Although low-density lipoprotein (LDL) cholesterol remains the lipid value commonly used to assess cardiovascular risk, apolipoprotein (apo) B may better reflect lipid risk. Six categories of evidence support this conclusion: small, dense LDL particles, as measured by apo B, are more commonly present in persons with coronary artery disease (CAD) than an increased LDL cholesterol level; increased very-low-density lipoprotein (VLDL) secretion by the liver results in increased small, dense LDL particles; small, dense LDL particles are more atherogenic than normal LDL particles; apo B more accurately identifies CAD risk than do LDL cholesterol levels; apo B assays do not require fasting and have been well standardized for use in routine laboratories; and the level of apo B continues to predict CAD risk during statin treatment. Sniderman reviews the evidence supporting the value of apo B in predicting CAD risk and its superiority over calculated LDL cholesterol levels.

LDL cholesterol levels can be inaccurate in patients with elevated triglyceride levels, diabetes mellitus, type 3 dyslipoproteinemia, nephrotic syndrome, and liver disease. Techniques to directly determine LDL cholesterol levels are expensive and poorly standardized. A target value of apo B of less than 90 mg per dL (0.9 g per L) in patients with CAD or at high risk for CAD has been established by the Canadian Cardiovascular Society, with recent evidence supporting the lowering of this optimal threshold to 80 mg per dL (0.8 g per L). The biochemistry behind this thinking is that LDL cholesterol particles vary in the amount of cholesterol they contain and that the small, dense LDL particles are cholesterol-depleted. Each VLDL and LDL particle contains one molecule of apo B, which allows for a more accurate quantitation of the atherogenic particles that are present.

Common clinical scenarios support the use of apo B in risk assessment and monitoring of dyslipidemia treatment. In patients with hypertriglyceridemia, LDL cholesterol may not be calculable or may not represent true CAD risk. In patients with hypercholesterolemia, apo B measurement will identify patients who are at higher risk because of an increased number of small, dense LDL particles. In severe hypercholesterolemia, apo B measurement is less useful because these patients are likely to have equally high CAD risk. In patients who have normal cholesterol and triglyceride levels, apo B measurement will again single out those at higher risk because it identifies the risk-increasing small, dense LDL particles.

Sniderman concludes that noting the number of LDL particles and their composition (lipoproteins) is more useful than noting the LDL cholesterol level. Apo B is a better measure of CAD risk than total- or LDL-cholesterol level in many situations, although its increased utility is negligible at extremes of LDL cholesterol values. Apo B quantitation also may be a better measure of statin therapy efficacy and can be performed on nonfasting blood samples.

editor’s note: Patients with elevated apo B levels have an increased risk of fatal acute myocardial infarction (Walldius G, et al. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocar-dial infarction (AMORIS study): a prospective study. Lancet 2001;358:2026–33). Phenotype B small, dense lipoprotein particles may have increased susceptibility to lipid peroxidative modification, resulting in higher atherogenic-ity and higher risk of CAD. Measurement of apo B allows quantitation of these small, dense lipoprotein particles, thus offering a sensitive test for CAD risk. Higher levels of apo B may identify patients with low levels of high-density lipoprotein cholesterol and normal plasma triglyceride and cholesterol levels who are actually at elevated risk and might benefit from statin therapy.—r.s.