Dalcetrapib and endothelial function

- Bridging the gap between pathological risk factors and adverse clinical outcomes

- DAL-VESSEL and DAL-PLAQUE: due to report at Hotline session at ESC Congress

- 79th EAS Congress, Gothenburg, Sweden, Sunday 26th June

Modulating high-density lipoprotein (HDL) by treatment with the cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib might impact vascular tone and normalise endothelial function. This is the hypothesis for the DAL-VESSEL study, the first large multicentre trial comparing the effects of treatment with dalcetrapib vs. placebo in statin-treated patients with low HDL cholesterol and appropriately treated LDL cholesterol. Flow mediated vasodilation (FMD) is the primary endpoint in the trial. Professor Deanfield, Professor of Cardiology and Head of Cardiovascular Prevention, University College London, UK announced that results from this study will be reported at a hot-line session at the European Society of Cardiology Congress later this year. He also reported preliminary findings in individuals with gum disease, a chronic inflammatory disease. Resolution of the inflammation improved FMD. These early findings were reported during the Educational Symposium: Modifying CETP to reduce cardiovascular risk?

The underlying atherosclerotic process precedes clinical evidence of cardiovascular disease by several decades suggesting the possibility to intervene early to reduce ‘lifetime’cardiovascular risk. Endothelial dysfunction is considered to be the first stage of atherosclerosis. Detection at this stage can help to decrease or prevent progression of atherosclerosis. Nitric oxide plays a key role in determining the health of the vascular endothelium, acting as a regulator of the inflammatory status in the vessel wall. The flow-mediated dilatory response of the vascular wall is dependent on NO availability, and can be measured non-invasively to characterise the vascular wall biology. FMD is also predictive of carotid intima-media thickness progression when measured at an early stage. FMD offers the possibility of studying the long pre-clinical phase of atherosclerosis.

Noninvasive measures of arterial function such as FMD are clearly useful in bridging the gap between pathological risk factors, endothelial function and adverse clinical outcomes. Such measures are valuable as surrogate tools for non-invasive assessment of cardiovascular risk, with the aim of intervening earlier to reduce this risk.