does inflammation cause heart disease? does it speed it up? is inflammation necessary? if we
keep it under control, are we safe from heart disease or can we still get it? we get these
questions all the time and I recently got the chance to discuss this topic with the president
of the European atherosclerosis Society, Professor kausik Ray. Professor Ray is a
cardiologist and a professor of Public Health at Imperial College London. he received his medical
degree from the University of Sheffield, a masters from Cambridge and also completed
a postdoctoral fellowship at Harvard before becoming a professor at Imperial. Professor Ray
has published over 200 peer-reviewed studies in cardiovascular disease treatment and prevention,
including dozens of seminal clinical trials, many of which we've covered here on the channel
over the years. he's one of the top experts in cardiovascular disease on the planet so it was
really a privilege to have him on and discuss many topics with him including the role of
inflammation in atherosclerotic cardiovascular disease. here's that part of our conversation
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we know that when you get cholesterol in the vessel wall, the body responds by producing
an inflammatory response in the vessel wall. if you have, let's say, generalized
inflammation, what happens is the vessel wall becomes more likely to attract inflammatory
cells, potentially you may get these particles entering the wall, so if you have inflammation
you accelerate this process, so it's an accelerant in that case, in that situation,
but similarly, if that wasn't true, if you didn't have inflammation accelerating that
process, if you had zero inflammation, you'd still get atherosclerosis but what would happen
is the particles get into the wall and your body produces an inflammatory response. so inflammation
accelerates the whole thing in the same way that diabetes accelerates the whole thing.
so the inflammation would still be triggered locally, just in the localized, in the plaque,
in the artery wall, as a secondary event to the cholesterol being, to the lipoproteins being
retained, is that right? yes. yes. and there is no... is there any way that someone could,
once there is a high concentration of lipoproteins and those particles are being retained, is there
any way to stop the process at that point and prevent the cascade to the inflammation? well, so,
thinking about this in a slightly different way, so what we know, to date there's only one
therapy that's really been clearly proven that targeting inflammation is beneficial,
but when you look at the people, they had a high inflammatory drive, their C-reactive proteins were
above 2 but the risk reduction was 15 percent, it wasn't like, okay, you've got a really high
CRP and I just abolish inflammation and I dropped that now by 50 percent. and these were people with
vascular disease already, so they've got that in the vessel wall, the furring of the blood vessels,
you've got all of that going on, so you can slow that down, reversing it is much much harder and
the only thing that we've seen that reverses that whole process is getting your cholesterol levels
really very very low with combination therapies. On a related note people ask if the benefit of
statins is, because they have an anti-inflammatory role in addition to lowering ApoB,
how much of the benefit is... I think we used to think about that a lot more,
so people refer to this as pleiotropic, so what statins do, like bempedoic acid does,
it reduces production of C-reactive protein in the liver. that's very different from saying
that something reduces inflammation i.e. something that's causing a problem and by
reducing that causal driver and then going to basically reduce the risk. so there is data
both from genetics and also from trials that when you standardize for LDL difference by different
ways of lowering LDL cholesterol, whether it's genes that mimic pcsk9 lowering, statins,
ezetimibe, you get exactly the same benefit, and the same is true when you look at randomized
trials, so that's basically telling you that actually the bulk of the clinically meaningful
effect in a general population is related to the magnitude of the LDL lowering and the duration
of that lowering, and nature doesn't care how you lower LDL cholesterol. I'll make a quick summary
of everything that was said, I think Professor Ray was pretty clear but you guys always ask for
a brief summary at the end so here it is. we can have generalized inflammation throughout the body,
for example with inflammatory conditions, autoimmune disease, inflammatory bowel disease,
that kind of thing, and that tends to accelerate cardiovascular disease, plaque formation. for
example, it can cause more lipoproteins to cross into the artery wall where they can get
stuck. but even in someone without generalized inflammation, with normal inflammatory markers,
when lipoproteins cross into the artery wall and get stuck, that triggers an inflammatory
process that's localized just in the plaque. so inflammation is not a necessary precondition for
plaque to begin. if there's a lot of inflammation everywhere in the body, that's clearly worse.
if there isn't, that's clearly better, but plaque can still form if ApoB is high and if
those lipoproteins can cross into the artery wall and get stuck. for example in clinical
trials that lower cholesterol and ApoB, we see reduction in heart attacks whether people have
elevated inflammatory markers or not. also, lowering apoB without significantly affecting
inflammatory marker levels still lowers risk, still reduces heart attacks. and this goes both
ways, people who have heart disease, who lower their cholesterol with a Statin for example,
can sometimes have high inflammatory markers, and they can have what's called residual risk,
so that's the fraction of risk that's left after you address the lipids. so generalized
inflammation and high cholesterol or apoB are independent risk factors, they're additive.
having both is worse, having one is better and having neither is ideal. and in fact, addressing
both lipids and inflammation is something that's getting a lot of increased attention in the
cardiovascular field recently. how do we lower our inflammation and ApoB? there are pharmaceutical
tools and there are lifestyle strategies. the main lifestyle strategies to control inflammation are
maintaining healthy body weight, not smoking and addressing any underlying inflammatory
diseases. those are not the only factors but they are the main ones as far as lifestyle,
and we have more content in the pipeline coming very soon on diet, nutrition and inflammation.
as far as lowering ApoB, we covered a lot of lifestyle strategies in this previous video, so
check that out, let me know your questions below, take care, I'll catch you guys next week, bye