Apolipoprotein B

Apolipoprotein B (apoB) is the structural protein of every atherogenic lipoprotein. VLDL, IDL, LDL, lipoprotein(a) and chylomicron remnants each carry one apoB-100 molecule, so serum apoB counts atherogenic particles, while LDL cholesterol (LDL-C) and non-HDL cholesterol measure the cholesterol those particles carry. It is measured by immunoturbidimetry or nephelometry, needs no fasting and is calibrated to an international reference material.

Arterial wall retention depends on particle number. When the cholesterol content of each particle varies, for example in insulin resistance, diabetes, obesity and hypertriglyceridaemia, LDL-C understates the number of particles and the risk. Discordance between LDL-C and apoB is common in these groups and in people on lipid lowering treatment. When the two disagree, apoB predicts vascular events better.

Indications. Triglycerides over 1.5 mmol/L (133 mg/dL), diabetes, metabolic syndrome, obesity, a low or borderline LDL-C with premature vascular disease, suspected familial combined hyperlipidaemia, monitoring of treatment when calculated LDL-C is unreliable, and investigation of a very low cholesterol (suspected hypobetalipoproteinaemia or abetalipoproteinaemia).

Specimen. Serum or plasma, non-fasting. Stable for several days at 2 to 8 °C, and for longer when frozen.

Reference range. About 0.6 to 1.3 g/L (60 to 130 mg/dL) in adults, slightly higher in men and rising with age. Multiply g/L by 100 to give mg/dL. Local ranges take precedence.

Decision thresholds. Targets follow cardiovascular risk and are approximately matched to LDL-C targets.

A value of 1.3 g/L (130 mg/dL) or more counts as a risk enhancing factor, roughly matching an LDL-C of 4.1 mmol/L (160 mg/dL). The ratio of apoB to apolipoprotein A-I carries similar information, with values over about 0.9 in men and 0.8 in women indicating raised risk, but it is used less often.

High apoB with normal or low LDL-C. Many small, cholesterol poor LDL particles. Causes are hypertriglyceridaemia with insulin resistance, type 2 diabetes, metabolic syndrome, familial combined hyperlipidaemia, obesity, chronic kidney disease, and treatment with corticosteroids, ciclosporin, protease inhibitors, atypical antipsychotics or retinoids. LDL-C then understates risk.

Low apoB with high LDL-C. Large, cholesterol rich particles, and a lower particle number than LDL-C suggests. Risk follows apoB more closely than LDL-C.

Causes of raised apoB. Familial hypercholesterolaemia (LDLR, APOB and PCSK9 variants), familial combined hyperlipidaemia, hypothyroidism, nephrotic syndrome, cholestasis, diabetes, obesity, high saturated fat intake, pregnancy, corticosteroids, ciclosporin, protease inhibitors, atypical antipsychotics and retinoids.

Causes of lowered apoB. Statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, inclisiran, hyperthyroidism, malnutrition, malabsorption, advanced liver disease, acute illness, and inherited disorders. Familial hypobetalipoproteinaemia (truncating APOB variants, apoB usually under about 0.5 g/L in heterozygotes) causes fatty liver and mild fat soluble vitamin deficiency. Abetalipoproteinaemia (MTTP variants) gives an undetectable apoB.

Effect of lipoprotein(a). Each lipoprotein(a) particle carries one apoB molecule, so a high lipoprotein(a) raises apoB modestly and also raises LDL-C through its cholesterol content.

Familial dysbetalipoproteinaemia. Cholesterol and triglycerides are both markedly raised, with apoB disproportionately low for the cholesterol, because remnant particles carry much cholesterol for each apoB molecule.

Critical findings needing immediate action. There is no emergency value in adults. An undetectable apoB in an infant or child with steatorrhoea, failure to thrive, acanthocytes, ataxia or visual loss suggests abetalipoproteinaemia and needs prompt specialist referral, because fat soluble vitamin deficiency causes irreversible neurological and retinal damage.

Interferences and pitfalls.

• Assays differ in design, so use a method traceable to a common calibrator and use the same method for serial values.
• Marked lipaemia (triglycerides over about 10 mmol/L) can interfere with turbidimetric assays, and very high concentrations can show antigen excess with a falsely low result on nephelometry.
• It does not separate LDL from other apoB-containing particles or measure particle size.
• Acute illness and the first weeks after a vascular event lower apoB, as they lower LDL-C.
• Within person variation is about 6 to 8%.
• It is not a substitute for a full lipid profile when triglycerides or HDL-C matter.

Special groups.

• Children: values are lower and age specific. Levels over about 1.0 g/L in childhood suggest a familial disorder, and the paediatric LDL-C thresholds apply.
• Pregnancy: apoB rises by about 30 to 50% in the third trimester, and testing is deferred until after delivery and lactation unless severe.
• Older adults: values rise with age, and risk based thresholds apply.
• Chronic kidney disease and HIV: raised apoB with high triglycerides is typical.
• South Asian populations carry higher risk at the same apoB, and risk estimates may understate it.

Follow up tests. Lipid profile with non-HDL-C, lipoprotein(a), TSH, HbA1c, liver function tests, urea and electrolytes, urine albumin-to-creatinine ratio, genetic testing for LDLR, APOB, PCSK9, MTTP and LPL variants, cascade testing of relatives, carotid ultrasound, coronary calcium score.