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 Texas Tech Health El Paso, look at the top medical stories of the week.
This week’s topics include GLP-1 receptor agonists and alcohol use disorder, impact of new lipid guidelines on cardiovascular disease risk calculation as well as prevalence of elevated LDL cholesterol, and no luck with a vaccine for gonorrhea.
Program notes:
0:38 New guidelines for cardiovascular disease risk
1:40 21% were reclassified
2:40 More contemporary populations and better data
3:30 Existing meningitis vaccine for gonorrhea
4:30 Incidence in both groups the same
5:30 Randomized trial important
6:18 Prevalence of elevated LDL
7:18 High risk 83% of individuals
8:18 Should be a primary focus
8:30 Taking a GLP-1 agonist and alcohol use disorder
9:30 Did result in fewer hospitalizations for alcohol use disorder when used
10:30 Relative risk reduction
11:30 Pretty low bar
12:41 End
Transcript:
Elizabeth: Can GLP-1s help with alcohol use disorder?
Rick: What’s the prevalence of people with an elevated LDL cholesterol based upon the new guidelines?
Elizabeth: Can the existing meningococcal B vaccine help prevent gonorrhea?
Rick: And what’s the cardiovascular risk reclassification with the new lipid guidelines?
Elizabeth: That’s what we’re talking about this week on TTHealthWatch, 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 Health El Paso.
Elizabeth: Rick, I think there’s been a lot of conversation, and this is from JAMA this week, about these new guidelines and what they’re going to do to people with regard to their calculation of cardiovascular risk. So why don’t we talk about that?
Rick: Great. So we’re going to highlight two studies — the risk reclassification with the new guidelines. There are new equations predicting the risk of cardiovascular disease. We take a person and their current condition. We say, what’s your risk over the next 10 or next 30 years of having cardiovascular disease? And based upon that, we’ll put them into a low risk — there’s a less than 3% chance they’re going to have a cardiovascular event over the next 10 years. If it’s between 3% and 5%, we’re going to call that borderline. If it’s 5% to 10%, we’re going to call that intermediate. Anything over 10% risk, we’re going to consider to be high. They’re thought to be better. The question is, when we apply them and compare them to the old risk classification in 2018, how does it change things?
When they took all individuals, about 21% of individuals reclassified. About two-thirds of them reclassified to a lower risk. That’s 14%. And about 7% were classified to a higher risk. Those that were reclassified lower were primarily males, Blacks, and individuals that are smoking, and females and individuals with diabetes were more likely reclassified to be at a higher risk. And this will change our recommendations about how we treat individuals and how aggressive we are, and what our goals are with regard to getting them to a specific LDL cholesterol.
Elizabeth: I find it interesting because, as we know, women, who have comprised a disproportionately smaller share of those on whom cardiovascular risk calculations have been predicated in the past, that women should move upwards is probably a good thing. People with diabetes, though, I would have thought that they would have already been high on the list of awareness. And then I’m wondering about ethnicities. I’m not sure exactly how to interpret that.
Rick: Yeah. With these newer studies, they give more contemporary populations and better data. Part of the concerns with 2018 is it sounded like we were treating a bunch of individuals. Almost everybody needed to be on statins. In fact, people remarked that we just should put statins in the drinking water.
These newer equations are much more accurate. These are called PREVENT equations or calculations. People can go on the website — and my encouragement is to do that — to look at your individual risk factors to see how it stacks up for not only the next 10 years, but 30 years. The other thing, Elizabeth, is for those that are considered to be in the borderline category, what do you do? We’re going to use other emerging risk factors — family history, for example, coronary artery calcium score — and we can personalize the therapy and obviously have shared decision-making with the patient.
Elizabeth: It would be good for people to go on and check out their own risk because what’s impressive is how many of those risk factors are modifiable.
Rick: Absolutely.
Elizabeth: Let’s turn from here to the New England Journal of Medicine, a disappointing study that’s using the existing Neisseria meningitidis vaccine, which is a four-component vaccine against gonorrhea, which is also a Neisseria in that genus organism. In this study, they took a look at men who have sex with men. And one reason they did that is because these men are at high risk to actually develop gonorrhea, and gonorrhea has been an increasing problem worldwide. And so trying to figure out, well, how can we get our arms around this, is there a vaccine that we can use, is really a pretty important public health issue.
Their primary outcome was a first Neisseria gonorrhoeae infection after the receipt of the vaccine or placebo. They had 587 men who were included in their primary analysis, and the incidence of Neisseria gonorrhoeae infection among the vaccinated group and the unvaccinated group were virtually the same. None of the other secondary outcomes really moved very much. Also, the men who ended up with the vaccine experienced more serious adverse events than the men who did not. As the authors point out, there are a large number of at-risk populations for gonorrhea infection, so this is really very disappointing.
Rick: Neisseria gonorrhoeae is really closely related to Neisseria meningitidis. One causes sexually transmitted infection, the other causes actually meningitis. And it looked like in observational studies, individuals that had received the Neisseria meningitidis vaccine had a 38% risk reduction with regard to getting gonorrhea in the future. Based upon these observational studies, that’s why they tested the vaccine in this high-risk group. These are all high-risk individuals. They’ve had gonorrhea previously. It’s males having sex with males.
The investigators opine several things. One is when you have observational studies, you can’t control for all of the confounding risk factors. That’s why doing a randomized trial is the gold standard. Perhaps the fact that you’re at a very high risk and you’ve already had a gonorrhea infection, subsequent infections may be evasive of the immune response. The authors are very careful to comment is that this applies to this particular population, but may not apply to other populations.
Elizabeth: I would also point out that the authors make the statement that their results cannot be generalized to genital infections in women because of differences in the mechanisms of gonorrhea infection between men and women. Does that beg the question of whether a vaccine that works well in men isn’t going to work in women?
Rick: Yep. For the reasons you mentioned, that’s an entirely different patient population.
Elizabeth: So it sounds like back to the drawing board.
Rick: It is.
Let’s go back to the lipid guidelines again and I’m going to ask a separate question. What’s the prevalence of having an elevated LDL cholesterol according to the recent guidelines? If you’re very low risk, we want your LDL cholesterol to be below 160. If you have an elevated risk, we want it to be below 100. In higher-risk individuals, below 70. And if you’ve already had a cardiovascular event, less than 55. If those are the goals, what’s the prevalence of having an LDL cholesterol above the guidelines?
This is a study conducted in individuals aged 30 to 79 from the NHANES [National Health and Nutrition Examination Survey] from 2021 to 2023. After looking at 2,300 individuals that represented 178 million U.S. adults, they estimated that at least 30% had LDL cholesterols above the guideline-recommended goals. It increased across the higher-risk categories. For example, if you were low risk, only about 10% had an LDL cholesterol that was above the guidelines. If you were borderline or intermediate risk, it was 64%. And if you were high risk, 83% of those individuals had higher cholesterol than the guideline recommends.
The other gap they realized is that about 40% of people who already had cardiovascular disease were not receiving lipid-lowering therapy. And about 76% with primary prevention who had an elevated LDL cholesterol weren’t receiving lipid-lowering therapy. So this shows substantial gaps in our LDL control.
Elizabeth: I’m going to first of all note parenthetically that, gosh, now we have an oral PCSK9 inhibitor. So gosh, even better than the injectables.
Rick: As you mentioned, we’ve got more effective therapies, but these are individuals, many of whom were not even on any type of lipid-lowering therapy to begin with.
Elizabeth: If you were going to rectify this situation, what approach would you take?
Rick: First of all, we need to make patients aware. We can’t put this all on the primary care physicians. We need to get rid of the clinical inertia that’s preventing either primary care physicians or patients from receiving the care. This ought to be a primary focus in terms of preventing cardiovascular disease, which still remains the number one killer across the U.S. and across the globe.
Elizabeth: There’s a public health message.
Finally, let’s turn to The BMJ: the association between taking a GLP-1 receptor agonist and alcohol-related hospitalizations among adults with alcohol use disorder. They had as their participants adults with alcohol use disorder and type 2 diabetes or obesity who started a newer GLP-1 receptor agonist, either semaglutide [Ozempic, Wegovy] or tirzepatide [Mounjaro, Zepbound], or a relevant active comparator between January 2018 and December 2024. They looked at a population who just took medicines for their diabetes alone, an obesity medication, medications for alcohol use disorder with type 2 diabetes, and medications for alcohol use disorder with obesity. And they looked at, well, what is your hazard ratio for alcohol-related hospitalization?
And what they showed basically was that in all four populations they did see a decrease in hospitalizations for alcohol use disorder when a GLP-1 was used. And they found that that was more pronounced with the more recent GLP-1s. So do I think this says we ought to be using this primarily for the treatment or management of alcohol use disorder? I’m not ready to go there. And I thought that the risk reduction was fairly modest.
Rick: I had a different take on it. You’re right. For individuals that had alcohol use disorder and were just taking the GLP-1 to treat their diabetes or their obesity, it lowered the hospitalization risk by about a third. If they were actually using it to treat alcohol use disorder in people with type 2 diabetes or obesity — and that was the specific purpose was to do that — it lowered the risk by two-thirds. That tells me that for individuals that seek treatment — and by the way, this is risk reduction compared to the other known things that are FDA approved — I actually think the data are pretty strong.
Elizabeth: It’s the relative risk reduction among these people. And we’ve talked before about what would it be like to use these things for a primary indication that is not treating diabetes or obesity. And I think that’s where I am. I’m not convinced yet that it’s significant enough that I would use it primarily for this reason.
Rick: It was more effective than the comparators — naltrexone [Vivitrol], disulfiram [Antabuse], acamprosate [Campral] — drugs used to treat alcohol use disorder that are currently available. And these were much more effective. Even in individuals that had alcohol use disorder and obesity, it was much more effective than other anti-obesity medications, about two-thirds more effective. I’m convinced that when I have a patient and they say, listen, I’m having a problem, and I have diabetes or I have obesity. What do you think about GLP-1s? So I’m going to give them a two-thumbs-up.
Elizabeth: The medical treatments for alcohol use disorder are really… they’re not all that persuasive. I mean, I’d like to see them be a lot more effective than they are. And so that these are more effective than that? OK. I’ll give you that.
Rick: What you’re saying is it’s a pretty low bar to come over. Many of our listeners don’t know, we don’t talk about these studies beforehand. We have the conversation in person. The fact that you and I don’t always see the study in the same light surely doesn’t bother me, and I hope it doesn’t bother our listeners as well.
Elizabeth: OK. Also, I just want to point out one other thing that the authors talk about here. They call out socioeconomic status and alcohol use disorder severity. And they say, what about using these things? It’s especially relevant given that the newer ones are higher-cost therapies and that people who may have really severe alcohol use disorder often are also economically challenged, and this might prevent their utility in that group.
Rick: It is. And so the nice thing is when they compare these to the older ones, which are less expensive, they had comparable results.
Elizabeth: 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.
