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High Sensitivity C-Reactive Protein

Policy Number: MP-062

Latest Review Date: May 2022

Category: Laboratory


High sensitivity C-reactive protein (hs-CRP) may be considered medically necessary as a marker of increased risk for cardiovascular disease when the patient has documented:

  • abdominal aortic aneurysm; and/or
  • clinical coronary heart disease (CAD); and/or
  • diabetes mellitus; and/or
  • first degree family member with history of early cardiovascular event (males before age 55 and females before age 65); and/or
  • hyperlipidemia; and/or
  • peripheral arterial disease; and/or
  • symptomatic carotid artery disease

Measurement of high sensitivity C-reactive protein is considered investigational when performed for screening or first line testing.


High sensitivity C-reactive protein (hs-CRP) is a nonspecific, acute-phase reactant produced by the liver as a marker of inflammatory processes, which can produce persistent increases in serum CRP concentrations, which are thought to have an association with low-level chronic inflammation that occurs during atherogenesis. The use of technologies, collectively known as hs-CRP, have allowed for high precision in detecting the lower levels of CRP that are related to chronic inflammation in otherwise healthy individuals. There is a correlation between hs-CRP levels and coronary artery disease. It is theorized that the increased sensitivity of an hs-CRP test should be able to detect that activity as a marker for cardiovascular disease, either current or future.


Policy was updated with literature review performed through May 9, 2022.

Summary of Evidence

The existing observational evidence establishes that CRP is an independent predictor of cardiovascular disease across a wide spectrum of patient populations. The evidence also suggests that using CRP as a component of a risk assessment tool will result in a more accurate cardiac risk prediction. Measurement of high sensitivity C-reactive (hs-CRP) protein to assess coronary heart disease risk may result in a change in treatment and/or lifestyle that could decrease the risk for future cardiac events, thus having a high likelihood of improving patient outcomes. The evidence is sufficient to prove the clinical utility of the technology for the conditions / populations listed in the policy statement.

A randomized double blind placebo controlled multicenter study investigated whether treatment with rosuvastatin would decrease the rate of first major cardiovascular events for healthy men and women with elevated hs-CRP levels, a calculated Framingham risk score of 10% or less, or an LDL cholesterol level of 100 mg per deciliter or lower. The observed relative reductions in the hazard ratio associated with rosuvastatin for the primary end point were similar to those in higher-risk groups. For subjects with elevated hs-CRP levels but no other major risk factor other than increased age, the benefit of rosuvastatin was similar to that for higher-risk subjects. This study shows the benefits of statin therapy, but it does not address the clinical value of hs-CRP testing for individuals with low cardiovascular risk. The study was prematurely terminated before the long-term safety and efficacy of the drug therapy could be established. Additional long-term studies are needed to determine the role of hs-CRP testing in the clinical management of individuals with low cardiovascular risk. The evidence is insufficient to prove the utility of using this technology in the general population for screening and first line testing.

Practice Guidelines and Position Statements

American College of Cardiology/American Heart Association (ACC/AHA)

In 2013, the ACC and AHA published guidelines for the assessment of cardiovascular risk focus on adults without clinical signs or symptoms of atherosclerotic cardiovascular disease (ASCVD). The guidelines state that “if, after quantitative risk assessment, a risk-based treatment decision is uncertain, assessment of 1 or more of the following— family history, hs-CRP, CAC score, or ABI—may be considered to inform treatment decision making.”

American Heart Association (AHA)/Centers for Disease Control and Prevention (CDC)

The AHA and CDC issued the following recommendation regarding the role of hs-CRP measurements in clinical practice in 2020: it is reasonable to measure hs-CRP as an adjunct to the major risk factors to further assess absolute risk for coronary disease primary prevention. At the discretion of the physician, the measurement is considered optional, based on the moderate level of evidence (Evidence Level C). In this role, hs-CRP measurement appears to be best employed to detect enhanced absolute risk in persons in whom multiple risk factor scoring projects a 10-year CHD risk in the range of 10% to 20% (Evidence Level B). However, the benefits of this strategy or any treatment based on this strategy remain uncertain. Individuals at low risk (10% per 10 years) will be unlikely to have a high risk (20%) identified through hs-CRP testing. Individuals at high risk (20% risk over 10 years) or with established atherosclerotic disease generally should be treated intensively regardless of their hs-CRP levels, so the utility of hs-CRP in secondary prevention appears to be more limited. In patients with stable coronary disease or acute coronary syndromes, hs-CRP measurement may be useful as an independent marker for assessing likelihood of recurrent events, including death, myocardial infarction, or restenosis after percutaneous coronary intervention. However, secondary preventive interventions with proven efficacy should not be dependent on hs-CRP levels. Further, serial testing of hs-CRP should not be used to monitor the effects of treatment.

U.S. Preventative Services Task Force

In 2009, the US Preventive Services Task Force (USPSTF) recommendation on using nontraditional risk factors in coronary heart disease risk assessment was updated. The USPSTF reviewed the evidence on using nontraditional risk factors in CVD risk assessment, focusing on the ankle-brachial index (ABI), high-sensitivity C-reactive protein (hs-CRP) level, and coronary artery calcium (CAC) score; the health benefits and harms of CVD risk assessment and treatment guided by nontraditional risk factors combined with the Framingham Risk Score or Pooled Cohort Equations compared with using either risk assessment model alone; and whether adding nontraditional risk factors to existing CVD risk assessment models improves measures of calibration, discrimination, and risk reclassification.

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of adding the ABI, hs-CRP level, or CAC score to traditional risk assessment for CVD in asymptomatic adults to prevent CVD events. (I statement).


C-reactive protein, high-sensitivity C-reactive protein, hs-CRP, CRP, cardiovascular risk assessment, ASCVD, Atherosclerotic cardiovascular disease


Several of the hs-CRP tests have received 510(k) marketing clearance from the U.S. Food and Drug Administration (FDA).


Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: FEP does not consider investigational if FDA approved and will be reviewed for medical necessity. Special benefit consideration may apply. Refer to member’s benefit plan.


CPT codes:


C-reactive protein, high sensitivity


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Medical Policy Group, August 2002 (2)

Medical Policy Administration Committee, August 2002

Available for comment August 26-October 9, 2002

Medical Policy Group, September 2006 (1)

Medical Policy Group, September 2008 (1)

Medical Policy Group, September 2010 (1): Description updated, Key Points updated and Governing Bodies information added

Medical Policy Group, September 2012 (3): Active Policy but no longer scheduled for regular literature reviews and updates.

Medical Policy Group, October 2013 (3): Removed ICD-9 Diagnosis codes; no change to policy statement.

Medical Policy Group, June 2019 (9): Updates to Description, Key Points, References, and Approved by Governing Bodies. Added key words: ASCVD, Atherosclerotic cardiovascular disease. No change to intent of policy statement.

Medical Policy Group, May 2021 (9): Updates to Description, Key Points, References. Policy statement updated to remove “not medically necessary,” no change to policy intent.

Medical Policy Group, October 2021 (9): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, May 2022 (9): Updates to Description, Key Points. Reviewed by consensus. References added. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.