Clinical Utility Of C-reactive Protein Research Articles

Early C-reactive protein after colorectal surgery is not predictive of anastomotic leak: a retrospective cohort study.

Prior studies suggest postoperative C-reactive protein (CRP) trends are sensitive for predicting anastomotic leak (AL) after elective colorectal surgery. However, in the setting of enhanced recovery pathways, multi-day CRP trends may not be feasible. This study aimed to assess the realistic and clinical utility of CRP in prediction of AL. A retrospective review of patients who underwent elective colectomy or proctectomy from January 2019 to October 2020 at a single institution was performed. Comorbidities, operative characteristics, and perioperative outcomes were recorded. CRP was checked routinely on POD1 and on a clinical basis subsequently. The association between 10-point change in CRP-POD1 and AL was evaluated using multivariable logistic regression. The relationships between CRP-POD3, CRP-POD1, and AL were assessed using exploratory analyses. Among 332 patients, 23 (6.9%) developed AL, of which 9 cases (39%) were diagnosed upon readmission. AL was not associated with mortality. Median length of stay was 3 days (IQR 2-5). Median days to AL diagnosis was 7 (IQR 4-15). Adjusting for diverting stoma, steroid use, diagnosis, and open surgery, each 10-point increase in CRP was associated with increased odds of AL (OR 1.12, 95% CI 1.03-1.21, p=0.008). CRP-POD1 had poor discriminant utility for detecting AL (AUC 0.62, 95% CI = 0.494-0.746; p=0.061). CRP on POD1 is not a reliable method to predict a leak, and trending CRP may not be practical with decreasing lengths of stay in colorectal surgery.

Clinical utility of C-reactive protein-based triage for presumptive pulmonary tuberculosis in South African adults

BackgroundIdentification of an accurate, low-cost triage test for pulmonary TB among people presenting to healthcare facilities is an urgent global research priority. We assessed the diagnostic accuracy and clinical utility of C-reactive protein (CRP) for TB triage among symptomatic adult outpatients, irrespective of HIV status. MethodsWe prospectively enrolled adults reporting at least one (for people with HIV) or two (for people without HIV) symptoms of cough, fever, night sweats, or weight loss at two TB clinics in Cape Town, South Africa. Participants provided sputum for culture and Xpert MTB/RIF Ultra. We evaluated the diagnostic accuracy of CRP (measured using a laboratory-based assay) against a TB-culture reference standard as the area under the receiver operating characteristic curve (AUROC), and sensitivity and specificity at pre-specified thresholds. We assessed clinical utility using decision curve analysis and benchmarked against WHO recommendations. ResultsOf 932 included individuals, 255 (27%) had culture-confirmed pulmonary TB and 389 (42%) were living with HIV. CRP demonstrated an AUROC of 0·80 (95% confidence interval 0·77–0·83), with sensitivity 93% (89–95%) and specificity 54% (50–58%) using a primary cut-off of ≥10 mg/L. Performance was similar among people with HIV to those without. In decision curve analysis, CRP-based triage offered greater clinical utility than confirmatory testing for all up to a number willing to test threshold of 20 confirmatory tests per true positive pulmonary TB case diagnosed (threshold probability 5%). If it is possible to perform more confirmatory tests than this, a ‘confirmatory test for all’ strategy performed better. ConclusionsCRP achieved the WHO-defined sensitivity, but not specificity, targets for a triage test for pulmonary TB and showed evidence of clinical utility among symptomatic outpatients, irrespective of HIV status. FundingSouth African Medical Research Council, EDCTP2, Royal Society Newton Advanced Fellowship, Wellcome Trust, National Institute of Health Research, Royal College of Physicians.

C-reactive protein, immunothrombosis and venous thromboembolism.

C-reactive protein (CRP) is a member of the highly conserved pentraxin superfamily of proteins and is often used in clinical practice as a marker of infection and inflammation. There is now increasing evidence that CRP is not only a marker of inflammation, but also that destabilized isoforms of CRP possess pro-inflammatory and pro-thrombotic properties. CRP circulates as a functionally inert pentameric form (pCRP), which relaxes its conformation to pCRP* after binding to phosphocholine-enriched membranes and then dissociates to monomeric CRP (mCRP). with the latter two being destabilized isoforms possessing highly pro-inflammatory features. pCRP* and mCRP have significant biological effects in regulating many of the aspects central to pathogenesis of atherothrombosis and venous thromboembolism (VTE), by directly activating platelets and triggering the classical complement pathway. Importantly, it is now well appreciated that VTE is a consequence of thromboinflammation. Accordingly, acute VTE is known to be associated with classical inflammatory responses and elevations of CRP, and indeed VTE risk is elevated in conditions associated with inflammation, such as inflammatory bowel disease, COVID-19 and sepsis. Although the clinical data regarding the utility of CRP as a biomarker in predicting VTE remains modest, and in some cases conflicting, the clinical utility of CRP appears to be improved in subsets of the population such as in predicting VTE recurrence, in cancer-associated thrombosis and in those with COVID-19. Therefore, given the known biological function of CRP in amplifying inflammation and tissue damage, this raises the prospect that CRP may play a role in promoting VTE formation in the context of concurrent inflammation. However, further investigation is required to unravel whether CRP plays a direct role in the pathogenesis of VTE, the utility of which will be in developing novel prophylactic or therapeutic strategies to target thromboinflammation.

Clinical Utility of C-Reactive Protein and White Blood Cell Count for Scheduling an [18F]FDG PET/CT in Patients with Giant Cell Arteritis.

2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT can be utilized in patients with giant cell arteritis (GCA), but pretest probability of established laboratory marker such as C-reactive protein (CRP) and white blood cell count (WBC) has not been defined yet. We aimed to elucidate the clinical utility of CRP and WBC for scheduling an [18F]FDG scan. 18 treatment-naïve GCA patients and 14 GCA subjects with anti-inflammatory treatment (glucocorticoids or comparable drugs), who underwent [18F]FDG PET/CT and who had no other inflammatory disease at time of scan, were identified. A semi-quantitative analysis in 11 vessel segments was conducted, with averaged jugular vein, healthy liver and lung tissue (Target-to-background ratio [TBR]VJ/liver/lung) serving as background. Derived TBR were then correlated with CRP and WBC at time of PET using Spearman's correlation. For all treatment-naïve patients, TBRVJ was 2.3±1.1 (95%CI, 2.2-2.5), TBRliver was 1.0±0.5 (95%CI, 0.9-1.0) and average TBRlung was 6.3±3.6 (95%CI, 5.8-6.8). No significant correlation was noted for either CRP (TBRVJ: R=-0.19; TBRliver: R=-0.03; TBRlung: R=-0.17; each P ≥ 0.44) or for WBC (TBRVJ: R=-0.40; TBRliver: R=-0.32; TBRlung: R=-0.37; each P ≥ 0.10). Similar results were recorded for patients under treatment at time of PET. Again, no significant correlation was reached for either CRP (TBRVJ: R=-0.17; TBRliver: R=-0.28; TBRlung: R=-0.09; each P ≥ 0.32) or WBC (TBRVJ: R=-0.06; TBRliver: R=-0.13; TBRlung: R=0.06; each P ≥ 0.65). In GCA patients with and without anti-inflammatory treatment, CRP and WBC did not substantially correlate with TBR at time of scan. Given the rather limited pretest probability of those parameters, such laboratory values may have less diagnostic utility to order an [18F]FDG PET/CT.

An evaluation of the clinical utility of C-reactive protein and antibiotic use in patients undergoing major head and neck reconstructive surgery with outcome assessment.

PurposeThis ambispective observational study aims to evaluate the local utility of peri-operative CRP testing and prophylactic antibiotics in relation to post-operative complications in patients who have undergone major head and neck oncological reconstructive surgery.ResultsA total of 79 patients were identified for inclusion; CRP testing was undertaken within the first 3 days postoperatively in 78/79 cases. Results demonstrated no benefit of extended prophylactic antibiotic use in reducing post-operative infection. Forty-two post-operative complications arose. In the prospective arm, CRP did not influence the decision to commence antibiotic therapy for any of the surgical site infections. Age, diabetes, smoking, or high body mass index (BMI) did not appear to affect the incidence of postoperative infection (p > 0.05). There is no evidence that more than 24 h of antibiotic prophylaxis is indicated for patients undergoing head and neck reconstructive surgery.ConclusionEveryone who is involved in peri-operative patient care should be educated regarding the appropriate use of CRP testing, with the implementation of protocols required to standardize CRP testing and prophylactic antibiotic prescription.

High serum C-reactive protein levels predict survival in patients with treated advanced lung adenocarcinoma.

BackgroundThe prognosis of non-small cell lung cancer (NSCLC) varies greatly depending on whether or not it can receive molecular-targeted drug treatment including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We investigated the clinical utility of C-reactive protein (CRP) levels measured at the time of diagnosis in EGFR-mutant and wild-type NSCLC patients who had undergone first-line therapy.MethodsSerum CRP levels were analyzed in 213 patients, of whom 89 patients had advanced EGFR-mutated NSCLC who underwent first-line EGFR-TKI treatment. We used Cox proportional hazards models to study the relationship between CRP and overall survival (OS). CRP cutoff values were obtained from the receiver operating characteristic curve.ResultsMean serum CRP level in treated NSCLC patients were not significantly different in patients with or without EGFR mutations. The optimal CRP cutoff values were 8.1 mg/L for EGFR-mutated NSCLC and 16.7 mg/L for EGFR-wild NSCLC. Based on multivariate analysis, high CRP level (EGFR-mutated, HR: 2.479, 95% CI: 1.331–4.619, P=0.004; EGFR-wild, HR: 3.625, 95% CI: 2.149–6.116, P<0.001) was a significant and independent negative prognostic factor for OS in patients with or without EGFR mutations.ConclusionsHigh CRP levels predicted a lack of response to treatment in patients with advanced lung adenocarcinoma with or without EGFR mutations. Thus, the CRP level is a good and easy to use prognostic factor and objective indicator for clinical practice.

Applicability of common inflammatory markers in diagnosing infections in early period after liver transplantation in intensive care setting

Infections remain an important cause of morbidity and mortality early after liver transplantation. The aim of this prospective longitudinal study was to evaluate clinical utility of c-reactive protein (CRP), procalcitonin, and neutrophil-to-lymphocyte ratio (NLR) in surveillance of infections early after liver transplantation in intensive care setting. A total of 60 liver transplant recipients were included. CRP, procalcitonin, and NLR assessed at 12-hour intervals were primary variables of interest. Infections and severe complications during postoperative intensive care unit stay were the primary and secondary end-points, respectively. Infections and severe complications were diagnosed in 9 and 17 patients, respectively. Only peak CRP beyond first 48 hours was associated with infections (p = 0.038) with AUC, positive and negative predictive value of 0.728, 42.9% and 92.2%, respectively (cut-off: 142.7 mg/L). Peak procalcitonin over first 60 hours was the earliest predictor (p = 0.050) of severe complications with AUC, positive and negative predictive value of 0.640, 53.3% and 80.0%, respectively (cut-off: 42.8 ng/mL). In conclusion, while CRP, procalcitonin, and NLR cannot be used for accurate diagnosis of infections immediately after liver transplantation, peak CRP beyond 48 hours and peak procalcitonin over first 60 hours may be used for initial exclusion of infections and prediction of severe complications, respectively.

Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations.

RationaleC-reactive protein (CRP) is a systemic marker of inflammation that correlates with disease status in cystic fibrosis (CF). The clinical utility of CRP measurement to guide pulmonary exacerbation (PEx) treatment decisions remains uncertain.ObjectivesTo determine whether monitoring CRP during PEx treatment can be used to predict treatment response. We hypothesized that early changes in CRP can be used to predict treatment response.MethodsWe reviewed all PEx events requiring hospitalization for intravenous (IV) antibiotics over 2 years at our institution. 83 PEx events met our eligibility criteria. CRP levels from admission to day 5 were evaluated to predict treatment non-response, using a modified version of a prior published composite definition. CRP was also evaluated to predict time until next exacerbation (TUNE).Measurements and main results53% of 83 PEx events were classified as treatment non-response. Paradoxically, 24% of PEx events were characterized by a ≥ 50% increase in CRP levels within the first five days of treatment. Absolute change in CRP from admission to day 5 was not associated with treatment non-response (p = 0.58). Adjusted for FEV1% predicted, admission log10 CRP was associated with treatment non-response (OR: 2.39; 95% CI: 1.14 to 5.91; p = 0.03) and shorter TUNE (HR: 1.60; 95% CI: 1.13 to 2.27; p = 0.008). The area under the receiver operating characteristics (ROC) curve of admission CRP to predict treatment non-response was 0.72 (95% CI 0.61–0.83; p<0.001). 23% of PEx events were characterized by an admission CRP of > 75 mg/L with a specificity of 90% for treatment non-response.ConclusionsAdmission CRP predicts treatment non-response and time until next exacerbation. A very elevated admission CRP (>75mg/L) is highly specific for treatment non-response and might be used to target high-risk patients for future interventional studies aimed at improving exacerbation outcomes.

Risk Factors for Cardiovascular Disease: Evidence from Studies

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the world [1,2]. Risk factors such as hypertension, metabolic syndrome, cigarette smoking, diabetes mellitus, elevated glucose and cholesterol levels, and obesity or being overweight are the top causes of death globally [3,4]. The Emerging Risk Factors Collaboration incorporating 160,309 study participants demonstrated the independent predictive value of C-reactive protein (CRP) for coronary heart disease (CHD) and stroke, the clinical utility of CRP and fibrinogen in CVD risk prediction, and the limited role of adding the novel lipid markers apolipoprotein A-I, lipoprotein (a), apolipoprotein B, and lipoprotein-associated phospholipase A2 to traditional lipid measures [5-7].

Clinical utility of C-reactive protein in patients with ileal pouch anal anastomosis†

Inflammatory and noninflammatory complications of ileal pouch-anal anastomosis (IPAA) are common after restorative proctocolectomy for ulcerative colitis (UC). The clinical utility of C-reactive protein (CRP) in ileal pouch disorders has not been investigated. All IPAA patients with underlying UC who had serum CRP tested within 2 weeks of pouch endoscopy were included. The correlation between the level of serum CRP and the Pouch Disease Activity Index (PDAI) scores were evaluated. Diagnostic accuracy of CRP in assessing disease activity by PDAI endoscopy subscores was evaluated. There were 83 patients (with a total 88 CRP tests), including normal pouches (n = 7), active pouchitis (n = 6), chronic pouchitis (n = 18), Crohn's disease of the pouch (n = 23), cuffitis (n = 13), irritable pouch syndrome (n = 10), and surgery-associated complications (n = 11). Levels of CRP did not differ significantly among healthy and diseased pouch groups. CRP levels significantly correlated with the PDAI endoscopy subscores in the pouch body (P = 0.006) and afferent limb (P = 0.03). A CRP level of greater than 0.7 mg/dL for CRP using the receiver operating characteristics curve obtained the best sensitivity of 69.7% and specificity of 63.6% to detect active pouch inflammation. Serum CRP levels correlated with endoscopic inflammation in the pouch and afferent limb. Elevated CRP levels might be useful to monitor the degree of inflammatory activity in pouch noninvasively. However, the CRP level as a snapshot had a limited role in distinction between healthy and diseased pouch conditions diagnosed based on longitudinal clinical and endoscopic evaluation.

Critical appraisal of CRP measurement for the prediction of coronary heart disease events: new data and systematic review of 31 prospective cohorts

Non-uniform reporting of relevant relationships and metrics hampers critical appraisal of the clinical utility of C-reactive protein (CRP) measurement for prediction of later coronary events. We evaluated the predictive performance of CRP in the Northwick Park Heart Study (NPHS-II) and the Edinburgh Artery Study (EAS) comparing discrimination by area under the ROC curve (AUC), calibration and reclassification. We set the findings in the context of a systematic review of published studies comparing different available and imputed measures of prediction. Risk estimates per-quantile of CRP were pooled using a random effects model to infer the shape of the CRP-coronary event relationship. NPHS-II and EAS (3441 individuals, 309 coronary events): CRP alone provided modest discrimination for coronary heart disease (AUC 0.61 and 0.62 in NPHS-II and EAS, respectively) and only modest improvement in the discrimination of a Framingham-based risk score (FRS) (increment in AUC 0.04 and -0.01, respectively). Risk models based on FRS alone and FRS + CRP were both well calibrated and the net reclassification improvement (NRI) was 8.5% in NPHS-II and 8.8% in EAS with four risk categories, falling to 4.9% and 3.0% for 10-year coronary disease risk threshold of 15%. Systematic review (31 prospective studies 84 063 individuals, 11 252 coronary events): pooled inferred values for the AUC for CRP alone were 0.59 (0.57, 0.61), 0.59 (0.57, 0.61) and 0.57 (0.54, 0.61) for studies of <5, 5-10 and >10 years follow up, respectively. Evidence from 13 studies (7201 cases) indicated that CRP did not consistently improve performance of the Framingham risk score when assessed by discrimination, with AUC increments in the range 0-0.15. Evidence from six studies (2430 cases) showed that CRP provided statistically significant but quantitatively small improvement in calibration of models based on established risk factors in some but not all studies. The wide overlap of CRP values among people who later suffered events and those who did not appeared to be explained by the consistently log-normal distribution of CRP and a graded continuous increment in coronary risk across the whole range of values without a threshold, such that a large proportion of events occurred among the many individuals with near average levels of CRP. CRP does not perform better than the Framingham risk equation for discrimination. The improvement in risk stratification or reclassification from addition of CRP to models based on established risk factors is small and inconsistent. Guidance on the clinical use of CRP measurement in the prediction of coronary events may require updating in light of this large comparative analysis.

Clinical Utility of C-Reactive Protein Measured at Admission, Hospital Discharge, and 1 Month Later to Predict Outcome in Patients With Acute Coronary Disease: The RISCA (Recurrence and Inflammation in the Acute Coronary Syndromes) Study

This study was designed to prospectively determine, in patients with an acute coronary syndrome, whether the inflammatory marker, C-reactive protein (CRP), measured at hospital admission, discharge, and 1 month later has incremental value to predict outcomes at 1 year. The clinical utility of CRP measurements in patients with acute coronary syndromes remains uncertain. Limitations of previous studies have been retrospective design and incomplete adjustment for readily available clinical prognosticators. The CRP marker was measured at admission, hospital discharge, and 1 month later in consecutive patients hospitalized for acute coronary syndromes in 8 tertiary and secondary hospitals. The primary outcome was a composite of death, nonfatal myocardial infarction (MI), and unstable angina (UA) with electrocardiogram (ECG) changes at 1 year. A total of 1,210 patients, age 62 +/- 12 years, 64% with acute myocardial infarction (MI) and 36% with unstable angina (UA), were recruited. At 1 year, the primary outcome occurred in 142 patients (11.7%) and included 58 deaths (4.8%), 79 nonfatal MIs (6.5%), and 26 UA episodes with ECG changes (2.1%). The unadjusted odds ratios (ORs) (95% confidence intervals) of CRP values at admission, hospital discharge, and 1 month later for the occurrence of the primary outcome were 1.20 (1.06 to 1.36), 0.98 (0.85 to 1.14), and 1.23 (1.00 to 1.50), respectively. After multivariate adjustment, ORs were 1.04 (0.91 to 1.20), 0.90 (0.77 to 1.06), and 1.12 (0.93 to 1.34), respectively. The individual components of the primary outcome were also not independently associated with any of the 3 CRP measurements. The modest predictive ability of CRP following admission for an acute coronary syndrome disappeared after adjusting for common clinical variables. This large prospective study does not support the incremental value of measuring CRP in this clinical setting.

C-Reactive Protein Concentration in Dogs with Various Diseases

To investigate the clinical utility of C-reactive protein (CRP) determination in dogs, its plasma concentration was measured by a laser nephelometric method in 928 dogs with various diseases, and was compared with other inflammatory parameters. CRP concentration was elevated in various inflammatory diseases, this was most frequently observed in cases with neoplastic and immune-mediated diseases. All cases of pyometra, panniculitis, acute pancreatitis, polyarthritis, and hemangiosarcoma showed significantly elevated CRP concentrations. On the other hand, the CRP concentration was elevated only in few cases of neurological diseases such as epilepsy, meningoencephalitis, and hydrocephalus and endocrine diseases such as hypothyroidism, hyperadrenocorticism, and diabetes mellitus. Only a weak correlation was observed between the CRP concentration and white blood cell (WBC) counts (r=0.44) but no correlation with band neutrophil counts. There was no correlation between the CRP and albumin concentrations, but a weak negative correlation (r=-0.40) when excluding chronic intestinal diseases and nephrotic syndrome, which can cause protein loss. Thus, CRP can be useful to detect inflammations that cannot be detected by WBC and, or band neutrophil counts, suggesting that the examination of CRP concentration is essential as routine diagnostic test.

C-Reactive Protein Concentration in Canine Idiopathic Polyarthritis

To investigate the clinical utility of C-reactive protein (CRP) in idiopathic polyarthritis (IPA), its concentration was measured in dogs with IPA. The CRP concentration was markedly increased in all the IPA dogs at the time of diagnosis and decreased significantly in response to the initial corticosteroid treatment; this indicated that CRP can be used as an index for therapeutic response in IPA cases. Furthermore, at 6 months after the diagnosis, a significant association was observed between the CRP concentration at follow-up (6-13 days after the treatment was started) and the frequency of medication ("no or seldom-medicated (NSM)" groups or "continuing medication (CM)" groups). These results suggest that the initial response of CRP to corticosteroid treatment may be a prognostic factor of canine IPA.