"We have to think of heart disease as an inflammatory disease, just as we think of rheumatoid arthritis as an inflammatory disease."
C-Reactive Protein:
The Track Your Plaque Perspective
We met Phyllis because her husband, Dick, had undergone two prior bypass operations and was seeking an opinion regarding why his disease kept progressing. Although Dick was too far along to engage in the usual Track Your Plaque approach (since his disease was no longer "scorable" due to bypass operations), we believed that he could still benefit from our preventive approach. We proceeded to uncover small LDL particles, low HDL, and lipoprotein(a), among a few other lesser patterns. As Dick became angina-free (chest pain-free) for the first time in years and the causes behind his heart disease came under control for the first time in his life, Phyllis decided it was time for her to explore her own heart health with a CT heart scan.
Phyllis' CT heart scan score: 598. At age 63, this put her well into the 99th percentile (a score in the worst 1% of women in her age group). Phyllis was shocked: her standard cholesterol panel had been near-perfect for years, including HDL cholesterol of 80 mg/dl. We dug deeper. Phyllis proved to have:
* Moderate excess small LDL particles (45% of total LDL)
* Moderate intermediate-density lipoprotein (IDL)
* Severe vitamin D3 deficiency with 25-OH-vitamin D3 of 14 ng/ml (in September)
* C-reactive protein (CRP) elevated at 8.9 mg/l
We surmised that inflammation, as evidenced by the dramatically elevated CRP, was a major factor behind Phyllis' substantial degree of coronary plaque, along with the modest lipoprotein abnormalities and severe vitamin D3 deficiency. We decided that reduction of CRP would be a priority for Phyllis.
C-reactive protein (CRP) is another blood test that many hope will improve the power to predict whether heart attack is in your future.
"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?
Keep in mind that the majority of physicians and the public have not yet gained an understanding of CT heart scans and the superior information they provide. Instead, many cling to the notion that "risk factors" like cholesterol can be used to predict future heart disease.
Cholesterol is an obvious failure to reliably predict future heart attack. While in large groups (thousands of people), cholesterol values (LDL cholesterol, HDL cholesterol, triglycerides, and the least helpful of all, total cholesterol) do indeed predict a spectrum of risk, when applied to a specific individual, it falls apart utterly. Only at extremes do cholesterol values predict the future with any sort of reliability. Very high LDL cholesterol, for instance, of 225 mg/dl, does predict increased risk. So does a very low HDL of, say, 26 mg/dl.
But let's say a person has the sort of average values shared by most of us: LDL 140 mg/dl, HDL 44 mg/dl, triglycerides 150 mg/dl, total cholesterol 214 mg/dl. Does this person have heart disease? Will they have a heart attack in the next year, 2 years, 5 years, 10 years?
The answer is that you cannot reliably predict the future with cholesterol values. So, CRP has emerged as another test, another "risk factor," that some advocate adding to conventional cholesterol values to yield a clearer glimpse into the future.
But those of us following the Track Your Plaque program already know that it's not risk factors we're looking for. We already know what heart attack risk is based on our CT heart scan scores, a reliable measure of the disease itself, coronary atherosclerosis. Why add another risk measure?
First of all, what is CRP?
CRP is nothing more than a blood protein expressed 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, usually to high levels. Inflammatory responses increase blood levels of the signaling molecule, interleukin–6 (IL–6) which, in turn, triggers the liver to increase CRP production for release into the blood. Although its exact function in the body is unknown, the blood concentration of CRP does seem to parallel the degree of inflammation.
Over the past decade it has been recognized that people who feel well and lack any obvious or perceptible source of inflammation may have modest elevations of CRP, so low it was previously felt to fall within the normal range. CRP at these low levels appears to add to the power of cholesterol values to predict whether or not you're at increased risk for heart attack (Everett BM et al 2006; Tsimikas S et al 2006).
A high C-reactive protein (>0.5 mg/l) suggests that inflammation may be a contributor to growth of coronary atherosclerotic plaque. It can also act as a trigger for heart attack. Inflammation is the fuel for the fire that leads to coronary plaque rupture, the event that results in heart attack. Inflammation also drives other conditions like diabetes, cancer, and arthritis. While very high C-reactive protein levels >10 mg/l nearly always represent inflammation outside of the heart (e.g., arthritis) 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.
Dr. Paul Ridker of Harvard University, the nation's authority on CRP, has shown that high CRP levels (of 3 mg/l) increase heart attack risk 3-fold, even when LDL cholesterol is low (Everett BM et al 2006; Tsimikas S et al 2006). When elevated CRP occurs in the company of small LDL particles, heart attack risk is 7-fold greater (St-Pierre AC et al 2003).
Studies are also now beginning to emerge suggesting that reducing CRP also yields a reduction in likelihood of heart attack, though the great bulk of this treatment experience is focused on the application of statin drugs (Willerson JT et al 2004).
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% (Deveraj S et al 2007). This is simply not true: there are many ways to reduce CRP as well as, or even more effectively, than the statin drugs. In the Track Your Plaque experience, we commonly see CRP drop dramatically, usually back to the perfectly normal range of =0.5 mg/l, with strategies listed below—whether or not a statin drug was part of the treatment picture.
How to Reduce CRP
Here are approaches to consider that reduce CRP and thereby help remove inflammation as a contributor to your risk for heart disease:
The way you live and eat can reduce inflammation:
* 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 (Selvin E et al 2007). 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 (Fredrikson GN et al 2004). An ideal level is no more than 10 mg/day.
* Choose low-glycemic index foods like lean proteins (egg whites or free-range eggs, lean red meats, baked skinless chicken and turkey, fish), 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 (Fredrikson GN et al 2004).
* Exercise leads to a modest reduction in inflammation; the longer the better (Kelley GA et al 2006).
Nutritional supplements that reduce inflammation:
* 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. We advocate a minimum dose of 4000 mg per day (to provide 1200 mg of the omega-3 fatty acids EPA + DHA), usually taken as two capsules twice a day with meals. CRP reductions of approximately 30% are generally achieved (Ciubotaru I et al 2003).
* Flavonoids are yielding a cornucopia of factors that hold potential for suppressing inflammation. Though the ideal combination most beneficial to humans is still being sorted out, it's still worth including plenty of flavonoid-rich foods in your daily food choices, such as deeply-colored fruits (citrus, blueberries, raspberries, plums, pomegranates, etc.) and vegetables (spinach, dark lettuces, green peppers, red peppers, etc.), red wine (southern French and Italian wines are the most plentiful sources), cocoa (dark chocolate), and green tea (Vayalil PK et al 2004; Kaszkin M et al 2004; Oak MH et al 2004; Tate P et al 2004).
* Vitamin D—Most of us are deprived of sun exposure, particularly if you live in a northern climate or work indoors. Sun activates vitamin D in the skin. At least 70% of Americans are substantially deficient in vitamin D. Supplementation can be among the most potent anti-inflammatory strategies available, reducing CRP dramatically. We start at daily doses of 1000–2000 units and frequently use 4000–6000 units per day, particularly when there's little sun exposure. (Note that these doses are much higher than the RDA of 300 units for women, 400 units for men, which was retracted by the Food and Nutrition Board.) Some people require much higher doses, especially in winter; dose is best judged by obtaining a blood level of 25-OH-vitamin D3 to gauge the extent of deficiency (Timms PM et al).
* Fibers—Healthy fibers, particularly raw almonds, walnuts, oat bran, wheat germ, ground flaxseed, and green vegetable sources, are easy and powerful suppressors of inflammation (Jenkins DJ et al 2005).
Drugs that lower inflammation
* Statin cholesterol drugs—Statin drugs are indeed an effective means to reduce C-reactive protein 30–50% over several months. Lipitor™ appears to be the stand-out for this effect when compared to other statins. The non-statin cholesterol-reducing drug, Ezetimibe (Zetia?), also reduces CRP modestly (Deveraj S et al 2007).
* Niacin—Doses of 1000 mg or higher (which should be used with medical supervision) reduces CRP 15–20%, in addition to raising HDL, reducing triglycerides, and reducing undesirable small LDL particles (Kuvin JT et al 2006). SloNiacin (Upsher Smith) is our preferred form, available over-the-counter in pharmacies.
* Doxycycline—this antibiotic can be used at low doses (too low to treat infections except gingivitis) to suppress an important class of atherosclerotic plaque enzymes, called matrix metalloproteinases, that provoke plaque rupture. It also lowers C-reactive protein significantly. 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 (Brown DL et al 2004). (A prescription is required.)
* A number of other prescription drugs reduce CRP: 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.). These tend to be modest effects.
* Aspirin— lowers C-reactive protein modestly, usually no more than 15% (Prasad K et al 2006).
Lifestyle strategies and supplements, particularly fish oil and vitamin D, are the cornerstones of your nutritional supplements to reduce inflammation. Correction of metabolic syndrome (low HDL, high triglycerides, high blood pressure, borderline or high blood sugar) is crucial. CRP will remain elevated unless the metabolic syndrome is eliminated. Correcting lipid and lipoprotein abnormalities will usually reduce inflammation and CRP significantly, usually to the normal range. You and your doctor should resort to medication only after a good try fails to fully suppress inflammation, usually gauged by a persistently elevated C-reactive protein. Here's a suggested starting regimen:
* Weight loss to ideal weight.
* Reduction in saturated fats, processed carbohydrates (especially wheat products), and increased use of fiber-rich foods, especially oat products, ground flaxseed, and raw nuts.
* Fish oil 4000 mg per day to provide 1200 mg of omega-3 fatty acids, EPA and DHA
* Vitamin D 1000–2000 units per day, if sun-deprived; more if blood level of 25-OH-vitamin D3 suggests a higher dose is necessary, as advised by your doctor.
References:
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Ciubotaru I, Lee YS, Wander RC. Dietary fish oil decreases C-reactive protein, interleukin-6, and triacylglycerol to HDL-cholesterol ratio in postmenopausal women on HRT. J Nutr Biochem 2003;14:513-521.
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