What is a high sensitivity C-Reactive Protein (hs-CRP) level concerning for in terms of cardiac risk?

High-Sensitivity C-Reactive Protein (hs-CRP) Levels and Cardiac Risk Assessment

An hs-CRP level above 3 mg/L indicates high cardiovascular risk, while levels between 1-3 mg/L suggest moderate risk, and levels below 1 mg/L represent low risk. 1, 2

Risk Stratification Using hs-CRP

• hs-CRP is an independent marker of cardiovascular risk that can be used to enhance risk assessment beyond traditional risk factors 2
• The established risk categories for hs-CRP in primary prevention are:
  • Low risk: <1 mg/L
  • Average risk: 1-3 mg/L
  • High risk: >3 mg/L 2, 3
• These cutpoints correspond to approximate tertiles in the adult population, with the high-risk tertile having approximately twice the relative risk compared to the low-risk tertile 2
• For patients with acute coronary syndromes, a higher cutpoint of 10 mg/L may have better predictive qualities for recurrent events 2

Clinical Application of hs-CRP Testing

• hs-CRP measurement is most useful for refining risk assessment in individuals at intermediate risk (10-20% 10-year risk of coronary heart disease) 2
• Two separate measurements of hs-CRP (similar to cholesterol testing) are adequate to classify a person's risk level due to within-individual variability 2
• Persistently elevated hs-CRP levels ≥10 mg/L after repeated testing should prompt evaluation for non-cardiovascular causes of inflammation 2
• hs-CRP adds predictive value at all levels of cholesterol, Framingham risk score, metabolic syndrome severity, and blood pressure 1

Limitations and Considerations

• hs-CRP is not a good predictor of the extent of atherosclerotic disease and correlates poorly with imaging tests that quantify atherosclerosis 2
• Several factors can increase hs-CRP levels independent of cardiovascular risk, including:
  • Elevated blood pressure
  • Elevated body mass index
  • Cigarette smoking
  • Metabolic syndrome/diabetes
  • Low HDL/high triglycerides
  • Estrogen/progestogen hormone use
  • Chronic infections and inflammation 2
• Serial testing of hs-CRP should not be used to monitor effects of treatment (Class III, Level of Evidence C) 2
• Application of secondary prevention measures and management guidelines for acute coronary syndromes should not depend on hs-CRP levels (Class III, Level of Evidence A) 2

Clinical Recommendations

• hs-CRP measurement is most beneficial in patients at intermediate cardiovascular risk (10-20% 10-year risk) to help guide further evaluation or therapy decisions 2
• Finding a high hs-CRP level (>3 mg/L) in intermediate-risk patients may justify intensification of medical therapy and lifestyle modifications 2
• Low-risk individuals (<10% 10-year risk) are unlikely to be reclassified into high-risk category based on hs-CRP testing alone 2
• High-risk individuals (>20% 10-year risk) or those with established atherosclerotic disease should receive intensive treatment regardless of hs-CRP levels 2
• In patients with stable coronary disease or acute coronary syndromes, hs-CRP may help assess likelihood of recurrent events, including death, myocardial infarction, or restenosis after percutaneous coronary intervention 2

Pitfalls to Avoid

• Do not use hs-CRP as an alternative to major risk factors for cardiovascular risk assessment 2
• Do not initiate treatment based on elevated hs-CRP alone without considering other cardiovascular risk factors 2
• Avoid measuring hs-CRP during acute illness or obvious infection, as this could obscure prediction of coronary risk 2
• Do not rely on a single hs-CRP measurement due to within-individual variability; confirm elevated levels with repeat testing 2
• Remember that hs-CRP values may be higher in certain populations; studies in India found mean hs-CRP values of 1.88 mg/L, higher than Western populations 4