How is high-sensitivity C-reactive protein (hs CRP) used for cardiac risk stratification?

High-Sensitivity C-Reactive Protein (hs-CRP) for Cardiac Risk Stratification

High-sensitivity C-reactive protein (hs-CRP) is most valuable as an adjunct to traditional risk factors for cardiovascular risk assessment, particularly in intermediate-risk patients (10-20% 10-year risk) where it can help guide further evaluation or therapy decisions.

Risk Categories and Interpretation

• hs-CRP levels are categorized into three risk tiers: low risk (<1 mg/L), moderate risk (1-3 mg/L), and high risk (>3 mg/L), with the high-risk tertile having approximately twice the relative risk compared to the low-risk tertile 1
• These risk categories correspond to approximate tertiles of values in population studies and reflect the inflammatory component of atherosclerosis 2
• Persistently elevated hs-CRP levels ≥10 mg/L after repeated testing should prompt evaluation for non-cardiovascular causes of inflammation 2

Clinical Application in Primary Prevention

• hs-CRP should be used as an adjunct to traditional risk factors, not as a replacement for established risk assessment tools like the Framingham Risk Score or Pooled Cohort Equations 2
• The optimal use of hs-CRP is in patients at intermediate risk (10-20% 10-year risk of CHD), where finding elevated levels may reclassify patients into a higher risk category 2
• For patients already at high risk (>20% 10-year risk) or with established atherosclerotic disease, intensive treatment is recommended regardless of hs-CRP levels 2, 1
• Low-risk individuals (<10% 10-year risk) are unlikely to be reclassified to high risk based on hs-CRP testing alone 2

Factors Affecting hs-CRP Levels

• Several factors can increase hs-CRP levels independent of cardiovascular risk, including: 2
  • Elevated blood pressure and body mass index
  • Cigarette smoking
  • Metabolic syndrome/diabetes mellitus
  • Low HDL/high triglycerides
  • Estrogen/progestogen hormone use
  • Chronic infections (gingivitis, bronchitis) and inflammatory conditions
• Factors associated with decreased hs-CRP levels include: 2
  • Moderate alcohol consumption
  • Increased physical activity/endurance exercise
  • Weight loss
  • Certain medications (statins, fibrates, niacin)

Role in Secondary Prevention

• In patients with stable coronary disease or acute coronary syndromes, hs-CRP measurement may help assess the likelihood of recurrent events, including death, myocardial infarction, or restenosis after percutaneous coronary intervention 2, 1
• However, secondary preventive interventions with proven efficacy should not be dependent on hs-CRP levels 2
• Serial testing of hs-CRP is not recommended to monitor treatment effects 2

Integration with Other Risk Assessment Tools

• The Reynolds Risk Score incorporates hs-CRP into its risk calculation, while other risk assessment models like the Framingham Risk Score do not 2
• hs-CRP adds predictive value above traditional established risk factors, showing independent associations with incident coronary events after adjusting for age, cholesterol levels, smoking, body mass index, diabetes, hypertension, exercise level, and family history 2, 3
• hs-CRP is not a good predictor of the extent of atherosclerotic disease and shows poor correlation with tests that quantify atherosclerosis, such as carotid ultrasound or coronary calcium scoring 2

Practical Recommendations

• Two separate measurements of hs-CRP are adequate to classify a person's risk level due to within-individual variability 1
• Population screening for hs-CRP is not recommended as a public health measure 2
• Finding a high hs-CRP level (>3 mg/L) in intermediate-risk patients may justify intensification of medical therapy and lifestyle modifications 1
• hs-CRP and abnormal heart rate turbulence both add to risk stratification in low-risk individuals, with hs-CRP showing a hazard ratio of 2.5 for cardiac mortality in this group 4

Limitations and Caveats

• Most studies on hs-CRP have been limited to white North American or European populations, with limited data for persons of African, South Asian, or Native American descent 2
• After adjustment for traditional cardiovascular risk factors, hs-CRP shows only weak associations with subclinical cardiovascular damage, suggesting it may be an integrated marker of multiple risk factors 5
• Regular CRP tests with lower detection limits (0.3 mg/L) highly correlate with hs-CRP tests and may be able to replace costlier hs-CRP measurements in some settings 6