Aspirin Overuse; Biotypes of Depression and Anxiety

— Also in TTHealthWatch: medications and the liver, and managing gestational diabetes


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 six biotypes for anxiety and depression, overuse of aspirin for primary prevention, managing gestational diabetes, and medicines and acute liver injury.

Program notes:

0:33 Overuse of aspirin for primary prevention

1:32 Discouraged use in those over 75

2:32 Our listeners need to talk with their doctor

2:52 Gestational diabetes management

3:52 Increased C-sections, macrosomia

4:52 Start in prepregnancy period

5:52 Eight to ten fold risk

6:54 Acute liver injury and medications

7:54 Seventeen medications associated

8:54 Six biotypes in depression and anxiety

9:54 Task and no task brain scans

10:52 Large number of things contribute

11:52 MRI before and after treatment

12:41 End


Elizabeth: Can we divide depression and anxiety into clinically actionable phenotypes?

Rick: Are we overusing aspirin in the prevention of stroke and heart disease?

Elizabeth: Rethinking gestational diabetes.

Rick: And drug-induced liver injury.

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 University Health Sciences Center in El Paso, where I'm also dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, since we have already talked a little bit before we started recording about your specialty, cardiology, why don't we turn first to Annals of Internal Medicine, looking at, "Gosh, there is an awful lot of adults out there who are taking aspirin."

Rick: It's been a roller coaster. When I graduated from medical school decades ago, we weren't even using aspirin routinely. Then we found out, gosh, it can be really helpful for both secondary prevention and for primary prevention.

We went through a period where we used aspirin in just about anybody over the age of 40. Then we realized, gosh, if you do that, it does have some side effects, causing bleeding and oftentimes gastrointestinal bleeding. We have actually tried to refine it now. The people that you might give it to for primary prevention are those that are at really increased risk of cardiovascular disease or stroke and those that are at minimal risk where the harms of aspirin outweigh the benefits.

In 2019, the American College of Cardiology and the American Heart Association discouraged primary prevention aspirin use in adults older than 70 years of age. Those individuals are particularly at high risk of bleeding. What these investigators did was they said, "If that's the encouragement, how often are we not following that advice?" They looked at a very large cross-sectional health survey of how many people are in primary prevention. What they found out was between the ages of 60 to 69, about 20% of individuals are receiving aspirin for primary prevention. For those over the age of 70, it's as high as 35%.

Elizabeth: Is this something that they are just choosing voluntarily or are their PCPs saying you're on aspirin? Certainly, if they are fessing up in a survey, I would think they are also fessing up when they see their PCPs.

Rick: Well, Elizabeth, that's a great question. Of that 30% that are taking aspirin, this is individuals over the age of 70, about 5% are self-medicating and the other 25% are taking it because their physician has recommended it.

Elizabeth: All right. How do we turn the Titanic here?

Rick: Well, this is part of it. It's first of all taking a look at it. Our listeners who are over the age of 60 or 70 need to talk to their physician.

Elizabeth: Speaking of trying to interrupt this gigantic ship that seems to be steaming in a certain direction, let's talk about gestational diabetes and that's in The Lancet. This is a series, so what I'm going to try to do is hit the highlights because it's a really big series.

At the beginning of this series, they cite the fact that gestational diabetes is the most common medical complication in pregnancy. In general, the medical thought has been that treatment of rising blood sugar starts happening late in the second trimester. Now, there is new evidence that's suggesting both pre-pregnancy and pregnancy-specific factors influence this gestational change in blood sugar, and that metabolic perturbations of early gestational diabetes -- which is a new kind of a thought for me, that we can subdivide this into two types, early and later gestational diabetes -- can produce a lot of troubling consequences for both the fetus and for the mom.

They estimate that about 14% of pregnancies worldwide are affected. We could cite all of the complications -- increased C-sections and macrosomia for the fetus. Basically, this early gestational diabetes is that that's detected before 20 weeks of gestation and late is that detected between 24 and 28 weeks of gestation.

Let's go on to the second article in this series. There are, of course, benefits to treating gestational diabetes and those are largely starting first with what they call a medical diet. Then they also talk about the use of metformin increasingly and also insulin. They talk about the fact that part of the increased rate of gestational diabetes is due to the increased rate of obesity that we're seeing worldwide and they used a term that's new to me, which is what they call the "diabesity epidemic."

Finally, the last part of this series says if we're going to manage this, we need to actually start with this in the pre-pregnancy period. We need to say, "If you're going to get pregnant, we need you to start paying attention to your diet. Pay attention to your weight. Let's look at whether you have impaired glucose tolerance and then let's try to head all of this off." They also say that a whole lifespan approach is needed because so frequently women who manifest gestational diabetes will end up with increased risks for diabetes later on in life and all of its manifestations, especially the cardiovascular ones.

Rick: First of all, you talked about some of the risk factors for gestational diabetes. Some of these are modifiable like someone's BMI, physical activity, and passive smoking. Other risk factors are not modifiable: the age of the mother, family history of diabetes, more than one child, a history of previous gestational diabetes, hypothyroidism, and pregnancy-induced hypertension. Those are all risk factors. We want to be able to detect it, and earlier rather than later, and then we want to be able to address it or treat it.

The thing that we have recently discovered is the identification of gestational diabetes means that the mother has an 8-to-10-fold risk of developing type 2 diabetes subsequently afterwards, and also an increased risk of having cardiovascular disease and stroke. Gestational diabetes is a marker for women that we need to, after they deliver the child, aggressively address the risk factors for these other conditions to minimize that in the future.

Elizabeth: No question. Then it's also worth noting, of course, that babies who are born to women with gestational diabetes are at risk not only for perinatal morbidity and mortality, but they also are at risk for long-term complications including their own development of type 2 diabetes, obesity, cardiovascular diseases, and neurodevelopment disorders.

Rick: These are three papers that are very exhaustive in identifying the epidemiology, the risk factors, how we should diagnose this, and then how we should address it. Definitely worth reading.

Elizabeth: Okay. Let's turn to JAMA Internal Medicine.

Rick: Liver disease related to medication initiation. Now, if somebody wondered whether one or more medications might be associated with liver disease, you can go to a national database called LiverTox and you can look it up. Just say, "Gosh, are there reports of liver disease associated with a particular medication?" These are really a compilation of case reports.

Unfortunately, when they grade whether there is a high or low association, they do it based upon the number of case reports. What these authors did was they tried to rethink how we should approach this and they used a VA [Department of Veterans Affairs] database. With that, they analyzed literally millions of individuals, almost 8 million patients, across 194 different medication cohorts -- what they described -- to look at how many of them had liver disease and could we associate it with particular medications.

They were able to identify 17 medications associated with hospitalization related to liver disease at high rates, more than 5 events per 10,000 patient-years. That takes into account the number of patients taking it. Of these 17 they identified, 11 weren't even included in the LiverTox database as being highly associated with liver disease, and many of them are antibiotics that are routinely used.

Elizabeth: Gosh, these are some really common things that are out there causing rates of liver injury.

Rick: They are. Overall, the incidence is fairly low, 5 to 10 events per 10,000 patient-years.

Elizabeth: Are there any identifications of other risk factors in this group that would predict who might be susceptible to acute liver injury relative to medication use?

Rick: They didn't identify it in this particular study. Because this is an older population, they are more likely to have comorbidities. They are more likely to have liver disease, more likely to have underlying kidney disease, hypertension, and diabetes.

Elizabeth: It sounds like something that we need to be aware of. Let's turn now to Nature Medicine and this is a look at what they call personalized brain circuit scores to identify clinically distinct biotypes in depression and anxiety. The authors say we really need to use something to sub-classify depression and anxiety because we have so much ineffectiveness of our treatments. If we could somehow pinpoint them more accurately, maybe we would be able to treat them more effectively.

They have 801 patients who had depression and/or anxiety and were treatment-free at the beginning of their study. They were randomized to pharmacotherapy or behavioral therapy, a subset of 250 of them. They did functional magnetic resonance imaging (fMRI) in these folks without having them do any tasks while they were in there. Then they also looked at task-related findings in looking at their brains.

They were able to subdivide this group of patients into six biotypes using these two strategies. Then they said, "Of the 250 of them that we treated, was there anything to show us that we could tailor the specific treatments?" That was where I really broke down on this because I felt like it was a stretch. Their N for that was 250 folks out of the original 801 and I just don't think that there were enough people represented to really say with any degree of certainty that this was the case.

I applaud this paper because I think that there has got to be something to this phenotype of depression and anxiety. There is an underpinning to that that I think probably is individually distinct. It's hard for me maybe to imagine that functional MRI is going to be undertaken in all of the folks who present with depression and anxiety.

Rick: When we're talking about depression and anxiety, there is just a large number of different things that can contribute to that. It's a little simplistic if you think that there is a single cause. What the author is trying to do is they say, "How is the brain wired in people who have depression or anxiety? Can we use that information to guide therapy?"

About a third of patients that are diagnosed with major depressive disorder don't respond to first-line treatment, and about a half the patients diagnosed with anxiety don't respond to first-line treatment. As you mentioned, they identified six different biotypes. Then a small group of individuals were on medication. How is that medication and its effectiveness associated at all with how they are wired? It's a small number. At least it's an attempt to try to get more information so we can target therapy more specifically. They don't say it's definitive, but they do say that it needs to spark additional research.

Elizabeth: I think it is an admirable attempt to try to characterize these things. Clearly, there are probably changes in this over time. I'm not sure that a single snapshot is the way to go. Perhaps, it's an fMRI both before and after treatment to see if there are things that are evoked differently.

Rick: Well, in fact, their point is previous studies have just looked at functional MRI at a particular point, either at baseline or sometimes after some tasks, but never comparing the two and never comparing that with on and off medication. Now, one of the other shortcomings of this particular study is that they use a specific set of MRI tasks that are not widely available. These imaging measures and what they are doing can't be really replicated at another site, but I do applaud the way they are trying to approach it.

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.