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HDL and Cardiovascular Risk: Rethinking the Relationship

17 Feb, 15 | by Alistair Lindsay

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 a measure of HDL particles’ ability to accept cholesterol from macrophages.  Using a novel fluorescent cellular assay, HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity were measured in 2924 adults with no history of cardiovascular disease.  The primary end-point was a cardiovascular event, which included a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes over a median of 9.4 years of follow-up.   more…

Lipid-related markers improve cardiovascular disease prediction

2 Jul, 12 | by Alistair Lindsay

While the measurement and management of cholesterol forms an integral part of cardiovascular risk management, it has been suggested that risk assessment could be improved by the assessment of various additional lipid-related markers either to supplement or replace traditional cholesterol measurements.  The aim of this paper was to determine whether cardiovascular risk prediction could be improved by adding information on other lipid-related markers, including: apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2. more…

AIM-HIGH fails to fly

1 Dec, 11 | by Alistair Lindsay

Despite the efficacy of statins in reducing the risk of cardiovascular disease a substantial number of patients go on to have further events, even when LDL cholesterol targets are achieved.  Consequently, interest has grown in combination therapy approaches and the HDL raising treatment niacin – a drug now over 50 years old – has enjoyed something of a renaissance of late in this regard. more…

When good cholesterol turns bad

14 Aug, 11 | by Alistair Lindsay

Increasing levels of circulating HDL (“good cholesterol”) has been targeted as an important therapeutic goal in reducing the risk of patients with coronary disease.  HDL has been shown to have a variety of potentially beneficial effects including cholesterol efflux from foam cells, promotion of endothelial repair mechanisms and stimulation of the enzyme eNOS to increase nitric oxide (NO) production.  Unfortunately, though a variety of therapies have been shown to be able to increase HDL levels, none have demonstrated significant clinical benefit with the CETP inhibitor torcetrapib even demonstrating harm, although off-target effects on blood pressure may have contributed to this.  The reasons for this profound lack of efficacy remain obscure, but in this mechanistic study the authors examine this question in greater detail. more…

HDL function and atherosclerosis

13 Feb, 11 | by Alistair Lindsay

There is a strong inverse relationship between serum levels of HDL and the risk of developing atherosclerotic cardiovascular disease.  This has fostered the search for pharmacological agents that raise HDL, but while several therapies have shown biochemical benefit – including nicotinic acid, fibrates and CETP inhibitors – there are little convincing data to associate these rises with significant reductions in clinical risk.  Indeed, there are increasing questions regarding the benefit of HDL increases per se, with HDL particle composition and biological activity being increasingly recognised as key metrics which static measurements are too blunt to identify. more…

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