The Case for Treating Cholesterol Before Plaque Appears | Dr Thomas Dayspring and Dr Dan Soffer

Simon Hill (0:04)

Off the top here, Tom, I think congratulations is in order.

I hear you've received the Master National Lipid Association Award or recognition or status. Congratulations.

Tom Dayspring (0:17)

Thank you. I think the NLA was just feeling sorry for an old man. Let's not make this a posthumous award.

But I'm so appreciative. I've worked long and hard.

Dan Soffer (0:29)

To be clear, we also serenaded him with a happy birthday rendition that brought tears to everyone's eyes.

Tom Dayspring (0:35)

The award came down on my 80th birthday.

Simon Hill (0:38)

Oh, gosh. Well, happy birthday as well. And I feel grateful to have two MNLA-esteemed cardiology experts with me to help us guide through all things primary prevention today.

Dan, you wrote to me recently, and you said that the foundation of managing atherosclerosis is the same for everyone, because the condition is ubiquitous. So I want to start right there. Remind us what atherosclerosis actually is when it starts, how prevalent it is.

Dan Soffer (1:12)

OK, that's a big topic. The atherosclerosis essentially is ubiquitous. I imagine there are humans that don't have any shred of it, but I don't think we have a really way to know that. We can assume that we all are developing atherosclerosis to some degree, but that the rate that we develop that condition varies tremendously between individuals and based upon a lot of different factors. We have talked in the past, and I know Tom has given treatise on this as well, about the atherogenesis process, like how atherosclerosis forms. There's a lot of different ways to describe it, but ultimately, the present model of how atherosclerosis forms is that there are APOB-containing lipoproteins at a particular range in the circulation, ranging from very low levels to very high levels and everything in between, and that those APOB-containing lipoproteins, most of which are able to penetrate through the interface between the bloodstream and the wall of the artery and get into the wall of the artery, and then once they're there, they are transformed in a way that makes them trigger a response by the white blood cells that reside in the arterial wall.

When that white blood cell consumes the atherogenic particle, when it consumes the APO-B-containing lipoprotein that's full of cholesterol, that's the initiation of atherosclerosis. And then you repeat that approximately a gazillion times throughout the course of a lifetime, and there are competing processes that slow it down. And so it's not just a straight line, this is the only thing that's happening, but this is the process. And as it repeats, there's an aggregation of these white blood cells. They're referred to as foam cells after they've consumed an ApoB containing lipoprotein.

And there's an aggregation, and they start acting the way white blood cells do. They start secreting inflammatory cytokines, they start secreting proteases. They actually change the nature of the artery wall. They change the actual structure of the artery wall. And they recruit new white blood cells to the area so that the process propagates. And the atheroma can enlarge, it can enlarge longitudinally, like along the length of the artery, but it can also enlarge centripetally, so that goes outward. And then when it's large enough, it actually will start to indent the area where the blood flows. So it can actually start to create an effect on the blood flow. So that's atherogenesis.

It all happens in all of us. The factors that drive it forward are how many of those atherogenic particles are in the circulation, and how susceptible your endothelium is to allow those particles to get in. And then there are some changes that occur in the artery wall that are very individual dependent.

So two different people on the surface can look like they have exactly the same factors. One person is loaded with plaque, the other person may not have any plaque. And that's the route because there are so many different variables involved. But ultimately, it's those APO-B containing lipoproteins that are the substrate that is necessary for atherosclerosis to form.

Simon Hill (4:41)

And that susceptibility that results in someone being more or less affected by these APO-B containing lipoproteins comes down to things like genetics, blood pressure, insulin sensitivity, smoking, all of these other risk factors.

Dan Soffer (4:56)

Yeah, exactly. The details of that I think are something that I can't say that I fully understand. But I can tell you that all those factors you just mentioned affect the endothelial ability to act as a permeable or impervious membrane to the particles in the circulation. But it goes beyond that. There's also activity in the subendothelium in that it's referred to as a glycoprotein matrix below that top layer, where there are changes occurring that can also affect how quickly this process is taking place. Some of these things are really easy to measure. We can measure someone's blood pressure in lots of different ways. We can measure their blood sugar and insulin sensitivity in a lot of different ways. We can measure all different types of lipid and lipoprotein parameters that tell us about these things too.