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.Part I. Cardiovascular Disease and
Lipoproteins
Cardiovascular (CV)
disease is becoming a global pandemic, pretty much the number one
cause of premature death (heart attack, sudden cardiac death) and
definitely the number one cause of premature permanent disability
(stroke) in the United States and rest of
the industrialized world. To put things into perspective, more
Americans die every single day from CV disease than all the
innocents murdered by radical Islamo-fascist terrorists on 9/11/01.
Despite medical advances in the recognition and management of CV
disease, the likelihood of CV events during the lifetime of the
typical "healthy" (non-smoking, non-obese, non-hypertensive,
non-diabetic) 40-year old adult remains very high – almost 49% for
men and 32% for women.
When we manage (as
patients and doctors) CV disease, we focus on managing the risk
factors for this condition. These risk factors include those that
are non-modifiable (genetics, gender, ethnicity, the aging process)
as well as those that are completely modifiable (lifestyle choices,
hypertension, diabetes and "cholesterol" problems). There is
obviously strong interaction between the non-modifiable and
modifiable risk factors. If the non-modifiable risk factors "load
the gun" in terms of future CV risk, it’s the modifiable ones that
"pull the trigger." Therefore, we focus on the modifiable risk
factors, since they’re the ones we’re able to influence and alter.
All the modifiable risk factors are important but, since CV disease
develops and progresses due to inappropriate deposition of
cholesterol within the walls of our arterial system (the best
non-invasive way to identify this process is the carotid
intima-media thickness [CIMT] test by CardioRisk [www.cardiorisk.us]),
dyslipoproteinemia (abnormalities of lipoprotein particles that
transport cholesterol and triglyceride [TG] in our bloodstream) is
probably the most influential of all the modifiable risk factors.
The lipoprotein
particles that exist within the bloodstream can be differentiated
from one another by their size as well as by their density.
Lipoproteins (lipid [fat] + protein) are just what the name implies,
spherical particles with fats (cholesterol and TG) in their cores
and proteins embedded into their surfaces.
The
more fat relative to protein these lipoprotein particles contain,
the more buoyant they are while the less fat relative to protein
they contain, the more dense they are. Imagine a glass of water (the
bloodstream is an aqueous medium). If you pour some olive oil (fat)
into that glass, the oil will float on the surface (buoyant) while
if you drop a piece of meat (protein) into that glass, the meat will
sink to the bottom (dense). Think of laboratory measurements of
lipids (total cholesterol [TC], LDL-cholesterol [LDL-C],
HDL-cholesterol [HDL-C] and TG) as "shadow markers" of the actual
lipoprotein particle concentrations
But, what can shadows
really tell us? If there was a shadow of a man and another shadow of
a horse on a wall, even a three-year old child could distinguish the
sources of those shadows. What about detail? What color are the
man’s eyes? Shadows can’t tell you detail – lipids can’t give you
detailed information about lipoproteins. And many times this detail
is required to make important clinical decisions. How tall is the
man? If his shadow measures 5’9”, he could actually be 5’ tall or
maybe even 6’6” tall – right? Shadows can significantly over- or
underestimate the size of things – lipids can significantly over- or
underestimate the actual number of lipoprotein particles that exist.
Lipoproteins
can be broken down into alpha(α)-lipoproteins
(HDL particles) as well as beta(β)-lipoproteins (mainly LDL
particles). Imagine a bucket (representing the arterial wall) with
β-lipoproteins being a measuring cup adding water (cholesterol) to
the bucket and α-lipoproteins being a separate measuring cup
removing water from the bucket. When cholesterol deposition exists
within arterial walls, it is almost always due to excess
β-lipoproteins rather than diminished and/or non-functional
α-lipoproteins (although the latter process is indeed possible). In
the physiologic state, both measuring cups are basically the same
size and the bucket remains empty. In the pathologic state, the
measuring cup adding water is larger than that removing water so the
bucket fills and might even later "explode" (heart attack, stroke,
sudden cardiac death). Thus, when cholesterol deposition exists
within arterial walls, the focus is on reducing the concentrations
of β-lipoproteins (if the measuring cup adding water is made smaller
than that removing water, eventually the bucket will
empty).
The most likely
β-lipoprotein to deposit cholesterol within arterial walls is the
LDL particle. LDL particles come in different sizes – small as well
as large. LDL-C usually represents large LDL particles while HDL-C
and TG usually represent small LDL particles. When the number of
total LDL particles in the bloodstream is low, the likelihood that
any one of those particles will penetrate arterial walls and deposit
cholesterol is low and thus the future CV risk is low. However, when
the number of total LDL particles is elevated, there is an increased
likelihood that some of those particles will penetrate arterial
walls and deposit cholesterol and therefore the future CV risk is
elevated.
Under
physiologic conditions (individuals who exercise daily, don’t
overeat and maintain an appropriate body weight), a relatively low
number of large LDL particles usually exist in the bloodstream
whereas under pathologic conditions (individuals who overeat, don’t
exercise and are overweight), a relatively high number of small LDL
particles usually exist in the
bloodstream.
Part II.
Pre-Diabetes
One very important
modifiable risk factor to consider is pre-diabetes – also termed
metabolic syndrome (MS), insulin resistance (IR) and/or syndrome X.
This condition occurs because of unwise lifestyle choices – lack of
appropriate physical activity, excessive caloric intake and
resultant obesity. Pre-diabetes is becoming quite prevalent among
American adults, men as well as women. This condition becomes more
common the older we get but is actually increasing the most in
younger individuals, especially
adolescents.
The presence of
pre-diabetes (compared to its absence) has been shown to increase
the likelihood of future CV mortality by up to 600%. This increased
risk is ENTIRELY reversible, however, if the unwise lifestyle
choices that caused the syndrome are corrected. Thus it is
IMPERATIVE for anyone having pre-diabetes to limit their
daily caloric consumption as well as increase their daily physical
activity level to attain a more appropriate body
weight.
If one looks at the
underlying pathology of pre-diabetes, one would find that elevated
levels of small LDL particles serve as the linchpin for this disease
state. Since in many clinical circumstances pre-diabetes obviously
represents a precursor state to actual type 2 diabetes mellitus
(T2DM), elevated levels of small LDL particles also serve as the
linchpin for T2DM.
Think of T2DM as an
iceberg. What sinks your Titanic is not the tip of that iceberg (the
elevated fasting blood glucose [FBG]) but rather the body of the
iceberg that exists beneath the water’s surface (the elevated levels
of small LDL particles). In fact, the tip of the iceberg basically
only serves as a warning that there’s a big iceberg lying underneath
that you’d better watch out for – or it WILL sink your
Titanic. The best way to rid your body of CV risk from pre-diabetes
as well as actual T2DM is to eat less, exercise more and lose weight
(which will decrease those levels of small LDL particles).
MELT the iceberg and you needn’t worry about your Titanic
sinking, right?
Part III. Advanced
Testing
So the total number of
LDL particles (large and small) determines CV risk and the presence
of elevated levels of small LDL particles determines the likelihood
of becoming a type 2 diabetic. However, what the vast majority of
clinicians currently measure are not LDL particle concentrations but
rather surrogate markers of these called LDL-C, HDL-C and TG. These
lipid values are nothing but shadows of the actual lipoprotein
particle concentrations as discussed
above.
The concept that any disorder of serum lipids (dyslipidemia)
is just a shadow of the true disease state (dyslipoproteinemia) is
not a new one. In fact, even in 1967 was it understood that
recognizing and managing patients based upon lipoprotein rather than
lipid data would obviously be advantageous. But, at that time, it
was technically impossible to measure lipoproteins so we have grown
accustomed to using lipids as surrogate markers for lipoproteins
because "lipids were better than nothing." However, an actual
lipoprotein-focused test has recently become commercially available
and finally has provided us the ability to directly measure large as
well as small LDL particle levels.
NMR technology (more
commonly referred to as MRI or magnetic resonance imaging) has
become widely utilized and respected for diagnosing various medical
conditions. Since 1999, a commercial lab test utilizing NMR/MRI
technology (in a microscopic sense) has become available and has
FINALLY allowed us the technologic capability to directly and
reliably measure lipoproteins.
This test is called the NMR LipoProfile and is currently
available through a lab headquartered in Raleigh, NC called LipoScience (www.liposcience.com). The NMR LipoProfile
utilizes NMR/MRI technology on a blood specimen to directly measure
lipoprotein particles and is the ONLY way of doing so at
present. It is almost 99% accurate (WAY better than
ANY lipid-based test).
The main reason that
NMR-derived lipoprotein testing is so currently underutilized is the
fact that doctors are human – like everybody else. Some of us are
concerned with "doing the right thing" while others of us are
focused on ‘"doing the easy thing." Some of us look for reasons and
ways to do the right thing while others of us look for excuses why
not to do it. Some of us are shepherds while others of us are sheep.
If
you care about your future CV health, you must find a physician who
is a passionate shepherd and not one who is a lazy sheep. Please
find one who is an early adopter of the truth because there are just
way too many late adopters out there. It is crucial to have
lipoprotein disorders appropriately diagnosed. If the diagnosis is
suspect, the therapy (whether nutritional alone or combined with
pharmaceuticals) will NEVER truly be appropriate and/or
optimal. In fact, in order for
you to utilize the dietary/lifestyle recommendations in The
HAPI Heart Diet and The HAPI Heart Cookbook in
the most optimal way possible, it would be very wise to have
NMR-derived lipoprotein testing performed to determine whether or
not you have increased amounts of large and/or small LDL
particles.
Call (239)
261-HAPI today for an appointment at the Heart Attack
Prevention Institute (HAPI) with Dr.
V. |
