The New Gold Standard of Cholesterol and Lipid Analysis
The standard lipid tests that most doctors order for you really belong to the age of the dinosaurs. They tell you the level of your total cholesterol, LDL and HDL. New testing breaks cholesterol down into fractions, appearances, and patterns, giving a much more accurate picture of what may or may not be a problem.
This test is the Lipoprotein Particle Profile (LPP) test offered by SpectraCell Laboratories in Houston, as developed by Texas A&M University.
This more comprehensive and detailed test helps doctors and patients make sense out of the cholesterol confusion. They break down the major cholesterol components and take you light-years beyond generalizations like “LDL cholesterol is the bad cholesterol and HDL cholesterol is the good cholesterol.” The reality is much more complex. It is not just about how high the LDL is, but what kind it is and how much of it you have. The same with HDL. Keep in mind that the liver – where a good chunk of your cholesterol is produced – dispatches cholesterol throughout the circulatory system in the form of protein-wrapped fatty bundles called LDL. As LDL travels through the system, the cholesterol is accessed and used by cells as needed. Similarly, spent and oxidized cholesterol is picked up by HDL particles for return to the liver and subsequent excretion.
The SpectraCell test, originally developed at Texas A & M University, hones in on research that has introduced the medical community to subgroups of lipoprotein particles and how their different sizes and numbers can play a role in the inflammatory destruction of arteries.
LDL particles, for instance, can be large or small. It is the small, dense LDL particles that can readily enter into compromised arterial walls and stoke the inflammatory process. Higher numbers of these LDL particles represent a higher risk. Genetics play a major role here, and not diet, as most people have been erroneously led to believe. If you have significant numbers of these factors present, in the presence of cigarette smoke, mercury, lead, trans-fatty acids, insulin, homocysteine, or radiation, the potential for arterial damage increases. This is where doctors and patients become concerned, and particularly when there is a significant presence of Lp(a) – the most dangerous of these lipids and truly what we can refer to as “ugly cholesterol.” This small, dense LDL entity is a major thrombotic factor. It inflames the blood and makes it sticky. Another small, dense particle that has emerged with an inflammatory reputation is called RLP (remnant lipoprotein). It plays a role in the formation of plaque.
You want to have fewer of these subtypes and instead have more of what are called large, buoyant LDL. That kind of result suggests less of a risk. With this kind of advanced testing, two people with the same total measurement of LDL cholesterol may be at opposite ends of risk. One, with a predominance of small, dense LDL particles, may have three times the risk of someone with mostly large, buoyant LDL.
Similarly, there are significant differences among subgroups of HDL that relate to how well or not they carry out their removal of excess lipids. You want to be high in the most functional HDL subgroup, labeled 2b. Not all HDL is created equal.
The worse scenario, with this kind of testing, would be to have a predominance of small, dense LDL particles and low HDL 2b.
What about your total cholesterol? you may be asking. Well, it doesn’t mean much unless you have a level over 320 or so, which increases the risk of stroke; and then it certainly behooves you to bring it down.
What about your total LDL level, according to standard tests? If your doctor thinks it is too high, I suggest having the advanced testing done.
Here’s what you have to remember if your standard cholesterol numbers are “high” and your doctor tells you to take a statin:
- Don’t do it. Ask your doctor to follow up with a VAP or LPP test that determines your individual cholesterol fractions.
- If you are a male between the ages of 50 and 75 and have coronary artery disease, and the advanced test shows you have a predominance of small, dense LDL, go for the statin drug. It’s a good idea. Statin drugs are also anti-inflammatory, and that’s the powerful effect you are looking for, not the cholesterol-lowering activity. I say thumbs down on statins over the age of 75.
- If you are a woman, and do not have unhealthy levels of inflammatory types of cholesterol and inflammatory substances such as homocysteine, fibrinogen, and C-reactive protein, I would pass on statins. I’ve been disappointed with the results. However, if you are a woman with arterial disease and have a profile of high inflammatory cholesterol and other substances, a statin may provide you benefit as an anti-inflammatory agent.
- Male or female, do not take a statin on the basis of high Lp(a). Statins do not lower Lp(a). Your best bet to neutralize the inflammatory activity of Lp(a) is the B-complex vitamin niacin (500 mg–2 g daily) of the type that causes a flushing sensation, along with 2–3 g of fish oil and 100 mg of nattokinase. That’s my most potent cocktail for neutralizing Lp(a).
Please read below for further information on the breakdown of cholesterol products that can be measured with a Lipoprotein Particle Profile.
LDL Cholesterol – the LDL protein is the major carrier of cholesterol. Consuming omega 3 fatty acids helps lower total LDL levels.
HDL Cholesterol – High Density Lipoprotein (HDL) has two important subgroups: the larger, more buyoant HDL2 and the smaller, denser HDL3. These subgroups are important indicators of the efficiency of reverse cholesterol transport by HDL, or how well HDL is clearing excess cholesterol from the body. HDL is formed in the liver as dense HDL3 and as it travels through the body and accumulates cholesterol, it becomes the larger and lipd enriched HDL2b, the largest and most buoyant HDL. Since HDL2b is an indicator of how well excess lipid are removed from cells, it positively correlates with heart health.
How is Low HDL 2b Treated? -A low HDL count indicates potential for atherogenic dyslipidemia. Beneficial therapies are similar to those which raise HDL and reduce elevated TG, such as exercise, niacin, omega-3’s. Certain nutritional deficiencies are associated with a low HDL, such as zinc and selenium.
- Large Buoyant HDL 2b – if this HDL particle is low, it represents a reverse transport system that is not working well to remove excess cholesterol.
- Large Buoyant HDL 2a, 3 – this value represents the remainder of the HDL fraction, and is less beneficial than HDL 2b.
Triglycerides – Triglycerides are the major transporters of dietary fats throughout the bloodstream. Specifically, it is composed of one glycerol molecule that is attached to three fatty acids, hence the term triglyceride. VLDL (very low density lipoproteins) and chylomicrons are made up largely of triglycerides. Besides transporting fat throughout the bloodstream so that it can be used for fuel, triglycerides also store fat in adipose tissue (fat cells) when the body’s demand for fuel is less than what is ingested from diet.
Why Measure Triglycerides? Elevated triglycerides are a major risk factor for heart disease and diabetes because high serum levels of triglycerides are indicative of abnormal lipoprotein metabolism. Extremely high triglyceride levels (0ver 500mg/dl) can cause pancreatitis. Triglyceride level should fall below 150mg/dl. SInce triglycerides do go up after a meal, they are typically measure after 12 hours of fasting.
Why Are High Triglycerides Harmful? High triglycerides negatively affect LDL particle size. Through a complex metabolic interaction, tryglycerides promote the formation of small, dense LDL particles, which are particularly atherogenic. Even in the presence of normal LDL cholesterol, patients with high triglycerides typically have endothelial dysfunction, where their blood vessels do not dilate and constrict properly, In addition, excess tryglycerides lower nitric oxide levels and increase many inflammatory compounds further contributing to vascular injury and endothelial dysfunction.
Elevated triglycerides set off a cascade of events that negatively alters a patient’s lipoprotein profile. For example, elevated triglycerides cause higher excretion rates of apolipoprotein A1 through the kidneys, thus leading to low HDL levels. This explains the strong inverse relationship between triglycerides and HDL.
How Are Triglycerides Treated? Diets high in carbohydrates increase triglyceride levels, particularly in those with insulin resistance or obesity. The glucose from simple carbohydrates is converted to glycerol to form a tri-glyceride molecule. Specifically, decreasing the amount of ingested simple sugars will usually lower triglyceride levels. Decreasing fat consumption can lower triglyceride level, but not without also decreasing your simple sugar intake. An increase in the consumption of omega 3 fatty acids, whether from food or supplements can reduce triglyceride level substantially in a dose dependent manner. Regular exercise also reduces triglyceride levels leading to better energy metabolism overall. Phamraceuticals commonly used to lower triglycerides include fenofibrates (such as Tricor or Trilipix) and omega 3 fatty acids.
Non HDL Cholesterol – the non-HDL particle numbers are the best overall indicator of cardiovascular risk. The lower the better. Non HDL is comprised of LDL and VLDL levels.
RLP (Remnant Lipoprotein) – RLP is a very atherogenic lipoprotein composed primarily of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL). RLP is considered to be one of the most harmful lipoproteins, RLP is very highly correlated with cardiovascular disease. In fact, studies show that the composition of arterial plaque closely resembles composition and density of RLP. Omega-3 fatty acids (fish oils) have been shown to reduce triglycerides and RLP.
Why is RLP So Harmful? Although the RLP is relatively large compared to most LDL particles, it is particularly harmful because unlike LDL particles, which have to undergo oxidation before they can be taken into the arterial intima by macrophage cells, RLP can be readily scavenged by macrophage cell even when they are not oxidized. Once scavenged by a macrophage, RLP is transformed into foam cells which are the building blocks of arterial plaque. In fact, elevated RLP has been found in the survivors of myocardial infarction and persons with significant coronary atherosclerosis.
Additionaly, RLP contributes to endothelial dysfunction by impairing the vascular relaxation process as well as enhancing platelet aggregation.
How Is High RLP Treated? Although heredity plays a large role in the levels of RLP, consumption of omega 3 fatty acids can significantly lower levels of RLP. Therapies that normally lower triglycerides are also effective at lowering RLP.
Small Dense LDL – There are five major subgroups of Low Density Lipoproteins (LDL); IDL (intermediate density lipoprotein), I, II, III and IV. IDL is the largest, least dense and most buoyant, while LDL IV is the smallest and most dense. LDL particles that are small are also dense and these terms are often used interchangeably. The smaller the LDL particle, the more dangerous it is. In fact, small dense LDL (LDL III and LDL IV) is three times more atherogenic than buoyant LDL.
Why Is Small Dense LDL So Harmful? Smaller particles of LDL can more easily penetrate the arterial wall than large LDL particles simply due to their size. Therefore, the smaller the LDL particle, the more likely it is to enter the arterial endothelium, where it becomes oxidized, is taken up by a macrophage cell which then becomes a foam cell, which eventually stick together to build plaque within the arteries. Evidence also suggests that small dense LDL is associated with vascular dementia.
It is also important to know how many LDL particles are present, in addition to their size. Just as small LDL particles can fit through the arterial lining more easily than large LDL particles, the more LDL particles there are, the more likely they will enter the arterial intima, regardless of size. It is therefore imperative to measure both the size (density) and the number of LDL particles.
How IS Small Dense LDL Treated? Therapeutic treatment for small dense LDL includes the use of niacin and fibrates. Lifestyle changed (diet and exercise) show beneficial effects as well.
VLDL Particles – the VLDL level correlates to triglycerides values.
Biomarkers and Risk Factors
Apolipoprotein B-100 – this is a measure of all non-HDL particles numbers and is more of a hereditary marker of cardiac risk. If it is elevated, it is an indication that life long treatment with a cholesterol lowering agent may be required.
Apolipoprotein A1 – Low levels of apo A-I are associated with low levels of HDL and impaired clearance of excess cholesterol from the body. Low levels of apo A-I, along with high concentrations of apo B, are associated with an increased risk of cardiovascular disease.There are some genetic disorders that lead to deficiencies in apo A-I (and therefore to low levels of HDL). People with these disorders tend to have hyperlipidemia and high levels of low-density lipoprotein (LDL – the “bad” cholesterol). Frequently, they have accelerated rates of atherosclerosis. The concentration of apo A-I reflects the amount of HDL in the serum. Since women tend to have higher HDL, they also have higher levels of apo A-I.
Apolipoprotein E Genotype – Apolipoprotein is an essential protein for the metabolism of cholesterol and triglycerides. It is a major component of plasma lipoproteins including chylomicrons, VLDL, IDL, and HDL. There are 3 common genetic variants of ApoE: E2, E3, E4, leading to three different conformations of the protein that affect its ability to perform its function. Because each person carries two copies of the ApoE gene, there are 6 possible genotypes.Testing can be done to determine the gene variant that you possess. ApoE genotyping can provide useful information concerning your risk of developing cardiovascular disease and can provide guidance for treatment regimens that would be more effective for managing your particular lipid profile based on your genetics.
- E2 – The ApoE e2 allele has been shown to greatly increase the risk of a rare condition called hyperlipoproteinemia type III. Most people with this disorder have two copies of the APOE e2 allele, leading researchers to conclude that the e2 allele plays a critical role in the development of the condition. Hyperlipoproteinemia type III is characterized by increased blood levels of cholesterol, certain fats called triglycerides, and molecules called beta-very low-density lipoproteins (beta-VLDLs), which carry cholesterol and lipoproteins in the bloodstream. A buildup of cholesterol and other fatty materials can lead to the formation of small, yellow skin growths called xanthomas and the development of atherosclerosis. E2 carriers with high cholesterol and triglycerides tend to respond well to statin therapy, may not respond as well to low fat diet alone.
- E3 – the most common allele. E3 is considered normal with no associated risk factors.
- E4 – the E4 Isoform of ApoE is associated with increased levels of plasma and LDL cholesterol and therefore an increased risk of coronary heart disease and atherosclerosis. People who carry at least one copy of the APOE e4 allele have an increased chance of developing atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. This progressive narrowing of the arteries increases the risk of heart attack and stroke.Evidence indicates that carriers of an e4 allele may not respond well to statin therapy for lowering cholesterol compared tot hose with normal or e2 alleles. Alcohol intake and smoking may exacerbate the risks associated with the presence of an e4 allele more than in others without the allele. The e4 version of the APOE gene increases an individual’s risk for developing late-onset Alzheimer disease. People who inherit one copy of the APOE e4 allele have an increased chance of developing the disease; those who inherit two copies of the allele are at even greater risk. TheAPOE e4 allele may also be associated with an earlier onset of memory loss and other symptoms. Recommendations: may respond less well to statin therapy; positive response to low fat diet and niacin predicted; alcohol consumption and smoking may additionally increase risk of disease progression.
Lp(a) -Lipoprotein (a) is an LDL particle with an apolipoprotein(a) attached to it. It is involved in the formation of plaque and is a very strong independent risk factor for cardiovascular disease. Lp(a) accumulates in atherosclerotic plaque and its plasma concentration is predictive of heart disease in many patients. Because the density of Lp(a) overlaps that of dense LDL and buoyant HDL, separation of Lp(a) by density alone is inherently difficult. For this reason,it is important to measure Lp(a) directly in order to get truly accurate results.
Why is Lp(a) So Harmful? Evidence suggests that Lp(a) may serve as the link between thrombosis and atherosclerosis. Because the Lp(a) is a small, very dense LDL, it can easily penetrate the arterial lining, become oxidized and build plaque, thus contributing to atherosclerosis.
How is High Lp(a) Treated? Lp(a) is highly associated with cardiovascular disease. Lp(a) is an inherited trait and does not respond to diet, exercise, or statin drugs. Treatment for high Lp(a) is typically niacin and agressive LDL treatment.
Metabolic Syndrome Traits – This test reports 2 of the 5 traits associated with the ATP III Metabolic Syndrome Definition: elevated TG (>150mg/dl) and Low HDL-C (<40mg/dL in mend and <50mg/dL in women). Other values include waist circumference, fasting blood glucose and blood pressure.
C-Reactive Protein – is a marker of inflammation tied to increased cardiovascular risk. CRP can be lowered with omega 3 fatty acid supplementation, which acts as an anti-inflammatory.
Insulin – High fasting insulin is associated with increased cardiovascular risk and/or metabolic syndrome.
Homocysteine – an elevated Homocysteine level is associated with increased risk of stroke, osteoporosis, dementia and cardiovascular disease. Certain nutrients help lower homocysteine levels such asB12, choline, riboflavin, B6, folate, serine, cysteine and glutathione. Exercise does not have an impact on homocysteine levels, nor does macronutrient levels.
HS-Omega-3 Index – This test determines the patient’s risk for sudden cardiac death (SCD). Half of all fatal heart attacks are due to SCD which is defined as death within one hour of the event. Most sudden cardiac deaths are due to cardiac arrhythmia. An adequate level of the omega-3’s EPA and especially DHA can reduce this risk by 90%. The HS-Omega-3 Index® measures the percentage of EPA and DHA levels in red blood cell membranes (RBC’s) which are highly correlated to myocardial membrane omega-3 levels. Most Americans have a 4% RBC omega-3 fatty acid percentage which represents normal risk; however an 8 % RBC level may reduce the risk of SCD by 90%. The HS-Omega-3 Index® is a great complement with the LPPTM test for cardiovascular risk reduction and the management and treatment of lipoprotein disorders. The HS-Omega 3 Index is the EPA plus DHA content of RBC membranes. Increasing the intake of EPA and DHA by 1/2 to 1 gram (500 – 1,000mg) per day, from either oily fish or fish oil supplements, shoudl significantly improve the index. The exact amount of EPA plus DHA will vary person to person. Decreased amount of HS-omega 3 Index is associated with a risk for depression, heart disease, alzheimer’s and PMS.
We carry Marine Fish Oils concentrate by Pharmahealth, which provides 1000mg of natural marine EPA and DHA, omega-3 fatty acids. Fish highest in omega-3 fatty acids, are salmon, herring, mackerel, oysters and sardines. It may take as long as 1 year to improve the HS-Omega-3 Index after beginning supplementation.
MTHFR Genotype Testing – MTHFR (methylenetetrahydrofolate reductase) is an enzyme involved in the metabolism of folate and homocysteine. Testing you for this gene can see if you may have a potential risk for developing heart disease. An MTHFR enzyme with reduced function can lead to elevated homocysteine levels, which is a known independent risk factor for development of cardiovascular disease and venous thrombosis. Reduced enzyme function can also affect folate status.