|
LE Magazine December 2002
C-Reactive Protein
A better diagnostic tool than cholesterol
for predicting cardiovascular disease risk
Mainstream medicine has adopted
cholesterol-lowering therapies as its first-line defense
against heart attack. Millions of people swallow drugs each
day to keep their cholesterol low, and drug companies continue
to campaign aggressively to get more people to take these
medications. A review of the scientific evidence, however,
shows that measurements of an inflammatory marker in the blood
called C-reactive protein can yield better diagnostic
information than measurements of cholesterol. The C-reactive
protein test is inexpensive and simple, but most physicians
don’t yet perform it. When doctors for George W. Bush
measured his C-reactive protein levels, they had to consult
with a research team to find out how to analyze his
results![1]
A chronic inflammatory state, as
evidenced by elevated C-reactive protein, results in
significant damage to the arterial system.
A series of landmark studies by Paul Ridker, M.D. and
colleagues indicates that 25 to 35 million Americans have
total cholesterol within normal range but above-average levels
of inflammation within their cardiovascular systems, and that
this inflammation has significant impact on heart disease
risk.[2-5] The Women’s Health
Study, which involved 39,876 healthy postmenopausal women,
supports the C-reactive protein link to cardiovascular
disease.[6] Those with the highest
levels of C-reactive protein had five times the risk of
developing cardiovascular disease and seven times the risk of
having a heart attack or stroke compared to subjects with the
lowest levels. C-reactive protein levels predicted risk of
these events even in women who appeared to have no other
pertinent risk factors.
The Physicians’ Health Study, which evaluated
C-reactive protein levels and heart disease risk in 22,000
initially healthy men, also supports the relationship between
inflammation and heart attack.[7]
Inflammation may explain why women taking Premarin have
slightly increased risk of heart attack; Premarin causes
C-reactive protein levels to climb.[8] Data from the Framingham cohort
correlated high C-reactive protein with calcification of the
coronary arteries.[9]
Research on C-reactive protein indicates that
cholesterol-filled plaques in blood vessels may not pose any
real danger unless they are affected by inflammation.
Inflammation weakens plaques, making them more vulnerable to
bursting or pinching off a clot that can then block coronary
vessels.[10-13]
|
AN
INFLAMMATION PRIMER
Inflammation is an immune response that occurs after
infection or injury. It involves a series of biological
actions that leads to the development of redness, heat
and swelling. All of these elements are created by the
activity of immune cells working to break down injured
and dying tissues so that new, healthy ones can replace
them. When you suffer a painful bump after hitting your
head, that’s inflammation at work. When you develop
a fever in response to an infection, you’re
experiencing a form of full-body inflammation that
creates an inhospitable environment for multiplying
pathogens. A boil is a highly localized inflammation,
while a sunburn is an inflammation that can cover large
areas of skin.
In any case, inflammation involves a delicate
balance: if the body’s inflammatory response is too
intense, harm can come to otherwise healthy tissues. The
production of C-reactive protein is an essential part of
the inflammatory process, and the measurement of this
substance reflects the level of inflammatory activity
deep within the body. It appears that certain conditions
create a state of excessive inflammation within the
circulatory system. High C-reactive protein levels are
evidence of this type of inflammation.
 Inflammation accelerates the production of
free radicals. When inflammation is limited, free
radicals can be controlled by antioxidant defenses; in
fact, the free radicals help the body get rid of
pathogens and make way for healing. But when
inflammation is chronic or intense, free radicals can do
more harm than good. They can do significant damage to
tissues and set in motion harmful chain reactions.
Allergies, asthma, eczema, autoimmune disease and
some types of arthritis are chronic forms of low-grade
inflammation. The immune system mounts defenses that go
beyond what is necessary, reaching an elevated plateau
where inflammation becomes damaging to otherwise healthy
tissues.
|
|
What is the source of this inflammation? Researchers have a
few different theories. Some posit that plaques are actually
an attempt on the part of the immune system to repair some
sort of damage to vessel walls. According to this theory, the
inflammation arises as the body sends immune factors to the
damaged area. Other theories implicate pathogens, including
Chlamydia pneumoniae and the ulcer-causing Helicobacter
pylori. Some research has indicated that people who are
seropositive for these pathogens are at significantly elevated
risk of a cardiac event,[14,15]
and that this may be due to a state of chronic, low-level
inflammation spurred by the continued presence of the
bacteria.
Well-established cardiac risk factors such as obesity,
smoking, hypertension and chronic periodontal disease all
increase inflammation and C-reactive protein levels in the
body. Fat cells literally pump out C-reactive protein, which
could explain why being overweight is so bad for the
heart.[16]
The real diet-heart connection
The so-called low-fat, low-cholesterol “heart-healthy
diet” may actually end up promoting inflammation.
Although a diet of whole foods that includes plenty of
vegetables and fruits will not have this effect, the average
American’s low-fat diet rarely fits this description.
Diets low in foods that supply omega-3 fatty acids and high in
refined grains and other processed foods usually supply fat in
the form of polyunsaturated vegetable oils and hydrogenated
oils. This dietary profile creates an imbalance of essential
fats in the body, with the intake of omega-6 oils and
hydrogenated oils far exceeding the intake of omega-3
fats.
|
Alzheimer’s, Diabetes and
C-Reactive Protein
Inflammatory processes have also been implicated in
Alzheimer’s disease. Subjects enrolled in the
Honolulu-Asia Aging Study were three times more likely
to develop Alzheimer’s during a 25-year follow-up
if they were in the highest quartile of C-reactive
protein levels (compared with those in the bottom
quartile). A correlation was evident: the more
C-reactive protein subjects had at the start, the higher
their risk of developing Alzheimer’s disease.*
Diabetics have elevated markers of deep inflammation.
Research by Dr. Ridker and colleagues have provided
support for a common inflammatory basis of these two
diseases — illnesses that often strike in the same
individuals.**
* Schmidt R, Early inflammation and
dementia: a 25-year follow-up of the Honolulu-Asia Aging
Study, Ann Neurol 2002 Aug;52(2):168-74.
** Pradhan AD, Ridker PM, Do atherosclerosis and type 2
diabetes share a common inflammatory basis? Eur Heart J
2002 Jun;23(11):831-4.
|
|
Omega-3 and omega-6 fats are the raw materials from which
eicosanoids, hormonelike substances with multiple effects on
body systems, are made. One of the most important duties of
eicosanoids is to regulate inflammation, and their manufacture
depends upon the supply of fats in the diet. When the
appropriate balance of omega-6 to omega-3 is consumed,[17] inflammation is kept in check,
occurring when necessary to heal the body but rarely getting
out of hand. With a diet high in omega-6 vegetable fats and
low in omega-3 fats, eicosanoid production shifts accordingly.
The end result is greater inflammation. An excess of saturated
fats from meats and dairy products also encourages
pro-inflammatory eicosanoid production.
C-reactive protein control
If you are forty years old or older, insist that your
doctor prescribe a C-reactive protein test for you the next
time you have your cholesterol measured.
Some members of the research community have suggested that
statin drugs—the drugs of choice for cholesterol
reduction—may prevent heart disease not because of their
effects on cholesterol, but because they have
anti-inflammatory activity. This helps to explain why statins
have been found to protect the heart regardless of their
effects on cholesterol levels.[18,19]
Aspirin, too, has consistently been found to lower the risk
of heart attack. The inflammation-heart disease connection
could explain this effect, rather than the blood-thinning
(anti-platelet) effect to which this decrease in risk has been
attributed. Some evidence indicates that ibuprofen may also
provide protection against elevated C-reactive protein and the
damage it can do.[20]
Vitamin E’s ability to protect against heart disease
has also been attributed to its blood-thinning effects, but
recent research has shown that it lowers C-reactive protein
levels considerably.[21,22]
Low levels of the steroid hormone DHEA have been correlated
with increased C-reactive protein levels in rheumatoid
arthritis (RA) patients. A ketogenic (low-glycemic) diet and
fasting both lowered C-reactive protein levels, raised DHEA
levels, and improved symptom states in people with RA.[23] Although more research is needed on
this topic, the prudent use of DHEA replacement seems to be a
promising avenue in heart disease prevention.
An anti-inflammatory diet includes abundant fresh
vegetables and fruits, small servings of whole grains and
protein from fish (especially salmon, mackerel, cod, sardines
and other deep-sea-dwelling species). Pumpkin seeds, walnuts
and flaxseeds are excellent sources of omega-3 fats. Ground
flaxseeds can be added to whole grains or sprinkled onto
salads to augment omega-3 intake. Avoid corn, soy and
cottonseed oils, especially those that have been hydrogenated.
Instead, use olive or canola oil when added fats are called
for. You can also use butter, but do so moderately.
One of the best ways to control inflammation is to take
fish oil supplements daily. Fish oil supplements should
contain both DHA (docosahexaenoic acid) and EPA
(eicosapentaenoic acid). A recent study[24] found that three grams of fish oil
a day was heart-protective. Antioxidant supplements help to
control free radicals produced by inflammation.
References
1. “Researchers find a new enemy of
the heart,” CNN.com news, August 4, 2002.
2. Rifai N, Ridker PM, Inflammatory markers and coronary
heart disease. Curr Opin Lipidol 2002
Aug;13(4):383-9.
3. Albert CM, et al, Prospective study of C-reactive protein,
homocysteine, and plasma lipid levels as predictors of sudden
cardiac death. Circulation 2002 Jun 4;105
(22):2595-9.
4. Bermudez EA, Ridker PM, C-reactive protein, statins, and
the primary prevention of atherosclerotic cardiovascular
disease. Prev Cardiol 2002 Winter;5(1):42-6.
5. Blake GJ, Ridker PM, Inflammatory mechanisms in
atherosclerosis: from laboratory evidence to clinical
application. Ital Heart J 2001
Nov;2(11):796-800.
6. Pradhan AD, et al, Inflammatory biomarkers, hormone
replacement therapy, and incident coronary heart disease:
prospective analysis from the Women’s Health Initiative
observational study. JAMA 2002 Aug
28;288(8):980-7.
7. Ridker PM, et al, Inflammation, aspirin, and the risk of
cardiovascular disease in apparently healthy men.
NEJM 1997 Apr 3;336(14):973-9.
8. Decensi A, et al, Effect of transdermal estradiol and oral
conjugated estrogen on C-reactive protein in retinoid-placebo
trial in healthy women. Circulation 2002 Sep
;106(10):1224-8.
9. Wang TJ, et al, C-reactive protein is associated with
subclinical epicardial coronary calcification in men and
women: the Framingham Heart Study. Circulation 2002
Sep 3;106(10):1189-91.
10. Rifai N, et al, C-reactive protein and coronary heart
disease. Cardiovasc Toxicol 2001;1(2):153-7.
11. Jialal I, Devaraj S, Inflammation and atherosclerosis:
the value of the high-sensitivity C-reactive protein assay as
a risk marker. Am J Clin Pathol 2001 Dec;116
Suppl:S108-15.
12. Zairis M, et al, C-reactive protein and multiple complex
coronary artery plaques in patients with primary unstable
angina. Atherosclerosis 2002 Oct;164(2):355.
13. Lowe GD, The relationship between infection,
inflammation, and cardiovascular disease: an overview. Ann
Peridontol 2001 Dec;6(1):1-8.
14. Davydov L, Cheng JW, The association of infection and
coronary artery disease: an update. Expert Opin Investig
Drugs 2000 Nov;9(11):2505-17.
15. Stone AF, et al, Effect of treatment for Chlamydia
pneumoniae and Helicobacter pylori on markers of inflammation
and cardiac events in patients with acute coronary syndromes:
South Thames Trial of Antibiotics in Myocardial Infarction and
Unstable Angina (STAMINA). Circulation 2002 Sep
3;106(10):1219-23.
16. Ramsay JE, Maternal obesity is associated with
dysregulation of metabolic, vascular, and inflammatory
pathways. J Clin Endocrinol Metab 2002
Sep;87(9):4231-7.
17. Schmidt MA, Smart Fats: How Dietary Fats and Oils Affect
Mental, Physical, and Emotional Intelligence, Frog, Ltd.,
Berkeley, CA:1997.
18. Kaplan RC, Frishman WH, Systemic inflammation as a
cardiovascular disease risk factor and as a potential target
for drug therapy. Heart Dis 2001
Sep-Oct;3(5):326-32.
19. Blake GJ, Ridker PM, Kuntz KM, Projected life-expectancy
gains with statin therapy for individuals with elevated
C-reactive protein levels. J Am Coll Cardiol 2002 Jul
3;40(1):49-55.
20. Ibuprofen enhances antioxidants and suppresses C-reactive
protein. Life Extension Magazine February 2001.
21. Devaraj S, Jialal I, Alpha tocopherol supplementation
decreases serum C-reactive protein and monocyte interleukin-6
levels in normal volunteers and type 2 diabetic patients.
Free Radic Biol Med 2000 Oct 15;29(8):790-2.
22. Patrick L, Uzick M, Cardiovascular disease: C-reactive
protein and the inflammatory disease paradigm: HMG-CoA
reductase inhibitors, alpha-tocopherol, red yeast rice, and
olive oil polyphenols. A review of the literature. Altern
Med Rev 2001 Jun;6(3):248-71.
23. Fraser DA, et al, Serum levels of interleukin-6 and
dehydroepiandrosterone sulphate in response to either fasting
or a ketogenic diet in rheumatoid arthritis patients. Clin
Exp Rheumatol 2000 May-Jun;18(3):357-62.
24. Nestel P, et al, The n-3 fatty acids eicosapentaenoid
acid and docosahexaenoic acid increase systemic arterial
compliance in humans. Am J Clin Nutr 2002
Aug;76(2):326-30.
Back to
the Magazine Forum
|