I'm going to talk about sleep and healthy aging.
Thanks to the organizers for having
me and thanks to the audience
for their attention to the lunch hour here.
By way of disclosure, I was an officer
of the American Thoracic Society a number of years ago.
I do have some industry connections that
I don't think are relevant to today's presentation,
but I'll disclose them. They're for completeness.
The vast majority of my funding comes from
the National Institutes of Health.
I'm going to talk about two topics which
should compliment what Dr. Lee has just addressed.
One is about sleep deprivation and the
other is about obstructive sleep apnea.
Obstructive sleep apnea is
a very common conditions we'll talk about.
We put out this statement in
the American Journal of Respiratory and
Critical Care Medicine a few years ago.
That was supposed to inform healthy people 2020,
which is a document the federal government puts
out to inform healthy behaviors.
This is an official statement that made
the recommendation that almost all of us require
between seven and nine hours of sleep at night.
There are plenty of people who think they
do well with less sleep than that,
but the vast majority of
them get into trouble with less sleep.
There are two famous examples of people
that said that did well on short sleep,
and one was Margaret Thatcher,
the other was Donald Trump.
You can draw your own conclusions about what
sleep deprivation might do for some individuals.
People who do this work,
measure things in alcohol equivalents,
how much you have to drink to make your brain
deteriorate versus how much do you
have to be sleep-deprived.
You can see over 18 hours of sleep deprivations,
if you wake up at six in the morning and go to
bed at midnight over the course of that 18 hours,
there's a minor deterioration in
brain function about it
in the order of one or two drinks.
It's not a big effect, but it's measurable.
But with 24 hours of sleep deprivation,
you actually are legally drunk as
far as your brain performance is concerned.
Doctors in training would routinely stay up all night,
and as far as brain performance
is concerned, it's not ideal.
This is a complex slide,
but let me go through it carefully
to make a couple of points.
On the y-axis here is the
stand for sleeping and scoring,
that's a subjective measure of daytime sleepiness.
The y-axis here is the psychomotor vigilance task,
it's an objective measure of brain function.
This is object of brain function,
this is subjective sleepiness.
What they do is they bring people into the lab at
University of Pennsylvania and sleep deprive them.
These are people getting total sleep deprivation,
you can see they get more and more
sleepy, not surprisingly,
a total sleep deprivation is
more and more lapses on the psychomotor vigilance task,
saying that the brain is deteriorating with
total sleep deprivation, again, not surprising.
You sleep eight hours per night,
your levels of sleepiness are quite
stable in terms of subjective sleepiness,
your object or brain performance also
reasonably stable with eight hours of sleep at night.
It's more interesting at these curves,
if you get six hours of sleep or four hours of sleep,
your subject of sleepiness gets worse,
your object of brain performance for
six hours with four hours also gets worse.
But what's interesting here is the following.
These curves have plateaued after a couple of days.
You ask this guys are they sleepy?
I'm sleepy but I'm used to it,
and that's pretty flat over the past 10 days or so.
There's no hint of a plateau in
either of these curves suggesting
brain functions deteriorating while
subjective sleepiness is quite stable.
The take-home message from this slide
is that we lose the ability to
perceive how sleepy we are.
The subject of sleepiness is quite stable,
while object or brain performance is deteriorating.
We don't realize how sleepy we are,
how impaired we are when we're sleep-deprived.
The other thing that's interesting is that
six hours to four hours look
super imposable on this graph
in terms of subjective symptoms.
But it's clear separation was
six hours and four hours of sleep shown here.
You can hear the conversation now.
Somebody says, well, I might as well stay up all night.
I feel crummy tomorrow no matter what,
and that might be true as far as
subjective sleepiness is concerned,
probably not for object of
brain performance and so again,
there is a dissociation between
symptoms and performances as
far as the brain is concerned.
There are other health factors though
they're important in terms of sleep.
This is a paper we published in
the Archives of Internal Medicine
almost 20 years ago now.
It's one of the first studies looking at
the consequences of short sleep,
and this is looking at incident heart disease
or myocardial infarction.
In the Nurses Health Study back in 1986,
they're asked, "How many hours do you sleep
in a 24 hour period?"
and they answer to the question here on the x-axis,
the relative risk is shown here.
Sleeping eight hours per night,
the relative risk was one, meaning baseline risk.
You slept seven hours per
night as far as sleep is concerned.
Risk went up trivially,
for six hours per night, it went up about 30 percent,
and with five hours per night of sleep,
risk of a heart attack went up about 70 percent.
The first thing people say is, well, the data confounded.
Sicker patients will sleep
less and sicker patients have
heart attacks and that's true.
The nice thing about a sample size of
72,000 is you can control for whatever you want,
be in control for all the known covariates,
and these data are independent of any known covariates,
it's not age or gender,
or depression or anxiety or personality.
Any other things you think might be important as
far as affecting sleep duration,
the risk of heart attack,
it's not any of those things.
There's other subsequent mechanistic data that come out
suggesting short sleep may
increase the risk of a heart attack.
It print a risk equivalent sleeping five hours per night,
is about on the order of
a cholesterol of 250 milligrams per deciliter,
high enough to instruct a statin,
like Lipitor or some atorvastatin,
some more of those kind of medications.
What happened during COVID was one
of the things they asked us to address.
Unfortunately, labs are shut down
for many months during the pandemic,
so when I work with Laura Crotty Alexander and I
published this paper in the American Journal of
Cardiology in 2020,
what we did was a Twitter survey.
Why did we do a Twitter survey?
Because our labs are closed and we didn't
have any other way to get data.
We surveyed people during the pandemic,
at the start of the pandemic, how much are you sleeping?
It turned up people are going to sleep
later, waking up later.
But in aggregate,
the sleep had improved by about an hour.
The reason that was interesting is around that time,
there was a report in
the New Int Journal of Medicine from
Kaiser looking a year over year
where the risk of heart attack had gone down about 50
percent at the start of
the pandemic and nobody can quite figure out why.
It turned out most things are going
the wrong direction, people are gaining weight,
people are smoking more, they're more stressed,
more anxiety, all the things
going in the wrong direction,
the only thing we can identify that it
improved was sleep,
and so we thought maybe the increase
in sleep that was seen early in
the pandemic may have led to
some improvement as far as
cardiovascular risk is concerned.
Is increased sleep responsible for reductions in
myocardial infarction or heart attack
during the COVID pandemic.
Sure, this is unknown, it looks like
sleep durations going back to where
it was pre-pandemic now,
but at least a natural experiment that's interesting.
There's some data as well in terms of
glucose control and glucose tolerance.
As a group at University of Chicago,
Karen Spiegel, Esra Tasali, and Van Kotter,
where they'll take normal people and sleep deprive them,
and they measure things during sleep deprivation.
Perfectly normal healthy person
starts to show impairments in glucose tolerance,
something called glucose effectiveness,
is a harbinger of insulin resistance or diabetes,
and that's imperative in normal person
if you sleep deprive them,
the stress hormones like the fight
or flight, adrenaline levels,
these things go up, cortisol
or stress hormone goes up as well,
and that may be part of the problem.
Slow-wave sleep or deep sleep
seems particularly critical if you suppress,
deep sleep people start to look diabetic.
There are also data in terms of appetite regulation.
Leptin is a hormone is made by fat cells that
tells our brain to stop eating, the fatter you get,
the more leptin you make and
hopefully eat less as a result of that,
to regulate your appetite.
Ghrelin is the opposite, it stimulates appetite.
What this group did in the University of Chicago,
they've put people under constant glucose infusion,
so it's not they're eating more or eating less,
and they measured the level of
these hormones in people getting
either inadequate sleep of four hours per
night or adequate sleep, 10 hours per night.
You can see the leptin levels are suppressed and
the ghrelin levels are increased with sleep deprivation.
Both hormones run the direction that be
predicted to stimulate appetite, I'll say it again.
Both hormones went in
a direction that be predicted to stimulate appetite,
and the reason that's interesting
is that people believe that
sleep deprivation may be
a risk factor underlying the obesity pandemic.
I'm trying to lose weight myself
right now, I'm trying to sleep,
the main point of
this part of the conversation it was the diet, exercise,
and sleep are three pillars of health,
and the dogma is if you ignore one,
the other two will suffer.
The three pillars of health are diet, exercise,
and sleep, if you ignore one,
the other two will suffer.
Jeff Flier, who was dean of Harvard Medical School the
time this came out in the Annals of Internal Medicine,
wrote the editorial suggesting that
sleep deprivation may be
a risk factor underlying the obesity pandemic.
When we saw that, we went back to
the Nurses Health Study and see what
would happen to their body weight.
You can see body weight on the y-axis
and the year on the x-axis.
The women sleeping five hours per night weighed
more at baseline than people sleeping adequately,
and then they gain more weight over time,
over the 15 years than the people sleeping adequately.
Everybody gained weight during this period, including me.
Put the five-hour sleepers gain more weight,
but on the order of five or 10 kilograms or 10,
15, 20 pounds with five hours
of sleep compared to sleeping adequately.
There had been some randomized trials
as well where they randomized
people to adequate sleep or
inadequate sleep when they go on a diet.
This is also published in
the Annals of Internal Medicine,
where they looked at sleep
depriving people going on a diet.
Sleep curtailment decrease the proportion of
weight-loss as fat by 55 percent,
eight and half versus five and half hours,
and increased a loss of fat-free body mass
by 60 percent, what does that mean?
The amount of human's sleep
contributes to the maintenance of fat-free body mass,
a times of decreased energy
intake that is going on a diet.
Lack of sufficient sleep may compromise
the efficacy of typical
dietary interventions for weight-loss,
and related metabolic risk production.
This is something I tell my patients,
if you want to lose weight,
you need to sleep adequately,
otherwise, the diet doesn't work.
I also take care of some professional athletes
and they're also aware
that exercise is impaired by poor diet or by poor sleep.
There are also some data on
coronary heart disease and coronary calcium.
The short sleepers of people sleeping inadequately,
will have more coronary calcium buildup as a marker of
hardening of the arteries or risk of heart disease.
Summarize that portion of the talk by saying
inadequate sleep has health consequences,
your mother was right.
Impaired brain function is not surprising,
we've all experienced that with young kids or
the jet lag or doing medical training or what have you.
Increased metabolic and cardiovascular risks and
the data here are rapidly evolving,
we didn't know anything about this topic 20 years ago.
I'm going to talk about obstructive sleep apnea as well.
It's a very common disease where
people stop breathing when they're asleep.
By way of background, the stoppages
in breathing can occur during sleep.
It's a very common issue as I mentioned,
I'll show you some data on that.
It's associated with neurocognitive
and cardiovascular sequelae,
so people with sleep apnea don't think as clearly,
lose creativity, lose memory,
consolidation, and may be a risk factor
for Alzheimer's as well, we're not sure yet.
In cardiovascular, they may be
a risk of heart attack and stroke.
There's a reason we take this disease seriously.
Risk factors for sleep apnea include aging,
nothing you can do about that, obesity,
hopefully, diet and exercise
and sleep can help you with that,
and then male gender,
nothing you can do about that either.
I'm trying to slide for a couple of reasons,
this is my most famous patient and it's not a heap of
violation because he tweeted this to 3.8 million people.
That's Shaquille O'Neal, he's a basketball player.
I'm a big LA Lakers fan.
He was playing for the Celtics at the time but he
was a Lakers fan as well when he was growing up.
The reason I'm showing this is he had
moderate sleep apnea at the time that slide was taken.
He tweeted that, so I'm not giving away
anything confidential.
But he's an elite athlete.
He's in incredibly good shape,
he doesn't look that way on TV,
but these are very
cut in terms of his musculature and all that.
Despite that, he had moderate sleep apnea.
My main point here is that the stereotype of
an older obese man is simply a stereotype.
I've plenty of skinny women and
post-menopausal women
and thin people that have sleep apnea,
they don't look like the stereotype.
The other reason I show you this, as
my wife says, it makes me look thin.
These are some data on
the global prevalence of obstructive sleep apnea.
It's a paper we published in
The Lancet Respiratory Medicine about two years ago.
We tried to estimate
globally the number of
people with obstructive sleep apnea,
and it's hard because they're
a 197 countries and only about 17 of them had data.
We did estimates based on existing age,
body weight, gender distributions,
tried to match on races and ethnicities and whatnot.
We came up with the estimate that is about 936 million,
almost a billion people worldwide
who have an apnea hypopnea index more than five.
That means they stop breathing or have a pause in
breathing five times per hour or once every 12 minutes.
That's a minimal threshold for sleep apnea but
about a billion people meet
that definition of sleep apnea.
We have a stricter definition for sleep apnea.
That is, you stop
breathing or have a breathing problem,
15 times an hour or once every four minutes.
That's about a half a billion people
worldwide that have that.
That's a huge problem and
whatever solution we come up with has to be
scalable to that extent.
Now, you might ask, who cares?
Why does it matter if the people at
home with sleep apnea,
if they're not coming to see a doctor?
Leave them alone, you don't have to
go impose diseases on people that don't.
The estimates are still
more than 80 percent of sleep apnea
is undiagnosed and untreated.
We did this study as well in Switzerland.
Raphael Heinzer is a former trainee of mine,
we did this study but also published at
the Lancet Respiratory Medicine six years ago now.
We went into the community and did what's called
polysomnography or sleep studies
in people in the communities.
These weren't people come to the doctor
or to the sleep clinic with a complaint,
we went to them and did assessments on them.
It turned out about 23 percent of
women and about 50 percent of
men had an abnormality as defined conservatively,
more than 15 events per hour.
That is a breathing problem once
every four minutes while asleep or 15 times per hour.
That conservative definition or cautious definition,
23 percent in women and 50 percent of
men met the definition of sleep apnea. Why do we care?
What turned out was predictive of hypertension,
high blood pressure, diabetes mellitus,
and depression, all of which we take seriously.
The concept here is that sleep apnea is highly prevalent.
You can't ignore it just because
people aren't coming to the doctor.
That's why we take this disease seriously.
Not all of them get cardiovascular benefit
from CPAP, why am I saying that?
I'll explain that in a slide or two.
But the take home message so
far is that sleep apnea
affects up to a billion people worldwide.
The numbers vary with which criteria
you use or what equipment you use,
but you need to think about this global burden of disease
before moving much further.
There was this study called the SAVE study that was
published in New England Journal about five years ago.
This is looking at CPAP for prevention of
cardiovascular events and obstructive sleep apnea.
What the authors thought maybe was that you could
treat sleep apnea and prevent heart disease.
It turned out as a negative study, it wasn't helpful.
When this came out,
there's all kinds of press releases saying, ''Well,
maybe we don't have to take sleep apnea that seriously.''
Perhaps that's true, but the study was well done,
but there's some limitations in terms
of drawing rigorous conclusions.
The conclusion that was drawn in
the New England Journal of Medicine
was a therapy with CPAP,
continuous positive airway pressure
for treating sleep apnea,
plus usual care, as compared to the usual care alone,
did not prevent cardiovascular events
in moderate to severe sleep apnea,
and so you could say it's a negative study.
In my view, we need better therapies.
People need to adhere to therapy.
It doesn't work if it's sitting on the shelf,
and so perhaps people need to use the CPAP more.
We need better treatments which we're working on.
We need to identify high-risk patients better,
just a one-size-fits-all approach,
giving every man in Switzerland a
CPAP and expecting 50 percent of men in
Switzerland have cardiovascular benefits
seems unlikely because they're
not at a cardiovascular risk from sleep apnea.
We need more basic research regarding mechanisms,
which is the main focus of my laboratory.
But people often get a very dismissive
attitude about sleep apnea saying,
''Well, the mass,
there's continuous positive airway pressure.
Nobody tolerates that. It's terrible treatment
and nobody likes it.''
That's simply not true.
It got a bad reputation, deservedly,
20 years ago because it was
clunky and it didn't work so well.
It's gotten better, still
not perfect, but it's gotten better.
Here's some data. There's a Cloud where
the information from
the CPAP machines goes up to the cloud.
We have more than seven billion nights
of data in the cloud, now that we can analyze.
There's a group called medXcloud,
which is an academic-industry partnership
between several academic centers and ResMed,
the company that makes the equipment.
A pointer that I get no personal financial income
from either medXcloud or from ResMed,
but I did give a philanthropic
donation to our university.
If you look at the blue guys here,
x-axis here is time,
y-axis here is cumulative percent of patients.
The blue guy is about 70 percent
of patients given the CPAP,
red here is the therapy based on Medicare criteria,
about 70 percent. That's pretty good.
It's not perfect, but it's pretty
good in terms of usual occurrence,
better than a lot of chronic medical therapies that we
give people inhalers in asthma
or anticonvulsants in epilepsy.
Seventy percent for CPAP is pretty good.
If you use modern technology through patient feedbacks,
they get patient engagement,
they get a thumbs up if they're
doing well, they get helpful hints.
If they're doing poorly, then
the adherence goes up to 87 percent,
which is really quite good.
A defeatist attitude about sleep apnea,
where nobody uses it, is really not appropriate.
We did this study in 2.6 million patients looking at
everybody who got a CPAP machine that
was able to plug it in. It was all comers.
Now with 2.6 million patients,
receive about 75 percent adherence with treatments.
This defeatist attitude about CPAP saying nobody
uses it or nobody tolerates it, is simply not true.
Nasal CPAP is the treatment of choice.
It certainly improves symptoms,
improves blood pressure in terms of people with
high blood pressure or reduces the risk
of developing high blood pressure.
It's transformative for some patients.
I saw a patient this morning
saying they can't sleep without it.
A defeatist attitude about CPAP is
not just about the data look pretty good,
it was general acknowledgment that we need
new therapies with
ongoing research and that's what we're doing.
I'd like to stop there.
Again, thank you for your attention.
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