Cardiovascular Disease Prevention - SD

Introduction

Hello, I'm Steve Feinstein.
I'm a professor of medicine at Rush University
Medical Center in Chicago.
My area of expertise is actually non-invasive imaging
with contrast ultrasound and preventive cardiology,
and the two of these actually merge quite conveniently
together today when we use contrast ultrasound
to non-invasively detect atherosclerosis, we do this
through myocardial perfusion imaging
and vascular imaging, which actually includes
angiogenesis in the carotid arteries and other tumor bodies.
Thank you very much.

Overview of Non-Invasive Cardiovascular Disease Prevention

Today we'll present a brief overview
of non-invasive cardiovascular disease
prevention 2009.
The first slide is a famous quote from Daniel Hudson Burnham
saying that Make no little plans.
They have no magic disturb men's blood.
Well, the presentation
that follows hopefully will stir your blood.
Cardiovascular disease prevention,
cardiovascular disease is truly a pan epidemic pan
worldwide problem.
What technology will we use
to create early diagnosis and therapies?
Who will build it? Who's going to pay for it
and how do we access it?

Global Impact of Cardiovascular Disease

Today over 58 million people die each year from
cardiovascular disease.
Diabetes and hypertension are the primary culprits of note.
On the third point, 90% of type two diabetes is linked
with excessive weight.
Important point to note,
the metabolic syndrome is a precursor oftentimes of diabetes
and is relevant to the public at large.
Today there are probably some 44 to 50 million people
with a metabolic syndrome.
The relative risk of a cardiovascular event
and death is increased if you have the metabolic syndrome
and most importantly is the second item.
Here. Women have roughly a third more death rate than men
who have the metabolic syndrome.

Challenges in Public Access and Technology

The current issue, public access
and technology right now, there do not appear
to be coordinated integrated programs within academic
industry and governmental centers.
We have an uneven distribution of high tech,
low cost resources with limited dissemination
of innovative technology.
We need more evidence of miniaturization, scalable products
and a wider distribution of these products.
If we focus, for example, on the baby boomer generation,
these are the group that we want to accelerate the use
of non-invasive imaging
and the use of biochemical markers
to detect premature atherosclerosis and inflammation.
The problem is it's not just the boomers,
it is also the children of the boomers.
As children have higher BMI in their youth,
they will be predisposed
to have higher cardiovascular death rates.
As adults, what possibly could we look at
for a center of excellence if we begin
to say there's the basic science work,
there's a translational work, and there's the diagnostic
and therapeutic side.
These are the processes that we go through
to end up both diagnosing and treating atherosclerosis
and many other disease processes.
Where is the end point on this?
Well, one suggestion,
and this is based on a recent AP
publication in 2007
or 2008, are we going
to be looking at retail based clinics?
RBCs, for example, in this slide, this is an example
of the Walmart clinic
and if you notice in the picture the insert,
there's cholesterol screening.
Now, as noted on the second highlighted point, Walmart plans
to open 400 co-branded walk-in clinics
by 210 by 2010.

Scientific Foundations: Cholesterol and Risk

Alright, let's back up
and go to the science for another moment.
This is an old slide now 11 years old, but
nonetheless, critically important on the Y axis,
notice the LDL cholesterol as it drops from two 20 to one 60
to 100 reduces the relative risk as seen
on the x axis.
Please note on the Z axis, the HDL cholesterol, again,
as the level is depressed,
so is the increased relative risk.
The next slide shows the relationship of the particle size.
Again, looking at the smaller denser particles of
LDL tend to have higher risks associated with them
of cardiovascular death rates.

Therapeutic Lifestyle Changes

Another issue we must look at in this country is not just
the biochemical markers, but therapeutic lifestyle change.
This was a paper published by O'Keefe in 2007.
The first point
and the fourth point are, are really important.
The first point processed calorie dense nutrient depleted
American diet leads
to post perennial spikes in blood glucose
and lipids, which leads to immediate oxidant stress
directly proportional to increases in
glucose and triglycerides.
If you drop to the third point,
these spikes are an independent predictor.
Cardiovascular events in non-diabetic subjects.
The fourth point exercise in diet obviously
profoundly affect favorable results
and the fifth point diet recommendations.
Metabolic syndrome diabetes
are best served by the uh, Mediterranean
diet and lifestyle.
Low processed, high fiber plant-based foods

LDL Lowering and Residual Risk

is LDL lowering enough, it's a good start
and major statin trials have consistently shown 25
to 40% reduction in LDL cholesterol.
Despite the LDL cholesterol lowering residual
risk remains high.

Cardiovascular Diagnostic Prevention Center

This is an example of the cardiovascular
diagnostic prevention center.
The center of the picture is the ultrasound system.
The upper left is the picture of the patient
with multiple organs of the body scanned with ultrasound
and with the use of contrast.
Now, for example, ultrasound contrast today is used
to highlight as you see on the picture on the left,
the endocardial surface
and the chamber of the echocardiogram.
The white material seen is the contrast agent.
The muscle is black or dark.
The area that is focused is the left
ventricular main chamber.
The left atrium is at the bottom of the, of the picture,
the right ventricle off to the left of the picture.
On the frame on the right side, you can see the chamber
of the left ventricle is highlighted in yellow
and the muscle is now orange.
This is an example of myocardial perfusion,
but this is not an approved FDA use of contrast.
At this point. Ultrasound imaging is going
through changing us, uh, and the changes are quantitative.
For example, what you see in this slide is an example
of a tissue speckle tracking to indicate both the function
and the timing of the heart contraction.
On this picture, it's still frame.
The next picture is a movie illustrating
this technique in a heart muscle of a patient
that is not working well
and as you can see right approximately from six o'clock
to nine o'clock there's been an infarct
and the heart no longer contracts accurately.
Also, there are new changes coming in volumetric imaging.
This is an example
of a tri plaine stress echo using contrast ultrasound.
Each frame is a different cut of the ventricle with the apex
of the ventricle at the peak
and the base of the heart at the bottom in all four frames.
Ultimately, you'll take the 2D, the tri plane
and do a composite 3D global image.
In this case, this is an example of 3D strain imaging,
not to forget the right ventricle also needs
to be quantified.
This is an example in a still frame of the right ventricle
with tissue speckled tracking.

Improving Stress Echo Results with Contrast

I had mentioned the use of ultrasound contrast
for improving stress echo results.
This is data taken from our lab
in 5,352 patients all undergoing
stress echocardiography.
Notice in group A,
the positive predictive value was roughly 70%.
Group A underwent stress echoes without the use
of ultrasound contrast Group B,
all patients received a stress echo
with ultrasound contrast.
Notice the positive predictive value is almost 80%.
There's roughly a 10% increase in positive predictive value
with the use of contrast in patients undergoing stress echo
at our institution.
What we find as the years have gone on is that the use
of contrast actually affects patient management based on the
outcome of the images.
This slide taken from
Kurt's work published in the Journal of American College
of Cardiology 2009, showed that the use
of contrast in a prospective Body
of patients 632 patients followed prospectively, revealed
that the uninterpretable studies decreased from 11% to 0.3%
and the technically difficult studies decreased from 87%
to roughly 10%.
Importantly, therapeutic decisions were changed in 10%
and additional procedures were avoided in over
35% of the patients.

Expanding Ultrasound Imaging Applications

It as we begin
to expand the use of ultrasound imaging in contrast,
this is an example of transesophageal echo imaging
with the use of contrast to highlight the aortic plaques
and thrombi in the descending aorta.
We can also extend the image to the kidney.
This is an example of renal artery perfusion imaging
and carotid imaging.
In the next slide,
when we image the carotid,
we can see the contrast clearly highlights the lumen
and helps us identify the IAMT border,
the intimate medial thickness border as noted by the green
software line identified in the red software line.
Ultimately, will we be using contrast for vascular imaging?
As these images show, it is possible.
The image on the left shows a standard ultrasound
examination of a carotid artery.
This is the common carotid on the right.
Following IRB protection
and the use of off-label indications for contrast agents,
we have begun to image R patients carotid arteries
with ultrasound contrast.
This is the same patient seen on the left without contrast
and on the right with contrast, I think it is apparent
that the far wall demonstrates a thin normal IMT surface,
whereas the near wall demonstrates early plaque progression.
In this patient,
we have also used automated software
to measure the inter medial thickness.
As you can see on the left, an unenhanced carotid image
with IMT measurements,
the upper left box indicates the average,
the max minimum standard deviation
and the number of points identified with this software.
The image on the right is the similar carotid artery,
though this time with contrast
is contrast artery imaging
and IMT imaging associated
with cardiovascular disease detection.
In fact, there are multiple meta-analyses demonstrating
that carotid IMT is directly correlated
to cardiovascular disease, which affects cerebral peripheral
and coronary artery disease.
It is correlated to IMT and to LV mass.
Are there studies showing that the use of statins,
for example, correlate
with reduction in cardiovascular death rates
and to IMT reduction?
These are old studies listed on the left side of the table,
but on the right, the effect reduction in IMT progression
reduced cardiovascular events,
stopped IMT progression, et cetera.
So there is and has been a correlation between the use
of carotid IMT imaging associated cardiovascular disease
and therapy interventions.
Thank you very much.