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Accumulation of cholesterol-rich lipoproteins, notably low-density lipoprotein (LDL) cholesterol, in the subendothelial matrix of the artery wall is a key pathological process in atherosclerosis. There is overwhelming evidence that lowering plasma LDL cholesterol concentrations with statins reduces future cardiovascular events, and the effect is proportional to the degree by which LDL cholesterol concentration is lowered.1 Guidelines recommend aggressive LDL reduction in the secondary prevention of coronary artery disease (CAD),2 but, despite this and the control of other well-established risk factors, such patients, particularly after an acute coronary syndrome (ACS), remain at substantial residual risk of further events.3 In patients treated with statins, the risk of recurrent events increases in proportion to the number of components of the metabolic syndrome that they exhibit.4 Clearly other factors, including other lipoprotein abnormalities that are not significantly affected by statins, are of importance in promoting atherosclerosis.
Other than LDL, the major lipoprotein classes in fasting plasma are high-density lipoprotein (HDL) and very LDL (VLDL), together with VLDL remnants formed by intravascular lipolysis of their constituent triglycerides. The fasting plasma triglyceride concentration is a surrogate marker for VLDLs and their remnants; these triglyceride-rich lipoproteins (TRLs) may be atherogenic, being sufficiently small to deliver cholesterol to the subendothelial matrix.5 The pathogenetic role of TRLs in atherogenesis is complicated by the inverse relationship that normally exists between the plasma concentrations of triglyceride and HDL cholesterol.6 Since cholesterol ester is transferred from HDL to VLDL, a process catalysed by cholesterol ester transfer protein, higher levels of VLDL promote this transfer, acting as a large sump for cholesterol ester, and so lead to lower HDL cholesterol concentrations. HDL has a number of properties that protect against cardiovascular disease (CVD), and HDL is well established …