Prof Julian Halcox, Professor of Cardiology, Swansea University College of Medicine, UK, speaks with Cardio Debate & Radcliffe Cardiology about Advances in the Management of Dyslipidaemia (Part 1 of 3 interviews), during the 2015 Cardiovascular Sciences Research Centre Annual Meeting held at the Royal College of Surgeons of England in London, UK.
I’m Julian Halcox, I’m Professor of Cardiology at Swansea Medical School. I’m a clinical cardiologist with an interest in cardiac disease prevention.
Can you describe the anti-inflammatory effects of HDLs?
So HDL is a complex lipoprotein. Epidemiologically there is a very strong relationship between levels of HDL cholesterol and cardiovascular events, with high levels appear to be conferring protection. Certainly associated with a reduced risk of cardiovascular events.
Now that’s rather complex because often we see the individuals with the high levels of HDL with better functioning HDL, and conversely people who have lower levels of HDL cholesterol have impaired HDL function. And that’s because HDL is a rather pleotropic lipoprotein. It has a number of effects with many proteins associated with the lipoprotein with a range of effects on the vasculature, and these include anti-inflammatory effects, anti-oxidative effects. It also confers protective effects on the endothelium, it helps with endothelial repair, and perhaps even endothelial-dependent vasodilatation.
So when it comes to understanding the relationship between changing HDL cholesterol levels and outcome, things may not be quite so straightforward.
As we’ve seen in clinical trials with agents that have quite profound effects on HDL cholesterol levels, treatment with these agents hasn’t necessarily translated into impact on outcome. And that’s because if we think of HDL cholesterol as a marker of function that’s probably incorrect.
So having higher levels of HDL doesn’t necessarily mean the HDL is working any better. And in fact it’s highly likely, given what we found out from the clinical trials, that the anti-inflammatory effects and the anti-oxidant effects are very, very important in conferring the protective effect that we seem to see in epidemiological studies.
So the challenge really is to be able to identify agents that influence the function of HDL cholesterol, particularly anti-inflammatory and anti-oxidant effects, but also importantly the reverse-cholesterol transport effects. And think of how we’re able to do that.
So just further to the idea of HDL cholesterol and it’s protective effects on atherosclerosis, it’s important to consider the case of the Apo-A Milano variation of Apo-A. And this is a type of Apo-A that was identified in a family from Italy, and possession of this type of Apo-A was associated with HDL that appeared to have extremely good reverse-cholesterol transport capability.
So interestingly these individuals appeared to have very low levels of HDL cholesterol, but despite that they had very low incidences of myocardial infarction and atherosclerotic cardiovascular disease. And this appeared to be related to the ability of their HDL to translocate lipid from the periphery back to the liver for recycling very rapidly. And indeed, when this Apo-A was reconstituted and put into animal models, and even in a small clinical trial, it seemed to be associated with reduced progression of atherosclerotic disease and indeed regression.
This suggests that it’s not just the HDL cholesterol, it’s how the HDL cholesterol is working, which is very, very important.
And the challenge will clearly be to identify agents that improve the function of the HDL rather than the amount of cholesterol that’s carried within the HDL sub-fraction.