C-reactive protein, serum
April 2003 NewsPath letter to our doctors, about false
If you use hs-CRP as a cardiac risk screening test, there is enough
natural variability of the level day-to-day that one should never
decide a risk status based upon just one result. Do at least 2
tests and average the results9. It is a stable molecule. Low-risk is less
than 1.0 mg/L; intermediate is between 1.0-3.0; and high risk is
greater than 3.09. Some consider 0.4 to be the
upper limit of "normal"10. The hr-CRP is reliable up to as high as 15 mg/L17.
At LMC, the CRP became a 3 shifts per day, 7 days per week in March 2008. C-reactive protein (CRP) is the first of the "acute
phase reactant" proteins to increase during states of acute
inflammation. A high or increasing amount of CRP in your blood suggests that you have an acute infection or inflammation (to include inflammed, sterile tumor necrosis or gouty pyoarthrosis [L08-12261]). That patients have high CRP during "attacks" of familial Mediterranian fever (FMF) further assures that elevations do not implicate bacterial infections...they implicate inflammatory reactions that contain polys. If the CRP level in your blood drops, it means that you are getting better and inflammation is being reduced. For uncertain reasons, CRP levels can be elevated in the later stages of pregnancy as well as with use of birth control pills or hormone replacement therapy (i.e., estrogen). Higher levels of CRP have also been observed in the obese.
Sepsis & CRP vs. procalcitonin: CRP is said to take 12-24 hours to rise following acute septic assault, whereas
procalcitonin (ProCT; PCT) is said to start rising within 2-4 hours15. A production of CRP stays up about 3-7 days after the infection is cured before it normalizes,
whereas ProCT normalizes quicker due to half life of only 24 hours15. Probably our support of neonatal sepsis management is
already optimal. Our adult ID internists are not interested in this test, and the neonatologists are satisfied with our
availability of STAT placenta exams (to include frozen sections of formalin-fixed tissue, if truly needed).
But, in early 2011, our emergency room doctors rquested the test; and we will have begun this test for them March 7th, 2011.
CRP is exclusively produced in the liver. In this
context of "rule in or rule out infection", less than 8 mg/L is considered "normal".
CRP elevation is thought to correlate with endothelial dysfunction6.
The plasma level can double every 8 hours, peaking in 50 hours;
upon removal of the stimulus, CRP drops rapidly, having a 5-7 hour
half life1. In the post-shock (trauma, sepsis,
etc.) period, the body swings into a catabolic phase and makes
acute phase reactants at the expense of such proteins as prealbumin
and albumin7. A sarcoidosis study normal
control group ranged in CRP levels from 3.7-5.9 mg/L13.
More recently, related to theories that CRP is a
surrogate reflector of the inflammatory component of the
pathogenesis of coronary artery obstructive/stenotic lesions, it
has been noted that screening risk of future initial acute myocardial
infarction (AMI) is increased in persons with sustained levels
of CRP above 2.0 mg/L. This "cardio-CRP" screen (CRP-H...high-sensitivity
CRP...hs-CRP, detect down to about 0.1 mg/L) should, like lipid
profiles, be done only during periods of good health, free from
any recent minor or major illnesses. NOTE: tests at different times
in the same non-sick person may vary by about 30%4 or
more10; so, as with cholesterol screening, it
is best to test your hs-CRP no less than on two, separate healthy
occasions. Aspirin, although having anti-inflammatory properties,
does not lower hs-CRP10.
Some (clinical chemist, Nader Rifai, of Harvard)
feel that hs-CRP is the single best predictor of future cardiovascular
disease risk (those with CRP levels in the upper 25% are 3 times
as likely to suffer a heart attack6). Sustained
elevations are also predictive of increased stroke and peripheral
vascular disease risk; and increased levels may predict increased risk of hip fracture in elderly women14. Post-stroke elevations should decrease to baseline within 3-6 months following a cerebral infarct & the inflammatory organization of the infarcted brain matter; failure to normalize suggests an underlying inflammatory process18.
In healthy adults, 75% of hs-CRP values
are < 0.32 mg/L3. The median normal concentration
of CRP is 0.8 mg/L, with 90% of apparently healthy individuals
having a value less than 3 mg/L and 99% less than 12 mg/L1.
Our lab's "normal" is <0.2 mg/dl (2 mg/L), but there
is significant personal day-to-day variation (and note 2nd paragraph,
And, different methodology in different labs will
likely not relate exactly to published quintile and quartile
risk categorization should be viewed somewhat loosely. AHA/CDC
2003 state divides into tertiles & says <1 mg/L is "low
risk", 1-3 mg/L is "moderate risk", and >3
mg/L is "high risk"9; these are the ranges
reported in our lab.
In situations (such as colonic diverticulosis) which have had a pyogenic complication adequately & conservatively managed, one can determine that patient's baseline CRP when patient is perfectly well. Then if suspect symptoms begin, a significantly elevated CRP would suggest prompt re-institution of conservative management, again.
CRP level below normal: consider protein calorie malnutrion (PCM).
Situations with CRP Within Normal Range:
lowest cardio-risk quintile (quintile #1)
is < 0.55 mg/L (or 0.1-0.6)...(low risk)
low-mid (low) cardio-risk (quintile #2)
is 0.55-0.99 mg/L (or 0.7-1.1)...(low risk)
mid-high (moderate) cardio-risk (quintile#3)
is 1.0-2.1 (or 1.2-1.9) mg/L...(intermediate risk)
is recommended as an additional screening
test for CVD in those at intermediate risk (10-20% risk of
attack of CVD in the next 10 years [calculate
by clicking on "health tools", then "risk
assessment"]) to decide additional diagnostic
assessment (imaging...exercise testing) or therapeutic intervention
(lipid-lowering, antiplatelet, cardioprotective agents)9.
even such smoldering important but non-acutely
threatening active chronic infections as gingivitis, periodontitis, or localized peri-apical bone inflammation
can cause elevations into one of the higher quintiles.
a normal CRP is highly unlikely in the face of
a significantly acutely threatening bacterial infection1.
in evaluating a patient with "fever and
night sweats", the signs and symptoms are almost certainly
NOT due to hidden infection when CRP is in normal range (therefore,
symptoms & signs could be due to malignant lymphoma).
may be normal in both temporal arteritis and
detecting supervening infection after "clean" surgery:
a potentially valuable marker to serially follow after surgery...in
search of early detection of postoperative, initially occult
(hidden) infection. Clean CRP pattern: begin increase from
baseline in 4-6 hours postop & peaks at (usually to intermediate
elevations) 48-72 hours, begins to decrease after 72 hours
and back near baseline by 5th-7th postop day5.
if serum CRP is not elevated, a failed joint prothesis is unlikely due to sepsis [HERE].
stable or even progressing, mild sarcoidosis
can have CRP less than 8...but very likely above 5...and sarcoidosis
unlikely if below 5 mg/L13.
Situations with CRP Elevations:
with cardio-risk screening in mind, values greater
than 15 mg/L suggest that the screening effort is confounded by
false positive situations (see link above) or recent
or acute inflammatory disease beyond what could be expected
related to coronary artery disease6; post-shock
(trauma, sepsis) catabolic phase can highly elevate CRP7
those with troponin-normal cardiac events who
have hs-CRP >3 mg/L at discharge have increased risk of
major event within the next 3 months and, if >5 mg/L on
admission, an increased risk of a major event on out for 6
hi-risk cardio-risk (quintile #4) is 2.0-3.8
mg/L...(high risk if greater than 3.09)
highest cardio-risk zone (quintile #5),
is from 3.9-15 mg/L...(high risk9)..."high
risk" levels reflect 4-7x normal risk10.
even such smoldering important but non-acutely
threatening active chronic infections as gingivitis/periodontitis,
chronic prostatitis , chronic gastritis, chronic bronchitis,
and urinary tract infections can cause elevations into one
of the higher quintiles9.
hs-CRP predicts a future stroke, AMI, or
PVD event in males & females, smokers & nonsmokers,
when in the highest quartile at a relative risk over "normals" of
2-fold, 3-fold, and 4-fold, respectively.
usually elevated in temporal arteritis
hs-CRP joined with TC:HDL-C ratio gives strongest
estrogen replacement therapy (HRT or ERT) increases
CRP level6; vitamin B6 deficiency will
cause CRP "elevations" (probably meaning as to cardio-risk
quintiles); elevated blood pressure, elevated BMI (obesity)[calculate
your BMI], cigarette smoking, "metabolic syndrome12" (see
below), diabetes mellitus, low HDL/high triglyceride lipid
profile, estrogen/progesterone hormone use, and chronic inflammatory
conditions (such as rheumatoid arthritis) all can innately cause elevations
of hs-CRP in the absence of inflammation9.
minor elevations1: SLE, scleroderma
(systemic sclerosis), dermatomyositis, ulcerative colitis,
leukemia, GVHD (graft vs. host disease)
major serum/plasma elevations:1
||due to RF, HAMA, etc.
||CSF CRP reported to increase in bacterial, not
|hypersensitivity complications of infections
juvenile chronic arthritis
Mediterranean fever (FMF)
urate pyarthrosis [L08-12261]
necrotizing glial tumor [L08-12261]
||kidney & marrow (not heart)5
|malignant but not benign tumors5
||carcinoma (breast, lung, GI)5
||acute myocardial infarction (AMI)
bacterial vs. viral infection: a very high level
(>100 mg/L) more likely bacterial than viral, while intermediate
levels (10-50 mg/L) can be either viral or bacterial
postoperative elevations, especially when they
can be concretely related to a normal or reasonably low-elevated
preoperative CRP baseline test value, tend to be reflective of
infection and not just organizing resolution of clean-surgical
monitoring extent & therapeutic response to
postoperative "dirty case" monitor
is the infection responding to the antibiotic
(pyelonephritis, pelvic infections, osteomyelitis, meningitis,
endocarditis)? CRP not affected by drugs or fever suppressants1.
detection and management of intercurrent infections:
in diabetics, lupus, ulcerative colitis, Crohn's disease, a major rise above
usual baseline CRP level suggests an infection1
An analysis of 3597 women with metabolic syndrome
showed that those with the highest CRP levels (greater than 3.0
mg/L) were 2.1 times more likely to have a cardiovascular event
within 8 years than those with the lowest CRP levels (less than
- Hunter Area Pathology Services...click on "information
sheets" & pick the test, Nov. 2001 [site]
- Specialty Labs manual, Jan 2001.
- Mayo Medical Lab manual, Jan 2001.
- Serum Markers of Risk for Coronary Artery Disease, Plaut D,
Advance for ...., 10(11):41-44, Nov. 2001.
- Interpretation of Diagnostic Tests, Wallach,
2000, 7th Ed., pages 843-847.
- Rafai & Ridker, Clinical Chemistry, 47(3):403-411,
- Proteins Used in Nutritional Assessment, Spiekerman AM, Clinics
In Lab. Medicine 13(2):353-369, June 1993..
- NEJMed, November 2002
- Pearson TA, et. al., Markers of Inflammation
and Cardiovascular Disease...[AHA/CDC Scientific Statement],
Circulation 107:499-511, 28 January 2003.
- Superko HR, Before The Heart Attacks, 334 pages,
- Epperly TD, et al. (2000) Polymyalgia rheumatica and temporal
arteritis. American Family Physician, 62(4): 789–796.
- Julie E. Buring, M.D.; Nancy R. Cook, M.D.; and Nader Rifai,
M.D., Circulation: Journal of the American Heart Association,
- Eur Respir J 2003; 21:407-413 Copyright ©ERS Journals Ltd 2003.
- letter to editor, page 1353, JAMA 296(11):1353-54, 20 Sept. 2006.
- McGee KA & Baumann NA, "Procalcitonin: Clinical Utility in Diagnosing Sepsis", Clinical Laboratory News 35(7):1-8, July 2009.
- Procalcitonin no advantage over CRP in adults in the ER
- NewsPath, July 2010, a periodical letter from the LMC Lab (KRM).
- Respected practitioner on our local medical srtaff.
(posted Jan. 2001; latest addition 23 March 2011)