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Gait and Aging; Statin Use in Kids: It’s PodMed Double T!

PodMed Double T is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, 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. A transcript of the podcast is below the summary.

This week’s topics include statins in kids, treating refractory heartburn, gait and aging, and managing agitation in people with dementia.

Program notes:

0:38 Gait and aging

1:38 Neuroimaging, hemoglobin A1c

2:37 First to look at middle age

3:32 Dementia and agitation and aggression

4:34 Multidisciplinary care better

5:36 People move out of it

6:00 Refractory heartburn

7:00 PPI refractory responded to surgery

8:00 PPI plus other meds

9:02 Statins in kids with high cholesterol

10:02 Followed over 20 years

11:02 Slows atherosclerosis and cardiac events

12:08 End


Elizabeth Tracey: What do we do about persistent heartburn?

Rick Lange, MD: How to treat aggression and agitation in people with dementia.

Elizabeth: Does gait speed pretty early in life predict aging?

Rick: And 20 years of statin therapy in children.

Elizabeth: That’s what we’re talking about this week on PodMed TT, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a medical journalist at Johns Hopkins, and this will be posted on October 18th, 2019.

Rick: And I’m Rick Lange, President of the Texas Tech University Health Sciences Center in El Paso, where I’m also Dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, I’d like to turn first to JAMA Network Open. I thought this was the most amazing study because of the unbelievable length of it and the amount of data they have collected in it. This was the one I served up as, “What does gait speed pretty early in life tell us about aging?” And this is a cohort study from the Dunedin Multidisciplinary Health and Development Study and that’s a population-based study from a 1972-1973 birth cohort in New Zealand. They’ve looked at data analysis to June 2019.

They had a total of 904 participants. They were able to obtain walking measurements and they did this with three different modalities, if you will. As I said, these are folks that they got at birth and have just gathered a truly, in my mind, amazing amount of information on all of them, not just things like the routine suspects: body mass index, smoking, general practitioner visits, but neuroimaging, hemoglobin A1c. What they found was that, sure enough, gait speed at age 45 years was associated with a lot of other metrics that indicated accelerated aging, including compromised brain health and neurocognitive functioning. These things they were able to identify when they looked retrospectively as early as age 3 years.

Now, we don’t know anything about outcomes for all of these people yet — and it’s going to be really interesting to see what happens as they follow them until death starts to take place in this cohort — but one of the things they say is, “Gosh, maybe we ought to be looking at gait speed a lot earlier to show people who are at risk for all the rest of the accelerated aging kinds of conditions.”

Rick: Elizabeth, usually we think about gait and gait speed associated with the geriatric population. It indicates comorbid disease, frailty, and even cognitive function. This is the first one to look at it in middle-aged individuals that should otherwise be healthy. Now, where you’d like to take it next is if we know there are individuals that have accelerated aging and we can identify them, perhaps we can intervene. There are some interventions already going on. For example, things like caloric restriction or administration of metformin. Well, this gait testing may be a relatively sensitive and easy way to identify individuals early on who are at risk for accelerated aging to see if these interventions, over the course of decades, could actually prevent or interrupt that process.

Elizabeth: Yeah, and 3 years of age? That’s pretty impressive.

Rick: The other thing I think we should note is when we talk about gait — use of gait in, obviously, the geriatric population — it may not identify just the geriatric issues, but issues that preceded that by decades as well.

Elizabeth: Now, let’s turn to one of yours. Which of yours would you like to go to?

Rick: Since we talked a little bit about aging, let’s talk about dementia and the treatment of agitation and aggression, because there are 50 million people worldwide that have dementia, and as many as three-fourths of them also have associated neuropsychiatric issues. Those are behavioral issues, psychological symptoms, and they include aggression, agitation, and anxiety.

We know individuals with dementia, who have these neuropsychiatric disturbances, are more likely to be institutionalized earlier. They have poorer cognitive function. They have a lower quality of life and increased risk of death, and it also affects the caregivers because it lowers their quality of life as well. The issue is how do we treat aggression and how do we treat agitation, those behaviors, in people that have dementia? Now, there are both pharmacologic ways of doing and non-pharmacologic ways, and there have been very few head-to-head trials.

What these authors did was they looked at all randomized, controlled trials comparing interventions for the treatment of aggression and agitation in adults with dementia and did a network meta-analysis. What they discovered was the multidisciplinary care, massage, and touch therapy, music combined with massage and touch therapy, and even recreation therapy were more efficacious than placebo and usual care. The non-pharmacologic interventions seemed to be more efficacious than the pharmacologic interventions for reducing aggression and agitation in these adults with dementia. Obviously, if you can use non-pharmacologic measures, you avoid the risk associated with pharmacology, that is the risk of fall and side effects as well.

Elizabeth: And that, of course, in Annals of Internal Medicine. We’ve talked before about the use of antipsychotic medications in this population and that they actually accelerate mortality. I, at least, am really happy to see there are some other — really more humane — kinds of interventions that could actually improve the situation. I would also note, as people go through that trajectory of dementia, this period of agitation is just one part of that. I guess I would offer that as a measure of hope, also, that in fact, people will move out of that at some point.

Rick: What this study didn’t do was it didn’t assess what the costs were, because it’s obviously easier to give somebody a medication to try to control agitation or aggression. It’s more time-intensive and requires more expertise and more personnel to do some of the non-pharmacologic things that we mentioned.

Elizabeth: Let’s turn now to the New England Journal of Medicine, an incredibly common problem: heartburn or gastroesophageal reflux disease (GERD). In this case, what they called the proton pump inhibitor-refractory GERD. This is clearly people who have had this condition for a while, been prescribed PPIs, or proton pump inhibitors, and still have an ongoing issue. This is a Veteran’s Administration population. They were able to recruit 366 patients at the beginning, and then they strategized on, “Gosh, are they going to respond to two weeks of omeprazole? Are they going to respond to other kinds of measures that we might try in order to alleviate this problem?” Ultimately, they whittled this down to 78 patients who underwent randomization.

What they did then was they used surgery in some of them, active medical treatments in some of them, or controlled medical treatments. The outcome of this one was that, for this very, very selected group of people who had PPI-refractory heartburn, the surgical procedure was actually superior to anything else they tried. So I think this is hopeful news for people who really truly have refractory heartburn, because people complain about it being an enormous impact on their quality of life.

Rick: Two take-home messages. Truly proton pump inhibitor-refractory heartburn is relatively uncommon. As you mentioned, three-fourths of the individuals that were enrolled in the trial with this diagnosis actually didn’t have it. Now, how did they figure that out?

All these individuals underwent endoscopy. They had esophageal biopsies, esophageal manometry — that is to measure the pressure in the esophagus — and also pH measurements in the esophagus. All those things were done to arrive at the correct diagnosis, and three-fourths of the time it wasn’t PPI-refractory heartburn. But in those individuals that truly had it, surgery was successful in relieving it in about 70% of the time, and continued medications either with a PPI plus baclofen or a PPI plus baclofen plus desipramine was only effective in about 28% of the individuals. So again, surgery is better in individuals with true PPI-refractory heartburn, although it was a relatively small group of individuals.

Elizabeth: Talk to me about laparoscopic Nissen fundoplication and what its upsides and downsides are.

Rick: Elizabeth, again, it’s a laparoscopic surgery as opposed to an open surgery. There’s always a risk with any type of surgery. It was difficult to quantitate it in this particular study because there was a small number of individuals, only about 40 that had it. But it’s a fairly routine procedure, and in the hands of experts, it could be done fairly well.

Elizabeth: So I guess the caveat we would offer to folks is make sure you get evaluated really, really carefully before you go and make this choice.

Rick: Absolutely. You wouldn’t want to undergo that if the diagnosis is not PPI-refractory heartburn.

Elizabeth: Very good. Now, we’re going to take a look still in the New England Journal of Medicine at 20-year followup, again, an impressive amount of time of statins in children with familial hypercholesterolemia.

Rick: We don’t usually think about giving statins to children. We don’t have any long-term studies about the outcomes in these individuals. That’s why this study fills a particularly important niche. These are kids that have familial hypercholesterolemia — that is, they inherited it from one of their parents. It’s a dominant inheritance. These were kids that were identified as having it and started on statin therapy 20 years ago. They followed their outcome, and they compared them to two groups: to their siblings that weren’t affected and their parents who were affected.

This study is 184 of the original 214 kids that received statin therapy as early as 8 to 10 years of age. The statin therapy lowered their LDL cholesterol, the bad cholesterol, by about 32%, from 237 to 161. By the way, we want it to be below 100. In fact, there were only about 20% of the kids that got to that point. But when you followed them over the course of 20 years and compared them to their siblings, they did very well. If we measured the carotid intimal-medial thickness — and that is how thick is the artery becoming — at baseline, the kids with hypercholesterolemia had a thicker carotid intimal-medial measurement. But over the course of 20 years, they progressed exactly the same as their unaffected siblings, so it slowed the progression of atherosclerosis.

When you compared them to their parents, about 26% of the parents, by the age of 40, had already had some cardiac event. Most of them, for example, had a heart attack and some had angina. Some had even died, one as young as 20 years of age. But in the kids, only 1% of those treated with statins actually had a cardiovascular event. Seven percent of the parents had died by the age of 40; 0% of the kids who had taken statins for 20 years had died. So this is really good evidence that initiation of statin therapy in the kids with familial hypercholesterolemia slows the progression of atherosclerosis and it reduces the risk of cardiovascular disease in early adulthood.

Elizabeth: And of course, it makes me wonder about expansion of this particular strategy now that we have so many kids who are obese and probably have pretty poor cholesterol profiles, I would think.

Rick: Well, in fact, Elizabeth, the American Association of Pediatrics now recommends all children have a cholesterol measurement so we can ascertain which of them have elevated LDL cholesterol. We certainly want to address that first with non-pharmacologic measures, but then with statins. These particular kids, it’s a genetic abnormality and just treatment with diet and exercise alone won’t lower their cholesterol sufficiently. It does require a statin, but you’re right. Identifying kids early on and getting them on a pathway to reduce LDL cholesterol will be important.

Elizabeth: Most interesting. Another cohort I’d like to see in 20 years to see what happens. 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.