Persistent Elevation Of C-reactive Protein Research Articles

2958. Investigating the mechanisms of persistent inflammation and the association with non-communicable diseases (NCDs), Tuberculosis (TB) recurrence, and other infections

Abstract Background TB continues to be a major cause of morbidity and mortality worldwide. Despite successful completion of anti-tuberculosis therapy (ATT), studies indicate that TB survivors (post-TB) have a significantly higher risk of mortality compared to the general population, primarily due to increased incidence of non-communicable diseases (NCDs; cardiovascular disease, cancer, lung disease) and recurrent infections. Furthermore, a considerable proportion of TB patients exhibit persistent inflammation even after ATT. Methods We enrolled 325 individuals with microbiologically confirmed pulmonary TB, diagnosed between 2014 and 2020. Blood samples were obtained at baseline and 12- months (6-months after completing antimicrobial therapy) to evaluate persistent inflammation. Plasma C-reactive protein (CRP) was used to measure inflammation. Lipid peroxidation (LP) was measured by oxidized (HNE) LDL. Redox capacity was measured via the Trolox assay. Immune activation was measured by the Indoleamine 2,3 dioxygenases (IDO) enzyme by measuring the Kynurenine-Tryptophan ratio. Results After successful TB treatment, 62% of participants exhibited persistent elevation of CRP (P< 0.001) (Figure 1a). Univariate analysis of the first 186 participants revealed no association between elevated post-TB inflammation and HIV status (Fig. 1B), gender, or age. Individuals with increased CRP levels had a lower redox capacity compared to those whose CRP normalized at the end of ATT (P< 0.001) (Figure 2). Analysis of Oxidized LDL in successfully treated TB patients demonstrated that low antioxidant capacity also had persistent LP (Figure 2b). IDO activity was increased among TB participants with high CRP, which persisted even after successful therapy in participants with high and low CRP levels (Figure 3). Fig 1a: CRP was evaluated on TB participants and their asymptomatic, healthy household contacts. The median CRP of the healthy contacts was <2 mg/L, whereas the median CRP for TB participants at baseline was 21 and decreased to 8 at the end of successful therapy (EOT). Previous studies have demonstrated that CRP levels >3 mg/L are associated with increased CVD risk . 62% (111/186) of TB participants have CRP levels >3 mg//L at the end of TB therapy. Fig 1b: All TB participants living with HIV (PLWH) are started on ART, with >90% having a viral load <1000 at end of therapy (EOT). At EOT, TB participants without HIV do not have lower CRP levels compared to PLWHIV, preliminarily suggesting HIV is not driving the persistent inflammation. Fig2a: The Trolox antioxidant capacity was evaluated on TB Participants with High CRP >3mg/L (n:36) vs Low CRP <3mg/L (n:32) and Healthy Controls (n:32). Conclusion This study shows that a substantial proportion of TB participants exhibit persistent inflammation and IDO activity even after ATT. Among TB participants who do not normalize inflammation at the end of successful therapy, there is also persistent LP and decreased redox capacity. This suggests that there is a bidirectional malignant relationship between LP and redox capacity. Potentially, this suggests that mitigating lipid peroxidation may help decrease post-TB inflammation. Fig2b: Oxidized LDL was measured in TB individuals with High levels of CRP High CRP >3mg/L (n:16) vs Low CRP <3mg/L (n:16) and Healthy Controls (n:4) Fig3 Plasma Kynurenine to Tryptophan ratio was evaluated in TB individuals with persistent augmented levels of CRP (n:19) at baseline and Heathy Controls. At the end of Therapy the KYN:TRYP was evaluated in TB individuals with high (n:22) and Low CRP levels (n:17) Disclosures All Authors: No reported disclosures

Single and persistent elevation of C-reactive protein levels and the risk of atrial fibrillation in a general population: The Ansan-Ansung Cohort of the Korean Genome and Epidemiology Study

BackgroundInflammation has been reported to cause atrial fibrillation (AF). However, it remains unclear whether C-reactive protein (CRP) levels predict AF. We investigated whether there was an association between serum CRP levels and the development of AF. MethodsA total of 10,030 subjects aged between 40 and 69 years were enrolled and followed biennially over a 12-year period in the Ansan-Ansung cohort study. Serum CRP levels were measured at baseline and high-sensitivity CRP (hsCRP) levels were measured at every revisit. AF was identified using 12-lead standard electrocardiography. Inverse probability of treatment weighting was applied to balance the confounders of AF development between groups. ResultsSerum CRP levels were higher in subjects with AF at baseline and those with new-onset AF than in those without AF. Cox-regression analysis showed that high CRP levels (>3 mg/L) and intermediate CRP levels (1–3 mg/L) at baseline were not associated with a higher risk of new-onset AF compared with low CRP levels (<1 mg/L) after adjustments for covariates. The weighted incidences of AF also did not differ according to the CRP levels. In contrast, persistent elevation of CRP or hsCRP levels (≥1 mg/L at all visits) was associated with a higher risk of AF compared with nonpersistent elevation of CRP or hsCRP levels after adjustment for covariates in both unweighted and weighted cohorts. ConclusionA high CRP level at a single measurement was not associated with the risk of AF, whereas persistently elevated CRP levels independently predicted the development of AF.

Association of increased CD8+ and persisting C-reactive protein levels with restenosis in HIV patients after coronary stenting.

The life expectancy of HIV-infected patients has recently been increasing. Although the mortality and morbidity associated with AIDS is decreasing, those associated with cardiovascular diseases and percutaneous coronary intervention (PCI) are receiving greater attention. Only limited data regarding coronary restenosis are available in these patients. In this prospective, systematic angiographic follow-up study, we enrolled HIV patients who underwent PCI for de-novo lesions and subsequent routine angiographic follow-up for 6-8 months. Angiographic restenosis was defined as stenosis of at least 50% of the in-segment area. Univariate and multivariate analyses were performed to evaluate restenosis and its predictors. Between May 2002 and March 2014, 47 patients with HIV underwent PCI in two high-volume centers in Munich, Germany. Of these patients, 41 with 131 de-novo lesions underwent invasive surveillance. One-quarter of the lesions treated subsequently presented with restenosis. Univariate analysis indicated that CD8 T-cell levels (P = 0.006), serum cholesterol (P = 0.042) and low-density lipoprotein-cholesterol (P = 0.042) levels at baseline, total number of stents (P = 0.047), and C-reactive protein level (P = 0.001) at follow-up were associated with restenosis. Multivariate analysis indicated that CD8 T-cell levels (P = 0.006) and persistent C-reactive protein elevation at 6-month follow-up (P = 0.00013) were independent predictors of restenosis. Inflammation, represented by CD8 T-cell levels, and persistent C-reactive protein elevation are independent predictors of angiographic restenosis and should therefore be closely monitored in HIV patients undergoing PCI.

Correlation Between Intense Postoperative Inflammatory Response and Survival of Esophageal Cancer Patients Who Underwent Transthoracic Esophagectomy.

The correlation between postoperative systemic inflammation and cancer survival needs to be elucidated. This study evaluated postoperative inflammation using the peak concentration of postoperative serum C-reactive protein (CRP) levels and duration of CRP elevation, then investigated its correlation with prognosis. The study retrospectively reviewed 216 consecutive patients who underwent curative transthoracic esophagectomy at the authors' institution between 2004 and 2012. The postoperative serum CRP levels in 215 patients were analyzed during 14 days after esophagectomy. The patients' characteristics, surgical procedures, postoperative complications, and survival were investigated. To evaluate postoperative inflammatory status objectively using CRP, patients with a delayed CRP level peak and persistent CRP elevation were classified as having an intense postoperative inflammatory response (IIR). The distributions of postoperative pathologic stages 0, 1, 2, 3, and 4 were respectively 5, 70, 58, 66, and 16. Regarding postoperative complications, pneumonia was diagnosed in 42 patients (20 %), anastomotic leakage in 32 patients (15 %), and superficial surgical-site infection in 21 patients (10 %). A delayed CRP level peak was observed in 88 patients (41 %) and persistent CRP elevation in 49 patients (23 %). Overall, 31 patients (14 %) were classified as having IIR. In the survival analysis, the patients with IIR showed a significantly shorter overall survival. In the multivariate analysis, using histology, neoadjuvant treatment, field of lymph node dissection, pathologic stage, and IIR as covariates, IIR was seen as a significantly independent predictive factor for overall survival (hazard ratio 2.019; P = 0.019). In this study, IIR was significantly correlated with postoperative survival. Therefore, the oncologic benefit of reducing postoperative inflammation in esophageal cancer needs to be investigated.

Longitudinal Patterns of CRP Elevation and Crohnʼs Disease Severity

Purpose: C-reactive protein (CRP) is a biochemical marker that correlates with inflammation in Crohn's disease (CD). CRP confirms active inflammation and may function as a prognostic indicator of poor outcome. CD currently lacks a severity index, which stratifies groups of patients based on their burden of illness over time. We hypothesized that patterns of CRP elevation in CD patients followed longitudinally may correlate with disease-related complications and function as a biochemical marker of severity. Methods: Prospectively recruited CD patients from a longitudinal IBD natural history registry followed between 2009 and 2011, with annual visits and CRP evaluation, were analyzed. Short IBD questionnaire (SIBDQ) and Harvey-Bradshaw Index (HBI) scores completed at each visit, patterns of IBD-related hospitalization, and emergency department (ED) use were analyzed. Mean SIBDQ scores over 3 years > 50 were considered good quality of life. Results: A total of 153 CD patients were included in our study; 42.5% (65) were males, while 57.5% (88) were females. Patients had a mean age of 43.4 years (SD 14.2; range 21.4-81.2 years). Sixty-five of the 153 patients (42.5%) had no CRP elevation during the study period, while 57.5% of patients (88) had at least one CRP elevation. Among the patients with elevation in CRP, 23.55% (36) had CRP elevation in 1 year, 20.3% of patients (31) had CRP elevation in 2 of the 3 years, while 13.7% (21) had CRP elevation in all 3 years of the study. When comparing ED visits, 54% of patients with at least one CRP elevation over 3 years had an ED visit, as compared to 30% of patients with normal CRP over 3 years (p=0.026). 67.2% of patients (43) with normal CRP elevation over 3 years had a good quality of life, which was significantly higher than CD patients with CRP elevations over 1, 2, and 3 years (41.7%, 33.3%, and 30%, respectively); p=0.002. When comparing hospitalizations, 64% of patients with at least one CRP elevation in any of the 3 years of the study period required a CD-related hospitalization, as compared to 20% of patients with no CRP elevation in these 3 years (p<0.001). The HBI was significantly higher in patients with any CRP elevation compared to no CRP elevation (3.4 vs. 5.3, p<0.001). Conclusion: Prospective evaluation of CRP elevation in CD patients over a 3-year study period correlated with increased rates of ED use and hospitalization. Persistent elevation in CRP over multiple years correlated with worse quality of life in CD. CRP elevation carries important prognostic ramifications for CD-related complications, and persistent CRP elevation may define a sub-group of CD patients with severe and refractory disease.

Advanced age influences the dynamic changes in circulating C-reactive protein following injury

BackgroundThe concentration of C-reactive protein (CRP), a biomarker of systemic inflammation, is determined by genetic, clinical and demographic factors including gender, smoking and body mass index (BMI). The influence of...

Rupture of Renal Mycotic Aneurysm that Developed during the Treatment of Streptococcal Infective Endocarditis and Vertebral Osteomyelitis

A 50-year-old woman received two weeks of cefozopran and two weeks of imipenem for streptococcal endocarditis and vertebral osteomyelitis. Subsequently she received four weeks of oral levofloxacin and eight weeks of oral clarithromycin due to persistent elevation of C-reactive protein. Finally, she was admitted to our hospital due to massive hematuria. Abdominal CT showed rupture of an aneurysm in the right kidney and emergent coil embolization was performed. Multiple sets of blood culture grew Streptococcus oralis, and transthoracic echocardiography revealed vegetation at the aortic valve. Retrospective review of the abdominal images revealed the emergence of the aneurysm during the treatment.

Elevated serum C-reactive protein as a predictive factor for anastomotic leakage in colorectal surgery

BackgroundC-reactive protein (CRP) has been used as an indicator of postoperative complications in abdominal surgery. Its short half-life makes it a reliable marker of the systemic inflammatory response secondary to a surgical procedure or to the appearance of complications, rapidly returning to normal values with the recovery of the patient. AimTo demonstrate the value of sequential serum determinations of postoperative C-reactive protein (CRP) and white blood cell counts (WBC) in the identification of increased risk of anastomotic leakage after colorectal surgery. MethodsWe reviewed the daily postoperative serum CRP and white blood cell counts in 173 patients who underwent surgery for colorectal disease with anastomosis, between January 2008 and October 2009. Patients with anastomotic leakage (Group A, n = 24) were compared to patients without leakage (Group B, n = 149). Patients with ongoing infections before surgery or with acquired postoperative infections other than leakage were excluded. Mean pre- and postoperative values of CRP and WBC were compared. ResultsThe diagnosis of anastomotic leakage was made between the 4th and 11th postoperative day (POD; mean 7th POD). The daily average values of serum CRP were significantly higher in group A starting at the 2nd POD and remained significantly elevated until the diagnosis of leakage (p = 0.003). The cut-off value of 140 mg/L on the 3rd POD maximized the sensitivity (78%) and specificity (86%) of serum CRP in assessing the risk of leakage. Comparison of postoperative serum WBC values did not show any significant differences between the two groups until the 6th POD. ConclusionAccording to these results, an early and persistent elevation of CRP after colorectal surgery with anastomosis, is a marker of anastomotic leakage. A cut-off value > 140 mg/L on POD3 maximizes sensitivity and specificity.

W1659 Persistent Elevation of C-Reactive Protein After Gastro-Oesophageal Cancer Resection as a Predictor of Post-Operative Intra-Abdominal Infective Complications

W1659 Persistent Elevation of C-Reactive Protein After Gastro-Oesophageal Cancer Resection as a Predictor of Post-Operative Intra-Abdominal Infective Complications

Prospective Association Between C-Reactive Protein and Fatigue in the Coronary Artery Risk Development in Young Adults Study

Fatigue is highly prevalent and causes serious disruption in quality of life. Although the underlying biological mechanism is unknown, increases in inflammation have been implicated. This prospective study examined the association between C-reactive protein (CRP), a biomarker of systemic inflammation, and fatigue 5 years later. The Coronary Artery Risk Development in Young Adults (CARDIA) study is a population-based longitudinal study conducted in four U.S. cities. Highly sensitive CRP concentration and fatigue were measured in 2983 African American and white adults at both year 15 (2000-2001, ages 33-45 years) and year 20 (2005-2006) examinations. Fatigue was assessed using the vitality subscale of the 12-item Short Form Health Survey. Plasma CRP concentration at baseline (i.e., CARDIA year 15) was a significant predictor of fatigue level 5 years later (unadjusted beta = .126, p < .001). After adjustment for potential confounders, this association remained significant (adjusted beta = .044, p = .033). Additionally, baseline CRP independently predicted fatigue in the subgroup of participants without medical comorbidity (adjusted beta = .051, p = .039). Fatigue was associated with a persistent elevation of CRP at both examinations but not with a transient elevation of CRP at only one of the examinations. This is the first study to demonstrate a prospective association between an inflammatory marker and fatigue in a general population. Furthermore, the association between low-grade systemic inflammation and fatigue seems primarily driven by persistent immune activation and not explained by the presence or development of medical comorbidity.

C-reactive protein as early predictor for infectious postoperative complications in rectal surgery

This study evaluated the role of the acute phase C-reactive protein (CRP) in the postoperative course of a large series of rectal resections on the basis of a prospective database. Main focus of this study was the early identification of complications. Three hundred eighty-three rectal resections with primary anastomosis for rectal cancer were screened for infectious postoperative complications. Forty-eight complicated cases were identified and matched with 48 patients with an uneventful postoperative course. In the postoperative setting, CRP peaked on postoperative day (POD) 2 with a median serum CRP of 140 mg/l and gradually declined thereafter in uncomplicated cases. In complicated cases, CRP elevation generally persisted after POD 2, whereas white blood cells and body temperature were within normal range in the early postoperative period. A cutoff CRP value of 140 mg/dl on PODs 3 and 4 resulted in predictive values of 85.7 and 90.5% (adjusted to the prevalence: 37.6 and 50.3%), sensitivities of 80.0 and 54.3%, and specificities of 81.0 and 92.3% for a complicated postoperative course (P<0.001), respectively. Persistent CRP elevation and elevation of serum CRP above 140 mg/dl on PODs 3-4 are predictive of infectious postoperative complications and should prompt intense clinical search for an inflammatory process, especially for an anastomotic leak if pneumonia and wound infection are unlikely or excluded.

Persistent Elevation of C-Reactive Protein May Predict Cardiac Hypertrophy and Dysfunction in Patients Maintained on Hemodialysis

Background: C-reactive protein (CRP), which reflects chronic inflammation, is a strong predictor of cardiovascular mortality in hemodialysis patients. We investigated whether persistent elevation of CRP is associatedwith cardiac function and morphology in patients maintained on hemodialysis. Methods: Predialysis high-sensitivity CRP (hs-CRP) was measured twice at an interval of 3 weeks in 52 stable hemodialysis patients, and echocardiographic studies were performed. Results: 25 patients showed persistent elevation of predialysis hs-CRP (>3 mg/l, high CRP group). Patients in the high CRP group had a lower dialysis dose (p < 0.01), higher troponin T (p < 0.01), and higher fibrinogen (p < 0.01). Echocardiographic studies showed that left atrial diameter (LA, p < 0.05), interventricular septal thickness (IVST, p < 0.05), left ventricular end-diastolic volume (LVEDV, p < 0.05), and left ventricular mass index (LVMI, p < 0.05) were higher in the high CRP group. However the ejection fraction (EF) was lower in the high CRP group (p < 0.05), which also contained more patients with low EF (<40%) (p < 0.01). There was no difference in diabetes mellitus, acute infection and type of vascular access between the groups. hs-CRP level was positively correlated with troponin T (r = 0.416, p < 0.01) and fibrinogen (r = 0.560, p < 0.001), and IVST with hs-CRP level (r = 0.291, p < 0.05), whereas the EF was negatively correlated with hs-CRP(r = –0.301, p < 0.05). In addition, the high CRP group correlated positively with IVST (r = 0.281, p < 0.05), LVEDV (r = 0.322, p < 0.05), and LVMI (r = 0.312, p < 0.05) and negatively with EF (r = –0.311, p < 0.05). On multivariate analysis, the high CRP group (β = –0.312, β = 0.238, and β = 0.318, respectively) was a significant predictor of EF (R = 0.62, p = 0.025), LVMI (R = 0.928, p = 0.02) and IVST (R = 0.64, p = 0.01). Conclusions: Persistent elevation of CRP, which is an independent risk factor for EF, LVMI and IVST, may predict cardiac hypertrophy and dysfunction in patients maintained on hemodialysis.

The prognostic impact of fluctuating levels of C-reactive protein in Brazilian haemodialysis patients: a prospective study

A single elevated C-reactive protein (CRP) value predicts mortality in haemodialysis (HD) patients, but the relative importance of repeated vs occasional positive systemic inflammatory response findings is not known. To assess the influence on survival of occasional inflammation, CRP, serum albumin (S-Alb) and fibrinogen were analysed bimonthly in 180 HD patients (54% male, 49+/-14 years). Clinically significant inflammation was defined as CRP >5.1 mg/l, based on the receiver operating characteristics curve for CRP as predictor of death. Based on four consecutive measurements of CRP, patients were assigned into three groups: group 1 (n = 74; 41%), no inflammation (CRP < or = 5.1 mg/l in all measurements); group 2 (n = 65; 36%), occasional inflammation (1-3 measurements of CRP > 5.1 mg/l); and group 3 (n = 41; 23%), persistent inflammation (all measurements of CRP >5.1 mg/l). The nutritional status was evaluated by subjective global assessment (SGA) and body mass index (BMI), and the survival (21 months of follow-up) by Kaplan-Meier curve and Cox model. The median and range of CRP values (mg/l) for group 1, 2 and 3 were: 3.2 (3.2-5.1), 3.6 (3.2-54.9) and 13.8 (5.2-82), respectively (P<0.001), whereas the prevalence of malnutrition, assessed by SGA and BMI, did not differ significantly between the groups. The survival rate by Kaplan-Meier analysis was significantly different among the groups (chi2 = 12.34; P = 0.0004). Patients in group 3 showed the highest mortality (34%; P = 0.001), compared with group 1 (8%) and group 2 (14%; P = 0.01), respectively, whereas there was no significant difference in mortality between groups 1 and 2. Age, CRP, S-Alb level and SGA were independent predictors of mortality. The patients with a persistent elevation of CRP had a higher mortality rate than the patients with occasional CRP elevation. Thus, persistent, rather than occasional, inflammation is an important predictor of death in HD patients.

C-reactive protein as a cardiovascular risk factor and its therapeutic implications in end-stage renal disease patients.

We observed the association between a persistent elevation of C-reactive protein (CRP) level and the presence of ischemic heart disease in 73 peritoneal dialysis (PD) patients. Twenty-six patients showed an elevation of CRP for more than 6 months. Seventeen (65%) of the 26 patients had positive thallium single photon computed tomography (SPECT). Three of 9 patients who had a persistent elevation of CRP and negative thallium SPECT had a history of cerebral infarction or peripheral vascular disease. Therefore, 77% (20/26) of an elevated CRP level that lasted longer than 6 months can be explained by the presence of atherosclerotic vascular disease. There are as yet no valid recommendations on how chronic inflammation should be handled. We found that aspirin 200 mg daily for 8 weeks induce no significant changes of the CRP levels in PD patients (0.22 vs. 0.18 mg/dL, p > 0.05). However, 62 HD patients were randomly assigned to treatment group (simvastatin 20 mg/day) and control group. After 8 weeks medication, hs-CRP levels significantly reduced from a median of 0.23 mg/dL to 0.12 mg/dL.

Persistent elevation of C-reactive protein and ischemic heart disease in patients with continuous ambulatory peritoneal dialysis.

We evaluated the association between a persistent elevation of C-reactive protein (CRP) level and the presence or severity of ischemic heart disease (IHD) in patients with continuous ambulatory peritoneal dialysis (CAPD). Seventy-three patients, who were over 40 years old, underwent dipyridamole thallium single photon emission computed tomography (SPECT), and followed-up for more than 1 year were enrolled. We measured stored plasma for CRP every 3 months. Elevation of CRP was defined as greater than or equal to 5 mg/L and persistent elevation of CRP as elevated CRP levels that lasted longer than 6 months. Serum albumin, cholesterol, lipoprotein(a), and plasma fibrinogen were measured at 3 months after the start of CAPD. Twenty-six patients showed an elevation of CRP for more than 6 months during the follow-up period. Twenty-eight patients showed positive findings on thallium SPECT. Coronary angiography showed significant stenosis (narrowing of the diameter more than 50%) in 23 of the 25 patients studied. Seventeen (65%) of 26 patients who had an elevated CRP level for longer than 6 months had positive thallium SPECT. The presence of diabetes, albumin, fibrinogen, and the presence of a persistent elevation of CRP were different between the patients with positive (n = 28) or negative thallium SPECT (n = 45). A multivariate logistic regression analysis showed that a persistent elevation of CRP is the only predictor of positive thallium SPECT (P = 0.002). There was a tendency of association, although it was not statistically significant, between the persistence of CRP elevation and the severity of IHD (P = 0.066). Three of 9 patients who had a persistent elevation of CRP and a negative thallium SPECT had a history of cerebral infarction or peripheral vascular disease. Therefore, 77% (20/26) of an elevated CRP level that lasted longer than 6 months can be explained by the presence of IHD or other atherosclerotic vascular disease. In conclusion, a persistent elevation of CRP level in patients with CAPD was strongly associated with IHD. For patients who have a persistent elevation of CRP without an apparent cause, we recommend a workup for IHD or other atherosclerotic cardiovascular disease.