Historia clinica

SAMJ FORUM

CLINICAL PRACTICE

Lp(a) and coronary disease: Rules of engagement – when to  measure and how to treat
R Jayasinghe, K M Kostner  Lipoprotein (a) (Lp(a)) has been described as an important component of the lipid profile and a significant coronary risk factor when elevated. Controversy surrounds the importance of this lipoprotein variant, and its management is often challengingfor clinicians. Important issues relate to the control and management of high Lp(a) levels, especially in patients at intermediate risk of cardiovascular disease. Clear guidelines are lacking on who needs Lp(a) measured, and when. We review practical points on investigating and managing Lp(a). atherogenicity of Lp(a) is 10-fold that of LDL, though the latter dominates in the circulation. Lp(a) isalso highly thrombogenic and bears structural resemblance to plasminogen, which explains its antifibrinolytic properties.4

Coronary risk association
The plasma levels of oxidised phospholipids present in Lp(a) have been implicated in contributing to the atherogenicity of Lp(a),5 which is a strong independent risk factor for CAD in various populations and ethnic groups.6 Lp(a) has a significantand well-described genetic heterogeneity. Its risk associations with vascular disease demonstrate racial and ethnic variations. Higher plasma concentrations are seen in blacks, postmenopausal women and people with hypercholesterolaemia. However, the strongest association with high Lp(a) levels and coronary disease is observed in middle-aged white men. High Lp(a) levels are associated with a highrisk of stroke in blacks and in white women, but not in white men.7 Not all studies associate Lp(a) with increased coronary risk. The Physician’s Health Study found no association between Lp(a) level and the risk of future ischaemic events,8 but this observation could have been due to sampling and/or measurement errors. Some studies measured Lp(a) in longterm, frozen samples with insufficientlyevaluated test kits. Moreover, owing to the wide range of plasma Lp(a) levels from less than 0.001 g/l to more than 3 g/l and the highly skewed distribution, studies that include small numbers of cases/ controls are prone to random deviations.

Background
Lp(a) was first described in 1963 as a genetic variant of β-lipoproteins.1 The physiological functions of Lp(a) remain a mystery. Most studiesstrongly suggest that it is an independent risk factor for cardiovascular disease.2 A meta-analysis concluded that an increased plasma level of Lp(a) is an independent predictor of the presence of coronary artery disease (CAD), particularly in patients with hypercholesterolaemia.3 The combination of high Lp(a) plasma concentrations and other cardiovascular risk factors, in particular lowhigh-density lipoprotein (HDL), strongly increases the risk of CAD. In addition to containing significant amounts of cholesterol and being able to oxidise like lowdensity-lipoprotein (LDL), Lp(a) can exert antifibrinolytic actions, stimulate the proliferation of smooth-muscle cells, facilitate wound healing, act as an acute-phase reactant and generate bioactive derivatives that are retained in the vascularextracellular matrix. Lp(a) has been identified as the link between atherosclerosis and thrombosis. Stoichiometrically the

Measurement
R Jayasinghe, MB BS, PhD, FRACP, an interventional cardiologist, is Professor of Cardiology at Griffith University, Gold Coast, Australia, Professor of Medicine at Bond University, Gold Coast, and Director of Cardiology and Cardiovascular Services at Gold CoastHospital. Studies are sometimes controversial, as it is difficult to standardise the measurement of Lp(a) due to its heterogeneity. Recognition of the biological importance of apolipoprotein (a) (apo(a)) is also reflected by the International Standardization Committee, which recommends that the previous practice of reporting Lp(a) as a total mass be superseded by the measurement of Lp(a) protein...