High-sensitivity C-reactive Protein Test Research Articles

Monomeric C-reactive protein as a biomarker for major depressive disorder.

Neuroinflammation has been postulated to be a key factor in the pathogenesis of major depressive disorder (MDD). With this is mind, there has been a wave of research looking into pro-inflammatory mediators as potential biomarkers for MDD. One such mediator is the acute phase protein, C-reactive protein (CRP). While several studies have investigated the potential of CRP as a biomarker for MDD, the results have been inconsistent. One explanation for the lack of consistent findings may be that the high-sensitivity CRP tests utilized in these studies only measure the pentameric isoform of CRP (pCRP). Recent research, however, has indicated that the monomeric isoform of CRP (mCRP) is responsible for the pro-inflammatory function of CRP, while pCRP is weakly anti-inflammatory. The objective of this minireview is to re-examine the evidence of CRP involvement in MDD with a view of mCRP as a potential biomarker.

HS-CRP Modifies the Prognostic Value of Platelet Count for Clinical Outcomes After Ischemic Stroke.

Background We examined whether the relationship between baseline platelet count and clinical outcomes is modulated by HS-CRP (high-sensitivity C-reactive protein) in patients with ischemic stroke. Methods and Results A total of 3267 patients with ischemic stroke were included in the analysis. The primary outcome was a combination of death and major disability at 1 year after ischemic stroke. Secondary outcomes included major disability, death, vascular events, composite outcome of vascular events or death, and an ordered 7-level categorical score of the modified Rankin Scale at 1 year. Multivariate logistic regression and Cox proportional hazards regression models were used to assess the association between the baseline platelet count and clinical outcomes stratified by HS-CRP levels when appropriate. There was an interaction effect of platelet count and HS-CRP on the adverse clinical outcomes after ischemic stroke (all Pinteraction<0.05). The elevated platelet count was significantly associated with the primary outcome (odds ratio [OR], 3.14 [95% CI, 1.77-5.58]), major disability (OR, 2.07 [95% CI, 1.15-3.71]), death (hazard ratio [HR], 2.75 [95% CI, 1.31-5.79]), and composite outcome of vascular events or death (HR, 2.57 [95% CI, 1.38-4.87]) among patients with high HS-CRP levels (all Ptrend<0.05). Conclusions The HS-CRP levels had a modifying effect on the association between platelet count and clinical outcomes in patients with ischemic stroke. Elevated platelet count was significantly associated with adverse clinical outcomes in patients with ischemic stroke with high HS-CRP levels, but not in those with low HS-CRP levels. These findings suggest that strategies for anti-inflammatory and antiplatelet therapy should be developed according to the results of both platelet and HS-CRP testing.

No change in interictal C-reactive protein levels in individuals with episodic and chronic migraine: A case-control study and literature review.

ObjectivesThe levels of some migraine biomarkers differ between episodic migraine (EM) and chronic migraine (CM), but information on C-reactive protein (CRP) levels in EM and CM is conflicting. Thus, this study aimed to evaluate CRP levels in participants with EM and CM in comparison to those in healthy controls.MethodsPlasma CRP levels were evaluated by high-sensitivity CRP tests in female participants with EM (n = 174) and CM (n = 191) and healthy controls (n = 50).ResultsThe results showed no significant difference in CRP levels among the EM, CM, and control groups (median and interquartile range, 0.40 [0.15–0.70] mg/L vs. 0.40 [0.15–1.00] mg/L vs. 0.15 [0.15–0.90] mg/L, p = 0.991). The ratio of individuals with elevated CRP levels (>3.0 mg/L) did not significantly differ among the EM, CM, and control groups (3.4% [6/174] vs. 2.1% [4/191] vs. 0.0% [0/50], p = 0.876). Multivariable regression analyses revealed that CRP levels were not significantly associated with headache frequency per month (β = −0.076, p = 0.238), the severity of anxiety (Generalized Anxiety Disorder-7 score, β = 0.143, p = 0.886), and depression (Patient Health Questionnaire-9 score, β = 0.143, p = 0.886). Further, CRP levels did not significantly differ according to clinical characteristics, fibromyalgia, medication overuse, preventive treatment, and classes of preventive treatment medications. Among participants with a body mass index ≥25 kg/m2, the CRP levels in EM (n = 41) and CM (n = 17) were numerically higher than those in the control (n = 6) (1.30 [0.28–4.25] mg/L vs. 1.10 [0.50–3.15] mg/L vs. 0.40 [0.15–0.83] mg/L, p = 0.249) but did not reach statistical significance.ConclusionsThe interictal CRP level is not likely to be a biomarker for EM or CM.

Lack of Associations Between C-Reactive Protein and Mood and Anxiety Symptoms in Adolescents.

Introduction: Increased peripheral inflammation has been consistently documented in both adult and pediatric depression. However, elevated levels of C-reactive protein (CRP), a nonspecific biomarker for inflammation, have been primarily reported in adults; whether CRP plays a similar role in adolescent depression has not been conclusively established. In our prior work, we identified relationships between CRP and reward neurocircuitry in adolescents with psychiatric symptoms (N = 64) but not with depressive symptoms. Extending this work, we sought to examine CRP across the full range of mood and anxiety symptom severity in a larger, clinically diverse cohort of psychotropic medication-free adolescents and healthy controls (HCs). Methods: Subjects were adolescents (N = 127, age: 15.17 ± 2.19 years, 78 female) with psychiatric symptoms (n = 96, including previous cohort of 64) and HC (n = 31). All completed a semi-structured psychiatric evaluation and dimensional assessments for depression, anxiety, anhedonia, and suicidality. Group-comparison and correlation analyses utilized nonparametric statistics controlled for body mass index, sex, and age at pFWE < 0.05. Results: No group differences were identified in CRP levels between the clinical cohort and HCs. In addition, correlations between CRP and clinical symptomatology were not significant in either the whole sample or the psychiatric group. Conclusions: We found that, unlike in adults, CRP was not associated with depressive symptoms. This suggests that inflammation in pediatric depression is more narrowly delimited at the onset of psychiatric symptoms and may only become systemic with chronicity.

Does Chronic Low-grade Systemic Inflammation Change Tumor Markers Levels in Patients on Hemodialysis?

End-stage renal disease (ESRD) patients are known to have a high risk of developing cancer-related inflammation. Elevated serum levels of tumor markers in ESRD/hemodialysis patients makes analysis and interpretation difficult.Aim: To verify the possible relationship between chronic low-grade systemic inflammation serum levels determined by C-reactive protein (CRP) and the tumor biomarkers in patients on hemodialysis.Materials and methods: A prospective study of prevalence was conducted in the Hemodialysis Sector of the University Hospital of the University of Brasília between July 2016 and December 2016 in men aged 18 to 60 years without clinically detectable cancer. We assessed inflammation by serum high-sensitivity CRP test (hs-CRP) and serum tumor in the case groups and controls. The hemodialysis group was split into two subgroups: group 1: patients with inflammation (CRP > 5 mg/L, n=27), and group 2: patients without inflam-mation (CRP ≤5 mg/L, n=33). There was no significant difference in age mean levels between case groups and controls (44.00±08.00 vs. 41.00±07.00, p=0.08). There was no difference or correlation (p>0.05) between tumor markers levels and patients with and without inflammation.Conclusions: The results of this study suggest that chronic low-grade systemic inflammation defined by C-reactive protein serum levels does not promote elevated serum PSA levels in chronic hemodialysis patients.

Assessment of high-sensitivity C-reactive protein tests for the diagnosis of hepatocellular carcinoma in patients with hepatitis B-associated liver cirrhosis.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, with high morbidity and mortality. Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma and the majority (~80%) of hepatocellular carcinoma patients in China exhibit co-morbidity with HBV-associated liver cirrhosis. The goal of reliable early diagnostic and prognostic techniques for HBV-associated HCC remains unrealized. The aim of the present study was to explore the efficacy of serum high-sensitivity C-reactive protein (hs-CRP) tests in the early diagnosis of HCC in patients with HBV-associated liver cirrhosis. A cohort of 493 patients with HBV-associated liver disease was divided into three groups: Chronic HBV (CHB) group; liver cirrhosis without HCC (LC) group; and liver cirrhosis with HCC (HCC) group. A further 47 healthy individuals comprised the healthy control (CN) group. Comparative analyses of clinical symptoms, histopathology, ultrasound imagery, computed tomography, magnetic resonance imaging, biochemistry [α-fetoprotein (AFP) and liver function enzymes], and hs-CRP tests were conducted across these four groups. Immunohistochemical analysis showed that CRP is strongly expressed in HCC tumor tissue, but is not expressed elsewhere. Analyses of the correlations between serum hs-CRP levels and HCC clinical parameters indicated that there was no correlation between serum hs-CRP levels, tumor Edmondson grade, tumor-node-metastasis stage and AFP status. Serum hs-CRP and AFP levels were found to be significantly elevated in the HCC group compared to those in the LC, CHB and CN groups (P<0.01). Receiver operator characteristic analysis showed that measurement of serum hs-CRP could differentiate HCC from HBV-associated liver cirrhosis, as well as increase the accuracy of HCC diagnoses. Additionally, measurement of hs-CRP and AFP together improved diagnostic accuracy for HCC compared with either test alone. Serum hs-CRP could have potential as an effective diagnostic tool to complement AFP in diagnosing HCC and improving the identification of AFP-negative HCC in patients with HBV-associated liver cirrhosis. The present findings may facilitate the earlier diagnosis of hepatocellular carcinoma, permitting more effective treatment and a broader spectrum of treatment modalities for patients with advanced hepatic disease.

Statin Helps Endothelial Function in COPD Subgroup

Statin Helps Endothelial Function in COPD Subgroup

Influence and Critique of the JUPITER Trial (Statins v No Statins for Primary Prevention of Cardiovascular Events in Patients with Normal Lipids and Elevated C-Reactive Protein)

Perhaps no recent trial in primary prevention of cardiovascular disease has resulted in more controversy than the JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial, which was first published in 2008. The study evaluated a patient cohort previously considered to be "healthy," ie, men 50 years of age or older and women 60 years of age or older, who did not have a history of cardiovascular disease and, at the initial screening visit, had a low-density lipoprotein cholesterol level of <130 mg/dL (3.4 mmol/L) and a high-sensitivity C-reactive protein level ≥2.0 mg/L. The trial showed that rosuvastatin is a powerful statin that, at lower doses, can reduce low-density lipoprotein cholesterol to levels previously not seen with other agents. Concurrently, it can also reduce high-sensitivity C-reactive protein to levels below what are considered normal, but that might be more physiologic. In the trial participants who achieved such lowering, major cardiovascular events, including venous thromboembolic events, were reduced even in the short term. Despite these results, many still question whether the trial results should influence high-sensitivity C-reactive protein testing or the prescription of statins for individuals at low risk for cardiovascular disease.

Immunoassay of C-reactive protein by hot electron induced electrochemiluminescence using integrated electrodes with hydrophobic sample confinement

C-reactive protein (CRP) was determined in the concentration range 0.01–10 mg L −1 using hot electron induced electrochemiluminescence (HECL) with devices combining both working and counter electrodes and sample confinement on a single chip. The sample area on the electrodes was defined by a hydrophobic ring, which enabled dispensing the reagents and the analyte directly on the electrode. Immunoassay of CRP by HECL using integrated electrodes is a good candidate for a high-sensitivity point-of-care CRP-test, because the concentration range is suitable, miniaturisation of the measurement system has been demonstrated and the assay method with integrated electrodes is easy to use. High-sensitivity CRP tests can be used to monitor the current state of cardiovascular disease and also to predict future cardiovascular problems in apparently healthy people.

Statin Therapy in Metabolic Syndrome and Hypertension Post-JUPITER: What is the Value of CRP?

Much evidence supports a pivotal role for inflammation in atherosclerosis. C-reactive protein (CRP), the prototypic marker of inflammation in humans, is a cardiovascular risk marker and may also promote atherogenesis. CRP levels are increased in metabolic syndrome and hypertension and confer increased risk of cardiovascular events in patients in these subgroups. Statins have been shown to lower low-density lipoproteins and CRP independently, and reduce cardiovascular events in subjects with and without metabolic syndrome and hypertension. In this review, we focus on the results from the primary prevention statin trial, Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), which showed reductions in LDL, CRP, and cardiovascular events. Post-JUPITER, the new guidelines will now need to consider recommending high-sensitivity CRP testing to intermediate-risk metabolic syndrome patients and those with hypertension and intermediate risk so that we can better identify candidates at greater risk and reduce cardiovascular burden in these subjects with statin therapy.

Expression of EMMPRIN (CD147) on circulating platelets in vivo.

EMMPRIN (CD147) is a matrix metalloproteinase inducer present on leukocytes and recently identified on platelets in vitro. We examined platelet CD147 expression in vivo and in correlation with markers of platelet activation and coronary artery disease (CAD). This prospective observational study involved 70 subjects (55 patients with CAD and 15 controls). Platelet CD62P expression, PAC-1 expression, platelet-leukocyte aggregates and CD147 (both platelet and leukocyte) expression were assessed by flow cytometry, and soluble CD62P expression was assessed by enzyme-linked immunosorbent assay. A full blood count and high-sensitivity C-reactive protein test were performed. CD147 was expressed on 20.45% +/- 1.63% (mean +/- standard error of the mean) of circulating platelets, whereas CD62P and PAC-1 were expressed on 0.87% +/- 0.12% and 0.90% +/- 0.27% of platelets, respectively. Platelet CD147 expression correlated with CD62P expression (r = 0.359, P = 0.002), PAC-1 expression (r = 0.428, P < 0.001), leukocyte CD147 expression (monocyte, r = 0.416, P = 0.001; granulocyte, r = 0.434, P < 0.001), C-reactive protein level and neutrophil/lymphocyte ratio (NLR). CAD patients had significantly higher CD147 mean fluorescence intensity than controls on circulating platelets (2.41 +/- 0.14 vs. 2.87 +/- 0.09, P = 0.014), monocytes (8.57 +/- 1.20 vs. 12.3 +/- 0.57, P = 0.006) and granulocytes (4.30 +/- 0.65 vs. 6.50 +/- 0.34, P = 0.005). Age adjustment eliminated the association between platelet CD147 expression and CAD, but the association between leukocyte CD147 expression and CAD persisted. According to multivariate analysis, the independent predictors of platelet CD147 expression were monocyte CD147 expression, NLR and age. Platelet CD147 expression is evident in vivo and correlates moderately with traditional platelet activation markers and leukocyte CD147 expression. Platelet CD147 expression shows a stronger association with age, and leukocyte CD147 expression a stronger association with clinical CAD, suggesting differences in the regulation of platelet and leukocyte CD147 expression in vivo.

Reduced serum levels of autoantibodies against monomeric C-reactive protein (CRP) in patients with acute coronary syndrome

Introduction Inflammation is pivotal in atherosclerosis. Minor C-reactive protein (CRP) response reflects low-grade vascular inflammation and the high-sensitivity CRP test with levels ≥ 3.0 mg/l predicts coronary vascular events and survival in angina pectoris as well as in healthy subjects. We and others recently reported autoantibodies against monomeric CRP (anti-CRP) in rheumatic conditions, e.g. systemic lupus erythematosus (SLE), and a connection between anti-CRP and cardiovascular disease in SLE has been suggested. Patients and methods Anti-CRP serum levels were determined with ELISA in 140 individuals; 50 healthy controls and 90 patients with angiographically verified coronary artery disease of which 40 presented with acute coronary syndrome (ACS) and 50 with stable angina pectoris (SA). Results Significantly lower anti-CRP levels were observed in ACS compared to SA and controls ( p = 0.019). ACS patients, who had not been prescribed statins before their respective cardiovascular event, had lower anti-CRP ( p = 0.049). BMI correlated directly to anti-CRP levels in cross section analysis ( p = 0.043), but there was no association between anti-CRP and smoking or cholesterol. Discussion In ACS, it is plausible that ruptured plaques and inflamed tissue may be more prone to opsonization by monomeric CRP leading to consumption of anti-CRP. Hypothetically, surface-bound anti-CRP could thereby enhance the local inflammation in plaques.

Basic Science for the Clinician 44

There has been a sea change in our understanding of atherosclerosis. We have come a long way from the days where eating too much fat and not getting enough exercise and having the wrong genetic background was thought to be the entire story. A few years ago, the cardiologists began to embrace inflammation as a possible pathogenetic mechanism and from that came high-sensitivity C-reactive protein testing for just about everyone. Chronic systemic inflammation became an area of interest. We have learned that it is more than just corticosteroid use that causes accelerated atherosclerosis in our rheumatoid and lupus patients. Even C-reactive protein may be a pathogenetic player, not only a diagnostic clue. Oxidized phospholipids and the cells that recognize them may be crucial in the evolution of the atherosclerotic plaque. Statins may be useful in suppressing inflammation, not only in suppressing cholesterol levels. And now even cardiologists are thinking about immune mechanisms! A strange world, but the beneficiaries of going through this looking glass will be our patients. A true understanding of this seems to have required a most circuitous route-sometimes you have to leave for a long journey before you can return and really see home for the first time.

High-sensitivity C-reactive protein test results predict fracture risk in elderly women

High-sensitivity C-reactive protein test results predict fracture risk in elderly women

Seasonal variation of C-reactive protein in apparently healthy Koreans

Background C-reactive protein (CRP) is known as an emerging recognized marker of the potential risk of myocardial infarction and stroke, and several studies have reported higher incidences of cardiovascular events during the winter months. Here, we investigated seasonal CRP variations using a high-sensitivity immunoradiometric assay in apparently healthy Koreans. Methods This study included 18,445 apparently healthy Koreans (12,064 men and 6381 women, 47.2 (11.5) years of age). Anthropometric indices of adiposity, metabolic variables, blood pressure (BP), and several cardiovascular risk factors were measured. High sensitivity CRP testing was performed by immunonephelometry. Results The mean (SD) CRP level in the study population was 1.66 (2.15) mg/L, and mean (SD) CRP levels in the spring, summer, fall and winter were 1.76 (2.30) mg/L, 1.51 (1.94) mg/L, 1.61 (2.08) mg/L, and 1.76 (2.30) mg/L, respectively. After adjusting for age, sex, diabetes, hypertension, regular exercise, smoking, and body mass index, the odds ratios of an elevated CRP in the spring, fall and winter season were 1.196 (95% CI, 1.024–1.396 p = 0.024), 1.086 (95% CI, 0.943–1.250 p = 0.251) and 1.258 (95% CI, 1.088–1.456 p = 0.002), respectively, as compared with the summer season. Conclusions Our results indicate a highly significant seasonal variation in CRP levels, with higher values during winter and spring than in summer. Elevated plasma CRP levels can be related to an increased risk of cardiovascular events, which are more prominent during the winter months. To further elucidate this relationship additional studies are needed.

Human Immunodeficiency Virus 1 Infection, Cocaine, and Coronary Calcification

Although cocaine use and human immunodeficiency virus (HIV) infection have been linked with clinical cardiovascular disease, the effects of cocaine use and HIV infection, especially the combination of the 2, on subclinical disease have rarely been reported. The objective of this study was to evaluate whether cocaine use alone, HIV infection alone, or a combination of the 2 is associated with coronary calcification, a marker of subclinical atherosclerosis. Between May 20, 2000, and March 31, 2003, 224 black study participants from Baltimore were enrolled in an observational study of subclinical atherosclerosis as related to HIV and cocaine use. Interviews about sociodemographic characteristics and drug use behaviors, clinical examinations, echocardiographic examinations, lipid profiles, high-sensitivity C-reactive protein tests, and computed tomographic scans for coronary calcium were performed. Although the overall investigation is a cohort study, the data presented herein are cross sectional only. The highest proportion (37.6%) of presence of coronary calcification was in the HIV-positive and cocaine-positive group, followed by 29.8% in the HIV-negative and cocaine-positive group, 28.6% in the HIV-positive and cocaine-negative group, and 18.8% in the HIV-negative and cocaine-negative group. Univariate analysis showed that HIV, cocaine use, and both were associated with a higher number of lesions, calcified area, volume, and calcium score. In multiple regression analysis with adjustment for age, body mass index, low-density lipoprotein cholesterol level, triglyceride level, mean corpuscular volume, and systolic blood pressure, HIV, cocaine use, and both were independently associated with coronary calcification. These results suggest that HIV infection alone, cocaine use alone, or the 2 combined may contribute to early subclinical atherosclerotic cardiovascular disease.

High Sensitivity C-Reactive Protein Tests: Ready for Widespread Use?

Atherosclerosis is viewed increasingly as a chronic inflammatory illness, a view that prompts strong interest in serum biomarkers of inflammation,

High-sensitivity C-reactive protein levels in players on a major league baseball team

We performed a high-sensitivity C-reactive protein test in major league baseball players. This test was of limited usefulness on preseason physical examination of 50 major league baseball players. The test is more likely to be of greater value performed on those whose 10-year risk of coronary heart disease is in the 10% to 20% range.

Coming of age of C-reactive protein: using inflammation markers in cardiology.

In a recently published prospective study comprising 28 000 women, Ridker et al1 showed that C-reactive protein (CRP) is a better predictor of the risk of cardiovascular events than low-density lipoprotein (LDL) cholesterol. The implication of this and many other supporting studies is profound and will change the way we screen and manage our patients with atherosclerosis and its associated clinical syndromes. CRP is one of the acute phase proteins that increase during systemic inflammation.2,3 Individuals without inflammation usually have CRP levels below 1 μg/mL; however, patients with bacterial infections, autoimmune diseases, and cancer frequently have CRP level as high as 100 μg/mL or even higher. It is clear that a high CRP level has no specificity in differentiating disease entities from one another. Despite its lack of specificity, CRP has now emerged as one of the most powerful predictors of cardiovascular risk. Even more remarkable, CRP’s predictive power resides in the range between 1 to 5 μg/mL, which was previously regarded to be normal in the era preceding the high-sensitivity CRP test. In fact, tests showing serum CRP levels greater than 10 μg/mL in apparently healthy men or women should be repeated to exclude occult infection or other systemic inflammatory process (see Figure). To understand CRP’s transition from an acute phase protein to a most useful inflammatory biomarker for predicting future cardiovascular events, we must know more about the role of the immune system in the pathogenesis of atherosclerosis. CRP level and cardiovascular risk. CRP levels are listed on the left and interpretations are on the …