I spoke with a friend recently who was very concerned about his cardiovascular
inflammation status. He's very much in touch with this discipline, this
knowledge, far more than most people. But it still made it clear that there's need
for review here. I've done a series on cardiovascular inflammation testing and
evaluation, but I'll do a slightly different type of coverage today just to
help you understand how do you have to evaluate it. One of his problems was that
his PLAC2 was a little bit elevated. So again, he was very emotional, very
concerned. But when you looked at the rest of his panel, he looked... it looked
pretty good. He did have some drivers from inflammation, and yes, it was what
you often see - he had some insulin resistance. But let me go through the the
inflammation panel just for a review. So just as a brief reminder. Inflammation...
cardiovascular inflammation, as a risk for heart attack and stroke, hit the news
big this past June when this fellow Paul Ridker, the principal investigator of
the CANTOS study (and this is a picture of him) doing press releases for the
CANTOS study. CANTOS... basically what he did was something he's been doing for
over a decade. Shows that inflammation is the cause of heart attack and stroke.
He started this information back with some other friends of his from
Harvard about what 20 years ago, even looking at risk factors associated with
old studies like Framingham. They went on to show decreased inflammation from
statins in the JUPITER trials and decreased heart attack and stroke. There
so again, it wasn't so much the LDL. That was the inflammation.
Now, so that's to help you put a little bit in context. The CANTOS study, by the
way, was canakinumab or Ilaris. it's an injection, very expensive, one of those
injections, anti-inflammatories, to decrease graft host versus graft disease.
It was that kind of anti-inflammatory, and yes, it did decrease heart attack and
stroke. Let's look at the cellular view of inflammation. This is progression in
cardiovascular inflammation. This is the bloodstream.
This is the intima layer or the endothelium. This is the media layer or
the muscle layer. And this is plaque. As you see, you progress here through some
plaque being laid down. More and more inflammation to where you're getting
what we call a necrotic core tissue material that's been almost completely
digested. It's dead tissue in the core of this plaque. When this stuff gets
like this, if it spews out and escapes into the bloodstream, it touches the
blood and creates a clotting, cascade that clotting. Cascade is what causes
heart attack and stroke. Let's go back up here, and look at a couple of the the
building blocks for this hot or inflamed plaque. These are what are called
neutrophils. They have vacuoles of an enzyme in there. That enzyme can be
released, and it's called myeloperoxidase (MPO).
There's actually a test for that. We'll go over it in just a second. There are
other types of cells as well - monocytes. Both of these are white cells or immune
cells. Monocytes are attracted to chemicals released by this process. They
come in and release another type of enzyme called PLAC2, Lp-PLA2. You'll
see that as a test as well.
There's another thing called an HS-CRP. CRP (C-reactive protein) is something
that most docs have not gotten deep into cardiovascular inflammation and
cause for heart attack. But those that have usually focus on CRP, if you go back
to Paul Ridker, they focus on C-reactive protein. Now, we use C-reactive
protein but we use it as a part of a panel. We don't use it alone because you
can get too many false positives with that. Here's another way of looking at
that plaque. Again, similar views. This is the bloodstream area. This is the
media or muscle layer of the artery wall. This is the intima. This is
the tissue we don't want to disrupt because if you get disruption,
you can get... release of this necrotic material. These are foams.
These are monocytes. As they continue to get active, they are called foam cells,
and they release that Lp-PLA2. Now, how do you test for it? Let's talk a little
bit more about the test. Cleveland Health Lab has had an
inflammation panel for a while. I think it's... I think it's about $300. It's
available to patients. You know, I don't think you have to get a physician's
order for it. John can tell us that when he gets back
from vacation. But that's one of the standard orders we have for our patients.
Now, since they've been purchased by Quest they've changed some of their
inflammation panel around. I will review the tests that we use. This is a
diagram. If you go to over here let me just go back to this last image for a
second, you can look this up, and I'll put the link on the discussion under the
video. It gives you a lot of information about testing for
cardiovascular inflammation. This is another look, a larger look at the artery.
Less disease to deeper disease. No plaque. You start to see an increase in plaque
here. These green dots are supposed to represent myeloperoxidase. Remember,
that's released by the neutrophils. It's a gross picture, but it helps you
remember and connect some dots here. You know, when a child gets a cold, the
mucus sometimes has a greenish tint to it.
Myeloperoxidase is what gives that greenish tint. And those white cells are
the same cell line as cells that attack plaque in here. So we can actually
measure it in the bloodstream. And that's why they made those little dots
green. So let's go back and review the tests individually. First of all
C-reactive protein. That's the one that if docs are aware of, the whole topic of
cardiovascular sensitivity and more and more cardiovascular inflammation and
more and more becoming aware, this is the one that they'll know of. Again, I use
that, but I don't use that alone. Typical false positive would be that somebody
has a flu, and then 2 weeks later, they have a positive
C-reactive protein. PLAC2 - I mentioned that a few minutes ago. It's the
enzyme released by monocytes. That's the one that my friend had a slightly
elevated level on. Myeloperoxidase (MPO), it's the one released by neutrophils.
So myeloperoxidase and PLAC2 are both enzymes that are actually released by
white cells as they're attacking plaque and digesting it. Now, here's the... this is
the most important test for cardiovascular inflammation -
microalbumin. We actually test for who are called microalbumin creatinine
ratio. Now, what does that mean? It's actually a test of kidney function. It's
a test the docs do in other situations even if they're not aware of
cardiovascular inflammation. Because they're looking at function of the
kidney. This may not look like a kidney to you, but this is called a glomerulus.
It is the filter component of the kidney. The kidneys are actually a coalescence
or a conglomerate of filters, these plus some other tubules that concentrate
fluid. Each kidney has about a million glomeruli. This is an artery... and the I've
got it upside down, that's me, I know my images are so good... let's make this a
little bit easier to understand. This is called an afferent artery. This is where
the artery is bringing blood into the kidney and then back. Afferent is bringing
it back out. When the blood goes into this yellow capsule (and that yellow is
it's called Bowman's capsule), it's where the urine collects to go down
into the ureter and bladder. Once it crosses here, it loses the media layer of
the artery. At this point, the filter is just the endothelium or the intima. So
when you go back and you think about... let's come back and look at some of the
original images. Remember, we kept talking about, you're looking for endothelial
health or intima health. Because you don't want this necrotic tissue, this hot
plaque to be released out into the bloodstream. The intima, that is the
filter membrane of the glomerulus, and that is why microalbumin is so
important and kidney function is so important. If you
have damage and holes in your intima within your arteries, you'll have them
here, have it here as well. And you'll be spilling the most highly concentrated
protein we have in our blood which is albumin. So if you're spilling
more microalbumin through those membranes, if it's leaking through those
membranes and your kidneys, you have significant evidence of inflammation and
holes in the intima or endothelial layers of the arteries. So again, it's as
usual I think I talked longer than then I plan, and I appreciate your patience
and your interest. But if you'd like to get in a little bit more information
about how to get tested for cardiovascular inflammation, just give us
a call. Thanks for your interest. Bye-bye.