Exercise According to Chronotrope Type; Estimating Kidney Function

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 deprescribing PPIs, kidney function equations, stenting for DVT, and timing of exercise according to chronotrope type.

Program notes:

0:34 Chronotrope type and timing of exercise

1:36 Sedentary adults and morning or evening type

2:36 Acting as your own control

3:10 Stenting for post-thrombotic syndrome

4:10 Severity lower with endovascular therapy

5:10 Patent in 2/3 at six months

6:10 Very diverse patient populations

6:28 Estimating kidney function

7:28 Currently underestimate compromise

8:27 Deprescribing proton pump inhibitors

9:27 Three different interventions

10:27 Almost 15% achieved outcome in both patient and physician

12:08 End

Transcript:

Elizabeth: Is there a way to deprescribe proton pump inhibitors successfully?

Rick: Doing a better job of estimating kidney function.

Elizabeth: Using stents for post-thrombotic syndrome.

Rick: Should being a morning or evening person influence our exercise?

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, as a devoted exerciser, I have to say that I am quite interested in this BMJ study, taking a look at, “Hmm, what about timing of exercise if you’re a morning person or an evening person?”

Rick: Well, everybody knows the value of exercise. When’s the best time to do exercise? As a cardiologist, people ask me, is it better to do it in the morning or in the evening? And I’ve never really known whether it really makes any difference or not. I do tell them that there is a circadian rhythm. We see that in blood pressures — higher in the morning, it goes down around noon, it goes up in the evening again — in people that have a normal job, that work from 8 to 5. And there are people that are night people where it’s just the reverse. So the question is, should we be timing our exercise based upon whether you’re a morning person or whether you’re an evening person? Chronotrope-aligned exercise.

So what these investigators did was they tried to decide whether aligning your exercise timing with your circadian rhythm enhanced the cardiometabolic and the sleep-related benefits. They did a 12-week randomized trial. They took 150 sedentary adults that had at least one cardio risk factor and they categorized them based upon a questionnaire, either are you a morning-type person or are you an evening-type person? And then they either align the exercise either with their circadian rhythm or against it, chronotrope-aligned or misaligned.

They did moderate exercise training, 5 sessions per week, and they looked at their blood pressure, heart rate variability, peak oxygen consumption, LDL cholesterol, their sleep. The reduction in all of these things was more substantial if your exercise was aligned than when it was misaligned. So if you want to get the most from exercise and you’re a morning person, do it in the morning. And if you’re an evening person, you’re better off doing it in the evening.

Elizabeth: So this seems like a pretty simple message, and it seems like it should be easy for people to implement. What are your thoughts?

Rick: You know, I think so. Aligning the exercise with your particular circadian rhythm provides the best bang for the buck.

Elizabeth: I guess I would say just one more thing about this. I would like to see people who did it intentionally discordantly, and see, if they acted as their own controls, what the delta was.

Rick: You’re absolutely right. It’s, okay, let’s do it where you’re aligned and then wait for a while and do it when you’re not aligned. The trouble is, at that particular point, the person is already exercise-trained. And these were all sedentary individuals to begin with.

Elizabeth: Well, the other thing that would be revelatory, I think, would be to take people who are lifelong exercisers, like thee and me, and have us do concordant and discordant chronotype exercise periods, and see what the impact of that would be.

Rick: That would be a nice follow-up study. I agree.

Elizabeth: Turning from here to the New England Journal of Medicine, let’s take a look at this notion of endovascular therapy for post-thrombotic syndrome. And this, of course, is common after DVTs. It can cause severe symptoms that often involve the limbs in patients, impair their activity and quality of life. Can we do endovascular therapy to eliminate chronic venous obstruction in these folks?

So they took 225 patients with moderate or severe post-thrombotic syndrome and imaging-confirmed iliac vein obstruction to receive either endovascular therapy, which involved an iliac vein stent and enhanced antithrombotic therapy, plus standard post-thrombotic syndrome care, or standard post-thrombotic syndrome care alone. And then they looked at the severity of that syndrome at 6 months using a couple of different tools.

What they found was that at 6 months, sure enough, the severity of the post-thrombotic syndrome was lower in those who received the endovascular therapy than in the no-endovascular therapy [group]. The quality of life was better in those folks who got the endovascular therapy, as was their overall quality of life. However, the bleeding was much more common in those folks who got the endovascular therapy, almost 12%, versus 4% of the patients who got standard care. So to me, this really suggests that because of all the sequelae of DBT and how impactful it can be on somebody’s life, sure enough, this seems like a good strategy. Then there has to be this high index of suspicion relative to bleeding if somebody takes it on.

Rick: Yep. And so, Elizabeth, a couple things about the study. A very well-done study, by the way. It only looked at 6-month outcomes. And we need to extend this for 12 to 24 months because when you put a stent in at that particular time, it was patent in only about two-thirds of the individuals who received it. So some, it closed off. And the question is, how durable is it at 12 to 24 months?

The second thing that you mentioned is, there was a 3-to-4-fold increased risk of bleeding — either bleeding or major bleeding — in the people that had the stent. And it wasn’t due to the stent. It’s the fact that once you put the stent in, it’s a more intensive antiplatelet and anticoagulant therapy.

So again, it’s a balance. On the one hand, this can decrease some of the post-thrombotic syndrome symptoms. On the flip side, the risk is an increased risk of bleeding. I think the physician needs to speak with the patient and say, “Which of these two things is most concerning to you and how do you want to proceed?”

Elizabeth: I agree. The authors note, of course, that there’s going to be training that’s going to be necessary to get a workforce that’s going to be able to deploy this in a larger number of people. I had no idea that post-thrombotic syndrome affects 20% to 50% of patients with deep vein thrombosis. And the other thing I would note is that this study had a very diverse population that was enrolled, and that’s a positive in terms of looking at the outcomes.

Rick: Yep. And all the things you mentioned are true, especially the fact this was done by experienced operators. So these are the best results that one can obtain and the safest results too, by the way. You’d like to take a study like this and then look at the real-world experience to see whether this carries over or not.

Elizabeth: On to your next one.

Rick: Can we do a better job of estimating kidney function? Chronic kidney disease is common because of the incidence of metabolic syndrome, diabetes, and hypertension, which all can affect kidney disease. They actually monitor what’s called the glomerular filtration rate or the GFR — how well is the kidney filtering the toxins in our body and excreting them in the urine?

You can actually measure it, and that’s not very easy to do, or we estimate it. And we estimate it primarily based upon the serum creatinine. And we have formulas, and there are a number of different formulas out there.

And there’s another more recent protein biomarker of kidney function called the cystatin C concentration. And there are formulas that deal with that. Let’s take a bunch of people. We determine what their creatinine is. We actually measure it and then we estimate it using those formulas to see how good they are. Formulas either use creatinine or cystatin, or the combination of both.

In general, the formulas underestimate the reduction of GFR that occurs in individuals. But it’s a little bit more accurate if you use both creatinine and cystatin than either one alone.

We have a little bit more work to do. What this tells me is if we’re going to do this accurately, let’s use both of those and realize that, even with that, the sensitivity is less than 55%. The specificity is good. It’s about 90%.

Elizabeth: I was really disappointed in that result. I think I would have landed a little bit harder on, “Wow, we really need something that’s better than this to really take a look at kidney function.”

Rick: If we have a longitudinal study like this, where we can compare a measured reduction with our estimated, we can actually refine those a bit.

Elizabeth: Let’s just mention this is in the BMJ. Would you say that this reminds you of where a lot of the cardiac risk equations were quite a while ago?

Rick: Absolutely. We have adjusted each of those individual components and added things as well that provide more information. And it always tweaks it a little bit better.

Elizabeth: We’ll look forward to more.

Finally, let’s turn to JAMA Internal Medicine. And this is a look at a protocol for deprescribing proton pump inhibitors in primary care settings. This is an important issue. We have discussed over the years PPIs and how they are associated with some pretty deleterious health impacts. This paper asserts that deprescribing these should be considered when inappropriate use is identified.

In this study, they took a look at 1 year of participants who were 18 years and older with at least 1 year of PPI use in general practice — practices in two regions of France. And they included their GPs in this study.

They had three different interventions. They were patient- and GP-facing deprescribing interventions, combining patient education and a letter with a deprescribing algorithm sent to their primary care docs; a solely primary care doc-facing intervention, in which only the physician received the letter and the algorithm, or usual care. And their primary outcome was defined as a 50% or more reduction in annual PPI use.

They had 1,498 primary care physicians, almost 35,000 patients included from 683 primary care practices. And they found that the dose reduction was highest in the patient- and GP-facing intervention group compared with usual care groups, and with the GP-facing intervention solely.

So, it’s sure looking like engaging patients in this intervention is helpful in getting this deprescribing down. It may not be as low as they’d like it to go and, again, suggests that we need to go back to the drawing board and figure out, well, what are the barriers here? And is there something else we can do that can reduce PPI use? Which I will note that almost 15% of those folks who were in this trial that had both the primary care doc and the patient intervention achieved the outcome. In the prescriber-only intervention, it was just shy of 8%, and usual care was 7%.

Rick: It clearly shows that when you involve the patient, provide them information, they can at least ask their doctor, “Hey, should I be on a PPI?” And most individuals start it because of gastroesophageal reflux disease, and it should only be used for a time-limited duration, usually months. And unfortunately, we’ve put people on it and it’s continued for years. I would note that in the individuals in whom it was stopped, they did not have an increased incidence of gastroesophageal reflux, so it can be done.

Elizabeth: The editorialist notes that one limitation of this trial is that they didn’t have just a patient-only intervention. And that would have been an interesting comparator because, as you suggest, if I receive a missive like that, will I go to my primary care doc and say, “Hey, this is interesting. I got this letter and it says maybe I don’t need to be taking this medicine any more.” And would that achieve the same result as also sending it to the physician?

Rick: We don’t know because they sent it to both the physician and the patient. We don’t know which was the most effective. With electronic medical records now is we can notify the patient alone or the physician, or both. I do think that there’s some value in notifying the physicians that we’re alerting your patients so that they can collaborate on this.

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.