The value of measuring apolipoproteins in the risk assessment of cardiovascular disease

In this article, we review evidence which supports a role for apolipoproteins in routine cardiovascular risk assessment. By measuring both apolipoproteins and cholesterol measures in a single assay, there is the potential to signficantly improve cardiovascular risk assessment.

Blood lipid assays are an integral part of the risk assessment of cardiovascular disease. Cholesterol measures - total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol - have traditionally been the main lipid measures used for this purpose. Blood cholesterol tests are considered to be a gold standard in cardiovascular risk assessment but in recent years, studies have shown that apolipoproteins are more effective at assessing cardiovascular risk than traditional cholesterol assays, especially in certain patient groups.

The development of atherosclerosis 

The distinction between apolipoprotein measurements and cholesterol assays

Measuring ApoB levels represents a possible alternative to standard blood cholesterol tests, providing us with an indication of the exact number of atherogenic particles present: every LDL particle only has one ApoB protein and ApoB is also the structural protein of IDL and VLDL particles. (6) ApoA1, on the other hand, provides an indication of the amount of anti-atherogenic HDL particles present. Apolipoprotein ratio, ApoB/ApoA1, has been found to associate with risk of myocardial infarction, irrespective of cholesterol levels. (7, 8) Several studies have demonstrated that apolipoprotein measurements are more effective at predicting cardiovascular disease events than routine blood cholesterol measurements. (9-12)

Cholesterol levels do not always reflect the amount of harmful lipoprotein particles

Atherogenic dyslipidemia is common in overweight individuals

Apolipoproteins in secondary prevention

Lipid assays are not only used in the primary prevention of cardiovascular disease but also in the monitoring of lipid-lowering medications among high risk patients (e.g. those with known atherosclerotic disease, familiar hypercholesterolemia, or those who have had a myocardial infarction). For these groups of patients, apolipoproteins can also provide valuable information for clinicians. For example, it has been found that some statin-treated patients have high levels of ApoB and an elevated cardiovascular risk, despite having on-target levels of LDL-cholesterol. (2, 17) Identification of such patients enables optimizing their treatment, thereby reducing risk of further illness.

The value of measuring apolipoproteins

Apolipoprotein assays can complement traditional cholesterol assays as they report on the number of lipoprotein particles, whereas standard blood cholesterol tests measure the amount of circulating cholesterol. In terms of cardiovascular disease risk, the concentration of atherogenic particles is more significant than the amount of cholesterol contained in them. This is especially true for overweight people and individuals with metabolic syndrome or type 2 diabetes. For these patient groups, blood cholesterol tests may significantly underestimate the risk of cardiovascular disease. Blood tests that measure apolipoprotein levels may then help clinicians to more accurately identify patients at high risk of disease.

Key points:

  • Blood tests that measure apolipoproteins complement traditional cholesterol assays, as they report on the number of atherogenic particles present, whilst cholesterol assays only indicate the amount of circulating cholesterol. For cardiovascular disease risk, the number of atherogenic particles present is more significant than the amount of cholesterol contained in those particles.
  • In addition to the number of LDLs, ApoB levels also indicate the number of other atherogenic particles.
  • About one-fifth of the population displays a discrepancy between LDL-cholesterol and ApoB levels. For these individuals, ApoB is a better indicator of cardiovascular risk than LDL-cholesterol.
  • Typical patient groups where LDL-cholesterol underestimates the risk of cardiovascular disease include overweight individuals and those with metabolic syndrome or type 2 diabetes.


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