What's your LDL-P and why should you care?

What's your LDL-P and why should you care?

Richmond.com column
April 2008
For what a man would like to be true, that he more readily believes.
Francis Bacon

Last week the American College of Cardiology (ACC) and American Diabetes Association (ADA) issued a consensus statement saying that the measurement of LDL particle number (LDL-P) is a more accurate method of quantifying cardiovascular risk than traditional measurement of LDL cholesterol (LDL-C).

OK, so what? Well remember, this is a column on health and new discoveries and treatments to test; treat and prevent illness and disease. Both men and women's number one health challenge is heart attack and stroke and since the 50's medicine has been screaming about cholesterol so any new test or strategy to better manage this risk IS big news. The funny thing is this test has been around since 1999. Medicine is slow to change, so it may be up to you to ask your doctor is this test is right for you.

Now for some basic science, keep reading, don't be afraid. Cholesterol is a naturally occurring substance in all our bodies and important for many things like making hormones, cell membranes and insulating the nerves in your brain. Cholesterol is carried in particles within our blood called lipoproteins. There are several types of lipoproteins including High Density lipoproteins (HDL), Low Density lipoproteins (LDL), Intermediate Density lipoproteins (IDL) and Very Low Density lipoproteins (VLDL). Within these various subclasses, there are still more distinctions which relate to particle size and function.

An American doctor, Ancel Keys, in 1953 using data from his 'Seven Countries Study', concluded that diets high in fat resulted in more heart disease. Thus, the start to find "the" substance that caused this increase in disease. Early science identified elevated levels of total cholesterol as being highly correlated to heart disease and stroke.

Much of our current practice of cholesterol management has come from information derived from the Framingham Heart Study, which started in 1948 and goes on today. During these early times, laboratory technology limits allowed only the measurement of total cholesterol and later discoveries allowed the refinement into the above mentioned subclasses.

We now know that it is the number of particles that carry cholesterol in the bloodstream, not the total amount of cholesterol that causes vascular disease. As the concentration of particles goes up inside the bloodstream, the more likely these particles are to enter the wall of the vessel resulting in the deposition of cholesterol inside the vessel wall, the earliest form of vascular disease. LDL-P is the measurement of these cholesterol transport particles.

Since 1999 LipoScience in Raleigh, NC, has been measuring the number of lipoprotein particles which carry cholesterol in our blood. This technology has resulted in large scale testing of LDL-P and has been used to retest the serum of patients in the Framingham Heart Study. This data shows people from the Framingham study who are in the lowest quartile of LDL cholesterol (LDL-C) measurement still had 37%  MORE cardiovascular events than those in the lowest quartile of LDL particle (LDL-P) measurement. In other words, you can have low cholesterol and still be at risk for vascular disease. This data is supported by another large trial more recently called the Multi-Ethnic Study of Atherosclerosis (MESA) trial.

Again, so what? Well here's the thing. There is something called discordance. Discordance is when your cholesterol measured by old fashion means, differs from your lipoprotein particle number. It is the number of lipoproteins which carry your cholesterol that is the BEST estimate of your cardiovascular risk, that thing that kills most of us, not your cholesterol level. If you cholesterol level looks low and you have discordance between your cholesterol level and your lipoprotein particle number, you can still be at a much greater risk; 37% greater in the Framingham study and that was in the people with the LOWEST LDL cholesterol!

I had the opportunity to recently visit the LipoScience headquarters and listen to Dr. William Cromwell their former Chief Medical Officer. Dr. Cromwell has spent the last 20 years researching the relationships of lipoprotein particles and vascular disease. LipoScience uses nuclear magnetic resonance to count the number of lipoprotein particles in a blood sample. Their technology has been available since 1999 and last week's policy statement from the ACC/ADA is the loudest pronouncement yet to the medical community to use this test for routine screening and ongoing management of elevated lipoproteins.

So, what your LDL-P?  I hope you have found this topic of interest, you should. Heart disease and stroke are preventable with today's proven technology. LDL-P is just one of several recent advances that are available to better understand your health risks. Carotid artery ultrasound scanning, high resolution coronary CT scanning, other high tech vascular inflammatory markers are all available to you to better predict your vascular risk. Many of these tests are not covered by your health insurance. Our medical system is ranked 37^th worldwide in preventative care. Health insurance companies exist to make money for their shareholders, not take care of your health. You should take care of your health!

Putting all these tests together, explaining their meaning, planning a your wellness program, making healthcare convenient and delivering it in an efficient manner is what the Executive Health Evaluation program does for 10 of the 13 Fortune 1000 companies here in Richmond.

Hypercholesterolemia Diagnosis - Wikipedia

Hypercholesterolemia Diagnosis - Wikipedia

Interpretation of Cholesterol levels
cholesterol type	mg/dL	mmol/L	interpretation
total cholesterol	under 200	under 11.1	desirable[20]
	200-239	11.1-13.3	borderline[20]
	more than 240	more than 13.3	high[20]
LDL cholesterol	under 100	under 5.55	most desirable[20]
	100-129	5.55-7.15	good[20]
	130-159	7.15-8.82	borderline high[20]
	160-189	8.82-10.5	high and undesirable[20]
	over 190	over 10.5	very high[20]
HDL cholesterol	under 40	under 2.21	undesirable; risk increased[20]
	41-59	2.21-3.27	okay, but not optimal[20]
	60	3.27	good; risk lowered[20]

Indications to lower LDL cholesterol
Persons whose coronary risk is...	because they have...	should consider lowering LDL if the level is over...	and LDL reduction is indicated if the level is over...
high	greater than 20% risk of heart attack in 10 years, or an extreme risk factor such as coronary heart disease, diabetes, peripheral-artery disease, carotid-artery disease, or aortic aneurysm	70 mg/dL, 3.88 mmol/dL especially if there are risk factors[21]	100 mg/dL, 5.55 mmol/dL[21]
moderately high	a 10-20% risk of heart attack in 10 years and two or more risk factors	100 mg/dL, 5.55 mmol/dL[21]	130 mg/dL, 7.21 mmol/dL[21]
moderate	less than 10% risk of heart attack in 10 years and two or more risk factors	130 mg/dL, 7.21 mmol/dL[21]	160 mg/dL, 8.88 mmol/dL[21]
low	No risk factors or only one	160 mg/dL, 8.88 mmol/dL[21]	190 mg/dL, 10.5 mmol/dL[21]

Cholesterol is measured as milligrams per deciliter (mg/dL) of blood in the United States and some other countries. In the United Kingdom, most European countries, and Canada, millimoles per liter of blood (mmol/L) is the measure.^[22]

For healthy adults, the UK National Health Service recommends total cholesterol of 5 mmol/L or less, and low-density lipoprotein cholesterol (LDL) of 3 mmol/L or less. For people at high risk of cardiovascular disease, the recommendation for total cholesterol is 4 mmol/L or less, and 2 mmol/L or less for LDL.^[23]

In the United States, the National Heart, Lung, and Blood Institute within the National Institutes of Health classifies total cholesterol of less than 200 mg/dL as “desirable,” 200 to 239 mg/dL as “borderline high,” and 240 mg/dL or more as “high.”^[24]

There is not an absolute cutoff between normal and abnormal cholesterol levels and interpretation of values needs to be made in relation to other health conditions and risk factors.

Higher levels of total cholesterol increase the risk of cardiovascular disease, particularly coronary heart disease. Levels of LDL or non-HDL cholesterol both predict future coronary heart disease, which is the better predictor is disputed.^[25] High levels of small dense LDL may be particularly adverse, although measurement of small dense LDL is not advocated for risk prediction.^[25] In the past LDL and VLDL levels were rarely measured directly due to cost. Levels of fasting triglycerides were taken as an indicator of VLDL levels (generally about 45% of fasting triglycerides is composed of VLDL), while LDL was usually estimated by the Friedewald formula:

LDL total cholesterol - HDL - (0.2 x fasting triglycerides).

However, this equation is not valid on non-fasting blood samples or if fasting triglycerides are elevated >4.5 mmol/L (> ∼400 mg/dL).

Recent guidelines have therefore advocated the use of direct methods for measurement of LDL wherever possible.^[25] It may be useful to measure all lipoprotein subfractions ( VLDL, IDL, LDL, HDL) when assessing hypercholesterolemia and measurement of apolipoproteins and lipoprotein (a) can also be of value.^[25] Genetic screening is now advised if a form of familial hypercholesterolemia is suspected.^[25]
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See also: High-density lipoprotein#Recommended ranges and Low-density lipoprotein#Normal ranges

Extracts - ATLCX (Episode 29): Dr. Thomas Dayspring | Cholesterol Testing: What Matters Most?

Extracts - ATLCX (Episode 29): Dr. Thomas Dayspring | Cholesterol Testing: What Matters Most?

"LDL particle concentrations is the type of testing we all need to have done"
Listen at the iTunes page for the podcast:

Listen and comment about the show at the official web site for the podcast:

Download the MP3 file of Episode 29 [109:15m]:

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Particle count - big picture

• HDL-cholesterol has as its surface apoprotein, apolipoprotein A-1
• ApoA-I measurement serves as an HDL particle count
• You can have a lot of HDL particles, but low HDL-cholesterol
• Thus although apoA-I and HDL-C usually correlate, in some folks they do not (discordance)
• People with low HDL-C but normal apoA-I tend not to get heart disease
• people with high HDL-cholesterol could have low Apo A-1 (low HDL particle count)

Evidence supporting LDL-P approach?

• His 2012 study of diabetics looking at LDL particles (American Journal of Cardiology Sept 2012)
• Check out information on why LDL particle tests good

Official standards?

• There are 5 US specialty Society guidelines do advise apoB or LDL-P testing
• These specialty societies are ADA, ACC, AACC, ACE, NLA
• Apo B is in the European guidelines, but not LDL-P (LDL-P by NMR is not available in Europe)
• Guidelines are never meant to be cutting edge
• The majority of doctors don’t know understand or know of Apo B and LDL-P
•  Apo B is a worldwide standard for lipid/lipoprotein health
• You can get Apo B test run in any lab in America
•   The VAP test offers a calculated Apo B–BOGUS!
• Calculated LDL-cholesterol is an imprecise equation
• If your trigs are under 100, divide by 5 for VLDL-cholesterol determination
• Once you have VLDL-C, you can calculate LDL-C using the equation: - LDL-C = TC minus HDL-C – VLDL-C

Particle count - what it should be

• LDL cholesterol levels under 100 mg/dL has long been the standard
• LDL-P of 1600 nmol/L is in the 80th percentile
• A desirable LDL-P of 1000 is the 20th percentile population cut point
• ie. 80% of the populations has a higher level
• LDL-P under 700 is in the 5th percentile population cut point
• ie. 5% of folks are less and 95% are higher

Particle count too high, causation and cure

• Insulin resistance is at the heart of high LDL-P\
• cutting carbs will reduce it
• a low-fat diet (without carb restriction)
• its the “worst thing you can do” in a person with IR and high LDL-P
• Drugs are almost always necessary unless you start eating low-carb ASAP

BACKGROUND


Particle count - physiology basics

• There is one apoB molecule per VLDL, IDL and LDL particle: 
apoB is not on HDL particles
Apo B testing measures how many VLDL, IDL and LDL exists per deciliter of plasma
Apo A-1 particle do not deposit cholesterol in the artery: they may in fact remove it.
• Apo B particles after entering the artery sticks
• White blood cells (macrophages) ingest apoB particle carrying cholesterol and initiate inflammation
• VLDL takes lipids (mostly TG, but also cholesterol) out of the liver;
• VLDL traffic TG to muscle and fat cells and as TG exit the VLDL shrinks, creating IDLs
• Most IDLs are cleared at the liver but some IDL shrink and become LDLs
• Liver isn’t as efficient at clearing LDL particles compared to IDL
• thus extending LDL plasma residence time
• A normally composed LDL half-life is 2-3 days; compared to VLDL 2-6 hours or IDL 1-2 hours
• Thus Apo-B test actually measures LDL-P in the blood (vast majority of apoB particles are LDLs)
• Can’t change LDL-P by eating carbs day before test (LDL half life is typically 3 days)
• Takes trigs a few days to alter lipoprotein metabolism and jack up your LDL-P
• Total cholesterol minus HDL is called non-HDL cholesterol
• it reveals how much cholesterol is in the apoB particles
• and thus serves as a better measure of atherogenic apoB particles than does LDL-C
• However, even Non-HDL cholesterol misses 30% of persons with high apoB (LDL-P) at-risk cases

Triglycerides

• Triglycerides is a key marker that few health care professionals truly, understand
• Trigs over 70 in an IR adult, LDL-P needs checking
• LDL is supposed to carry primarily cholesterol with only small amount of TG (4:1 ratio)
• Increased LDL/triglyceride level occurs when LDLs are trafficking more TG than normal –
• in such cases they are therefore carrying less cholesterol than they should
• These are therefore cholesterol-depleted LDLs.
• It takes 40-70% more cholesterol-depleted particles to traffic a given amount of cholesterol
• In such cases we need a therapy to remove triglycerides from LDL
• High triglycerides/low HDL-cholesterol ratio (> 3.0) is very indicative “insulin resistance”


ApoE genotype

• What Apo E genotype issues you should be aware of
• Apo E4 is a marker of elevated risk of heart disease
• ApoE2 is usually desirable
• but Apo E2 with high triglycerides is a high risk lipoprotein abnormality
• ie - with normal LDL-P: but they have too many VLDLs and IDLKs, but not LDLs.
• Apo E4 is also associated with Alzheimer’s disease
• A ketogenic diet might ward off Alzheimer’s longer
• Drown yourself in omega-3 fatty acids” if Apo E4
• Whether an Apo E4 needs to lower their fat intake is truly not known at present
• Are they REALLY over-absorbing fat–maybe, maybe not
• If your lifestyle controls Apo B, no need to worry
• What one test gives most info on heart disease risk: ApoB and LDL-P
• No matter what Apo B is, other tests such as inflammatory markers can also tell about CV risk
• The totality of tests help doctors treat you better
• Triglycerides and Apo B/LDL-P gets most info needed to start

Discordant test results

• LDL cholesterol might be low, but LDL-P could be high:
• How you can have low LDL-cholesterol and yet high LDL-P numbers (discordance)
• normally the two tests should correlate very well
• when they do they are concordant and when they do not they are discordant
• If Apo B and LDL-P come back one high, one normal – discordance is present
• It happens in 10-12% of people; repeat test again
• If LDL-P is high and Apo B is normal, there is no consensus on what to do
• LDL-P tends to “outperform” Apo B as a key marker

LDL particle size

• Particle size has no bearing on whether LDL enters the artery wall or not
• Insulin resistant Diabetics typically have the small LDL regardless of LDL-C

Not keen on heart scan testing

•  What he thinks about having a heart scan conducted
•  His concern over having a CT scan of your chest: too much radiation