What is the lower limit of high-sensitivity C-reactive protein (hs-CRP) before co-morbidity?

Lower Limit of hs-CRP Before Co-morbidity

The lower limit of detection for high-sensitivity CRP assays is 0.3 mg/L, and values below 1.0 mg/L are associated with low cardiovascular risk, with the lowest measurable concentrations (<0.5 mg/L) serving as the reference category for minimal inflammatory burden. 1

Technical Detection Limits

• High-sensitivity CRP assays can accurately and reproducibly detect concentrations down to 0.3 mg/L, which represents the analytical lower limit of sensitivity for commercially available automated assays 1
• This detection threshold is substantially lower than conventional CRP assays, which typically had a lower reporting level of 3 mg/L 1
• The enhanced sensitivity allows measurement in the concentration range necessary to evaluate atherosclerotic risk in apparently healthy individuals 1

Clinical Risk Stratification Thresholds

The CDC/AHA guidelines establish three risk categories based on hs-CRP levels:

• Low risk: <1.0 mg/L 1, 2
• Average/moderate risk: 1.0 to 3.0 mg/L 1, 2
• High risk: ≥3.0 mg/L 1, 2

These approximate tertiles are based on aggregated population studies and represent relative cardiovascular risk categories 1

Prognostic Value at Very Low Levels

• Values below 0.5 mg/L define the lowest risk category, with progressively increasing cardiovascular risk observed at higher concentrations 3
• In a large prospective study of 27,939 women, those with hs-CRP <0.5 mg/L served as the reference group (relative risk 1.0), while even the 0.5 to <1.0 mg/L category showed increased risk (RR 1.6 after adjustment for Framingham Risk Score) 3
• Approximately 15% of the general population has hs-CRP levels <0.5 mg/L, representing the group with minimal inflammatory burden 3

Clinical Context for "Before Co-morbidity"

If your question refers to the threshold below which chronic inflammation-related co-morbidities are unlikely:

• Normal CRP concentrations are typically below 3 mg/L in healthy individuals 2, 4
• Values <1.0 mg/L indicate low cardiovascular risk and minimal chronic inflammatory activation 1, 5
• The relationship between hs-CRP and cardiovascular events is continuous and graded, with risk increasing linearly from the very lowest to highest levels 3

Important Clinical Caveats

• Multiple non-pathological factors influence hs-CRP levels including age, sex, race, body mass index, smoking, exercise, diet, sleep, and medications 1, 2, 4
• Measurements should be obtained when patients are metabolically stable, either fasting or nonfasting, with the average of two measurements expressed in mg/L 1
• Values >10 mg/L warrant evaluation for acute inflammation or infection rather than chronic cardiovascular risk assessment 1, 2
• The assay's ability to measure down to 0.3 mg/L does not mean values at this detection limit have clinical significance—the clinically relevant lower threshold for risk stratification remains <1.0 mg/L 1, 3