When it comes to predicting heart attack risk, two blood markers are often discussed: LDL cholesterol (LDL-C) and apolipoprotein B (ApoB). While LDL-C has long been the standard in clinical practice, a growing body of evidence—and recent international guidelines—suggest that ApoB is the superior marker for assessing cardiovascular risk.
LDL counts cholesterol mass, and is sometimes calculated
LDL cholesterol, or “bad cholesterol,” measures or calculates the mass of cholesterol carried within low-density lipoprotein (LDL) particles. High LDL-C is associated with increased risk of atherosclerosis and heart attacks, and lowering LDL-C has been a mainstay of cardiovascular prevention for decades.
However, LDL-C is an often calculated from total cholesterol, HDL cholesterol, and triglycerides. A common approximation is the Friedewald equation:
LDL-C = Total Cholesterol - HDL-C - (Triglycerides / 5)
This equation is less accurate when triglycerides are high. Even when LDL is measured directly, however, it’s a less accurate measure than ApoB.
ApoB counts atherogenic cholesterol particles
ApoB (apolipoprotein B) is a protein found on the surface of all atherogenic lipoproteins: LDL, VLDL, IDL, and Lipoprotein(a). Critically, each atherogenic particle carries exactly one ApoB molecule. This means that measuring ApoB in the blood provides a direct count of the total number of atherogenic particles.
Why does this matter? Research shows that the number of these particles is a stronger driver of plaque buildup and heart attack risk than the total cholesterol they contain. Even if LDL-C is normal, a high number of cholesterol-poor LDL particles (reflected by high ApoB) can still increase risk.
Why ApoB outperforms LDL-C
A comprehensive 2023 review in the European Heart Journal (Sniderman et al., 2023) summarizes decades of research:
- ApoB is a more accurate predictor of cardiovascular events than LDL-C or non-HDL cholesterol.
- Discordance between ApoB and LDL-C is common, especially in people with metabolic syndrome, diabetes, or high triglycerides.
- When ApoB and LDL-C disagree, ApoB is the better predictor of risk.
For example, the CARDIA study found that young adults with high ApoB but normal LDL-C had a 55% higher risk of developing coronary artery calcification (a marker of plaque) 25 years later, while those with high LDL-C but normal ApoB did not show increased risk.
Why Does ApoB-LDL Discordance Happen?
LDL-C can underestimate risk in people who have many small, cholesterol-poor LDL particles. This is common in insulin resistance, obesity, and diabetes. In these cases, LDL-C may appear “normal,” but ApoB reveals a high number of atherogenic particles.
Guidelines on ApoB vs LDL are changing
Recognizing this evidence, major international organizations now recommend ApoB as the preferred marker for cardiovascular risk. The European Society of Cardiology and Canadian Cardiovascular Society both recommend ApoB over LDL-C for risk assessment and treatment targets. The U.S. is slower to adopt ApoB testing, with less than 1% of insured Americans getting ApoB measured each year.
Summary: ApoB vs LDL-C
Feature | LDL Cholesterol (LDL-C) | ApoB |
---|---|---|
What it measures | Cholesterol mass in LDL | Number of atherogenic particles |
Direct or indirect? | Indirect (calculated) | Direct (measured) |
Affected by triglycerides? | Yes | No |
Best for risk prediction? | Sometimes | Yes, especially when discordant |
References
- Sniderman AD, et al. “Apolipoprotein B versus non-HDL cholesterol: and the winner is…” European Heart Journal, 2023.
- Wilkins JT, et al. “Discordance Between Apolipoprotein B and LDL-Cholesterol in Young Adults Predicts Coronary Artery Calcification: The CARDIA Study.” J Am Coll Cardiol, 2016.
- Sniderman AD, et al. “Apolipoprotein B versus non-HDL cholesterol and LDL cholesterol as the preferred marker of cardiovascular risk.” J Am Coll Cardiol, 2012.