Apolipoprotein(a) and atherogenesis

Lipoprotein(a) (Lp(a)) consists of a unique apolipoprotein, apolipoprotein(a), (apo(a)) linked by a disulphide bridge to apolipoprotein B of low density lipoprotein (LDL). Apo(a) is homologous with plasminogen and exhibits genetic polymorphism with the commoner phenotypes due to larger forms being associated with lower plasma levels and the less common phenotypes associated with smaller forms and higher plasma levels. The later are more common in patients with macrovascular disease. In a study of 6448 patients with established coronary heart disease we found that 43% had apo(a) levels above 300 units/litre and 10% had levels above 1000 units/litre and a geometric mean of 201 units/litre in contrast to 140 normal controls in whom 25% exceeded 300 units/litre, 1% exceeded 1000 units/litre and the geometric mean was 107 units/litre. Amongst patients with cholesterol levels < 5.5 mmol/L undergoing coronary artery surgery were patients with low HDL levels and raised apo(a) levels who would not be identified in screening focusing primarily on total cholesterol. In patients with both insulin dependent and non insulin dependent diabetes mellitus those with microalbuminuria or albuminuria (known to be at high risk for macrovascular disease) had apo(a) levels comparable to non diabetic patients with coronary artery disease while diabetic patients without microalbuminuria had normal levels of apo(a). It is likely that apo(a) has a role in the accelerated macrovascular disease in diabetic patients with renal disease.