typically every 3-6 months initially and then annually once levels stabilize. According to the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline, an ApoB level above 130 mg/dL is considered a risk-enhancing factor for ASCVD, and statin therapy should be considered in these individuals 1.

From the FDA Drug Label

Rosuvastatin 20 mg significantly reduced LDL-C, total cholesterol, ApoB, and non-HDL-C compared to placebo ApoB (mg/dL)268235-17.1% (-29.2, -2. 9) Results are shown in the table below Table 15: Lipid-modifying Effects of Rosuvastatin 10 mg and 20 mg in Adult Patients with Primary Dysbetalipoproteinemia (Type III hyperlipoproteinemia) After Six Weeks by Median Percent Change (95% CI) from Baseline (N=32) Apo-E16.0-42.9 (-46.3, -33.3) -42.5 (-47. 1, -35. 6)

Apolipoprotein B (ApoB) reduction: Rosuvastatin reduces ApoB levels.

• The reduction in ApoB levels was 17.1% in pediatric patients with HoFH.
• In adult patients with primary dysbetalipoproteinemia, the reduction in Apo-E levels (which is related to ApoB) was 42.9% with rosuvastatin 10 mg and 42.5% with rosuvastatin 20 mg. The use of rosuvastatin may help reduce ApoB levels in patients with high ApoB 2.

From the Research

Apolipoprotein B and Cardiovascular Risk

• Apolipoprotein B (apoB) is a more accurate measure of cardiovascular risk than low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) 3, 4
• ApoB levels indicate the atherogenic particle concentration independent of the particle cholesterol content, which is variable 5
• The 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines concluded that apoB was a more accurate measure of cardiovascular risk and a better guide to the adequacy of lipid lowering than LDL-C or non-HDL-C 4

Relationship between Apolipoprotein B and LDL-Cholesterol

• LDL-C can vary considerably in its cholesterol content, and lowering LDL-C as a goal of statin treatment implies the existence of considerable variation in the extent to which statin treatment removes circulating LDL particles 3
• An LDL-C concentration of 1.8 mmol/L (70 mg/dL) during atorvastatin treatment was equivalent to a non-HDL-C concentration of 2.59 mmol/L (100 mg/dL) or an apoB concentration of 0.8 g/L 3
• To reach an apoB target of <90 mg/dl, it was necessary to reduce non-HDL-C to <100 mg/dl or to reduce LDL-C to <70 mg/dl (in high-triglyceride patients) or <80 mg/dl (in lower-triglyceride patients) during statin therapy 6

Therapeutic Targeting of Apolipoprotein B

• There is strong evidence that apoB is a more accurate indicator of cardiovascular risk than either total cholesterol or LDL cholesterol, and apoB should be the primary metric to guide statin/ezetimibe/PCSK9 therapy 4, 7
• Reduction in all-cause mortality was limited to statins, and for major adverse cardiovascular events (MACE), the relative risk per 10 mg/dL reduction in apoB was 0.93 for all therapies combined 7
• ApoB levels can be measured more accurately than LDL-C or non-HDL-C, and 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 4