Transcriber: Dylan Myers Reviewer: Amanda Chu
How many of you know somebody who's had a heart attack?
Raise your hand.
A lot of you.
That's actually not surprising,
because heart attack is the leading cause of death in the world.
And some of you may already know that,
but what I bet you didn't know
is that half the people who die of a heart attack
have normal cholesterol levels.
Let me say that again:
Half of the people who die of a heart attack
have normal cholesterol levels.
Clearly we are missing something.
For instance, my 44-year-old friend Mike
went to his mother's house in 2002 for Father's Day.
And while he was there,
he had his first, and only, heart attack
and died in her living room.
44 years old, with a wife and a family.
The problem is that current tests for heart attack risk
rely on a scoring system that was developed in 1998.
So it's over two decades old now.
It's called the Framingham Score.
And sure, it's been updated since then,
but it only takes into account a few limited metrics:
your age,
your gender,
your total cholesterol levels,
your HDL cholesterol levels,
your blood pressure
and whether you smoke.
That's it.
And worse, it was developed
by studying people in Framingham, Massachusetts,
which is a mostly white suburb of Boston.
So it may not predict your risk of a heart attack
unless you happen to be a white Bostonian.
(Laughter)
Now, you may ask,
"Why aren't there any DNA tests for heart attack risk?
There's lots of them for cancer, right?"
Well, turns out
that heart attacks and cancer are two entirely different animals.
Cancer is essentially caused by your exposure to carcinogens
and the reaction of your genes to that exposure.
So it makes sense
that there are genes that you can test for
that would determine your risk for cancer.
But heart attacks are mostly caused by your lifestyle.
Do you smoke?
Do you exercise?
Do you eat right?
Are you overweight?
Do you keep your blood pressure under control?
So, very different from cancer.
And so, there are a few genetic diseases that will cause heart attacks,
that will do things like astronomically raise your cholesterol levels.
But those are rare.
Heart attacks are primarily caused by your lifestyle.
Now, there's a newer risk score called the Reynolds score,
and it incorporates your family history,
and it also incorporates a marker of inflammation.
Now, I'm going to have to digress for just a moment
to explain why inflammation can be used to predict heart attacks.
Before you have a heart attack,
you have a plaque growing in the wall of an artery
that's filled with cholesterol.
And it gets bigger and bigger
as you get nearer to having your heart attack
until finally,
it gets so large that it ruptures
and causes a blood clot to form in that artery,
which then clogs the artery completely
and stops the current of your blood flow.
That happens in a coronary artery,
you have a heart attack.
If it happens in a cerebral artery,
you have a stroke.
So both diseases can be caused by the same mechanism,
and both of those can be caused by the same risk factors.
Now,
the way inflammation comes into this
is that that cholesterol-rich plaque
needs an environment in which inflammation is ongoing
in order to continue to grow,
an inflammation environment such as when you smoke chronically.
And that's why markers of inflammation
are predictive of your risk of a heart attack.
So given that, it would be nice
if we could test people with a marker for inflammation
that would then help predict your risk of a heart attack.
The problem now
is that the current markers for inflammation
are far too variable day to day
to be able to establish your baseline.
For instance, the gold standard inflammation marker
that was used in the Reynolds Score is called C-reactive protein,
which is usually abbreviated CRP
or, as I like to pronounce it, crap.
(Laughter)
And CRP is so variable day to day
that Kaiser Permanente no longer even offers this test to their patients.
It would take multiple blood draws over a period of weeks
just to guesstimate what your level is.
So our big idea
is to use a new marker of inflammation that's much more stable,
that we discovered in my laboratory,
called "gamma prime fibrinogen."
Say that fast five times.
Gamma prime fibrinogen.
(Laughter)
Since I'm a professor,
there'll be a quiz shortly after my talk.
(Laughter)
Let's just call it GPF for short.
We've been studying GPF in my lab for the over 25 past years
and shown that it's a blood clotting factor
that makes blood clots
that are mechanically stronger and are slower to break down.
And after studying this, we got to thinking,
"What if you had too much of that?
Could that maybe predispose you to forming a blood clot in an artery
that would lodge and not break down and lead to heart attacks?"
So we started doing human studies.
And,
it's been shown now in the intervening years,
and particularly in a study of 10,000 people
that was sponsored by the National Institutes of Health,
that GPF is in fact a predictor of heart attack death,
and stroke, by the way.
And because it's a predictor of this,
we've got to thinking,
"Well, what could we do with that?"
So we've studied its stability over time,
and we've shown that in fact, GPF is much more stable than CRP,
which allows you to do precision medicine on an individual person.
And we've shown that in fact, it's six times more stable than CRP.
And this is an example of one patient over a period of one year;
in fact, it's me,
and I have the scars to prove it.
(Laughter)
So you can see
that the GPF in the red line is much more of a stable, flat line
than is the CRP, which is shown in black.
And that makes it a lot more reliable
to be able to determine your baseline than other inflammatory markers
like CRP.
And I can tell you exactly what happened at that peak of CRP.
I had a sinus infection that day and I was on antibiotics.
Does that mean that I was at sudden risk of having a heart attack?
No.
So we think that GPF has a lot more potential
to be used on individual patients
than CRP does.
And we've gone on to show in studies
with patients who actually have plaque formation in their arteries
that GPF is higher in those people.
And it's also higher in people who have coronary heart disease,
peripheral artery disease,
which is a disease of the extremities that's more common in smokers;
it's higher in people with heart failure;
and it's higher in people with stroke.
And if you have more than one of these diseases at the same time,
it can be even higher.
And in people who were closer to having their heart attack,
it was even higher.
Which leads us to believe
that in fact, we may be able to track people
as they get closer to having their heart attack
and be able to identify them early.
Because that's the goal.
So, now that we have this new marker,
we're trying to get FDA clearance for this,
but any of you who know about FDA clearance
realize just how difficult and slow that particular process can be.
But nevertheless, we're moving ahead
because we think it has value for individual people.
The other part that is very interesting
is that we've found that it's higher in African-American populations.
And coincidentally, African Americans
have higher rates of heart attacks and stroke
than many other ethnic groups.
And so we're continuing to do research
to see whether GPF may contribute
to their increased risk of having a heart attack or stroke.
And this could identify an underserved population
who otherwise would be misidentified as being at low risk.
So, if your GPF is high,
is that a death sentence?
Is it all over? Just check out?
Well,
we've started a pilot study on children,
very small study so far,
but the results were quite compelling.
If we had children do aerobic exercise
for 30 minutes a day,
three days a week,
for three months,
we could see a measurable reduction in their GPF level.
So we think that although this isn't quite as easy as taking a pill
like you can for cholesterol,
at least there's something you can do about it.
So, if we could identify even 1% of people
who were going to die of a heart attack
worldwide,
we could save 70,000 lives a year
worldwide
from premature death from heart attack.
So we think GPF could help in that process.
So thank you all
while I led you down the rabbit hole.
(Laughter)
And thank you for your attention.
(Applause)