Uncovering a Hidden Source of Cardiovascular Disease Risk

Anatomy of a portion of the cardiovascular system, showing the heart, aorta, and prominent arteries of the upper torso. An arteriole (small branch of an artery) is shown in cross-section.

If you’ve seen a loved one suffer and die from cardiovascular disease, knowing that your own cholesterol is normal can be a relief. Unfortunately, standard cholesterol panels based on fasting blood samples may overlook a hidden, potentially deadly cause of cardiovascular disease: dysfunctional lipid (fat) metabolism patterns known as postprandial disorders.

Postprandial (after-meal) disorders are characterized by abnormally persistent lipid (fat) remnants that persist in the bloodstream for up to 24 hours after eating. Hours after dinner, and even during sleep, these abnormal fat particles can inflict serious damage to your arteries. In fact, postprandial disorders are among the most potent—yet widely ignored—causes of heart disease, stroke, and aneurysm.

In this article, we examine lipid remnants that lurk in the blood between meals, how you can detect the presence of these deadly compounds, and nutritional strategies that can help you reduce and eliminate them.

As you eat a meal of, say, steak, buttered rolls, salad dressing on your lettuce, and cream in your coffee, food passes through your digestive tract. The fats contained within this food are first broken down by enzymes, and then absorbed into veins passing through the liver. From there, they go into the body’s circulatory system.

Four to six hours later, the remnants of your meal should be history. Digestion and clearance from the blood should be quick and efficient. After six hours, these remnants should no longer be detectable in the bloodstream.

In some people, however, meal remnants persist in the blood even 10, 12, or 24 hours later. The longer they stick around, the more opportunity they have to trigger the growth of atherosclerotic plaque in arteries. Clinical studies show that these postprandial lipoproteins (lipids that are transported by protein carriers known as “lipo-proteins”) are powerful instigators of coronary plaque, carotid plaque, and aneurysms of the aorta.

Cut-away view of the primary parts of the digestive system. After processing in the stomach, food passes to the duodenum (the first portion of the small intestine). Here, it is combined with bile (fat-digesting juices made in the liver and stored in the gall bladder), pancreatic juices and enzymes (made by the pancreas), and intestinal enzymes for further digestion.

These post-meal lipid remnants lurk in the blood from the moment you begin eating, but usually dissipate by the time your “fasting” blood is drawn to assess your risk for vascular disease. Postprandial disorders are therefore almost always overlooked or ignored, and rarely enter into a doctor’s assessment and treatment of vascular risk and disease. Although their presence may not be apparent from a fasting blood sample, postprandial lipoproteins can still be a critically important instigator of vascular disease.

Postprandial Patterns: Potent Causes of Vascular Disease

When postprandial lipoproteins linger for many hours after eating, they are afforded ample opportunity to exert damaging effects on vascular structures. Postprandial lipoprotein particles insert themselves into atherosclerotic plaque, fueling its growth.1 They contribute to atherosclerosis through other paths as well:

• Postprandial lipoproteins block the natural artery-relaxing agent known as nitric oxide, while increasing the artery constrictor called endothelin. This induces endothelial dysfunction (an impaired ability of the arterial walls to dilate),2,3 which in turn contributes to the formation of atherosclerotic plaque.4
• Postprandial lipoproteins increase blood levels of cellular adhesion molecules, allowing inflammatory white blood cells to more readily adhere and gain entry to the arterial wall, which also leads to atherosclerotic plaque formation.5
• Postprandial lipoproteins activate blood clotting by increasing factors that both promote blood clotting and inhibit clot breakdown.6
• Postprandial lipoproteins trigger the formation of a cascade of other abnormal lipoprotein particles that contribute to heart and vascular disease, such as small low-density lipoprotein (small LDL) particles.7

Carotid ultrasound studies show that people who have elevated postprandial lipoproteins have more carotid plaque than people who do not, independent of their cholesterol values.8,9 Postprandial lipoproteins also predict a greater likelihood of coronary atherosclerotic plaque, and people with excessive postprandial abnormalities experience more rapid plaque growth.8-11

Triglycerides: Building Block of Postprandial Lipoproteins

Because triglycerides are a principal component of postprandial lipoproteins, elevated fasting triglycerides—which can be readily measured using a standard lipid or cholesterol test panel—can serve as an indirect index of increased postprandial lipoproteins.

If triglycerides are high, postprandial lipoproteins are likely to be present. What constitutes “high” is arguable, though fasting triglycerides equal to or greater than 100 mg/dL are clearly associated with greater postprandial lipoproteins. This issue is essentially ignored in the national guidelines for cholesterol and lipid management (the National Cholesterol Education Program Adult Treatment Panel III),12 which specify that triglyceride levels of 150 mg/dL or higher are associated with an increased likelihood of postprandial lipoprotein elevation.13,14 It has long been the position of the Life Extension Foundation that aggressive steps (such as using fish oil supplements) should be taken to reduce triglycerides over 100 mg/dL.

Simply put, the higher your triglycerides, the more likely postprandial lipoproteins are also present, potentially putting you at risk for atherosclerotic disease. However, fasting triglycerides are not foolproof, and an excess of postprandial lipoproteins can still occur even with triglyceride levels of less than 100 mg/dL.1

Metabolic Syndrome Promotes Postprandial Lipoproteins

Metabolic syndrome is a frighteningly common precursor to diabetes that can create an excess of postprandial lipoprotein abnormalities.

Metabolic syndrome—the cluster of metabolic abnormalities that include high triglycerides, high blood pressure, high blood sugar, excess abdominal fat, and low HDL—is rampant throughout America, with one in four adults now showing established degrees of this condition.15 The more features of metabolic syndrome present, the more likely postprandial lipoproteins are elevated—even if fasting triglycerides are normal. In the presence of metabolic syndrome, postprandial lipoproteins are not only present at higher levels, but may persist longer in the bloodstream.16 Full-blown metabolic syndrome is not required for a person to exhibit excessive postprandial lipoproteins. Having hypertension alone, for example, suggests the presence of greater postprandial lipoprotein levels.16,17 People with metabolic syndrome exhibit higher blood sugar after meals (usually 140 mg/dL or more), since sugar is unable to enter into the body’s tissues. Now deprived of sugar, these tissues (particularly muscle) turn to burning fat for energy, which causes the release of free fatty acids in the blood. This cascades into an increase of postprandial triglycerides and other abnormal particles.18

Increased blood insulin levels associated with metabolic syndrome trigger the liver to overproduce very-low-density lipoprotein (VLDL) particles, a principal postprandial lipoprotein particle. Postprandial lipoproteins, including VLDL, are ineffectively cleared from blood, permitting their accumulation and raising blood levels of VLDL as much as several-fold.19,20

Postprandial lipoproteins such as VLDL spark formation of potentially harmful small LDL particles, a leading cause of coronary plaque. The abundant triglycerides in postprandial lipoproteins are inserted into LDL particles by an enzyme known as cholesteryl-ester transfer protein, which is the crucial first step in creating small LDL particles.21 Thus, persistent postprandial lipoproteins not only cause atherosclerosis, but also set in motion a “domino effect” of other particles that likewise contribute to atherosclerotic disease.22

While the elevated insulin levels associated with metabolic syndrome cause postprandial lipoproteins to persist in the blood, the reverse also occurs: postprandial lipoproteins block the body’s response to insulin, aggravating pre-diabetes.23 Thus begins a vicious cycle that accelerates toward full-blown diabetes.

Although metabolic syndrome is an important indicator of increased and persistent postprandial particles, increased postprandial lipoproteins commonly occur without metabolic syndrome and when fasting triglycerides are at desirable levels. This has led doctors and scientists to wonder whether a better indicator of persistent and elevated postprandial particles exists.

Critical Role of Intermediate-Density Lipoprotein (IDL)

Beyond fasting triglycerides and VLDL, there is a measure of postprandial lipoproteins that is reliable and readily available: intermediate-density lipoprotein (IDL).

After being released into the blood by the liver, VLDL particles are processed in the blood over several hours, yielding IDL. IDL persists longer than VLDL and signals the persistence of postprandial particles.

A normal amount of IDL is none—that is, no IDL whatsoever should be detected in fasting blood. If present, IDL triggers atherosclerotic plaque growth.24,25 It may also be a potent risk factor for abdominal and thoracic aneurysms of the aorta (a bulging of part of the wall of the body’s largest artery). The presence of IDL also heightens the likelihood of pure soft plaque in carotid arteries, the kind that easily fragments, releases debris, and causes strokes.26,27

IDL can be measured using the Vertical Auto Profile lipoprotein test (VAP™ test). For lipoprotein testing, blood is usually drawn after an 8- to 12-hour fast. IDL particles can persist up to 24 hours after a meal and thus may remain elevated even during the “fasting” period. If IDL particles are present in a fasting blood sample, a substantial postprandial abnormality is clearly present, which can play a major role in causing atherosclerotic disease.

Testing for Postprandial Lipid Disorders

Unlike LDL and total cholesterol, postprandial patterns lack clear-cut guidelines to follow. Nonetheless, some general guidelines can still be useful to gauge whether a postprandial lipid disorder is a factor in your cardiovascular risk profile. Standard blood test indicators of postprandial lipid disorder include: Fasting triglycerides equal to or greater than 100 mg/dL.13 If fasting triglycerides are over 150 mg/dL1,13, you almost certainly have a postprandial disorder. On blood samples drawn four to six hours after a meal, triglycerides over 250 mg/dL indicate a postprandial disorder.28 In most cases, if fasting triglycerides are equal to or greater than 100 mg/dL, increased postprandial triglycerides and other lipoproteins, like VLDL and IDL, are also present. Specific measurement of postprandial (after-meal) blood samples does add more telling information, but in practicality is usually not necessary. Because IDL persists for a long period after eating, even beyond the four- to six-hour after-meal window during which triglycerides are increased, any amount of fasting IDL is among the best and most powerful indicators of a postprandial disorder. IDL is among the additional measures available through advanced lipoprotein testing, such as the VAP™ test.

Strategies for Reducing Postprandial Lipoproteins

Saturated fats, like those found in butter, shortening, and fried foods, are especially potent inducers of excess postprandial lipoproteins. Because postprandial disorders cause fats to linger longer, avoiding unhealthy fats is doubly important. Minimizing these fats is advisable for other reasons, such as reducing LDL, blood pressure, inflammation, and cancer risk. While avoiding saturated fats will not eliminate postprandial lipoproteins, it will help reduce them.29 A polyunsaturated omega-6 fatty acid—linoleic acid derived from safflower oil—also raises postprandial lipoprotein levels, just as saturated fats do.3

Although the immediate cause of persistent and increased postprandial lipoproteins is an unhealthy fat-containing meal, two varieties of fat reduce postprandial lipoproteins:

• Monounsaturated oils, like olive oil, modestly reduce postprandial lipoproteins. Monounsaturated oils may thus be a preferable form of oil for cooking and everyday use.3,30

• Polyunsaturated omega-3 fatty acids reduce postprandial lipoproteins dramatically. It is not uncommon to see omega-3 supplementation eliminate abnormal postprandial patterns entirely. Sources of omega-3 fatty acids include fish oil, flaxseed oil, and walnuts.

If undesirable saturated fats lead to increased postprandial lipoprotein particles, does a low-fat diet reduce postprandial lipoproteins? Paradoxically, it does not. All too often, low-fat diets can evolve into diets rich in processed carbohydrates, which cause postprandial lipoprotein particles to multiply out of control.31 Diets that are rich in monounsaturated fats, omega-3 fats, fiber, and lean proteins, and low in saturated fats and processed carbohydrates, are effective tools in reducing postprandial lipoproteins.32

The following strategies can reduce triglycerides dramatically, and help reduce or eliminate IDL and postprandial lipoproteins:

• Weight loss can greatly reduce triglycerides and postprandial lipoproteins, particularly with a diet that is low in carbohydrates and high in protein and monounsaturated fats. Cutting out processed carbohydrates (such as breads, crackers, breakfast cereals, bagels, and pretzels) alone can yield a 30% reduction in postprandial lipoproteins.33,34 Increasing your intake of yogurt, cottage cheese, and other low-fat dairy products, raw almonds and walnuts, and fish, chicken, turkey, and other sources of lean protein will also yield substantial reductions in postprandial lipoprotein particles. Weight loss restores the insulin responsiveness lost in metabolic syndrome, which also reduces postprandial lipoproteins.31

Illustration of the structure of a low-density lipoprotein (LDL) particle, a form of cholesterol found in the blood.

• Omega-3 fatty acids in fish oil exert powerful effects in reducing postprandial lipoproteins. Ingesting just 1200 mg of EPA/ DHA from fish oil can easily lower IDL by 50%, and higher doses can produce even greater reductions. When fasting triglycerides are higher than 200 mg/dL, or when IDL is increased, higher doses of fish oil may be indicated to fight excess postprandial lipoproteins. Omega-3 fatty acids decrease liver production of VLDL by 30% or more, and lower IDL by 70% or more.35,36 Omega-3s also activate the enzyme known as lipoprotein lipase, which accelerates clearance of postprandial lipoproteins from the blood.37 Fish oil can safely augment the cholesterol-lowering effects of statin drugs such as Lipitor®, yielding dramatic improvement in triglycerides, VLDL, and postprandial lipoproteins.38

• Soy protein (20 grams per day) from tofu, soy milk, soy protein powder, and other sources can lower LDL by 10-20 mg/dL and reduce postprandial lipoproteins by 10%.39

• Green tea contains catechins (flavonoids) that can decrease postprandial lipoproteins by up to 30%. Approximately 600-700 mg of green tea catechins are required to achieve this effect, the equivalent of 6-12 servings of brewed tea. Nutritional supplements also provide green tea catechins at this dose.40 Green tea’s effectiveness in accelerating weight loss may augment its ability to reduce postprandial lipoproteins.

• White bean extract blocks the sugar-digesting enzyme known as alpha-amylase, thereby reducing the absorption of sugars. A recent study showed that participants who took 1500 mg of white bean extract twice a day for eight weeks lost an average of four pounds and lowered their triglycerides by an average of 26 mg/dL.41

• Vigorous exercise can reduce postprandial lipoproteins by 30%.42

• Diabetes treatment (with insulin or oral hypoglycemic drugs, for example) significantly reduces postprandial lipoprotein levels.43,44 The thiazolidinedione drug Actos® may be especially effective for its postprandial lipid-suppressing effects; a similar agent, Avandia®, may be modestly effective.45,46 The agent metformin also reduces fasting and postprandial triglycerides by 25%.47 (Caution: Like other thiazolidinediones, Actos® and Avandia® can cause fluid retention, which may lead to or exacerbate heart failure. Actos® and Avandia® should be discontinued if any deterioration in cardiac status occurs.)

• Statin drugs such as Zocor®, Crestor®, and Lipitor® not only lower cholesterol, but can reduce postprandial lipoproteins by 30-80%.48

• Fibrates (cholesterol-lowering drugs such as Lopid® and Lofibra®) can reduce postprandial lipoproteins by 70%. They can be a useful second-line strategy if fish oil, weight loss, and nutritional efforts fail to do the job.49

Clearly, choosing the right foods and fish oil supplements should be your first choice in controlling a postprandial disorder. Fish oil is safe, inexpensive, and easy to take, yet it provides an extraordinary array of benefits, including reduced risk of sudden cardiac death, stroke, and depression.50 Weight loss, exercise, soy protein, and green tea can all increase your likelihood of success. Because of their possible side effects, prescription drugs should always be your last choice for correcting postprandial patterns and other disorders.

Why Fasting Is Necessary for Blood Work

When you have blood drawn to measure cholesterol and other markers, you are instructed to fast for 8-12 hours beforehand. If postprandial disorders (such as IDL or an exaggerated increase in triglycerides) become apparent only after eating, why not have blood drawn after a meal?

Doctors instruct their patients to fast for cholesterol tests because triglycerides rise after a meal, and triglycerides are used to calculate LDL. Because LDL is usually the sole focus of the conventional approach to heart disease prevention, the fact that triglycerides are elevated, postprandial or fasting, is simply ignored. Thus, over the years, doctors have failed to recognize elevated triglycerides in the after-meal period as a powerful, independent indicator of risk.

In the future, there will be growing recognition of our over-reliance on LDL as the only important value for gauging the risk of atherosclerotic disease, and measures of postprandial triglycerides and other postprandial lipoproteins will gain increased recognition. Rather than fasting for your blood work, it may be obtained in the first few hours after a meal. Right now, however, there are insufficient data to justify this practice on a broad scale, though we occasionally do such testing on certain patients in our clinical practice.

Improvements over conventionally calculated LDL that requires fasting will also allow blood to be drawn in a non-fasting state. Measures that are superior to calculated LDL—such as directly measured LDL, VLDL, and LDL particle number and size (all available through VAP™ lipoprotein testing)—can eliminate the need for fasting while providing more clinically useful information.

As experience grows, standard meals (that is, specific preparations of known fat, protein, carbohydrate, nutrient, and fiber composition) will be used to develop standards to better diagnose postprandial disorders. This way, people and populations can be compared based on their response to a standardized meal. Because the meals you choose yourself can vary tremendously in composition, postprandial blood obtained for analysis can likewise vary, whether or not you have a postprandial disorder.

Until then, we are left with reasonably good insight into postprandial patterns provided by fasting triglycerides, VLDL, and IDL levels. Mindful attention to these critical blood markers can greatly enhance and preserve your vascular health.

Dr. William Davis is an author and cardiologist practicing in Milwaukee, Wisconsin. He is author of the book, Track Your Plaque: The only heart disease prevention program that shows you how to use the new heart scans to detect, track, and control coronary plaque. He can be contacted through www.trackyourplaque.com.