Both CRP and hs-CRP tests measure the amount of C-reactive protein in circulation. The high-sensitivity CRP test was developed to detect very low levels of CRP more accurately. However, conventional methods of measuring CRP have become more sensitive
C-reactive protein (CRP) is an acute-phase reactant and inflammatory marker produced by the liver. Levels increase with inflammation, infection, and malignancy and are controlled by cytokines in circulation, primarily IL-6, which directly increases CRP production.
The use of CRP as a cardiovascular biomarker was first considered in 1999. However, there was concern that available testing methods could not reliably detect levels below 10 mg/L (95 nmol/L), levels that may reflect subclinical inflammation and could be relevant to CVD risk. The immune-particle enhanced high-sensitivity CRP test was developed to detect these lower levels better and became the preferred test for CVD testing.
However, conventional measurement of CRP has become more sensitive with a lower detection limit of 0.3 mg/L (2.9 nmol/L). The lower detection limit for hs-CRP is 0.15 mg/dL (1.4 nmol/L). Researchers suggest that conventional CRP testing may be sufficient to identify cardiac risk associated with subclinical inflammation.
A review of data from 570 subjects referred for CVD assessment found that CRP and hs-CRP results correlated significantly, with an average difference of 0.19 mg/L (1.8 nmol/L) between the two methods. The review found that CRP or hs-CRP above 3 mg/L (28.57 nmol/L) increased the risk of a cardiac event, especially in older patients with a history of coronary artery disease. The group with the lowest CVD risk had a median CRP and median hs-CRP of 0.6 mg/L (5.7 nmol/L)(Han 2022).
Review of C-Reactive Protein
Synthesis of CRP is initiated by antigen-immune complex, bacteria, fungi, and damage to heart tissue. Elevated CRP can be seen with chronic inflammation (including rheumatoid arthritis), chronic infection (including gingivitis), hypertension, metabolic syndrome, diabetes mellitus, cigarette smoking, and estrogen and progesterone therapy. Hs-CRP is considered an independent and better marker for predicting serious events such as myocardial infarction or cardiac death than LDL cholesterol. Due to individual variability, at least 2 separate measurements of hs-CRP should be obtained to optimize assessment, especially in high-risk patients. Levels of CRP increase in association with increases in muscle/brain creatine kinase isoenzyme, and persistently high CRP may indicate ongoing heart damage (Pagana 2021).
Levels of hs-CRP were found to correlate significantly with the severity of atherosclerosis in one study of 267 patients with dyslipidemia and 121 controls. Subjects without atherosclerosis had a mean hs-CRP of 0.87 mg/L (8.29 nmol/L), while those with atherosclerosis had a mean hs-CRP of 1.46 mg/L (13.9 nmol/L). The most severe atherosclerosis was associated with a mean hs-CRP of 1.83 mg/L (17.43 nmol/L). Significant correlations were also observed between elevated hs-CRP and elevated fasting glucose, triglycerides, and BMI (Swastini 2019).
The Bottom Line
Measurement of CRP using conventional methods that can detect lower levels of at least 0.3 mg/dL (2.9 nmol/L) may be comparable to using the high-sensitivity methodology, which has a lower detection limit of 0.15 mg/dL (1.4 nmol/L). Some research suggests that a level below 1 mg/L (9.5 nmol/L) may indicate lowest CVD risk using either method.
A comprehensive assessment that includes history, symptomatology, and past blood chemistry trends should accompany the assessment of C-reactive protein in order to best evaluate risk for cardiometabolic and inflammatory disorders and guide therapeutic interventions.
References
Han, Emilie et al. “Comparison of High-Sensitivity C-Reactive Protein vs C-reactive Protein for Cardiovascular Risk Prediction in Chronic Cardiac Disease.” The journal of applied laboratory medicine vol. 7,6 (2022): 1259-1271. doi:10.1093/jalm/jfac069
https://academic.oup.com/jalm/article/7/6/1259/6711153
Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.
Swastini, Dewa Ayu et al. “Atherosclerosis Prediction with High Sensitivity C-Reactive Protein (hs-CRP) and Related Risk Factor in Patient with Dyslipidemia.” Open access Macedonian journal of medical sciences vol. 7,22 3887-3890. 14 Nov. 2019, doi:10.3889/oamjms.2019.526