The Value of Testing Beyond Cholesterol and LDL For The Prevention of Heart Disease

Preamble By William Faloon

This article describes newly available blood tests that will likely save the lives of millions of humans if they are incorporated into widespread screenings of the general population.

Standard blood tests measure the amount of LDL in one’s blood. They do not, however, reveal the degree to which the LDL is oxidized or other factors that increase LDL’s vascular risk profile.

New tests are available to measure these atherogenic variables. These tests are suited for people with existing vascular disease, those with family histories of heart disease or other risks of heart problems, and for individuals who can afford the additional cost.

At this time, we don’t know if all Life Extension^® members need these new tests that measure oxidized LDL (and its byproducts). That’s because the nutrients members already take may be sufficiently neutralizing these forms of atherogenic risk.

Once Life Extension^®’s medical experts review members’ results, we’ll be able to determine which individuals may be at higher risk for having oxidized LDL and the steps needed to reverse this common cause of arterial occlusion.

Doctor’s today routinely measure cholesterol levels with a standard lipid profile blood test. But this test omits some diagnostic information that could leave you at significant cardiovascular risk.^1,2

A much better approach is to directly measure the oxidized fats and their immediate consequences within arteries.^3,4 New studies are revealing the dangerous association between three fundamental measures of lipid oxidation and increased heart disease risk.

These three new tests measure:^3-5

1. Oxidized LDL
2. Myeloperoxidase
3. F2-isoprostanes

These three tests assess vascular damage as well as markers of oxidized fat in the blood, which provides predictive value for cardiovascular disease that goes beyond standard lipid panel testing.^3,4,6

For many years these cutting-edge tests were not available to the public. They were used primarily at universities for research and were far too expensive for general use. However, Life Extension^® has worked long and hard to bring these innovative tests to its members to help further diagnose and reduce potential risk factors for cardiovascular disease.

Testing For Oxidized LDL Cholesterol

 

We have long known that oxidized LDL (OxLDL) triggers dangerous inflammatory changes that lead to atherosclerosis.^7,8 But most physicians were unable to test for this cardiac risk factor as the test was expensive and restricted to research labs and universities. OxLDL is now proving to be a risk predictor for metabolic syndrome, cardiovascular disease in general,^9-11 and acute myocardial infarction (heart attack) in particular.¹²

Oxidized cholesterol (OxLDL) levels show a strong correlation with having acute coronary syndromes (angina, or chest pain, ischemia, or evidence of low blood flow on ECG) and the risk of heart attacks.⁸ In fact, the higher the OxLDL level, the more severe the signs and symptoms of heart disease. People with more advanced ischemic heart disease show significantly more OxLDL in the macrophages.⁸ And the higher the OxLDL level in blood¹³ and plaques, the greater the risk of plaque rupture, with devastating consequence.^14,15 Higher OxLDL levels should raise concern and prompt interventions to extinguish this vascular risk factor.

Measuring OxLDL is now possible with a simple blood test. Research shows that even apparently healthy men with elevated OxLDL levels have a more than 4-fold increased risk for a future coronary heart disease event compared with those with the lowest levels.¹⁶ What makes this test so important for avoiding heart disease is that plasma OxLDL is a stronger predictor of such events than a conventional cholesterol blood test.¹⁶ As OxLDL levels rise, so does the presence and extent of coronary artery disease; that risk is three times greater for those with the highest versus the lowest OxLDL levels, and nearly 17 times as great in those who also have high cholesterol.¹⁵

OxLDL levels also predict your risk of having metabolic syndrome, that combination of being overweight and hypertension with disturbed regulation of blood sugar and lipids that dramatically raises risk for heart disease, stroke, diabetes, and cancer.^17-19 One study showed that those with the highest levels were at nearly four times the risk for metabolic syndrome than were those with the lowest.²⁰

What You Need To Know

Testing Beyond Cholesterol and LDL

• Knowing your lipid profile numbers is an important way to identify your risk for cardiovascular disease.
• But a standard lipid profile can only provide general information, based on population-level statistics.
• More personalized and individual assessment of your cardiovascular risk provides unique insights.
• Newly available advanced risk factor testing can now evaluate oxidized LDL and myeloperoxidase, and/or urinary F2-isoprostanes.
• These tests can more accurately detect hidden risks for cardiovascular disease, even in people with normal traditional lipid profiles.
• You can take steps through diet, exercise, and supplementation to lower your risk levels based on these tests.

Myeloperoxidase: A Direct Measure Of Arterial Damage

Myeloperoxidase (MPO) is an enzyme produced by inflammation-generating white blood cells in your body.²¹ The enzyme demonstrates a wide range of atherosclerosis-promoting effects, including production of OxLDL and oxidized HDL cholesterol and increased fragility of plaque lesions.^1,2,22,23 MPO also reduces the availability of nitric oxide,²⁴ a signaling molecule that tells blood vessels to relax and lower blood pressure.^25,26

When arterial walls are damaged by elevated pressure,²⁷ plaque, or even inflammation²⁸ alone, white blood cells invade to repair the damage, releasing MPO.²⁹ MPO is a direct measure of plaque-promoting blood vessel inflammation; it also activates enzymes that degrade the protein-rich “cap” on arterial plaques,³⁰ making them increasingly vulnerable to catastrophic rupture.^31,32

MPO levels are significantly higher in apparently healthy adults who go on to develop coronary artery disease. Those with the highest MPO levels have a nearly 50% increase in risk versus those with the lowest.^2,6 Of extreme importance, the increased risk associated with elevated MPO levels was seen even in people with normal LDL, HDL, and CRP measurements.²

Similarly, in people with chest pain or ECG abnormalities, a raised MPO level predicted the risk of a heart attack even when they had normal levels of troponin T, a marker of heart muscle injury frequently used in emergency rooms to detect an early heart attack.^22,33,34 In other words, MPO elevations revealed hidden risk in people who otherwise would have thought their arteries were in good shape. Such early detection can help people make important changes to reduce their risk.

People with acute coronary syndrome (chest pain and/or ECG changes, even without a heart attack) are at vastly increased risk for developing a heart attack in the near future.^35,36 With that said, there is always a need to identify new and accurate independent biomarkers that predict heart attack risk.³⁷

Measuring MPO can reveal a person’s risk more accurately. By way of example, people with acute coronary syndrome with MPO levels below about 20 ng/mL have an 88% chance of evading a heart attack over the next 24 months, compared with a 74% chance of such survival in those with elevated MPO levels.³⁷ Those with the highest MPO levels have a 2.4-fold increase in their risk for dying of cardiovascular disease over 13 years versus those with the lowest levels.⁴

Combining MPO, which provides direct evidence of arterial damage, with C-reactive protein (CRP), a more general measure of inflammation, can further refine an individual’s risk prediction for cardiovascular disease: Having both MPO and CRP elevated puts you at more than four times the risk of dying from heart disease.⁴

Taken together, these figures suggest that MPO can be used to give you a lifesaving early warning to turn your cardiovascular health around while there’s still time.

Interpreting Your Test Results

Here are some numbers to help you interpret the results of your advanced testing for cardiovascular disease.

Oxidized LDL (OxLDL): If your level is less than 60 U/L, your risk is considered low; from 60 to 69 defines moderate risk, and levels of 70 or higher put you at high risk.⁶⁸

Myeloperoxidase (MPO): A level below 480 pmol/L indicates normal risk, while 480 or higher suggests increased cardiovascular risk.⁶⁹

F2-isoprostanes: Your risk is low when your level is less than 0.86 ng/mg; at or above that level places you at high risk.⁷⁰

F2-isoprostanes: Detecting A Culprit In Vascular Inflammation

Your body uses signaling molecules to announce the presence of damaged tissue and to trigger the healthy inflammatory response.^38,39 Cytokines,⁴⁰ leukotrienes,⁴¹ and prostaglandins⁴² are all families of such pro-inflammatory signals. Under normal circumstances, these molecules are degraded and disappear, ending the inflammatory stimulus. But if inflammation-promoting molecules continue to be manufactured, the inflammation will persist, leading to long-term damage.

One of the major sources of inflammatory prostaglandins is arachidonic acid, a major component of cell membranes.⁴³

In the presence of oxidizing free radicals, prostaglandin-like molecules called F2-isoprostanes can be produced from arachidonic acid resulting in unregulated outpourings of this pro-inflammatory signal.^44-46

The damage done by F2-isoprostanes is not restricted to blood vessel inflammation. Like their normal prostaglandin counterparts, F2-isoprostanes promote the clumping of platelets, the tiny cell fragments in blood that participate in the clotting mechanism. Under the stimulus of F2-isoprostanes, platelets clump more aggressively, contributing to increased risk of arterial blockage, particularly at the site of an existing plaque.^45,47,48 Note that, because formation of F2-isoprostanes does not require the COX enzyme, the use of COX-inhibiting medications like aspirin will not counteract the platelet effects, rendering useless an important form of prevention in cardiovascular disease.⁴⁷

F2-isoprostanes are easily measured in a urine specimen, making them especially attractive as a means for long-term monitoring of cardiovascular risk. People with elevated urinary F2-isoprostanes are at a more than 30-fold risk for developing coronary heart disease compared with those with normally low levels.³

People who smoke⁴⁹ and those who eat red meat,⁵⁰ both known cardiovascular risk factors, have been shown to have significantly higher plasma or urinary F2-isoprostanes than do people with healthier lifestyle habits, while those who regularly exercise have lower levels.^46,51,52 Intriguingly, it is becoming evident that high urinary F2-isoprostanes also signal an increased risk of certain cancers, further attestation to the powerful interactions of oxidative damage and inflammation in the body.^53,54

What To Do If Oxidation-Inflammation Levels Are Elevated

Testing for blood levels of oxidized LDL (OxLDL), myeloperoxidase (MPO), and urinary F2-isoprostanes provides tremendous insight into what is going on at the molecular level in one’s body.

If your levels are elevated, you’ll find precious little help from mainstream medicine, despite its enormous stock of chemical drugs.

A better approach is to choose from among the growing list of supplements that are proven to reduce these markers (and mediators) of cardiovascular disease. Here is a partial listing of supplements that can reduce markers of lipid oxidation:

• Omega-3 fatty acids from fish oil⁵⁵
• Vitamin E⁵⁶
• Gamma tocopherol combined with sesame lignans⁵⁷
• L-carnitine⁵⁸
• Zinc⁵⁹
• Grape seed extracts and/or resveratrol^60,61
• Pomegranate⁶²
• Superoxide dismutase (SOD)⁶³
• CoQ10⁶⁴
• Whole grape extracts⁶⁵
• Indian gooseberry⁶⁶

Summary

Measurement of blood cholesterol, LDL, HDL, and triglycerides (lipid profile) as a means of identifying people at high risk for cardiovascular disease is more than four decades old.⁶⁷ There is no doubt that early detection and intervention has saved lives. But in today’s world, simply knowing your cholesterol levels provides only partial protection.

Low cholesterol and LDL levels may not indicate safety, while elevated levels may not paint an accurate picture of the true risk situation. More precise markers of cardiovascular risk are now available at relatively affordable prices.

• Measurements of oxidized LDL (OxLDL) offer insights into how much damage is being done to the lipids in your bloodstream.
• Measurement of myeloperoxidase (MPO) can indicate the impact of inflammatory changes on your blood vessels.
• Measurements of F2-isoprostanes in a urine specimen can tell you to what extent your body’s own fat molecules are participating in inflammatory changes that can dramatically affect your health.

You now have the following options that can be added to the recommended Male or Female Panels:

If any result comes back elevated, you are in a position to initiate a sensible program of dietary changes, regular exercise, and appropriate nutritional supplements.

If you have any questions on the scientific content of this article, please call a Life Extension^® Health Advisor at 1-866-864-3027.

Dr. Scott Fogle is the Director of Clinical Information and Laboratory Services at Life Extension^®, where he oversees scientific and medical information as well as its laboratory division.

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