Next, each of these categories – NormoapoB and HyperapoB – is subdivided into two groups on the basis of plasma triglyceride. A plasma triglyceride ≥ 1.5 mmol/l was chosen as the cut point because this is the level at which small cholesterol-depleted LDL particles become common. We will start with NormoapoB, which is divided into NormoTG NormoapoB and HyperTG NormoapoB.

NormoTG NormoapoB includes normal – those with normal lipids and normal apoB and two other phenotypes. First, an important variant of normal is an increased LDL-C ≥ 3.5 mmol/l (> 130 mg/dl) with a normal apoB ( < 1.2 g/l), a phenotype that corresponds to a normal number of cholesterol-enriched particles. This phenotype is present in between 5-10% of the American population and is not associated with any increased cardiovascular risk over a 20-year follow-up period. Unless apoB is measured, these patients cannot be distinguished from those with elevated LDL-C and elevated apoB, who are at increased cardiovascular risk. Unless the correct diagnosis is made, unnecessary concern and treatment may well ensue. Second, an increased cholesterol, also without elevated apoB, can be due to increased LpX, the abnormal lipoprotein particles that are present in biliary cirrhosis and cholestasis and do not appear to convey any increased cardiovascular risk.

The first step to separate the NormoapoB phenotypes with hypertriglyceridemia is to separate them based on TG/apoB ratio. Those with a TG/apoB ratio ≥ 10 (TG in mmol/l and apoB in g/l) are then subdivided into those with an apoB ≥ 0.75 g/l and those with an apoB < 0.75 g/l.

Patients with a TG/apoB ≥ 10 and an apoB ≥ 0.75 g/l are characterized by an increased number of chylomicron and VLDL particles. Most commonly, this phenotype is present in those with a partial deficiency of lipoprotein lipase (LPL) plus a secondary factor such as diabetes mellitus, glucocorticoids, or estrogen therapy (further reading in Chapter 3 and 4 ). Typical values for this phenotype compared with normal are presented in Table 2.1 . Plasma total cholesterol is dramatically elevated as are plasma triglycerides. Plasma total cholesterol is elevated due to cholesterol in chylomicron and VLDL particles, whereas cholesterol in LDL and HDL particles is low. Plasma triglyceride levels are elevated due to the presence of an increased number of chylomicron and VLDL particles. Plasma apoB and LDL apoB are normal although VLDL apoB is twice normal. Given that cardiovascular risk is not substantially elevated in these patients, this argues against normal VLDL particles markedly increasing cardiovascular risk. In this and the other hypertriglyceridemic states LDL particles will be cholesterol depleted and triglyceride enriched whereas VLDL particles are cholesterol and triglyceride enriched.

Patients with a TG/apoB ≥ 10 and an apoB < 0.75 g/l are characterized by an increased number of chylomicron particles. The primary causes of this phenotype, which markedly increases the risk of pancreatitis, are complete deficiency of LPL or apoCII, the essential cofactor for lipoprotein lipase (LPL). Very unusual causes of this phenotype include systemic lupus erythematosus, due to antibodies which interfere with the action of LPL and defect in GPI-anchored HDL binding protein and apoAV deficiency (further reading in Chapter 3 and 4 ). Average values for affected patients compared with normal are given in Table 2.2 . Whereas plasma triglyceride is profoundly elevated, indices of plasma cholesterol are not and apoB is frankly low. Plasma total cholesterol is the consequence of the cholesterol in an increased number of chylomicrons whereas the mass of cholesterol in LDL and HDL particles is profoundly low. Plasma triglycerides are elevated due to presence of the increased number of chylomicron particles, whereas the contribution of LDL and VLDL particles to plasma triglyceride levels is nil. Plasma apoB is low due to the very low number of LDL particles. These create the diagnostic features of the disorder.