C Reactive Protein
MEDICAL RENAISSANCE GROUP
FOOD FOR THOUGHT
Biomarker and
Cardiovascular Risk Factor—What to do About
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C-Reactive Protein
by Ward Dean, MD
Inflammation is triggered
within days of tissue injury or infection, stimulating a number of systemic and
metabolic changes. One of the most dramatic changes is an increase in blood
serum levels of an inflammatory marker known as C-Reactive
Protein (CRP).1 CRP is one of a group of substances
known as "acute phase reactants." Among all acute-phase reactants,
CRP rises the fastest and is the most reliable indicator of clinical disease
and its severity (Fig. 1).2 CRP was first described in 1930 as
a protein found in the blood of patients with pneumococcal pneumonia. It was
named C-reactive protein because of its ability to react with and precipitate
the C-polysaccharide of the pneumococcus.3 In
the 1940s and 1950s, CRP was one of the most frequently requested clinical
laboratory tests for initial evaluation of patients with acute inflammation of
any origin,2 but because of the costs involved
in its measurement, its lack of quantifiability (at
that time), and the ease of measuring the Erythtroycyte
sedimentation rate (ESR—an indirect measurement of acute phase reactants), CRP
determinations fell out of favor. In recent years,
however, with the development of highly sensitive quantitative tests for CRP,
it is being used much more commonly.
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CRP in Health
and Disease
Any clinical disease characterized by tissue injury and/or inflammation is
accompanied by significant elevation of serum CRP.2 The magnitude of the CRP
elevation reflects the extent of tissue injury: more extensive lesions cause
longer periods of rising levels and higher peak concentrations.1
Causes of CRP elevations
include acute bacterial, viral and other infections, pulmonary tuberculosis, noninfectious illnesses such as rheumatic diseases
(rheumatoid arthritis, Polymyalgia Rheumatica and Giant Cell Arteritis), heart
attack, inflammatory bowel disease, and various malignant diseases. Other
causes include Systemic Lupus Erythematosus (SLE), obesity, diabetes, uremia, hypertension, physical exertion, hormone
replacement therapy, sleep disturbance, chronic fatigue, high levels of alcohol
consumption, low levels of physical activity, and even depression.1,2
CRP concentrations less
than 0.05 mg/dL are considered normal; between 0.06
and 10 mg/dL as moderate increases; and more than 10
mg/dL as marked increases. The majority of patients
with very high levels have bacterial infection, whereas more moderate degrees
of elevation are seen in most chronic inflammatory states.3 In general, CRP
values rarely exceed 6 or 8 mg/dL in patients with
chronic inflammatory states or malignancies. Concentrations
greater than this should raise the possibility of superimposed bacterial
infection. CRP levels average about 3 to 4 mg/dL
in adult rheumatoid arthritis patients with moderate disease activity.3
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CRP and
Cardiovascular Disease
Half of all heart attacks occur in people with normal
blood cholesterol levels. Atherosclerosis is now recognized to be an
inflammatory process, and CRP has been identified as one of the most significant
risk factors for cardiovascular disease and heart attacks. One large study
(28,263 healthy postmenopausal women) assessed the significance of twelve serum
markers of cardiovascular risk over a period of three years. The scientists
found that of the 12 measures, CRP levels were the most powerful risk predictor
of subsequent heart attacks. Of the lipid variables, the ratio of total
cholesterol to HDL cholesterol and Apolipoprotein B-100 were the most powerful
predictors. Homocysteine was also associated with
increased risk. [Fibrinogen, a major risk factor, was inexplicably not
investigated in this study]. Four markers of inflammation were found to be
significant predictors of the risk of future heart attacks — CRP, Serum Amyloid
A, interleukin 6, and sICAM-1 (Soluble Intracellular Adhesion Molecule type 1).
However, CRP was the strongest and most significant predictor (Fig. 2).4
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In another study, patients
with unstable angina were followed for one year post-diagnosis. Sixty-nine
percent of the patients with elevated CRP suffered a heart attack within one
year. Conversely, there were significantly fewer heart attacks and increased
survival in the group with CRP levels less than 0.3 mg/dL
(Figures 3 and 4).5
In a year-long study of
patients with stable angina who had undergone coronary artery stenting, those with the highest levels of CRP had the
shortest survival time (Fig. 5).
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CRP to
Monitor Disease and as a Biomarker of Aging
Serial determinations of CRP have been recommended as the best single means of
monitoring postoperative recovery and to follow the course of disease.2 It is probably of greatest value in following patients
being treated for chronic inflammatory diseases.3 In recent years, aging has been recognized as the ultimate chronic
inflammatory disease.
Lowering CRP
Not only does CRP rise as a result of inflammatory processes, but it now has
been found to promote inflammation and contribute to the pathogenesis of
coronary artery disease, as well.6,7 Thus, not only is it important to treat the
underlying disease process to reduce CRP, but it is important to reduce CRP to
prevent and speed recovery from the disease. A number of substances have been
shown to effectively reduce C reactive protein, from whatever cause.
Statins/Red Yeast Rice Extract
Statin drugs and Red Yeast
Rice Extract, the natural prototype of statins, have
been found to significantly reduce CRP. In one long-term (5 year) study,
treatment with the statin drug Pravastatin
resulted in an overall 38% reduction in mean CRP levels, and a 54% reduction in
coronary artery disease.8
Vitamin E
Researchers at
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Vitamin B6
Scientists from the USDA Human Nutrition Research Center
on Aging at Tufts University in Boston reported that low levels of vitamin B6
are associated with higher levels of C-Reactive Protein (and vice-versa).10
Aspirin
In the Physician's Health Study, men who regularly used aspirin had a 44% lower
incidence of heart attacks. Significantly, the benefit was highest in those
with the highest CRP.11 Thus, the
anti-inflammatory properties of aspirin may contribute to its efficacy in
preventing cardiovascular disease.5
Gugulipid
In a recent article in the Journal of the American Medical Association, it was
found that gugulipid resulted in significant
reduction of total cholesterol in only 20% of the people who took it.12 The article appeared to be a "take-out" piece
designed to discredit any purported benefits of this nutrient. However, buried
in the data was the fact that gugulipid consumption
resulted in an overall lowering of CRP of nearly 30 percent! This article was
recently reviewed in VR News.13
Proteolytic
Enzymes
Anti-inflammatory proteolytic enzymes, like those contained in VRP’s UniZyme formula, have been
shown effective in reducing CRP levels. In one double-blinded study, German
researchers treated patients with proteolytic enzymes prior to dental surgery,
and post-operatively for several days. By the third day after surgery, CRP
levels were 300% higher in the placebo group compared to those treated with the
proteolytic enzymes.15
Conclusion
Other anti-inflammatory substances, such as the herbs,
Turmeric and Boswellia, and fish oil, have all been
reported to have dramatic CRP-lowering properties. In any condition
characterized by an elevation of CRP, measures to ameliorate the disease and
lower CRP should be used simultaneously. The higher the level of CRP, the more
aggressively the treatment program should be implemented. It is likely that the
most effective results will be obtained from a combination approach.
References
1. Kushner,
2.
3. Kushner, I. The acute-phase response in humans.
Whys is it important? Internal Medicine for the Specialist, 1988, 9: 5, 59-65.
4. Ridker, P., Hennekens,
C., Buring, J., and Rifai,
N. C-Reactive Protein and other markers of inflammation in the prediction of
cardiovascular disease in women.
5. Patel, V., Robbins, M. and Topol, E. C-reactive
protein: A "Golden Marker" for inflammation and coronary artery
disease.
6. Kushner,
7. Pasceri, V., Willerson,
J., Yeh, E. Direct proinflammatory
effect of C reactive protein on human endothelial cells. Circulation, 2000,
102:2165-2168.
8. Ridker, P., Rifai, N., Pfefer, M., Sacks, F., Braunwald,
E. Long term effects of pravastatin on plasma
concentration of C-reactive protein. Circulation, 1999, 100: 230-235.
9. Devaraj, S., and Jialal,
I. Alpha tocopherol supplementation decreases serum C-Reactive Protein and
Monocyte interleukin 6 levels in normal volunteers and type 2 diabetic
patients. Free Radical Biology and Medicine, 2000, 29: 8, 790-792.
10. Friso, S., Jacques, P.,
11. Ridker, P., Cushman, M., Stampfer,
M.,
12. Szapary PO, Wolfe ML, Bloedon
LT, Cucchiara AJ, DerMarderosian
AH, Cirigliano MD, Rader DJ. Guggulipid
for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA. 2003 Aug 13;290(6):765-72.
13. Dean, W. Guggulipid ineffective as lipid-lowering
agent? Vitamin Research News, 2003,
14. Tomassi, S., Carluccio,
E., and Bentifoglio, M, et al. C reactive protein as
a marker for cardiac ischemic events in the year after a first, uncomplicated
myocardial infarction. Am J. Cardiol,
1999, 83: 1595-1599.
15. Cichoke A. Enzymes hasten pain relief. Nutrition Science News. Feb. 2001.
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