Learning to Harness Circadian Rhythms for Better Hypertension Management

Learning to Harness Circadian Rhythms for Better Hypertension Management

(gentle music) – I’m John Flack, member of
the hypertension council, and I’m from Southern Illinois University, a hypertension specialist. You want to tell us about you? Sure, I’m Michelle Gumz, I am
at the University of Florida in the Division of
Nephrology, Hypertension, and Renal Transplantation,
and I run a basic research lab where we study the role of
circadian clock proteins in the kidney, and how they
affect blood pressure regulation and renal sodium handling. – Dr. Gumz, can you tell us a bit about chronotherapy and that circadian rhythm, and how it’s potentially going to impact, say, patient care. – Sure, sure. So the idea behind chronotherapy
is using the time of day to maximize efficacy
and reduce side effects. And so, part of the way we
hope that our work contributes to this area is in
studying the basic biology of these circadian rhythms. Blood pressure has a circadian rhythm. It’s higher when we’re up and active, and lower at night while we rest. And when you lose that circadian
rhythm to blood pressure, it’s associated with adverse
cardiovascular outcomes. So the idea, in people who
might have high blood pressure in the nighttime, is that perhaps giving an antihypertensive in
the night instead of in the morning could be more effective. And there are ongoing studies to test that in larger patient populations. But I think part of the appeal
of chronotherapy is that it could be applied as part
of a precision medicine or personalized approach, where
we target the right people to take the right drug at the right time. – You gave a fascinating
presentation this morning about clock genes, sodium handling, knockout models of this. Do you see any way to leverage, or to change the activity
of those clock genes, other than by dosing
medicines in the evening, say in drug development,
there any hope there? – So, I think there are a
lot of things on the horizon. There are a couple of
groups around the country and in Europe who are
working on developing a circadian blood test,
and that could be something that would be used clinically
that you might be able to identify patients who
have circadian disruption, and then perhaps, you know,
design treatments around that. Some of the other things that can be used, and this is something I
practice in my own life, is good circadian hygiene,
is the way I refer to it. And there’s been quite a bit
of work done on this idea by some researchers in Germany actually. The idea that, you know, you take care of your circadian rhythm
and your circadian rhythm will take care of you. So, one of the things that I do, I try to keep the same
schedule that I have during the week on the weekend. And you kind of avoid this
idea of social jet lag, where you follow one schedule
Monday through Friday, and then a totally different
schedule on the weekend. And it’s the reason that most of us feel terrible on Monday morning. And so that idea of getting adequate sleep and keeping a consistent schedule is one sort of low tech, if you will, way to address some of these problems. – One final question,
given some of the data that’s already out there
about Hermida’s group and showing the nighttime dosing of drugs improves cardiovascular risk
compared to daytime dosing, fewer side effects, lower
blood pressure at night, why hasn’t this caught on more? – That’s a great question, and I think some of the discussion
after today’s session was centered around some of the skepticism that some of these
studies have encountered, and something one of
my physician colleagues has shared with me is
that it’s hard enough to get people to take their medication, let alone take it at
a certain time of day. And so that’s one barrier
would be with adherence. I think something else, some
of the data that come out that are mixed is because this
chronotherapeutic approach, as I mentioned, I think it
lends itself to the idea of precision or personalized medicine, and so taking a study with
all comers and applying a nighttime dosing of an antihypertensive, you know, you may or
may not see an effect. I think it’s really, and
something that the studies coming out of Spain have done, because they use the ambulatory
blood pressure monitoring, they’re well aware of who
has nocturnal hypertension, or who has non-dipping hypertension, because those are perhaps
the people that would most benefit from this
type of intervention. – Well as an inn of one, our practice is actually nocturnally
dosed, non diuretic trust, given once daily in the evening,
for the last several years, and we have firstly, no problems
in getting patients to– – Interesting. – Actually do it, and
when we explain to them lower blood pressure at night, and we have ambulatory monitoring on some, fewer side effects, and there
is at least a possibility, a probability, that there is a greater cardiovascular risk reduction.
– Right, right. – And none of those studies have shown that nighttime dosing is
worse than the daytime, but I think one of the
problems it’s running into is our conditional default
for dosing of once daily drugs has been in the morning. – Right. – And it just goes against convention. – Right, yeah, that’s a terrific point, and I think it’s something
that I hope will gain more recognition, not just that
the targets of these drugs, but as the second speaker today mentioned, the metabolism of those
drugs can also vary with the time of day and so the, it comes back to the right
drug at the right time. – And I think your work
also basically highlights how important sodium
handling is into knowing what our blood pressure is,
but it’s circadian rhythm and I think it’s going to
make a great contribution to what we know about
the science and hopefully will lead us to better
clinical interventions and even maybe drug development. – Thank you. (gentle music)

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