Dr. Budoff, how are you? Good, good to be back with you. Last time we talked, we were discussing a study yet to happen.
Now it's happening, right? Yeah, we are more than halfway enrolled, moving along very well. So, I think you'll agree with me on some caveats. While this data is very exciting, one, it is preliminary, and two, of course, we'd want everyone to continue working with their doctor. Absolutely, yeah.
We never want to try to supplant anyone's healthcare needs. I've answered some questions for people, but definitely they need to maintain their normal health and their normal relationships with their physician. Now, of course, this was pretty exciting for many reasons.
One, the group of people that I was going to bring to you were those who were actually kind of going the opposite way of the guidelines. The ketogenic diet is well known for being rich. in saturated fat, commonly lots of high animal protein and red meat and often very low fiber.
So before we go into the data, if I told you that these were the folks we'd be looking at on top of having LDL cholesterol in the very top percent of the U.S. population, would you guess they'd probably be high risk? Yeah, I would think for all of those reasons you stated that they would be increased cardiac risk. So let's go ahead and talk about the top line aggregates because it's pretty interesting.
64 participants, average age is 53 years, two-thirds of which are 50 and older. 66% male, so that's another checkbox in the risk side of the equation. Mean LDL cholesterol before the diet was 135, which is just a little above the mean of the average for the population. But the mean average now...
And this group is 233, which isn't just in the top 1%. I checked and per NHANES, it's in the top 10% of the top 1%, so the very highest of LDL. And this is probably one of the most fascinating bits is that even though our eligibility was supposed to be two years or longer, our average for this group is around four years.
So that's quite a cohort that we have here. In spite of this, and this is probably the most relevant, two-thirds of this cohort have calcification of zero and no total plaque score. What does that mean? Well, so despite four years of, on average, of LDLs that are, as you said, in the top 0.1% in the U.S., they have not yet developed any atherosclerosis in their coronary arteries as best as we can detect, and there's nothing. right now more sensitive non-invasively than a coronary calcium scan plus a CT angiogram combination, which is what we're using in this study.
Now I'm very interested with this total plaque score of the remaining third that did have some detectable levels of plaque. They had a total plaque score between one and eight. Where does that land in the overall risk level? Yeah, and we'll formally quantify that data more. This is a semi-quantifiable number right now just to give us some idea early on for safety reasons as well as for early population-based reasons to look at the data.
But we look at the plaque as mild, moderate, or severe. We look at how many segments are involved. So given that we're using a 15-segment model and you can have a score of 3 for severe, That can go up to 45. So the maximum score you can get on this total plaque score is 45. Wow.
And the highest we've seen so far is 8. So that's definitely low overall. So even among those participants so far that have had some plaque, it's been quite modest or mild. It's honestly, I mean, even for as much as we tried to explore scenarios on each end of the perspective, This is like actually turned out, am I wrong to say this has been almost a very surprisingly low level of risk given what we expected at baseline?
Yeah, I mean we have to remember that some of the caveats on the flip side of that is we did exclude patients who had diabetes and other established risk factors. So this is a healthier population, but despite that, very low, very low scores and much lower than I anticipated when I, you know, just as I would have thought. when I started the trial.
Of those that have come in, have we found any that have monogenetic FH? So we found one participant out of, we've probably screened about 100 people so far total. We found participant who's had heterozygous FH genetically and had to exclude them based on that on that finding.
That is impressive though because given the again the mean being at 233 clearly there's something going on with the ketogenic diet and full disclosure you and I are now of course on a paper with the lipid energy model do you think this may add substance to the to the possibility that this is in fact very metabolic centric. Yeah, I think it adds a lot of strength to that argument. I think if you had told me you had a population of patients who had LDLs of 233, I'd say 90% at least are heterozygous FH, if we just look at the statistics based on people whose LDLs are at that level.
Clearly, we have 1% in this population. Do you think at this point in time, it's too early to discuss possibly expanding on that? the research, maybe looking at other future kinds of studies that we could do, maybe larger groups over longer periods of time? I think it would be a huge one. To really establish this, we'd really want a confirmatory study.
Like science, one study is interesting, one study is important, but having a confirmatory study is always going to really lend a lot of strength to the argument and it's going to take away any potential for people to assume that. it came out by chance one way or the other, which is unlikely given the statistics involved, but always can never be fully excluded. Would it be fair to say, hey, we're onto something?
This is truly novel data, perhaps unlike any we've seen up to this point. Yeah, and I can't think of any cohort that's well characterized like this. You know, we have a lot of baseline preliminary data, a lot of data on genetic.
genetics, a lot of data on lipid values, a lot of historical data on this population. And to be able to look at their plaque burden or lack of plaque burden at this point is very interesting. I think, again, I really want to encourage everybody to stay in the trial and let us fully enroll the study because we're really not powered to look at the final answer here until we get our full cohort enrolled. So hopefully we can finish the trial and then start really getting... getting out some robust information to the world on what this looks like.
And then what happens over the course of another year in a closed environment. We'll soon be looking at this data against Miami Heart. You brought that up in the prior interview, why this cohort would be of value. Why Miami Heart and what would we be doing in order to best match it?
Yeah, so Miami Heart is a population-based study of CT and geography along with. with coronary calcium scanning done. We analyzed the data here. We were the core lab. They were recruited obviously in Miami, but we were the core lab for reading.
So the readings would be done at the same lab by the same people. So that's a nice parallel as far as the results go between that group and our group. The other thing is that we can exclude patients who have high LDLs from either ketogenic diet or FH because we have all of the demographics in the Baptist Heart, Miami Heart Study. And finally, we can find people who are similar in cardiovascular risk factors, age, gender, ethnicity, and really see what is the prevalence of plaque in the population of people who look like this, lean mass hyper responders, without the LDL, and what the LDL adds or doesn't add as far as cardiovascular risk.