Life Extension Magazine®

Issue: Aug 2009

Understanding Risk Factors for Heart Disease

A return-to-basics discussion about the tests that predict risk for heart disease—and what nutritional supplements help correct them. In the first part of a two part article, Dr. William Davis discusses lipids and C-reactive protein (CRP) as risk factors for cardiovascular disease.  Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, triglycerides, and CRP are discussed, along with the best therapies to help correct abnormal levels.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in May 2022. Written by: Dr. William Davis, .

A return-to-basics discussion about the tests that predict risk for heart disease—and what nutritional supplements help correct them

Well before coronary heart disease itself gets underway, so-called risk factors for heart disease declare themselves. Atherosclerotic plaque initiates and grows for good reason. Risk factors identify some of those reasons. 

This is the role of risk factors: To provide an indication that potential for atherosclerosis is present.

If you’ve become a bit confused about this conversation over the past few years, you are not alone. Controversy over the importance of risk factors, the overselling of cholesterol drugs, and the emergence of newly identified risk factors for heart disease has made this a rapidly changing, and often difficult to follow, discussion.   

The understanding of risk factors for heart disease has come a long way since the 1940s, when it was not at all clear just what aspects of diet, lifestyle, or genetics lay behind the disease. Even cigarette smoking was still being advertised as a healthy habit: “Camels: Smoked by more doctors than any other brand!”   

But, even after nearly 60 years of research and heated debate, there is not uniform agreement on what causes heart disease. We’ve zigzagged around the role of diet, cholesterol, and fats, while newly appreciated phenomena like inflammation, genetic factors, and vitamin D deficiency emerge and even further transform the discussion.  

We might regard it as 60 years of confusion—or 60 years of wisdom gained. Despite the controversies and persistent uncertainties, surely there are some nuggets of wisdom to be learned. 

The ASTEROID Trial: Good-bye to heart attack?

Glowing pronouncements about reversal of heart disease followed in the wake of the AstraZeneca-sponsored clinical trial of the statin drug, rosuvastatin, that showed modest reductions in the volume of coronary plaque after participants took two years of rosuvastatin, 40 mg per day.1   

Is it true? If coronary atherosclerotic plaque is reduced by this drug, does this single trial signal the end to all heart attacks and coronary heart disease?

The cure for coronary heart disease, according to this line of thinking, has already been discovered and its name is rosuvastatin.

But before you indulge in an evening at the local fast food restaurant, park yourself in front of the TV with a quart of Ben and Jerry’s Chunky Monkey® ice cream, and throw your fish oil and niacin in the trash, let’s reconsider this argument.

How is heart disease caused? What role do cholesterol and other risk factors for heart disease play? Is it conceivable that a strategy as simple as a single drug (rosuvastatin) can essentially halt heart disease for good?

In the ASTEROID Trial, 346 participants completed a two-year course of treatment with the cholesterol drug, rosuvastatin (Crestor®), 40 mg (the maximum FDA-approved dose). The volume of coronary atherosclerotic plaque was assessed using intracoronary ultrasound (IVUS), both at the start and after 24-months of treatment. (IVUS is an invasive procedure performed during heart catheterization.) Dr. Steven Nissen of the Cleveland Clinic, lead investigator of ASTEROID, reported that, on rosuvastatin, LDL cholesterol was reduced from 130 mg to 60.8 mg/dl, HDL increased from 43 mg/dl to 49 mg/dl plaque. In addition, plaque volume was reduced by an average of 6.9% in the (10 mm) segments studied in each participant.

More recently, the Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin, or JUPITER, Trial, of rosuvastatin, 20 mg per day, in 15,000 participants was prematurely halted because of a clear statistical benefit in reducing cardiovascular events in those taking the drug vs. placebo. (Publication of the results is pending.)

The trial results are, undoubtedly, good news for prevention of heart disease. It sure beats three stents and bypass surgery, or a fatal or debilitating heart attack. It also adds to the national conversation on prevention of heart disease and subtracts from the notion that heart disease should be addressed only with major heart procedures like stents and bypass surgery.

But there are several major reasons to view the ASTEROID results with skepticism:

  • The ASTEROID study was industry sponsored. (The financial disclosures of the lead investigators also read like a Who’s Who of the drug industry.) This is, unfortunately, true of much of the data behind statin drug trials: Paid for and thereby potentially influenced by the people most likely to benefit from positive results.  
  • Contrary to the results of the trial, in real-life, the dose of drug used in the study is generally an intolerable dose that, in my experience, results inevitably in incapacitating muscle aches and weakness. (Though I used this strategy initially, I do not have a single patient who has been able to tolerate more than a few months of this drug at the ASTEROID dose.) Taking it for a lifetime (since it can only work as long as you take it) seems inconceivable. 
  • Though not reflected in the ASTEROID trial, it is highly unlikely that a single drug can correct and eliminate the ill-effects of many other sources of heart disease risk, and the results are therefore not able to be applied generally to a broader population. For instance, the genetic pattern, lipoprotein(a), present in 17-20% of people with coronary disease, is not corrected with the drug.       

To reverse all coronary atherosclerotic plaque, an agent(s) would have to address inflammatory processes, genetic factors like lipoprotein(a), phospholipase A2, small LDL, low HDL (including genetic variants), the effects of obesity, deficiency of vitamin D, etc. Sure, rosuvastatin reduces LDL, raises HDL modestly, and reduces C-reactive protein (a measure of inflammation). That still leaves many other crucial factors uncorrected.   

Is this another tool and another choice for the prevention of heart disease? Yes, it is. Is it a cure for heart disease? Hardly.

Risk factors: One at a time

Let’s begin with the four common values present on the standard lipid panel.

LDL cholesterol

LDL cholesterol has become a frequent fixture in the modern lexicon, a topic as common as money and the weather. It has also proven to be the number one most profitable entity—ever—for the drug industry. While this flood of revenue has driven enormous research (and marketing) efforts, it has also served to muddy the waters of truth, since much research behind LDL cholesterol is drug industry-driven and paid-for.

LDL cholesterol is one of the four values provided on any standard cholesterol panel. It is meant to reflect the amount of cholesterol present in the low-density fraction of lipoprotein blood particles (as opposed to those in the high-density fraction, or HDL). It is the basis for most conventional predictions of heart disease risk, since it has been statistically connected to occurrence of heart attack and is recoverable from atherosclerotic plaque when examined.

It is often called "bad" cholesterol, since the higher the LDL, the greater the likelihood of cardiovascular events like heart attack, an observation documented repeatedly from the Framingham Study to other populations.2-4 Despite the controversies the drug industry has created by its overenthusiastic marketing of the LDL-reducing statin drugs, reduction of LDL cholesterol, whether with statin drugs, diet, fibers like oat bran or ground flaxseed, or other strategies (see below) has been confidently tied to reduction in heart attack.5

But there are some limitations.

While LDL is a predictor of heart disease, it is far from a perfect predictor. High LDL cholesterol doesn’t always mean risk for heart disease; low LDL cholesterol doesn’t necessarily mean low risk for heart disease. Most people are unaware that LDL cholesterol is a calculated value, not measured. It is obtained by subtracting measured HDL and triglycerides from total cholesterol, based on an equation developed in the 1960s by Dr. William Friedewald at the National Institute of Health. Because it is calculated, LDL is frequently inaccurate, not uncommonly under- or over-estimating the true value by 50% or more when compared to more accurate measures (like apoprotein B or LDL particle number obtained through lipoprotein testing).6 Nonetheless, calculated LDL is, at least, a reasonable starting place to gauge risk, meaning, the lower the LDL, the better.

Several foods and supplements can be used to reduce LDL cholesterol:

  • Raw nuts—1/4-1/2 cup or more per day of raw almonds, walnuts, and pecans can reduce LDL cholesterol 20-30 mg/dl. Because of their very low carbohydrate content and relatively inefficient absorption of this high-fiber food, I advocate plenty of raw nuts, virtually unrestricted quantities. (But not processed nuts like mixed nuts roasted in hydrogenated oils, “honey-roasted,” or roasted and salted; these are the variety that do indeed make you fat and cause increased LDL cholesterol.)
  • Pectin—found in apples, the rinds of citrus fruits, as well as in supplement form.
  • Oat bran—3 tbsp per day as a hot cereal or in other foods like yogurt, fruit or protein smoothies, granolas.
  • Ground flaxseed—2 tbsp per day, also as a hot cereal or added to yogurt or other foods. This is a first choice for fiber in people with high blood sugars, since it contains no digestible carbohydrates. 
  • Psyllium seed—Known better as Metamucil®, this soluble fiber preparation, like oat bran and flaxseed, reduces LDL cholesterol when two tablespoons per day are taken (usually in water or juice).
  • 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®, as well as other products.
  • Green tea—In a recent randomized, controlled trial, participants taking green tea extract capsules (375 mg per day) reduced LDL by 16%.7
  • Cocoa—As cocoa powder or dark chocolates, cocoa flavonoids are proving to exert cholesterol-reducing effects, in addition to blocking LDL oxidation and raising HDL.8
  • Red yeast extract—A nutritional supplement that showed more promise initially, while it still contained the statin agent, lovastatin. Since the FDA forced manufacturers to remove the lovastatin, leaving the mixed mevinolins, its effects have become rather erratic, ranging from moderate LDL-reducing power to none. If you come across a preparation that yields genuine effect, stick with it.
  • 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).    

All of these strategies reduce the entire range of LDL cholesterol particles, big and small. However, there are also strategies that reduce the most dangerous small LDL preferentially. That will be a topic for future discussion.

Total cholesterol

Total cholesterol is a source of great confusion, but one that seemingly has cast an indelible impression on the minds of most Americans.

That’s because the conversation on the dangers of high cholesterol—in both the blood as well as in diet—was the focus of early conversations dating back to the 1950s and 1960s. Back then, you had high cholesterol or you didn’t; the discussion did not include the various sub-fractions of cholesterol like LDL and HDL. It was just total cholesterol.

But total cholesterol is (and always has been) a composite value, a combination of undesirable fractions (LDL and triglycerides), as well as desirable (HDL). Does high total cholesterol therefore represent high LDL cholesterol (bad) or high HDL cholesterol (good), or some combination? Does low total cholesterol signify low LDL cholesterol or low HDL cholesterol? Total cholesterol is a flawed value that often clouds the significance of cholesterol issues, rather than clarifying it.

There is no doubt that total cholesterol does, in a broad population, correlate with heart attack and other cardiovascular events.9 Total cholesterol >240 mg/dl, for instance, carries a three-fold increased risk of cardiovascular events compared to people with total cholesterol <210 mg/dl.2 However, total cholesterol is a miserably inaccurate value when applied to a specific individual, whose total cholesterol can mean a number of different things. We’ve all known someone with high cholesterol who has never suffered any evidence of heart disease, or someone with low cholesterol who has. Cholesterol is a flawed measure of hidden heart disease in any specific individual at any one point in time. This flawed measure is also the value often cited by critics of the lipid hypothesis—and they’re right. 

Clouding the issue further is the early concern that cholesterol in foods will increase blood cholesterol—makes sense, doesn’t it? However, this phenomenon has since been shown to exert only modest blood cholesterol-increasing potential.10 Dietary cholesterol, because of inefficient absorption, does not appreciably impact on blood cholesterol.

While it proved modestly useful in the past, the time for total cholesterol has come and gone. It is now the model-T of cholesterol testing, which means it’s time to advance. 

High-density lipoproteins (HDL)

Subtract the cholesterol contained in LDL, along with the cholesterol in the very low-density lipoprotein fraction (VLDL, represented by triglycerides) and you’re left with HDL cholesterol. But the cholesterol from HDL is different.

Greater levels of HDL are protective because this particle removes cholesterol from vessel walls and carries it to the liver for disposal, a processed called “reverse cholesterol transport,” sort of like traffic flowing in the opposite lane. For this reason, HDL is often called "good" cholesterol.

Plenty of studies have demonstrated, beyond any doubt, that the higher the HDL, the less the risk for heart attack and other cardiovascular events. While we need more clinical data on the benefits of increasing HDL (or, perhaps, its reverse cholesterol transport capacity, or some fraction of HDL), studies like the VA-HIT show that cardiovascular events are reduced 11% for every 5 mg/dl increase in HDL (with the drug gemfibrozil, in this study).11

More than high LDL, low HDL values are common in people with heart attacks and heart disease. In fact, even the Framingham Study has determined that, more than LDL, low HDL is a better predictor of future heart attack.12 Unfortunately, due to the dominance of statin cholesterol drugs to reduce LDL, HDL is often neglected in clinical practice.   

The most important fraction of the HDL family is large HDL, sometimes called “HDL 2b,” the 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 shift particles towards the large fraction, as well.

Both total and large (HDL2b) HDL can be increased with:

  • Niacin—Doses of 500–1500 mg are a very effective method of raising HDL and shifting HDL towards the healthiest large particles. Niacin also reduces triglycerides, undesirable small LDL particles, and reduces LDL. When used in combination with statin agents, there is a profound reduction in heart attack risk.13 Doses exceeding 500 mg per day should be taken under medical supervision, since there is a small risk of liver toxicity at higher doses. Generous hydration helps minimize the “hot flush” side-effect that is common with niacin. We usually begin with 250-500 mg per day at dinner, with increases of 250-500 mg every four weeks until the desired dose is reached. 
  • Omega-3 fatty acids (EPA, DHA) from fish oil, through its effects on reducing triglycerides and VLDL, increases HDL modestly, since triglycerides modify HDL structure and accelerate degradation. Total daily EPA + DHA of 1200 mg per day is a confident starting dose; higher doses should be discussed with your physician. We commonly use 1800-3,000 mg per day, occasionally up to 5000 mg or more, without ill-effect.
  • Vitamin D is proving to be among the most exciting ways to raise HDL. Rises in HDL of 5, 10, sometimes 20 or more mg/dl are common.
  • The fibrate class of prescription drugs (fenofibrate, gemfibrozil) increases HDL between 2-4 mg/dl.
  • Nutritional strategies that increase HDL include dramatic reduction or elimination of high-glycemic index (rapid sugar release) foods like sweets, soft drinks, and wheat (even whole wheat and whole grain) and cornstarch products. Foods that increase HDL include lean proteins like lean red meats, chicken, fish, eggs, almonds, walnuts, sunflower and pumpkin seeds; fibers like oat bran and ground flaxseed (but not wheat bran or wheat products); monounsaturated oils like olive and canola.
  • Alcoholic beverages—Red wine may be the best source, since it is richest in healthy flavonoids, as well. Increases in both total HDL, as well as large HDL, are seen.
  • Exercise—The effects can vary, but increases of up to 5-10 mg/dl are common with high levels of exercise.
  • Weight loss—This can be a very significant effect, depending on how overweight a person is when they start. However, be aware that, with substantial weight loss, there is an initial drop in HDL in the first few weeks, followed by a long-term rise.
  • Flavonoids—such as dark chocolates and green tea have the power to raise HDL, generally by a few milligrams.7,8

Triglycerides and Very low-density lipoproteins (VLDL)

After LDL cholesterol and HDL cholesterol, very low-density lipoproteins (VLDL) are a third class of blood particles that contain cholesterol. On a standard cholesterol panel, VLDL cholesterol is estimated by measuring triglycerides (since triglycerides ¸ 5 yields VLDL cholesterol levels.) 

VLDL particles are formed in the liver by combining cholesterol, triglycerides, and the protein, apoprotein B, in addition to other “ingredients.” VLDL production is very sensitive to the availability of triglycerides, and any increase in triglyceride availability also increases VLDL production in the liver. This is a very common situation with excess carbohydrates in the diet, diabetes, metabolic syndrome and insulin resistance.

After release from the liver, VLDL particles encounter enzymes that transform them into LDL particles. Increased VLDL can therefore lead to increased LDL. In addition, when triglycerides and VLDL particles are plentiful, they also interact directly with LDL particles, which cause the excess triglycerides to be deposited in LDL particles. This triggers a chain of events that leads to the most undesirable small LDL particles (discussed in Part II). Excess triglycerides and VLDL also interact with HDL particles, which also causes a reduction in HDL, as well as a shift in HDL to the less beneficial smaller varieties of HDL particles.14

Both triglycerides and VLDL can be effectively managed with:

  • Fish oil—Omega-3 fatty acids from fish oil are an extremely effective means of reducing both triglycerides and VLDL. Benefits begin at 1000 mg per day of total omega-3 fatty acids (EPA + DHA); the dose of fish oil depends on the concentration of EPA and DHA in the fish oil brand you choose. Higher doses of EPA and DHA, e.g., 3000 mg, 5000 mg, even 8500 mg per day, can be considered for very high triglycerides or VLDL (though this should be managed with the assistance of your health care practitioner). The FDA has approved a prescription form of fish oil for treatment of a genetically-determined form of high triglycerides, familial hypertriglyceridemia. Having used both prescription and non-prescription forms for this genetic disease, as well as for lesser degrees of elevated triglycerides, I can confidently say that, beyond the concentration of EPA and DHA per capsule, there is virtually no difference in my experience (beyond the exorbitant cost for the prescription form).
  • Niacin—Niacin (vitamin B3) reduces triglycerides up to 60-70% and is an effective strategy to reduce excess VLDL at doses of 500–2000 mg. Any niacin dose >500 mg per day should be prescribed and monitored by your health care practitioner.
  • The fibrates (gemofibrozil, fenofibrate) are two prescription agents that substantially lower VLDL and triglycerides. Statin drugs like LipitorÒ and CrestorÒ, while principally prescribed for LDL cholesterol reduction, can also reduce triglycerides by up to 30%.

Nutritional strategies can be enormously effective for reduction of triglycerides and VLDL. In past, low-fat diets were used to reduce triglycerides but proved miserable failures that eventually made triglycerides worse. Instead, reduction in carbohydrates, especially refined carbohydrates, can reduce triglycerides and VLDL.15 Low-glycemic index foods like proteins and healthy oils; exercise; weight loss, when appropriate; and adequate sleep can all contribute to reducing triglycerides and VLDL. One unique strategy we have used with enormous success is to eliminate all wheat products (refined and whole grain), along with elimination of any food made with cornstarch, as well as other high-glycemic index foods (e.g., fruit drinks, candies, snacks, etc.). This has yielded drops in triglycerides of hundreds of milligrams.

It is important to minimize exposure to fructose, particularly processed foods made with high fructose corn syrup, since this common sweetener boosts triglycerides significantly, as well as possibly increasing risk for diabetes and increasing appetite.16

National guidelines (ATP-III) recommend that triglycerides be kept at 150 mg/dl or lower. However, in our experience in reversal of heart disease, we aim for triglyceride levels of 60 mg/dl or lower. At this triglyceride level, VLDL is also minimized.  

C-reactive protein (CRP)

While inflammation can serve a protective function at the site of an injury, it has another face: a silent process that erodes health and lies at the source of multiple conditions, including diabetes, cancer, and heart disease.17 

CRP is a blood protein produced by the liver whenever any inflammatory process is active in the body, whether or not you’re aware of it. Obvious sources of inflammation, like pneumonia and knee arthritis, will raise CRP to high levels. Although its exact function in the body is unknown, the blood concentration of CRP does seem to parallel the degree of inflammation.

CRP is therefore a commonly available blood test that can serve as a gauge of inflammation. While very high C-reactive protein levels >10 mg/l nearly always represent inflammation outside of the heart and do not necessarily indicate increased coronary risk, lower levels (<10 mg/l) can be used to gauge low-grade inflammation that stimulates coronary plaque activity. Levels >3 mg/dl increase risk for heart attack three-fold, even when LDL cholesterol is low.17 When elevated CRP occurs in the company of other risks for heart disease (increased LDL, small LDL, etc.), there is as much as a 6 to 7-fold greater risk of heart attack.19  

“We have to think of heart disease as an inflammatory disease, just as we think of rheumatoid arthritis as an inflammatory disease.”

Paul Ridker, MD
Harvard University

Why another blood test?

Though cholesterol and the values from the standard lipid panel are helpful, they all too often fail to reliably predict future heart attack. As inflammation that lurks beneath the surface is proving to be a potent cause of heart disease, increased CRP has also proved to improve the predictive power of lipids, perhaps yielding a clearer glimpse into the future.  

Predictably, drug manufacturers have tried to persuade us that the only effective way to reduce CRP is with statin drugs, which reduce CRP from 20–50%.20 This is simply not true: there are many ways to reduce CRP as well as, or even more effectively, than the statin drugs.

Here are approaches to consider that reduce CRP and thereby help remove inflammation as a contributor to your risk for heart disease:

Nutritional supplements that reduce inflammation:

  •  Vitamin D—Vitamin D can be among the most potent anti-inflammatory strategies available, reducing CRP dramatically.21 In our clinic, we start at daily doses of 1000–2000 units and frequently increase to 4000–6000 units per day, particularly when there’s little sun exposure. Some people require much higher doses, especially in winter; dose is best judged by obtaining a blood level of 25-OH-vitamin D to gauge the degree of deficiency. (We aim to achieve 25(OH) vitamin D levels of 50-60 ng/ml.)  
  •  Omega-3 fatty acids—Omega-3 fatty acids from fish oil are the foundation for any heart disease prevention program. CRP reduction is just one of the many beneficial effects. Cardiovascular benefits begin at a dose of 1000 mg of omega-3 fatty acids, EPA + DHA, including CRP reductions of approximately 30%.
  •  Niacin—At doses of 1000 mg per higher (which should be used with medical supervision) reduces CRP 15-20%.22
  •  Flavonoids suppress inflammation. Resveratrol or red wine (southern French and Italian wines are the most plentiful sources); green tea; cocoa (dark chocolate); and flavonoid-rich foods, such as deeply-colored fruits (citrus, blueberries, raspberries, plums, pomegranates, etc.) and vegetables (spinach, dark lettuces, green peppers, red peppers, etc.) have all been demonstrated to reduce inflammatory responses.23-25
  •  Fibers—Healthy fibers, particularly raw almonds, walnuts, oat bran, wheat germ, ground flaxseed, and green vegetable sources, are easy and powerful suppressors of inflammation.   

Besides statin drugs, other medications that reduce inflammation and CRP include aspirin, which reduces CRP modestly, usually no more than 15%; glitazones (Actos™ and Avandia™) for diabetes or insulin resistance; anti-hypertensive drugs in the ACE inhibitor or angiotensin-receptor blocker categories (lisinopril, enalapril, valsartan, irbesartan, etc.); anti-hypertensive agents in the beta-blocker category (metoprolol, atenolol, etc.).26 One fascinating agent that has shown promise in preliminary studies is the antibiotic, doxycycline. At low doses (too low to treat infections except gingivitis), doxycycline suppresses an important class of inflammatory enzymes called matrix metalloproteinases. It also lowers CRP dramatically. Preliminary studies from England suggest that doxycycline, 20 mg twice per day for 6 months, shuts down the inflammation that drives heart attack and abdominal aneurysm expansion.26

In addition, lifestyle practices can also substantially reduce inflammation and CRP:

  •  Weight loss—the number one most powerful factor of all. Returning to an ideal weight or BMI<25 leads to profound reductions of C-reactive protein.28 The magnitude of CRP reduction is roughly proportional to the amount of weight lost, i.e., the more you lose, the greater the reduction.
  •  Saturated fats have been shown to increase inflammation. Reduce saturated fat from cheeses, red meats, sausage, bacon, butter, and full-fat dairy products).29
  •  Choose low-glycemic index foods like lean proteins (egg whites or free-range eggs, lean red meats, baked skinless chicken and turkey, fish); flaxseed, oat bran or slow-cooked oatmeal; vegetables; raw nuts and seeds. Reduce or eliminate high-glycemic index foods, particularly processed starches like cookies and crackers, candies, cakes, breads, bagels, and breakfast cereals. Note that whole grain products are only slightly better than refined white products in this regard.29
  •  Exercise leads to a modest reduction in inflammation; the longer the better.
What is a “good” cholesterol?

Warren, a 56-year old accounting manager at a manufacturing plant, recently asked, “My doctor said my LDL cholesterol was 141. He said that’s too high. But I’ve talked this over with some of my co-workers, and they tell me that they had LDL cholesterols a lot higher than that. Is my LDL really too high?”

At first blush, it seems like a straightforward question: Either cholesterol is too high and you’ll have heart disease in your future, or it’s low and you won’t. End of story.

Not so fast. There are a number of issues to factor into you and your doctor’s thinking about cholesterol. Unfortunately, it’s more than just a matter of too high or too low.

Current conventional practice is more or less dictated by the consensus statement issued by the National Cholesterol Education Panel Adult Treatment Panel-III, or ATP-III, the most recent guidelines issued by a panel of experts in cholesterol and followed by most doctors. ATP-III advises the following general scheme (below).

ATP III Consensus Guidelines: Classification of LDL, Total, and HDL Cholesterol

LDL Cholesterol (mg/dl)

<100 Optimal

100-129 Near optimal/above optimal

130-159 Borderline high

160-189 High

>190 Very high

Total Cholesterol (mg/dl)

<200 Desirable

200-239 Borderline high

>240 High

HDL Cholesterol (mg/dl)

<40 Low

>60 High

ATP-III provides for adjustment of target LDL cholesterol based on risk factors present in a specific individual. They define “risk factors” as:

Cigarette smoking

Hypertension (BP >140/90 mmHg or on antihypertensive medication)

Low HDL cholesterol (<40 mg/dL)

Family history of premature CHD (CHD in male first degree relative <55 years; CHD in female first degree relative <65 years)

Age (men >45 years; women >55 years)

LDL cholesterol targets are adjusted to:

Coronary heart disease or “risk equivalents” present (e.g., diabetes or other forms of atherosclerotic disease such as aortic aneurysm or carotid disease)


LDL target <100 mg/dl

Multiple (2+) risk factors  

LDL target <130 mg/dl

Zero to one risk factor  

LDL target <160 mg/dl

More recently, the ATP-III target for LDL cholesterol was reduced optionally to 70 mg/dl, to be applied in people felt to be at particularly high-risk, such as survivors of a recent heart attack, smokers, or people with combined diabetes and heart disease, based on the favorable outcomes of some of the clinical trials of more intensive LDL cholesterol reduction by statin drugs.   

From Third Report of the Expert Panel on Detection, Evaluation, and Treatment of the High Blood Cholesterol in Adults (Adult Treatment Panel III): Executive Summary, 2001.4

In our clinic, we disregard total cholesterol, since it is a vague and sloppy measure that can be increased or decreased in misleading ways by good factors (like increase in HDL) as well as bad (increase in LDL or triglycerides); this is discussed above. For purposes of coronary plaque reversal, we aim for (calculated) LDL cholesterol of 60 mg/dl.


What the ATP-III guidelines and your doctor probably won’t tell you

If I were to echo conventional advice, I would refer you to the guidelines provided by ATP-III, then say “Discuss it with your doctor.” You and your doctor would then be taking notes from the same page.

But I won’t.

Though, in my view, the guidelines provided by ATP-III are helpful as a starting point for crude advice on cholesterol, for truly effective advice on how to gain control over heart health, you need to go farther.  

First of all, let’s dismiss the value of total cholesterol. Total cholesterol is the combination of LDL (“bad”) cholesterol, HDL (“good”) cholesterol, and triglycerides (another “bad” blood fat), all lumped together. Total cholesterol is therefore a mixture of both good and bad factors and can yield confusing, often misleading, information. If, for instance, HDL goes way up (a good thing), so does total cholesterol (an apparently bad thing). That makes no sense. Yes, total cholesterol can serve to predict heart disease on a broad statistical basis in a large population. But you’re just one person, not thousands. You require information that applies to you.  

Two, the LDL cholesterol number provided by your doctor is not actually measured, but calculated. It is calculated from the three other measured values (total cholesterol, HDL, triglycerides) by a nearly 50-year old equation, known as “the Friedewald equation”. Dr William Friedewald developed his equation years ago, when measured LDL cholesterol values were not widely available and calculation was a necessity. When measured more precisely, calculated LDL is commonly 20, 40, 50% or more inaccurate. It can be higher, it can be lower, but you and your doctor can’t tell which just by looking at the calculated LDL. 

Calculated LDL cholesterol by the Friedewald equation has about much remaining value as tie-dye T-shirts and hippie haircuts. It was relevant for its time, but it is now faded and worn. More recent analyses have suggested that, while the higher LDL cholesterol is, the greater the risk for heart disease, many people with low cholesterols can also have substantial risk. And not all people with high cholesterol do indeed face increased risk. How do we make sense out of this jumble? No wonder it’s not clear what exactly “high” cholesterol means!  

Fast forward 50 years from Dr. Friedewald’s day and LDL cholesterol is now widely available as a measured value. A step farther, superior measures of risk with better power to predict whether heart disease is in your future or not are available, such as apoprotein B and LDL particle number, values obtained through advanced lipoprotein testing.

Allow me to make a set of bold predictions for the future: 

One:Total cholesterol will join 8-track tape players in the junk heap of technology, and you will no longer see it on your standard cholesterol panel.

Two: Calculated LDL cholesterol will become less commonly the number used to gauge risk from cholesterol issues. More accurate measures like measured LDL, apoprotein B, and my favorite, LDL particle number (obtained through a more sophisticated though highly accurate test called the NMR LipoProfile, Liposcience), will replace this rusty old model-T called calculated LDL. Measured LDL and apoprotein B are already available in most modern laboratories; the NMR and other lipoprotein tests are also available, but must be specified by your doctor.

Three: Even with measures superior to calculated LDL, your doctor will pay more attention to HDL and triglycerides, both values that yield a wealth of information about your eating habits, genetics, and future potential for heart disease.

Four: Measures that go even farther than the cholesterol panel, measured or calculated, will become mainstream. This may include measures of high-risk for heart disease like lipoprotein(a), C-reactive protein and other indexes of hidden inflammation. Although all cholesterol panels are now drawn while you are fasting, there will be a time when we also examine blood patterns immediately after eating to study how you handle food digestive by-products. This, too, can shed light on heart disease risk.

Five: Examination of risk factors will always be conducted in tandem with measures of the disease itself. In other words, risk factors will not be viewed in isolation, but as a part of an overall view of you and your risk by factoring in whether or not and how much atherosclerosis you may already have. This way, a person with advanced coronary atherosclerosis will be viewed differently (and treated more intensively) than someone with similar blood patterns but no disease whatsoever.   

For some, the future is now, and these more advanced concepts are already underway. But mainstream preventive cardiology, I predict, will follow this blueprint for development over the next decade or two.

So if you and your doctor decide to adhere to the ATP-III guidelines for LDL cholesterol, fine. You can get some rough sense for what is desirable and what is not that way.

But if you want something better, it’s time to starting being aware of the available ways to improve the power to predict and gain control over risk for heart disease.


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


1. Nissen SE, Nicholls SJ, Sipahi I et al for the ASTEROID Investigators. Effect of Very High-Intensity Statin Therapy on Regression of Coronary Atherosclerosis: The ASTEROID Trial. JAMA. 2006;295:1556-65.

2. Kannel WB, Castelli  WP, Gordon T. Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham Study. Ann Intern Med 1979 Jan;90(1):85-91.

3. Kannel WB. Range of serum cholesterol values in the population developing coronary artery disease. Am J Cardiol 1995 Sep 28;76(9):69C-77C.

4. ATP III. Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection. JAMA. 2001;285(19):2486-2497.

5. Selwyn AP. Antiatherosclerotic effects of statins: LDL versus non-LDL effects. Curr Atheroscler Rep 2007 Oct;9(4):281-85.

6. Cromwell WC, Otvos JM. Low-density lipoprotein particle number and risk for cardiovascular disease. Curr Atheroscler Rep 2004 Sep;6(5):381-87.

7. Maron DJ, Lu GP, Cai NS et al. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med 2003 Jun 23;163(12):1448-1453.

8. Baba S, Natsume M, Yasuda A et al. Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in normo- and hypercholesterolemic humans after intake of different levels of cocoa powder. J Nutr 2007 Jun;137(6):1436-1441.

9. Prospective Studies Collaboration; Lewington S, Whitlock G, Clarke R et al. Blood cholesterol and vascular mortality by age, sex and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 2007 Dec 1;370(9602):1829-39.

10. Miettinen T, Kesaniemi YA. Cholesterol absorption: reugulation of cholesterol synthesis and elimination and within-population variations of serum cholesterol levels. Am J Clin Nutr 1989:49:629-35.

11. Robins SJ, Collins D, Wittes JT et al. Relation of gemfibrozil treatment and lipid levels with major coronary events. JAMA 2001;285:1585-91.

12. Boden WE. High-density lipoprotein cholesterol as an independent risk factor in cardiovascular disease: assessing the data from Framingham to the Veterans Affairs High--Density Lipoprotein Intervention Trial. Am J Cardiol 2000 Dec 21;86(12A):19L-22L.

13. Matthan NR, Giovanni A, Schaefer EJ et al. Impact of simvastatin, niacin, and/or antioxidants on cholesterol metabolism in CAD patients with low HDL. J Lipid Res 2003 Apr;44(4):800-6.

14. Siri P, Krauss RM. Influence of dietary carbohydrate and fat on LDL and HDL particle distributions. Curr Atheroscler Rep 2005 Nov;7(6):455-59.

15. Jeppesen J, Chen YD, Zhou MY, Wang T, Reaven GM. Effect of variations in oral fat and carbohydrate load on postprandial lipemia. Am J Clin Nutr 1995 Dec;62(6):1201-5.

16. Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 2004 Apr;79(4):537-43.

17. Aggarwal BB, Shishoda S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link? Biochem Pharmacol 2006 Nov 30;72(11):1605-21.

18. Tsimikas S, Willerson JT, Ridker PM. C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol 2006 Apr 18;47(8 Suppl):C19–31.

19. St-Pierre AC, Bergeron J, Pirro M et al. Effect of plasma C-reactive protein levels in modulating the risk of coronary heart disease associated with small, dense, low-density lipoproteins in men (The Quebec Cardiovascular Study). Am J Cardiol 2003 Mar 1;91(5):555–58.

20. Deveraj S, Rogers J, Jialal I. Statins and biomarkers of inflammation. Curr Atheroscler Rep 2007 Jan;9(1):33–41.

21. Timms PM, Mannan  N, Hitman GN et al.    Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM 2002 Dec;95(12):787-96.

22. Kuvin JT, Dave DM, Sliney KA et al. Effects of extended-release niacin on lipoprotein particle size, distribution, and inflammatory markers in patients with coronary artery disease. Am J Cardiol 2006 Sep 15;98(6):743–745.

23. Vayalil PK, Mittal A, Katiyar SK. Proanthocyanidins from grape seeds inhibit expression of matrix metalloproteinases in human prostate carcinoma cells, which is associated with the inhibition of activation of MAPK and NF kappa B. Carcinogenesis. 2004 Jun;25(6):987–995.

24. Kaszkin M, Beck K, Eberhardt W, Pfeilschifter J. Unravelling green tea’s mechanisms of action: more than meets the eye. Mol Pharmacol 2004;65:15–17.

25. Oak MH, El Bedoui J, Anglard P, Schini-Kerth VB. Red wine polyphenolic compounds strongly inhibit pro-matrix metalloproteinase-2 expression and its activation in response to thrombin via direct inhibition of membrane type 1-matrix metalloproteinase in vascular smooth muscle cells. Circulation. 2004 Sep 28;110(13):1861–1867.

26. Prasad K. C-reactive protein (CRP)-lowering agents. Cardiovasc Drug Rev 2006 Spring;24(1):33–50.

27. Brown DL, Desai KK, Vakili BA, Nouneh C, Lee HM, Golub LM. Clinical and biochemical results of the metalloproteinase inhibition with subantimicrobial doses of doxycycline to prevent acute coronary syndromes (MIDAS) pilot trial. Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):733–738.

28. Selvin E, Paynter NP, Erlinger TP. The effect of weight loss on C-reactive protein: a systematic review. Arch Intern Med 2007 Jan 8;167(1):31–39.

29. Fredrikson GN, Hedblad B, Nilsson JA, Alm R, Berglund G, Nilsson J. Association between diet, lifestyle, metabolic cardiovascular risk factors, and plasma C-reactive protein levels. Metabolism 2004;53:1436-1142.