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CRP vs ESR
Assessing & Measuring the Inflammatory Response
Reminder

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NZ GPs respond to campaign messages – CRP tests more than doubled, ESR tests reduced by half

In July 2005, bpac distributed a campaign on the appropriate use of CRP and ESR. These two tests are among the most frequently requested laboratory tests by GPs in New Zealand. At the time of the campaign, ESR was being performed approximately three times as often as CRP. However evidence shows that in most situations CRP should be the preferred test. In addition, there is usually no value in requesting both an ESR and CRP test simultaneously.

Figure 1: Total number of CRP and ESR tests performed
(July 2004 and December 2006)
Fig 1

Analysis of laboratory claims data showed that in the year following the bpac campaign, the number of CRP tests has more than doubled, with an average increase of 152%. During the same time period, ESR tests have dropped by 50%. Simultaneous testing of ESR and CRP reduced by an average of 25% (Figure 1).

Figure 2: Ratio of ESR to CRP tests and Simultaneous tests (ESR & CRP) to CRP tests requested
(July 2004 and December 2006)
Fig 1

In July 2004, one year before the campaign, for every one request for a CRP test there were over four requests for an ESR test and just under two requests for simultaneous testing of ESR and CRP (Figure 2). There is now less than one ESR test or simultaneous tests requested for every CRP test alone. The average ratio of ESR to CRP alone dropped from 3.5:1 in the year before the campaign to 0.7:1 in the year following. The ratio of simultaneous testing to CRP alone dropped from 1.6:1 to 0.5:1 in the same time period. The overall number of ESR and CRP tests requested has decreased by 13%.

Evidence not convincing for using CRP to differentiate between bacterial and viral pneumonia

When selecting treatments for lower respiratory tract infections, physicians can find it difficult to differentiate between bacterial and other causes of infection. There is no convincing evidence that CRP assists with this dilemma.

Infections of the lower respiratory tract are common in the community and comprise both acute bronchitis and pneumonia. Differentiating between them by history and physical examination is challenging but the distinction is important due to the therapeutic consequences. Bacterial pneumonia should be treated with antibiotics, whereas acute bronchitis is usually self limiting. Although bacterial pneumonia occurs much less often than other infections of the lower respiratory tract, in some studies more than 70% of acute infections of the lower respiratory tract are treated with antibiotics.

van der Meer et al performed a systematic review to determine the ability of CRP to detect radiologically proved pneumonia and to evaluate how well it can discriminate between bacterial and viral infections of the lower respiratory tract. In general the studies were of poor quality, therefore the reviewers concluded that testing for CRP is neither sufficiently sensitive to rule out nor sufficiently specific to rule in an infiltrate on chest radiograph and bacterial aetiology of lower respiratory tract infection. The evidence does not sufficiently support the introduction of CRP as a rapid test to guide antibiotic prescription. It is also interesting to consider the essential and subtle difference between what we call “no evidence of effect and the evidence of no effect”. Therefore while this study does not support the use of CRP to differentiate between bacterial and viral infections of the lower respiratory tract, the lack of high quality studies means we can not be sure it is not useful.

Reference:

van der Meer V, Neven AK, van den Broek PJ et al. Diagnostic value of C reactive protein in infections of the lower respiratory tract: Systematic review. BMJ 2005;331:26-9.

Hs-CRP adds little to traditional CVD risk assessment

Over the last few years there have been increasing numbers of reports of the use of high sensitivity CRP (Hs-CRP) as a risk factor for the prediction of cardiovascular disease.

In a recent review of the literature published up to January 2006, the authors describe what is known about the additional utility of CRP in risk prediction. While a test may appear appealing it is important it be assessed in the context of existing predictors. The authors say tests should be examined in terms of sensitivity, specificity, predictor values, and clinical likelihood so a qualitative value of the test can be determined. The true value of the test in terms of other current predictors can be calculated.

By using this approach the authors were able to estimate the usefulness of CRP:

  • CRP is consistently, although weakly, associated with CVD after adjustment for current established risk factors.
  • Elevated CRP levels are in large measure attributable to traditional CVD risk factors (including age, smoking, obesity, diabetes, alcohol intake, hormone replacement therapy, fibrinogen and other thrombotic and inflammatory markers).
  • For people at low or high CVD risk, CRP does not change the magnitude of risk. The test should remain, at most, a “tie breaker” test, measured selectively in individuals at intermediate risk for CVD when the merits of beginning drug therapy for other risk factors are unclear.
  • There is no evidence that independent lowering of CRP levels reduces subsequent events.

When CRP is examined critically, it does not improve risk discrimination enough to recommend its routine adoption for population screening. Specific individuals may benefit from knowledge of their CRP level, but many questions still must be answered before it is accepted as a standard CVD risk factor. Future evaluations of CRP should focus not on associations between independent risk factors but on test characteristics such as likelihood ratios and the additional utility of CRP over and above traditional risk factor measurements.

Reference:

Lloyd-Jones DM, Liu K, Tian L et al. Narrative Review: Assessment of C-Reactive Protein in Risk Prediction for Cardiovascular Disease. Ann Intern Med 2006;145:35-42.

When requesting CRP or ESR, bpacnz recommends:

  1. Choose CRP first on most occasions
  2. Seldom request ESR and CRP simultaneously

Infection

CRP maybe useful when considering an undifferentiated infection. As the CRP increases above 100 mg/L, the likelihood of a bacterial infection becomes greater than a viral infection.

Screening asymptomatic patients

CRP and ESR are not suitable for screening asymptomatic patients. When there is no strong evidence of disease, the tests are of little value.

Polymyalgia rheumatica (PMR)

Both CRP and ESR are recommended in the diagnosis of PMR, while CRP is recommended for monitoring. The initial CRP level should be used as the baseline for monitoring treatment. An absence of a clinical response or no improvement of the CRP within one to two weeks of therapy, should suggest reconsideration of the diagnosis.

Temporal (giant cell) arteritis

While overall there is good correlation between CRP and ESR in the diagnosis of temporal arteritis, cases with normal ESR and elevated CRP are reported. It is therefore recommended that CRP and ESR are tested simultaneously, which will result in a higher sensitivity for diagnosis. CRP is also recommended for the monitoring of temporal arteritis, and appropriate treatment results in improvement in the CRP level.

Rheumatoid arthritis

Neither CRP nor ESR are included in the diagnostic criteria for rheumatoid arthritis. However CRP should be used for monitoring because it is a better measure of the disease activity and it is known that sustained high levels of CRP are associated with worse outcomes.

Systemic lupus erythematosus (SLE)

There is a lack of correlation between CRP and disease activity in SLE. A more useful role of CRP is to distinguish between a lupus flare and infection: it usually remains normal in a flare but is elevated in infection, while the ESR is often elevated in both.

Malignancy

Given the non-specific nature of the acute phase response, a definite role of CRP measurements in the management of cancer patients has not yet been established, other than in cases of intercurrent infection. Neither CRP nor ESR should be used as a screening test for malignancy in the general population, since any increase in these is non-specific.

CRP as a cardiovascular disease risk factor

High Sensitivity-CRP (Hs-CRP) has been reported as predictor for cardiovascular disease, although when compared with major established risk factors (such as elevated cholesterol and smoking status) the Hs-CRP added only marginally to the predictive value of the current risk factors.

CRP or ESR?

  • Choose CRP first
  • Seldom request both
CRP
Infection
Monitoring:
  • PMR
  • Rheumatoid arthritis
  • Temporal arteritis (GCA)
Both CRP and ESR
Diagnosing
  • PMR
  • Temporal arteritis (GCA)
ESR
Mostly superseded by CRP
May be elevated in multiple myeloma when CRP normal
No established role for either CRP or ESR in:
  • Asymptomatic patients
  • Malignancy
Results affected by: ESR CRP
Gender tick tick
Age tick tick
Pregnancy tick tick
Temperature tick tick
Drugs (e.g. steroids, salicylates) tick tick
Smoking tick tick

For more detailed material please see “CRP vs ESR: Assessing & Measuring the Inflammatory Response”.