Cholesterol is a vital substance in our bodies. It is the building for all sex hormones and vitamin D. The widely
advertised concept that “the lower your cholesterol the better off you are” is flawed. Cholesterol needs to be
corrected to normal levels and sometimes below normal levels in those at high risk for cholesterol related
illness.


On the other hand those form a long line of people who die of sudden death, heart attacks or strokes are at
high risk for developing cholesterol related disease even with normal or borderline cholesterol levels.
Furthermore, those with elevated inflammatory markers, diabetes, obesity, hypertension, tobacco, emotional
stress use or autoimmune disease are at higher risk for developing cholesterol related disease and need
more aggressive treatment. All such individuals require additional testing to discover risks not revealed on a
routine cholesterol panel.


Furthermore, the concept that all hyperlipidemia is high cholesterol is also flawed. Treatment of hyperlipidemia
in the 21st century goes far beyond looking at a simple cholesterol panel and reducing cholesterol to below
200.


LPP Testing


For assessing additional risk factors for cardiovascular disease we routinely use LPP panel assessment
offered through Spectracell Laboratory in Texas. This panel is by far the most comprehensive testing
available for assessing additional risks for developing cholesterol related disease at any level of total
cholesterol. Additional factors ascertained through LPP testing include:


C-reactive protein (CRP): protein that is formed in blood in response to inflammation. Levels of this protein
are important risk factor for cardiovascular disease but disproportionately so in women. Levels of CRP are
often elevated in inflammatory conditions such as autoimmune disease but it is important to recognize that
autoimmune disease is an independent risk factor for developing cardiovascular disease.


Lipoprotein (a) (Lp(a)): Lp(a) is a protein on the LDL (bad cholesterol) that significantly increases the
propensity of the LDL to deposit and lead to formation of cholesterol plaques in arteries. This is a genetic
factor that can not be modified by either exercise or diet. High levels of Lp(a) can only be modified by niacin
and to a lesser extent by medications like Tricor or Trilipix. Very high levels of Lp(a) may not be normalized
despite high doses of the above medications. The only solution for such individuals can only be negated by
lowering LDL levels below 70, which often involves the use of statins.


Homocysteine: Homocysteine is a by product of inappropriate metabolism of folic acid. Accumulation of this
substance is hypothesized to lead to a higher tendency of LDL deposition at any level of LDL. It is important to
recognize that therapy with niacin although very beneficial for the most part can lead to a rise in
Homocysteine. High Homocysteine levels can be treated in some individuals by using folic acid. In many,
inappropriate metabolism of folic acid can not be overcome by folic acid alone due to a genetic deficiency  in
the enzyme responsible for activating folic acid to the methylated form. A newer product, methylated folic acid
marketed under the brand name Deplin, is touted as an effective treatment. It is also found to be useful as an
adjunct therapy for depression. Experience is limited with this new product and more data is required to verify
its effectiveness but in lieu of other alternatives we recommend use of this product for those at high risk.
Recent large scale studies have identified Homocysteine as a marker for those with metabolic dysfunction and
cardiac risk however have not demonstrated definite benefit in correcting Homocysteine to normal levels. As a
result we reserve therapy for this problem or those at highest risk only.

Buoyancy: Another reason why the simple testing of lipid panels is not fully effective is that a large buoyant
LDL is unlikely to deposit in arteries whereas a small dense LDL is likely to deposit at any given absolute
level. At the same time not all HDL cholesterol is protective against cholesterol deposition. Testing the
buoyancy of HDL can safeguard against misinterpreting a high HDL level as necessarily protective against
cardiovascular disease.

Apo-lipoprotein A (good) and Apo-lipoprotein B (bad): These markers are questionably useful in further
assessing cardiovascular risk in those with abnormal lipid profiles. Another marker, Apo-lipoprotein C, has
shown great promise as a single indicator outside of a traditional cholesterol panel to supersede all other
marker in predicting cardiovascular risk. Unfortunately, to the best of my knowledge, this marker is still only
available in the research setting and is not available to the public at large.

Other tests that can be useful in assessing include:

Hemoglobin A1C (Hgb A1C or glycated hemoglobin): This test reveals a 3 month average of blood sugar.
Elevated levels of Hgb A1C are now accepted as a diagnostic criteria for diabetes and it is also widely
accepted that even at borderline levels many perdiabetics begin to accumulate the complications of diabetes
including cardiovascular disease.

Glycomark: This test reveals a 6 week average of post-prandial blood sugars. Most pre-diabetics will have
low glycomark levels, correlating with high blood sugars after a meal. Many diabetics will remain at high risk for
cardiovascular disease despite having relatively normal Hgb A1C. These individuals benefit from specific
therapies aimed at lowering post-prandial blood sugars.


C-peptide: This refers to the level of naturally produced insulin. Most pre-diabetics will have elevated fasting
C-peptide levels while fasting. By definition, they all have higher than normal C-peptide secretion in response
to a standard intake of carbohydrates. To our knowledge, we are the only place where you can assess serial
C-peptide levels in response to a carbohydrate challenge. Blood sugar response to a standard carbohydrate
challenge was long considered the standard for diagnosing diabetes. However, the value of finding out the cat
is already out of the bag as opposed to diagnosing the problem before it gets too far is questionable. Early
diagnosis of pre-diabetes is valuable because once the pancreas is burned out return to normal becomes
much more difficult. Lifestyle and pharmaceutical interventions can prevent the development of diabetes in
such individuals thus greatly reducing risk.


Thyroid Function Testing: Hypothyroidism (low thyroid) is a common cause of metabolic derangements
leading to multiple issues including abnormal cholesterol panels. The abnormalities can range form pure
elevated cholesterol to those typically seen in metabolic syndrome including high triglycerides and low HDL. In
many such patients as long as the cholesterol abnormalities are not severe the treatment of high cholesterol
can be delayed until thyroid abnormalities have been appropriately treated.  Guidelines for the assessment
and therapy of hypothyroidism are summarized elsewhere on this website.


Testosterone: Andropause, the lowering of free testosterone levels in aging men is extremely common after
the 6th decade of life. It is associated with multiple symptoms and signs which can lead to abnormal
cholesterol metabolism. Similar to the therapy of cholesterol in hypothyroidism, in men with abnormal
testosterone levels and mild to moderate cholesterol abnormalities treatment for cholesterol can be safely
delayed until testosterone levels are normalized. Guidelines for the assessment and therapy of
hypothyroidism are summarized elsewhere on this website.


Carotid Ultrasound: The carotid artery is the most accessible major artery for direct visualization. Deposits
in this artery and the thickness of the arterial wall correlate well with deposits of cholesterol elsewhere in the
body.  Furthermore, large deposits of cholesterol are an independent risk for developing strokes. Besides the
size of these plaques the actual shape and architecture of these plaques can be visualized. Actual presence
of ulcers within these plaques and presence of loose pieces of plaque are extremely concerning and
constitute ground for immediate surgical intervention.

CT Calcium Score: This is frequently employed as a means for screening for cholesterol deposits in the
arteries of the heart. If a score of zero is obtained then we can rest assured that there is no coronary disease.
However, the majority of these tests reveal intermediate results. Thus we are obligated to proceed with
cardiac stress testing in many individuals who do not otherwise require such testing. As a result, we do not
utilize this modality frequently. This test coronary disease.

Cardiac Stress Testing: Standardized protocols for gradually raising heart rate to maximum predicted levels
based on age are widely accepted as a means for assessing the presence of flow limiting coronary disease.
Traditional testing using electrocardiographic (EKG) monitoring are sufficient for most patients. The accuracy
of these tests can be improved by combining them with echocardiography. For still equivocal results from both
above tests nuclear stress tests can be utilized. For those unable to exercise on a treadmill medications can
be used to speed up the heart to target levels. We prefer to proceed with stress testing over screening with
CT calcium scoring as they provide information regarding functionally significant disease rather than detecting
calcium that even in large amounts deposited in the arteries may never produce flow limiting lesions in the
arteries.


Emotional Stress: It is vital to recognize the role of stress in the development of cholesterol related disease.
Cholesterol levels can rise quickly in response to emotional stress. Furthermore, the spasm in the arteries,
common in high stress situations, with any level of cholesterol deposit can lead to heart attacks and strokes.
Appropriate counseling and use of medications to help with stress management can be as effective if not
more effective than cholesterol lowering medications at managing such stress related diseases. We
recommend laughter yoga as a healthy means of increasing laughter in your life and adjusting  your
perception of the stressors in your life.


Who needs Treatment for Elevated Cholesterol


We always begin this process by assessing the individual and their risk factors for cholesterol related disease.
To begin with if a patient comes from a family where everyone lives to be over 80 and no one dies of a stroke
or heart attack then this single factor supersedes much of anything you see on a cholesterol test. These
individuals are likely suffering from the coveted disease called “longevity syndrome”. They won’t die of
cholesterol related disease but may suffer from side effects of cholesterol medications while not deriving any
benefit from such therapy. The typical cholesterol panel of a person with longevity syndrome is as follows

Example 1


Total Cholesterol 280

LDL (bad cholesterol) 140

HDL (good cholesterol) >100

Triglycerides (fats) 82


Although the idea of not treating someone with a cholesterol of 280 is foreign to most physicians this is the
typical profile of someone who will never die of cholesterol related disease. To insure the safety of our
patients we routinely recommend further testing for such individuals by further testing other risk factors in
cholesterol panel included in an LPP panel.


In general, those with very high HDL levels have elevated levels of enzymes that make HDL. This is sometimes
accompanied by mild elevations of liver enzymes detected in routine blood analyses of liver enzymes. These
individuals sometimes undergo unnecessary work up for abnormal liver enzymes. We routinely rule out the
presence of hepatitis but further work up with liver biopsies are usually not indicated.


Another group of people with similar cholesterol panels are those who over absorb cholesterol. Although most
such individuals truly do not treatment medications such as Zetia are effective in reducing the absorption of
cholesterol. Treatment with other medications is unnecessary.


Example 2


A patient with metabolic syndrome (combination of obesity, hypertension and high cholesterol) typically has
the following cholesterol panel:


Total Cholesterol 240

LDL (bad cholesterol) 180

HDL (good cholesterol) 25

Triglycerides (fats) 282


Although none of the findings on this cholesterol panel are all concerning, the low cholesterol and high
triglycerides are even more problematic than the high total cholesterol and LDL. This individual needs further
testing for diabetes and pre-diabetes. The treatment of this patient should focus more on weight loss,
reduction of carbohydrate intake and use of supplements and medications aimed at increasing insulin
sensitivity. Furthermore, LPP testing for assessing additional risk factors and 2 hour glucose and C peptide
testing may be helpful to assess the extent of insulin resistance.


Example 3


Total Cholesterol 290

LDL (bad cholesterol) 210

HDL (good cholesterol) 35

Triglycerides (fats) 182


This patient suffers from a pure high cholesterol condition. Although the triglyceride and HDL are still not very
favorable the main issue is related to the LDL and total cholesterol levels. This is a typical cholesterol panel of
someone with both a genetic propensity towards this problem as well as a diet likely high in meats, cheese
and things that include the word “cream”. Simple reduction in intake of these substances may improve the
panel. However, it is important to recognize that even with the most strict of diets this panel can only be
improved by 25%. This person needs therapy with a statin medicaiton (lipitor, crestor, simvastatin, ...). LPP
testing can identify other risk factors and help define the appropriate target levels for cholesterol therapy in
such patients.


Example 4


Total Cholesterol 190

LDL (bad cholesterol) 150

HDL (good cholesterol) 15

Triglycerides (fats) 600


This panel reveals a patient with metabolic syndrome who is at high risk for developing pancreatitis.
Triglycerides at concentrations above 500 are a clear risk factor developing pancreatitis. Additionally, those
with this high of triglyceride level will have a change in the color of their blood: Blood appears white.
Treatment is often with medications like Lovaza (highly concentrated fish oil), Tricor/Trilipix, niacin, resins. See
pro’s and con’s of medical therapy for abnormal lipids.