Free Shipping on All Orders $75 Or More!

Your Trusted Brand for Over 35 Years

Life Extension Magazine

<< Back to August 2009

Understanding Risk Factors for Heart Disease

Part I: Lipids and C-Reactive Protein

August 2009

By Dr. William Davis

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.