Weekly Medical Highlights: Cardiovascular Risks of ADHD, Hospice Care Disparities, CTE, and IV Iron

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, examine the top medical stories of the week.

This week, the discussion covers chronic traumatic encephalopathy (CTE) and dementia, the use of intravenous iron for anemia prior to cardiac surgery, disparities in hospice care between urban and rural settings, and the link between ADHD and cardiovascular disease.

Elizabeth: What is the difference in hospice care between rural and urban settings?

Rick: Patients undergoing cardiac surgery, is there a benefit of IV iron if they have anemia?

Elizabeth: What is the relationship between chronic traumatic encephalopathy and dementia?

Rick: And is there an association with ADHD and cardiovascular events in people with hypertension?

Elizabeth: That is what we are 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 am Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I am Rick Lange, president of Texas Tech Health El Paso.

Elizabeth: Rick, I would like to start first with this issue of chronic traumatic encephalopathy at death in National Football League players and the relationship between the presence of that and dementia in their lifetime. And this is in The BMJ.

This has been an ongoing issue that we have been talking about for quite a long time. This notion that repeated head trauma results in a condition, CTE, chronic traumatic encephalopathy, and that that, of course, results in a number of deleterious outcomes. And in this case, they are looking more closely at dementia.

They had among their participants over 1,700 former NFL players who died in the time period 2008 to 2021, of whom 338 donated their brains for neuropathological evaluation. They were able to, of course, access lots of personal information and causes of death in these folks. And they asked neuropathologists who were masked to their clinical and playing histories to look at their postmortem CTE diagnosis and stage of CTE. Among that 338 whose brains were studied, 315 had a diagnosis of CTE.

When they run that backwards and they look at the potential prevalence of CTE among all of those NFL players who died, I love this, they estimate a range between 18.5% and 98.7%. Among the brain donors, about 31% of them did have stage 4 CTE. About 60% of them had study clinician-diagnosed dementia with an age of onset at 63.4 years. They definitely seem to land on this space that if you have CTE, you have a high risk of having dementia also. They do not really nail down very well, though, what the risk is.

Rick: Yeah. And, Elizabeth, that is difficult. Here is why. In the past, we took NFL players that died of dementia, we looked at their brain, and they had CTE. What you really want to know is let us make sure we look at all the brains of all the NFL players that die over a certain period of time. CTE can only be diagnosed in an autopsy, and you have to have a pathologist that knows what they are looking for. And that is why it has been very difficult to nail down.

The great value of this particular study is they had a large number of NFL players that had had a postmortem exam. Now, not every NFL player did and that is why this big range. Their estimate is that about a quarter of the individuals have CTE, but it actually could be higher because you do not know about the ones that died that you never examined. The flip side is oftentimes people have dementia, but it is not recorded on their death certificate. So trying to link these two together has been very difficult. And that is why this particular study, I think, adds some value.

Elizabeth: I have some questions about why we cannot diagnose CTE when someone is still alive. They say that the lesion that is present in CTE is perivascular accumulation of hyperphosphorylated tau in neurons at the depths of the cortical sulci. So I get it. It is way down in there. But gosh, I would think that with PET or with something else, we would be able to come up with something that would be able to say, yeah, there is an aberration here.

Rick: Well, you can detect tau. It is a particular deposition in particular areas of the brain. Current imaging techniques we have for looking at tau are not that specific yet.

Elizabeth: I will note that dementia was common among these donors, and it was dementia of all kinds of different types. And there did seem to be, if you had stage 1 CTE, how many, and so forth, with 90% plus of those with stage 4 CTE having dementia at death. So that relationship seems to be pretty substantial. The authors come to this lukewarm conclusion that for right now, we ought to be advising people who are going to play American-style football that repeated head injury might result in an increased rate of this inflammatory condition, as well as dementia and early death.

Rick: We have known about CTE in football players for a number of years now and still it is a lot of people playing it. Is it related to duration? Is it related to when you play? Is it in high school or college or later in life? Is it related to the number of head blows you have? Because of the glamour and glitz, and money associated with football, there are people that are willing to do that, much in the same way as boxing, for example. All the information we can provide is valuable to individuals that are considering either playing that particular sport or maybe going to something different.

Elizabeth: Speaking of different, why do we not stay in The BMJ? But let us look at this notion of intravenous iron infusions to treat anemia before cardiac surgery.

Rick: For individuals who have cardiac surgery, somewhere between 20% and 50% need to have transfusions as a result of the surgery because there is some blood loss. The risk is higher if you go in and you are anemic to begin with. Oftentimes, if a person is going to have elective cardiac surgery, they will tell the patient to take oral iron a month beforehand. Some individuals cannot tolerate it. It takes a little while for the iron to work. The alternative is to give one single dose of intravenous iron. Does giving IV iron improve their outcome? Specifically, are they able to spend more time at home in the first 90 days after surgery? That means either they get out of the hospital earlier or they are less likely to be readmitted.

They took 920 individuals who were undergoing cardiac surgery and randomized them to either receive placebo or intravenous iron about a month before the procedure. And then they had cardiac surgery. They measured what their blood loss was. They measured whether they were anemic before the surgery or not, and then they followed them. How many days did they spend at home over the next 90 days?

There was an improvement with IV iron, but it was pretty minimal. Those that received IV iron, they were at home 81 of 90 days afterwards. Those that did not, 80 days. However, during surgery, the individuals that received IV iron were less likely to receive a transfusion, about 33% versus 43%. The estimate was that they would save 44 units of blood over the course of 100 patients having cardiac surgery if they gave IV iron. There was no downside to it. There was not an increased risk of complications, no infections associated with it.

Elizabeth: It sounds to me like it is a useful strategy because getting a transfusion is not a free lunch. And I will say one of my colleagues, who is a hematologist and an expert in this area, [mentioned] that it is like a liquid transplant.

Rick: You are right. If we can save 44 units of blood for every 100 people that have surgery, and all we have to do is give them a 15- or 30-minute IV infusion of iron, it sounds like a pretty good tradeoff.

Elizabeth: Okay. Let us turn to JAMA. This is an issue near and dear to my heart, of course, hospice. And I actually think this research letter provides us with some really good news. What it is looking at, of course, is a disparity that is between the provision of hospice services between rural and urban areas. Previous studies have determined that rural residents are more likely to die in nursing homes, less likely to receive paid caregiving support at home, and have a higher reliance on unpaid family caregivers.

So this study was looking at, well, what about hospice care? How does that vary across the rural-urban continuum in terms of length of stay, setting of care, visits by hospice staff, and rates of higher-level hospice care? Because as we are both aware, as people progress, sometimes they need to go on to an inpatient unit, or sometimes they get provided with 24-hour care at home by the hospice.

So they looked at, from 2013 to 2022, the master beneficiary summary file identifying people who had died 66 years or older within 1 year of Medicare claims and a sub-cohort of those who had a hospice claim within the last year of their life. They linked zip codes with that particular data, and they assessed the calendar year, age, Medicaid enrollment, Medicare Advantage enrollment at time of death, sex, race, and ethnicity. They also looked at cancer and dementia diagnoses.

What they found was that in a cohort of 21 million folks who died, 51.5% had a hospice claim in the last year of life. And from somebody in the chaplain role, the fact that over 50% of people accessed hospice services is actually a really good thing. When they took a look at 814,000-plus folks who died in isolated rural zip codes, they found out that they had lower hospice use, but not that much lower hospice use. They also found out that their length of stay was shorter, their location of hospice care was more often in private or nursing homes, less often in assisted living, and that their use, and this is the place where there is a big disparity of inpatient hospices, hospitals, and other facilities, when they needed more intensive care was significantly lower at about 14% versus 21% if you were in an urban area. As I said, though, I think that in general, the fact that they are not that dissimilar, except for that one factor, is really pretty good news.

Rick: Yeah. Not only, as you mentioned, Elizabeth, it is not very dissimilar, that gap has been narrowing. The difference between hospital care, rural versus urban, was about an 8% difference in 2013 and narrowed to about 4% difference in 2022. A lot of rural areas do not have inpatient facilities. I am thinking about places in rural Texas, counties that not only do they not have any hospitals, they oftentimes do not have any healthcare providers at all. It is nice to know that that does not limit hospice care. It is provided in a different way in rural areas, but it does not mean individuals cannot get it.

Elizabeth: Actually, I am somewhat encouraged by it, and I like those notes of encouragement. Let us finally turn to The Lancet.

Rick: In individuals with hypertension, does ADHD increase the risk of cardiovascular events? There are studies that have shown that ADHD is associated with increased risk of cardiovascular events. People think it is because of the comorbidities associated with it. If you have ADHD, you are more likely, for example, to have hypertension, to smoke, to have a sedentary lifestyle. You are more likely to have obesity. Are all those things the things that contribute to it, or does ADHD in and of itself increase the risk of cardiovascular disease?

If you have a group of individuals that are being followed, seven different settings — like Australia, England, Denmark, Netherlands, Norway, Sweden, and even the USA — for hypertension, we know that they are going to be treated. Does the presence or absence of ADHD, in addition to that, confer an increased risk of cardiovascular disease?

In almost 6 million adults that were undergoing first-line antihypertensives in these seven countries that I mentioned, ADHD was associated with a higher risk of major adverse cardiac events, about a 30% increase, about a threefold increase in all-cause mortality. There is some concern that treating ADHD with medications increases the risk of cardiovascular disease. So then they looked at those treated with ADHD medications, those without, and what they discovered was that the use of medications did not make that any worse at all.

Elizabeth: The authors, of course, suggesting that this is a factor that clinicians need to be aware of when they are managing their patients. Outside of that, though, what about a mechanism? I do not get it.

Rick: We also know that there are behavioral or psychosocial things that also increase the risk. So is there something with regard to ADHD, regarding the behavior or psychological issues, that if we treat those, we can lower the risk? The real answer is we do not know the mechanism.

Elizabeth: No doubt there is more coming since this is such a prominent condition all around the world.

Rick: Yeah.

Elizabeth: On that note then, that is a look at this week’s medical headlines from Texas Tech. I am Elizabeth Tracey.

Rick: And I am Rick Lange. Y’all listen up and make healthy choices.

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