HDL and Cardiovascular Risk: Rethinking the Relationship

Although lower HDL levels are associated with increased cardiovascular risk, therapies to raise HDL levels have failed to reduce cardiovascular events.  In this sub-study of the longitudinal Dallas Heart Study, the authors turn their attention from absolute levels of HDL to reverse cholesterol transport in the shape of HDL efflux capacity.  This efflux capacity is […]

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Gene mutation reduces risk of coronary disease  

Niemann-Pick C1-like 1 (NPC1L1) protein is expressed in the small intestine and liver and facilitates the transport of intraluminal dietary cholesterol into enterocytes. This transporter is the target of the drug ezetimibe and inhibition of the transporter is known to significantly reduce plasma levels of LDL cholesterol. In this genetic study, the authors first sequenced […]

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PCSK9 shows benefit in cholesterol lowering

Despite the potency of high dose statins, many patients fail to reach targets for LDL cholesterol reduction.  Whilst the addition of a second agent such as niacin or ezetemibe results in an additional 10-20% reduction in cholesterol, there remains an unmet need for more potent therapies.  Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density […]

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Novel cholesterol lowering agent shows promise

Serum PCSK9 plays an active role in controlling the expression of LDL receptors by targeting them for lysosomal destruction.  REGN727/SAR236553 (REGN727) is a novel human monoclonal antibody which inhibits PCSK9 binding to the LDL receptor; a previous phase 1 proof of concept trial suggested the potential for significant reductions in LDL in familial hypercholesterolaemia. […]

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Statins show benefit regardless of CRP

Some previous studies – most noticeably the JUPITER trial – have suggested that the vascular benefits of statin therapy may be greater in the presence of inflammation.  C-reactive protein (CRP), a systemic marker of inflammation, has been associated with the risk of ischaemic heart disease, stroke, and vascular mortality, but its ability to act as […]

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Anacetrapib shows promise

Despite the success of statins for both primary and secondary prevention, many patients continue to have a high residual risk of cardiovascular events related to sub-optimal lipid control.  One approach to raising HDL cholesterol is to inhibit the cholesteryl ester transfer protein (CETP), a plasma protein that promotes the transfer of cholesteryl esters from HDL […]

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