TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.
This week’s topics include implications of protein S, endothelial cell genetic assessment and lipid lowering, global burden of oral conditions, and cardiac rehab on an app.
Program notes:
0: 44 Protein S
1:44 If you have it you’re 14 times more likely to form a clot
2:41 Survey of oral conditions worldwide
3:41 Untreated caries and periodontitis most common
4:41 Highest in 45-62 year olds
5:01 Deliver cardiac rehab via phone app
6:01 Comparison with normal cardiac rehab
7:03 Having access used to be limiting
7:28 Endothelial cell polygenic risk score
8:30 Used in three cohorts to assess benefit
9:30 Relative risk reductions significant
10:30 On par with other factors that predict risk
11:12 End
Transcript:
Elizabeth: What is the burden of oral conditions worldwide?
Rick: Protein S and its role in thrombosis or formation of clots.
Elizabeth: What does your blood vessel lining have to do with whether you ought to be on a statin or another cholesterol-lowering drug?
Rick: And home-based cardiac rehab using mobile health technologies.
Elizabeth: That’s what we’re talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.
Rick: And I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also dean of the Paul L. Foster School of Medicine.
Elizabeth: So, Rick, I’d like to turn straight to JAMA because I was totally unfamiliar with this protein S, so let’s talk about that.
Rick: We’ve known about it for a long period of time. It’s one of many different proteins that are involved in clot formation. It’s that delicate balance between having adequate clot formation and not too much, and protein S plays an important role in that. People that have a protein S deficiency are more likely to form clots.
What these investigators did — they said, “Okay, how often is it that we have a genetic abnormality that results in abnormal protein S, the most severe type?” Since it’s influenced by things like not only genetics, but environmental things and extragenetic things, how often does that occur? They looked at over 600,000 individuals, 400,000 in the UK Biobank, another 200,000 in the NIH study. They had in many cases both genetics and also proteomics.
The most severe form of genetic abnormality occurs in 0.0009% of individuals. But if you have it, you’re 14 times more likely to form a clot. More likely you have the protein and it’s abnormal, that occurs in about 0.02% of individuals, and it’s about twice as likely to cause clots in the vein.
So when do we need to test this? Well, if someone is going to be on a blood thinner anyway, there’s no need to test for this. But if someone isn’t going to be on a blood thinner and they’ve had a clot, then first check for their protein S levels, and if they’re low, then they’re recommending [to] do the genetic testing.
Elizabeth: So, I guess I’m wondering about the practicality of this study for that very small, less than 1%, of people who end up having this.
Rick: Two practicalities. One is, do we need to test protein S in everybody that has a clot? The answer is no. But in an individual with low protein levels, who have a 14-fold increased risk of having a clot formation, we’re probably going to put those people on lifelong anticoagulation.
Elizabeth: I’d like to go from here, then, to something that does have a lot of global impact and that’s in The Lancet. This is a survey of the global, regional, and national burden of oral conditions between 1990 to 2021 and it’s from the Global Burden of Disease Study 2021.
It turns out that there is just this tremendous amount of untreated dental caries — otherwise known as cavities, of course — severe periodontitis, edentulism, or loss of teeth, and other oral disorders, including lip and oral cavity cancers and orofacial clefts. They calculate the years lived with disability and then years of life lost relative to these oral conditions.
And it turns out that this prevalence of these oral conditions, sans the cleft lip and palate and oral cancers, is just shy of 46,000 per 100,000 population in 2021 with almost 4 billion people affected globally. Among these conditions, untreated cavities — or dental caries — of permanent teeth, and severe periodontitis were the most common.
I just have to add parenthetically, we know already that this notion of periodontitis or gingivitis is associated with some of these other conditions that we know are related to early death like heart disease. Their conclusion is that there have only been minor changes in the burden of oral conditions over the past 30 years, so clearly this is something that we need to focus some attention on.
Rick: Periodontitis, or you call gingivitis, it’s gum disease, is associated with cardiovascular disease, hypertension, diabetes, cancer, things that are stimulated by the inflammation that occurs with this. The prevalence is going up because we have billions of people that haven’t been treated. Oh, by the way, we’re adding millions and millions more each year. A lot of work to do.
Elizabeth: They do note that there are no differences in counts and rates found between sexes and that the compromise of activities of daily living rates were the highest in individuals 45 to 64 years of age, so prime working age. That’s when people are really being impacted by this.
Rick: We’re not talking just about having an occasional cavity. We’re talking about the gum disease, people that are edentulous — don’t have teeth at all.
Elizabeth: Among all the other things that we need to focus some attention on. Let’s turn to your next one. Gosh, can we deliver cardiac rehabilitation at home?
Rick: This is in The Lancet Digital Health. It centers on the fact that coronary heart disease is the leading cause of death and disability globally, and there are numerous studies that show that cardiac rehab can be helpful, and the cardiac rehab usually has multiple phases. If someone has been admitted to the hospital, cardiac rehab starts there. That’s called phase 1. They’re discharged from the hospital; that’s phase 2. Phase 3 is the postcardiac rehab to extend phase 2 throughout the rest of your life.
The unfortunate thing is it’s not accessible to everybody, it’s not convenient, and oftentimes we can’t assemble that cadre of individuals that help, so the number of people that actually participate is somewhere between 15% and 35%.
Can we do better by making it more available to individuals and using mobile health apps? Your cell phone doesn’t require broadband. You can take it with you whenever you go. It can be personalized. So what these investigators did was they looked at all the studies that have been done that have compared mobile health to either usual care or to a normal cardiac rehab in an outpatient setting.
When they compared the mobile health technology to usual care, those individuals had a better walk time, quality of life, a lower blood pressure. They seemed to receive benefit. When they compared the mobile health technology to usual cardiac rehab, it was equivalent and the fact that we can extend it to more individuals means we’re more likely to get them involved.
Elizabeth: Here’s what I’m wondering. As we know, we saw in the study that we talked about a couple weeks ago about people with advanced cancer engaging in their own care by assessing their symptoms and then reporting that, so that the team could then impact on their care. I’m wondering if these mobile health technologies are really going to select for a group of people who have the technology, are willing to work with the technology, and those might be the people who already would be involved in cardiac rehabilitation subsequent to an MI.
Rick: Yep, great question. At one time, having access to mobile health technology was a limiting thing. You can’t find anybody that doesn’t have a mobile phone. You are correct, is that there’ll be some sort of a self-selection bias, but that will be true regardless. But it does help. I think it’s an important tool in our tool chest.
Elizabeth: I agree with that and, as you know, I’m a fan. I think we deliver things to people where they are and we have to figure out, well, what are the barriers to having them adopt it?
Rick: Yeah.
Elizabeth: Finally, let’s turn to Nature Medicine. Endothelial cells, of course, are those cells that form the inside lining of blood vessels. In this case, these folks are taking a look at genetic variants among those endothelial cells to identify LDL cholesterol-sensitive individuals who get the greatest benefit from aggressive lipid-lowering.
Rick: Elizabeth, we’re always looking for ways of identifying who is most likely to benefit. Anytime we can do that and eliminate therapy that’s not going to be helpful, I think it’s good. So tell us a little bit more about this particular study.
Elizabeth: Okay. This is a genome-wide significant single nucleotide polymorphism, or SNPs, that are associated with coronary artery disease, where they identified variants that did have effects on the endothelial cells, from that constructed a 35 single nucleotide polymorphism polygenic risk score that comprised these endothelial cell-specific variants. And then they used this in three different cohorts: a primary prevention population in the UK Biobank that was almost 350,000 people, a trial that tested a statin — the Jupiter trial, just shy of 9,000 — and a secondary prevention cohort that tested a PCSK9 inhibitor, the FOURIER trial, with just shy of 15,000 folks. So, really important populations.
Let me just reiterate: primary prevention, testing a statin in a primary prevention cohort; and then a secondary prevention cohort. Also among these folks their LDL-C concentration, and we’re able to discern that the clinical benefit of LDL-C lowering was greater in individuals who had a high score in this polygenic risk score that they had than in individuals with low or intermediate endothelial cell polygenic risk scores. Their relative risk reductions of 68% in that high group versus 29% in the primary prevention cohort, and then 33% versus 8% in their secondary prevention cohort — so it really does capture those folks who would potentially benefit greatly from having aggressive LDL-C lowering.
Rick: In the past, polygenic risk scores haven’t really added very much to what we know clinically. If this particular thing can capture a risk factor that’s currently not in medical practice, that will be beneficial.
This is a retrospective study, so we need to prospectively study this and then it will only be useful if we can routinely do this. The real question is, in people that otherwise aren’t going to be aggressively treated, can we use this risk score to identify people that we should treat more intensively?
Elizabeth: So I’m going to note that the authors state that their high endothelial cell polygenic risk score was on par for independent risk projection with modifiable risk factors that include systolic blood pressure, high sensitivity, C-reactive protein, and hemoglobin A1C. It could be very accretive if it really is on par with those factors.
Rick: Those things are easy to get. They’re universally available. So if it provides additional information to those, it’s great. If it doesn’t, meh.
Elizabeth: I think what we will agree is that it’s only time that’s going to show us whether this is going to turn out to be practical. On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.
Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.
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