Lipoprotein Analysis:
What tests are measured and a summary of treatments to consider
TYP SITE
Lipoproteins can be among the most important parts of your coronary disease prevention program. Here we list the measures that we use in our program and a summary of treatments, nutritional, lifestyle, and by prescription, that we've used successfully. Discuss your lipoprotein results with your doctor. These comments are intended to help alert you and your doctor to the treatment options available.
The information contained is not intended to represent a medical diagnosis, treatment or medical advice in any way, as it is general information and cannot be relied on without consultation with your physician. These comments are intended to alert you and your physician to issues and treatments that may be helpfuI. It is not intended nor is it implied to be a substitute for profession medical advice. As medical information and your health can change rapidly, we strongly encourage you to discuss all health matters and concerns with your physician before beginning new diagnostic or treatment strategies.
Here is a list of the major lipoproteins we "track" as part of the Track Your Plaque program followed by an explanation of why they are important and the various methods of correcting them.
The List of Major Lipoproteins
1. LDL particle number or apoprotein B or direct LDL
2. Small LDL
3. HDL cholesterol
4. Deficient large High-Density Lipoprotein (HDL) or HDL 2b
5. Very Low-Density Lipoprotein (VLDL)
6. Intermediate-density lipoprotein (IDL)
7. Lipoprotein(a)
8. Homocysteine
9. C-reactive protein
10. Insulin
11. Fibrinogen
Low-density lipoproteins (LDL), Apoprotein B, LDL particle number
These three measures—LDL cholesterol, apoprotein B, and LDL particle number—measure approximately the same thing, but apoprotein B and LDL particle number are more accurate. LDL cholesterol can, in fact, be highly inaccurate and underestimate the true value by 50% in some cases. Apoprotein B and LDL particle number are therefore superior gauges of heart disease risk. LDL, often called "bad" cholesterol, is formed primarily by breakdown of VLDL. Apoprotein B is the main recognition protein on both VLDL and LDL.
Treatment:
Statin agents—The statins are popular prescription drugs that lower LDL cholesterol (and apoprotein B and LDL particle number) up to 60% by increasing liver uptake of cholesterol particles. They have the advantage of potency and convenience. Data consistently show a reduction in heart attack risk of about 30% over 5 years of treatment. Side-effects include muscle damage and liver problems (evidenced by elevations in blood tests) which occur in 1-2% of people. Much more commonly (40-50% of people in our experience), vague muscle aches and weakness occur. The statin agents are, from most potent to least potent: rosuvastatin (Crestor™), atorvastatin (Lipitor™), simvastatin (Zocor™), pravastatin (Pravachol), lovastatin (Mevacor™), and fluvastatin (Lescol™).
Ezetimibe (Zetia™) is in a class of its own. Zetia blocks absorption of cholesterol into the intestinal wall. LDL cholesterol is reduced around 18% when Zetia alone is used. Zetia's greatest application is in combination with a statin drug. The therapeutic potency of a statin agent is quadrupled when combined with Zetia, and is therefore a useful agent to achieve very low LDL cholesterol, apoprotein B, or LDL particle number.
Several foods and supplements can be used to lower LDL cholesterol:
Raw almonds—1/4-1/2 cup per day.
Soy protein powder—Three tablespoons a day in fruit smoothies, protein shakes, or blended in yogurt or other foods lowers LDL around 12%. Also consider other soy protein sources like soy nuts, soy cheese, soy milk, soy butter, and low-carb pasta (if made with soy protein).
Pectin—Found in apples and the rinds of citrus fruits.
Oat bran—3 tbsp per day as a cereal or in other foods like yogurt, fruit or protein smoothies, granolas.
Beans— Starchy varieties like black, pinto, Spanish, red, and kidney; ½ cup per day.
Phytosterols—A soybean oil derivative available as butter substitutes, Take Control and Benecol. Two tbsp per day is the recommended dose. Also available as an orange juice (Minute Maid Heart Wise®).
Track Your Plaque target: LDL cholesterol 60 mg/dl or less; apoprotein B 70 mg/dl or less; LDL particle number 700 nmol/l or less.
Small LDL
LDL particles can vary in size and chemical structure, with smaller LDL particles more likely to enter and adhere to plaque, induce oxidative damage, and lead to heart attack (up to 3-fold greater risk than large LDL). Small LDL occurs often, though not exclusively, along with low HDL (<60 mg/dl) and high triglycerides (>100). Small LDL can occur with any level of LDL cholesterol.
Treatment:
Niacin in doses of 500–1500 mg is a very effective method of reducing or eliminating small LDL. Niacin also raises HDL, increases large HDL, reduces VLDL and triglycerides, and modestly reduces LDL. When used in combination with statin agents, there is a profound reduction in heart attack risk. The preferred forms are Niaspan® and Slo-Niacin®, the safest and best tolerated.
Fish oil, through its effects on reducing triglycerides and VLDL, reduces small LDL, since triglycerides are a necessary ingredient to produce small LDL. Fish oil 4000 mg per day is a good starting dose; higher doses should be discussed with your physician, though we commonly use 6000-10,000 mg per day without ill-effect.
The fibrate class of prescription drugs (fenofibrate, gemfibrozil) reduce small LDL significantly.
Nutritional strategies that reduce small LDL include lean proteins like baked chicken and fish, egg whites, almonds, walnuts, sunflower and pumpkin seeds; fibers like oat bran but not wheat bran or wheat products; monounsaturated oils like olive and canola.
Track Your Plaque target: <10 mg/dl small LDL
High-density lipoproteins (HDL)
HDL, often called "good" cholesterol, removes cholesterol from vessel walls and carries it to the liver for disposal. The most important fraction of the HDL family is large HDL, sometimes called "HDL 2b," that is most active in removing cholesterol ("reverse cholesterol transport"). The large fraction is commonly deficient when total HDL is less than or equal to 60 mg/dl. Treatments that increase total HDL tend to increase the large fraction, as well.
The lower the HDL, the greater the risk for coronary plaque; the higher the level, the lower the risk. The same holds true for large HDL.
Treatment:
The strategies that raise HDL and increase the fraction of large HDL are the very same as those used to reduce the unwanted small LDL particles (see above).
Track Your Plaque target: Total HDL 60 mg/dl or greater; large HDL 35 mg/dl or greater; HDL 2b 20 mg/dl or greater.
Very low-density lipoproteins (VLDL)
VLDL particles are formed in the liver by combining cholesterol, triglycerides, and apoprotein B. VLDL contains only 10-15% of a person's total cholesterol. Increased VLDL usually occurs along with increased triglycerides, low HDL cholesterol, and small LDL, although the relative proportions of each can vary. Increased VLDL can add to coronary plaque growth.
Treatment:
Fish oil is an extremely effective means of reducing both triglycerides and VLDL because of fish oil's omega-3 fatty acid content. Benefits begin at 1200 mg per day of total omega-3 fatty acids (EPA + DHA), obtained with a dose of 4000 mg of fish oil, or four capsules (4 x 300 mg= 1200 mg). Higher doses (up to 10,000 mg fish oil per day) can be considered for very high triglycerides or VLDL.
Niacin (vitamin B3) lowers triglycerides up to 60-70% and can virtually eliminate excess VLDL at doses of 500–2000 mg. These doses should be prescribed and monitored by a physician.
The fibrates (gemofibrozil, fenofibrate) are two prescription agents that substantially lower VLDL and triglycerides.
Stategies that promote insulin sensitivity can lower VLDL and triglycerides to a variable degree. These include low glycemic index foods like proteins and healthy oils; avoidance of refined carbohydrates including wheat products; exercise; weight loss, when appropriate; adequate sleep; and the prescription thiazolidinediones (pioglitazone, rosiglitazone) usually prescribed for pre-diabetes.
Track Your Plaque target: Triglycerides 60 mg/dl or less; Total VLDL <10 mg/dl.
Intermediate-density lipoprotein (IDL)
Increased IDL means that your body struggles to clear fat from the blood after eating, with many more hours required to clear the blood than normal. The longer IDL persists in the blood, the more opportunity it has to cause plaque growth. Only 10% of people with heart disease have elevated IDL. Increased IDL can also be a potent cause of soft carotid plaque, a risk for stroke.
Treatment:
This abnormality responds to a broad variety of treatments, including cholesterol-lowering medicines, niacin, fish oil and weight loss. Fish oil is among the most effective. Avoiding unhealthy fats, such as saturated and hydrogenated, is essential.
Track your Plaque target: 0 milligrams IDL
Lipoprotein(a)
Lipoprotein(a), Lp(a), identifies a person at potential high-risk for heart attack. Lp(a) tends to heighten the ill-effects of other lipid and lipoprotein abnormalities, especially LDL cholesterol. It's also associated with increased blood pressure and blood clotting tendency. Many families with clusters of high risk often share this abnormality. Unfortunately, high Lp(a) levels may not respond to treatment aimed at high LDL.
Treatment:
Niacin (vitamin B3) is the most specific treatment available to reduce Lp(a), although higher doses than that required to raise HDL or reduce small LDL may be required. The minimum dose is 1000 mg/day; occasionally, doses of 3000 mg or greater may be required. This should be administered only under medical supervision.
Estrogen for women and testosterone for men can lower Lp(a) 25%. Discuss these complex treatments with your doctor.
L-carnitine is an amino acid that can reduce Lp(a) around 10% at doses of 2000 mg/day or greater.
Supplements that may provide modest Lp(a) lowering effects include fish oil, coenzyme Q10, almonds, lysine, and vitamin C.
Track Your Plaque target: <20 mg/dl
Homocysteine
Homocysteine is an amino acid that causes arterial injury, oxidizes LDL particles (making them more damaging), constricts arteries, increases inflammation, and provokes blood clot formation leading to heart attack. Homocysteine levels above 12 µmol/l increases heart attack risk 3-fold. It is also a risk for stroke, aneurysm, and depression.
Treatment:
Treatment for homocysteine consists of vitamins B6 (25-100 mg), B12 (500 mcg or more), and folic acid (1-5 mg), all B vitamins. Doses can be tailored to your homocysteine levels. A typical starting regimen would be folic acid 2 mg (2000 mcg), B6 50 mg, B12 1000 mcg. Folic acid can be obtained in doses up to 0.8 mg (800 mcg) over-the-counter. Higher doses of 1.0 mg or higher are available only by prescription.
Track Your Plaque target: <8 µmol/l.
C-Reactive Protein
C-reactive protein, or CRP, is a gauge of inflammation in the body, including inflammation affecting coronary plaque. High levels (>3) place you at 3-fold increased risk for heart attack, even when LDL cholesterol is low. When an elevated CRP occurs in the company of small LDL particle size, there is a 6 to 7-fold greater risk of heart attack. Increased CRP also predicts future diabetes.
Treatment:
Treatments that address the causes of coronary plaque all seem to reduce CRP, and there is no specific inflammation-reducing therapy. The prescriptions statin cholesterol drugs, ezetimibe (Zetia™), and the thiazolidinediones for diabetes (Avandia™, Actos™) can lower CRP. Aspirin and omega-3 fatty acids (fish oil) lower CRP modestly. A healthy diet, low glycemic index foods, weight loss (when appropriate), and exercise are all healthy methods of lowering CRP. Vitamin D can lower inflammatory measures, including CRP, particularly for people living in northern climates who lack sufficient sun exposure; 1000 units per day is a very confident dose. Low doses of the antibiotic, doxycycline, can be used in selected instances and can lower CRP and inflammation substantially.
Track Your Plaque target: < 1 mg/dl
Insulin
Hyperinsulinemia, or high insulin levels, is among the earliest signs of future diabetes due to insulin resistance at the cellular level. Increased insulin causes a cascade of effects, including lower HDL, increased triglycerides, small LDL, increased blood pressure, and increased coronary plaque growth. Increased insulin can precede high blood sugars by several years, signaling an earlier phase of diabetes.
Treatment:
Treatments intended to increase sensitivity to insulin include the thiazolidinedione prescription agents (Actos™, Avandia™); lifestyle changes such as adequate sleep; exercise; increasing low-glycemic index foods like oat fibers, raw nuts and seeds; and monounsaturated oils like olive and canola. The most powerful corrective strategy is weight loss, when appropriate, which can often "turn-off" this abnormality completely.
Track Your Plaque target: <10 µmol/ml along with blood glucose <100 mg
Fibrinogen
Fibrinogen is a blood clotting protein that increases with high-fat, refined diets and physical inactivity. Fibrinogen can also promote plaque growth without rupture. Like Lp(a), fibrinogen magnifies the dangers of other abnormalities with a resultant 5-fold increase risk of heart attack when the level exceeds 350 mg/dl.
Treatment:
Although there is no specific fibrinogen-lowering medicine, fish oil does an excellent job of lowering fibrinogen at doses of 4000 mg or greater per day. Green vegetables, avoidance of saturated and hydrogenated fats, and exercise significantly lower fibrinogen. The fibrate class of prescription drugs (especially fenofibrate) can lower fibrinogen 15-40%. Niacin also helps by lowering fibrinogen 10-30%.
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