Baseline hs-CRP Levels Research Articles

Clinical impact of systemic inflammation across the spectrum of different high-sensitivity CRP values in patients undergoing percutaneous coronary intervention

Abstract Background Systemic inflammation enhances atherosclerosis progression and is a well-established determinant of cardiovascular risk. High-sensitivity C-reactive protein (hsCRP), the most widely available biomarker of inflammation, has indeed been associated with the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). However, some heterogeneity exists in the threshold to define high hsCRP associated with increased cardiovascular risk, with the 2 and 3 mg/L cut-offs being used more commonly. Purpose We aimed to evaluate the clinical impact of systemic inflammation in patients undergoing PCI across the spectrum of baseline hsCRP values. Methods We retrospectively evaluated consecutive patients undergoing PCI with drug-eluting stent implantation from 2012 to 2022 at Mount Sinai Hospital (NY, USA). We excluded patients presenting with acute myocardial infarction or active cancer and those for whom baseline hsCRP was not available or was above 10 mg/L. Patients were stratified into three groups according to baseline hsCRP levels: <2.0, 2.0 to 3.0, and >3.0 mg/L. We estimated the risk of 12-month adverse events using the lowest hsCRP group (<2.0 mg/L) as reference. The primary endpoint was MACCE, defined as the composite of all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints were MACCE individual components, target vessel revascularization (TVR), stent thrombosis and bleeding. Results A total of 10,811 patients were included in the analysis. Of these, 6,210 (57.4%) had hsCRP <2.0 mg/L, 1,624 (15.0%) between 2 and 3 mg/L and 2,977 (27.6%) >3.0 mg/L. Incidence of anemia, diabetes mellitus, peripheral and cerebrovascular artery disease, atrial fibrillation and chronic kidney disease increased stepwise across hsCRP groups. Moreover, patients with higher hsCRP tended to present more frequently with unstable angina and higher baseline LDL cholesterol levels. As regards procedural variables, coronary artery disease severity and PCI complexity did not differ significantly across groups. When compared with patients with hsCRP < 2, hsCRP > 3 mg/L was associated with a greater adjusted risk of MACCE (4.9% vs 2.4%; HR 1.75 % CI 1.35 - 2.28), all-cause death (2.5% vs 0.9%, HR 2.34, 95%CI 1.57-3.47) and MI (2.5% vs 1.3%; HR 1.58 95%CI 1.11-2.26) (Figure 1). Risks of stroke, TVR, stent thrombosis and bleeding did not significantly differ across hsCRP groups (Table 1) Conclusions In patients undergoing PCI, elevated hsCRP values exceeding 3 mg/L exhibit a more robust association with the risk of MACCE and all-cause mortality, as compared with both hsCRP < 2.0 and between 2.0 and 3.0 mg/L. In this context, the use of hsCRP might improve the stratification of patients associated with higher inflammatory burden.

Evaluating the effects of empagliflozin in preventing myocardial injury in patients undergoing percutaneous coronary intervention: A double-blind, randomized clinical trial.

Percutaneous Coronary Intervention (PCI) is a fundamental procedure for coronary artery disease management, yet the risk of adverse events such periprocedural myocardial injury (PMI) persists. This double-blind, randomized clinical trial aims to assess the efficacy of empagliflozin in preventing myocardial injury during PCI procedure. A total of 90 patients were randomly assigned to two groups A and B; Group A as the intervention group received empagliflozin 25 mg 24 hours before and empagliflozin 10 mg 1-2 hours before coronary intervention and group Bas the control group received placebo at similar intervals. The primary outcome involved comparing baseline, 8-hour, and 24-hour cTnI and baseline and 24-hour hs-CRP levels after PCI in both groups to measure the incidence of periprocedural myocardial injury (PMI) and anti-inflammatory effects of empagliflozin. Baseline cTnI levels with P=0.955, 8 hours after PCI with P=0.469, and 24 hours after the intervention with P=0.980 were not statistically different in the two groups. Baseline levels of hs-CRP in both intervention and control groups were not statistically significantly different (P=0.982). Also, there was no statistically significant difference in hs-CRP levels 24 hours after PCI in two groups (P=0.198). Finally, the results showed that MACEs did not occur in any of the groups. The results of this trial could not express the advantages of acute pretreatment with empagliflozin in preventing PCI-related myocardial injury.

High-sensitivity C-reactive protein predicts microalbuminuria progression in essential hypertensive patients: a 3-year follow-up study.

To determine the independent effect of high-sensitivity C-reactive protein (hs-CRP) and the combined effects of hs-CRP and other traditional risk factors on microalbuminuria in hypertensive patients during the 3-year follow-up period. Baseline hs-CRP levels and other risk factors were measured in 280 adults in 2007. In the third year of examination, 199 patients (mean age 62.5 ± 9.5, men 59.3%) were approached for the measurement of microalbuminuria. The subjects were classified into two groups by the median of baseline hs-CRP. Compared to the patients with baseline hs-CRP below the median group ( n = 99, 50%), the group with baseline hs-CRP above the median ( n = 100, 50%) had higher urinary albumin-to-creatinine ratio (ACR) ( P = 0.007) at the end of follow-up period. ACR at the end of follow-up period was significantly correlated with baseline diabetes ( β = 0.342; P < 0.001), baseline SBP ( β = 0.148; P = 0.02), and baseline log-transformed hs-CRP ( β = 0.169; P = 0.01), while adversely correlated with baseline estimated glomerular filtration rate (eGFR) ( β = -0.163; P = 0.02) in multivariate stepwise linear analysis. In addition, ACR change during follow-up period was significantly correlated with baseline diabetes ( β = 0.359; P < 0.001) and baseline log-transformed hs-CRP ( β = 0.190; P = 0.004) in multivariate stepwise linear analysis. The combined effects of baseline hs-CRP and conventional risk factors, such as male sex, diabetes, smoking status, hyperlipidemia, hyperuricemia, and mildly reduced eGFR had a greater risk for microalbuminuria progression. There was no difference in eGFR changes during the follow-up period between two groups. Our findings offer a new piece of evidence on the predictive value of baseline hs-CRP for microalbuminuria progression in essential hypertensive patients, and highlight those who combined with traditional cardiovascular risk factors had a greater risk for developing microalbuminuria.

A retrospective study on the efficacy of Roxadustat in peritoneal dialysis patients with erythropoietin hyporesponsiveness.

Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.

Abstract P108: Stroke Incidence and High Sensitivity C-reactive Protein Among African Americans: The Jackson Heart Study

In the United States, strokes are a leading cause of death and disabilities, especially for older adults; however, effective biological markers to predict stroke remain elusive. The objective of this study was to investigate the association between inflammation, as measured by high-sensitivity c-reactive protein (hs-CRP) and stroke incidence among African Americans (AA) enrolled in a community-based longitudinal observational study, the Jackson Heart Study.Baseline hs-CRP levels were categorized in quintiles: Quintile 1 (0.0084 mg/L); Quintile 2 (0.0085 - 0.0189 mg/L); Quintile 3 (0.0190 - 0.036 mg/L); Quintile 4 (0.037 - 0.0675 mg/L); Quintile 5 (≥ 0.0676 mg/L). Stroke risk factors/covariates were compared across hs-CRP tertiles. Continuous variables were compared using a one-way ANOVA, and a Chi-Square test was used for categorical variables. To determine whether baseline hs-CRP levels were associated with stroke incidence, Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CI).Results from the unadjusted model of the Cox regression indicates hs-CRP levels in quintile 2 (HR 1.48; 95% CI 0.96-2.29), quintile 3 (HR 1.44; 95% CI 0.93-2.24), and quintile 4 (HR 1.09; 95% CI 0.68-1.74) were not associated with stroke incidence when compared to quintile 1 (reference). Participants with the highest hs-CRP levels, quintile 5, were at an increased risk for stroke (HR 1.78; 95% CI 1.17-2.72) compared to the reference quintile. In a fully adjusted model including risk factors and mediators for stroke/hs-CRP (demographics, anthropometrics, health condition covariates, health behavioral risk factors, and cardiovascular disease history), the increased stroke risk incidence remained present for quintile 5 (HR 1.87; 95% CI 1.17-2.98) compared to reference quintile 1.Overall, these results corroborate previous studies’ findings in Black Americans that hs-CRP is associated with stroke incidence only at most severe levels. Although several studies have demonstrated higher hs-CRP in AAs, there have been a lesser association of hs-CRP and cardiovascular disease; hence, these findings provide new insights that hs-CRP l may not be a reliable predictor for stroke incidence among AAs.

Impact of Bleeding Risk and Inflammation on Cardiovascular Outcomes After Percutaneous Coronary Intervention

BackgroundMarkers of systemic inflammation, such as high-sensitivity C-reactive protein (hsCRP), have been associated with the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). Whether this risk varies according to the presence of high bleeding risk (HBR) conditions is unclear. ObjectivesThe aim of this study was to evaluate the impact of systemic inflammation, as measured by hsCRP levels and cardiovascular outcomes in patients stratified by HBR status following PCI. MethodsConsecutive patients undergoing PCI between 2012 and 2019 with baseline hsCRP levels were included. High hsCRP was defined as >3 mg/L, and HBR was defined per the Academic Research Consortium HBR criteria. The primary outcome was MACCE, including all-cause death, myocardial infarction, or stroke at 1 year. All bleeding was assessed as a secondary outcome. ResultsA total of 15,150 patients were included, and 40.4% (n = 6,125) qualified as HBR. The adjusted risk for MACCE was consistently higher in patients with high hsCRP in both HBR (adjusted HR [aHR]: 1.49; 95% CI: 1.18-1.87) and non-HBR (aHR: 1.87; 95% CI: 1.31-2.66) subgroups, with no interaction between HBR status and hsCRP level (Pinteraction = 0.26). Conversely, although bleeding risk was higher in the HBR cohort, hsCRP did not predict the occurrence of bleeding in either the HBR (aHR: 1.04; 95% CI: 0.82-1.31) or the non-HBR (aHR: 0.99; 95% CI: 0.71-1.39) subgroup (Pinteraction = 0.539). ConclusionsElevated hsCRP at the time of PCI is associated with a higher risk for ischemic but not bleeding events, irrespective of HBR status.

Longitudinal changes in high sensitivity C-reactive protein associated with serum uric acid in the Korean Genome and Epidemiology Study

Cross-sectional studies support the role of serum uric acid (SUA) in inflammation, but evidence from cohort studies is scarce. Longitudinal associations between SUA and high-sensitivity C-reactive protein (hs-CRP) were examined in the general population. Data for participants from the Health Examinees-Gem cohort (n = 50,028; 40–69 years; 67% women) who were examined between 2004 and 2013 and followed up until 2016 were analyzed. SUA and hs-CRP were measured at baseline and during follow-up. SUA was evaluated as a continuous variable and was also divided into sex-specific quartiles. Mean hs-CRP levels at follow-up were evaluated using multivariable proportional odds regression, with non-linear smoothed baseline hs-CRP levels serving as a covariate. Selected pathological markers were also examined in relation to hs-CRP. Increased levels of SUA at baseline were related to increased levels of hs-CRP at follow-up [regression coefficient per mg/dL increase in baseline SUA (β) = 0.08, 95% confidence interval (CI), 0.040–0.128]. A dose–response relationship was observed, (P for linear trend = 0.0015). The mean values of hs-CRP were highest among participants with the highest follow-up but lowest baseline SUA levels. Elevated hs-CRP levels at follow up (> 3 mg/L) were positively related to fasting blood glucose levels, triglycerides levels, liver enzymes, and blood pressure, but negatively related to high density lipoprotein cholesterol levels per unit increase in baseline hs-CRP. High SUA levels were associated with high hs-CRP levels, suggesting a potential role of SUA in inflammation. However, additional research is needed to confirm these findings.

Biomarkers of chronic inflammation and cognitive decline: A prospective observational study.

We sought to determine whether the biomarkers of chronic inflammation predict cognitive decline in a prospective observational study. We measured baseline serum soluble urokinase plasminogen activator receptor (suPAR) and high sensitivity C-reactive protein (hs-CRP) levels in 282 participants of the University of Michigan Memory and Aging Project. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the Clinical Dementia Rating (CDR) scale for up to five time points. SuPAR and hs-CRP levels were not significantly higher in participants with mild cognitive impairment (n=97) or dementia (n=59), compared to those with normal cognitive function (n=126). Overall, 14% of participants experienced significant cognitive decline over the study period. The change in MoCA or CDR scores over time did not differ significantly according to baseline suPAR or hs-CRP levels. Chronic systemic inflammation, as measured by serum suPAR or hs-CRP levels, is unlikely to contribute significantly to cognitive decline.

Roxadustat on Renal Anemia with Macroinflammation: A Retrospective Cohort Study

Introduction: Roxadustat, the first-in-class drug for the treatment of renal anemia, has demonstrated efficacy in renal anemia with microinflammation. Additional data are needed regarding the efficacy of roxadustat on renal anemia with systemic macroinflammation. Methods: Three cohorts of renal anemia based on the basic level of high-sensitivity CRP were included. Patients with hsCRP ≤2 mg/L were selected as non-inflammation (NI) group; 2< hsCRP ≤10 mg/L as microinflammation (MI) group; hsCRP≥10 mg/L as macroinflammation (MA) group. Patients received oral roxadustat three times per week for 52 weeks. The primary end point was the hemoglobin level over weeks 12–52. The second end point was the cumulative proportion of patients achieving hemoglobin response by the end of week 12. Results: A total of 107 patients with chronic kidney diseases (CKDs) were enrolled. Overall, the baseline hemoglobin level of patients was 79.99 ± 11.20 g/L. Roxadustat could significantly increase the hemoglobin level in all of the three groups and did not show any significant difference (p > 0.05, respectively). Meanwhile, compared with that of the NI group, there was no significant difference in hemoglobin response rate in the MA group both at week 12 (p = 0.06; 95% confidence interval [CI], 0.9531–13.75) and week 52 (p = 0.37; 95% CI, 0.5080–7.937). Moreover, the hemoglobin response was independent of baseline hsCRP level (p = 0.72, 95% CI, −0.1139 to 0.0794). More importantly, roxadustat significantly reduced ferritin and serum iron levels and increased total iron-binding capacity in the three groups, which showed no significant differences among the three groups (p > 0.05, respectively). Conclusion: Roxadustat significantly improves anemia in CKD patients with systemic macroinflammation.

Proportion of patients with systemic inflammation and their characteristics for groups at high cardiovascular risk in phase 3 randomized placebo-controlled trials of semaglutide (SELECT, SOUL, FLOW)

Abstract Introduction Inflammation is a pathophysiological process associated with increased cardiovascular (CV) risk, with high-sensitivity C-reactive protein (hsCRP) used as a biomarker to predict CV risk. However, the prevalence of systemic inflammation (defined as hsCRP ≥ 2 mg/L) in contemporary cohorts with high CV risk, including CV disease (CVD), chronic kidney disease (CKD), obesity and/or type 2 diabetes (T2D), is not well characterized. Purpose To evaluate the proportion of individuals with systemic inflammation and the characteristics of individuals with and without systemic inflammation among groups at high risk of CV events, using baseline data from three ongoing randomized, placebo-controlled, phase 3 trials investigating the efficacy of semaglutide versus placebo in high CV risk populations (SELECT, SOUL and FLOW). Methods SELECT (NCT03574597) recruited adults ≥ 45 years old with a body mass index (BMI) ≥ 27 kg/m² and established CVD (previous myocardial infarction, ischaemic or haemorrhagic stroke, or symptomatic peripheral artery disease [PAD]), without diabetes. SOUL (NCT03914326) recruited adults ≥ 50 years old with T2D and at least one of coronary heart disease, cerebrovascular disease, symptomatic PAD or CKD (estimated glomerular filtration rate [eGFR] &amp;lt; 60 mL/min/1.73 m²). FLOW (NCT03819153) recruited adults ≥ 18 years old with T2D and CKD (eGFR ≥ 25–≤ 75 mL/min/1.73 m² and urinary albumin-to-creatinine ratio &amp;gt; 100–&amp;lt; 5000 mg/g) treated with renin-angiotensin-aldosterone system-blocking agents. Baseline hsCRP levels were measured in the three trials. Descriptive statistics were used to analyse the baseline characteristics of participants; p values were calculated with chi-squared tests using Yates’s correction for continuity. Results Baseline characteristics were available for 17 487 individuals from SELECT, 9577 from SOUL and 3519 from FLOW (Table), with systemic inflammation present in 47.2%, 49.5% and 56.8% of the trial populations, respectively. Across trials, PAD and heart failure were significantly more prevalent in individuals with hsCRP ≥ 2 mg/L than in those with hsCRP &amp;lt; 2 mg/L; in addition, CKD stage 3–5 and stroke were more prevalent in groups with hsCRP ≥ 2 mg/L in SELECT and SOUL. The following factors were characteristic of the groups with systemic inflammation in the three trials: female sex, younger age, higher BMI, lower levels of high-density lipoprotein cholesterol, and higher levels of glycated haemoglobin (HbA1c), total cholesterol, low-density lipoprotein cholesterol and triglycerides. Conclusion In these large phase 3 trials, systemic inflammation was present at baseline in approximately 50% of individuals and was associated with several CV and kidney risk characteristics. The large proportion of participants with systemic inflammation in the groups with high CV risk shown here supports systemic inflammation as a plausible therapeutic target for the prevention of recurrent CV events.

Prevalence of systemic inflammation in individuals with atherosclerotic cardiovascular disease: baseline characteristics from the SELECT, SOUL and FLOW phase 3 trials of semaglutide

Abstract Introduction Elevated levels of high-sensitivity C-reactive protein (hsCRP ≥ 2 mg/L) are a marker of systemic inflammation and a risk factor for atherosclerotic cardiovascular disease (ASCVD). We set out to determine the prevalence of systemic inflammation among individuals with ASCVD participating in the SELECT, SOUL and FLOW trials, three ongoing randomized, placebo-controlled, phase 3 trials investigating the efficacy of semaglutide versus placebo. Purpose To evaluate the prevalence of systemic inflammation among people with ASCVD with or without chronic kidney disease (CKD) who are enrolled in SELECT, SOUL and FLOW, and to characterize populations with ASCVD and CKD with and without systemic inflammation. Methods SELECT (NCT03574597) recruited adults ≥ 45 years old with a body mass index (BMI) ≥ 27 kg/m2 and established CVD (previous myocardial infarction, ischaemic or haemorrhagic stroke, or symptomatic peripheral artery disease [PAD]), without diabetes. SOUL (NCT03914326) recruited adults ≥ 50 years old with type 2 diabetes (T2D) and at least one of coronary heart disease, cerebrovascular disease, symptomatic PAD or CKD (estimated glomerular filtration rate [eGFR] &amp;lt; 60 mL/min/1.73 m2). FLOW (NCT03819153) recruited adults ≥ 18 years old with T2D and CKD (eGFR ≥ 25–≤ 75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio &amp;gt; 100–&amp;lt; 5000 mg/g) treated with renin-angiotensin-aldosterone system-blocking agents. Baseline hsCRP levels were measured in all trials; systemic inflammation was defined as hsCRP ≥ 2 mg/L. Descriptive statistics and chi-squared test with Yates’s correction for continuity were used to analyse the baseline characteristics for individuals with ASCVD (defined as at least one of previous myocardial infarction, stroke or PAD) and CKD stage 3–5 (eGFR &amp;lt; 60 mL/min/1.73 m2). Results A total of 4087 individuals with ASCVD and CKD and 20 331 with ASCVD without CKD were included. Systemic inflammation was present in a significantly larger proportion of individuals with ASCVD and CKD than with ASCVD but without CKD (56.2% vs 46.7%; p &amp;lt; 0.001). In the group with ASCVD, CKD and hsCRP ≥ 2 mg/L, heart failure, PAD and stroke were significantly more prevalent than in the group with hsCRP &amp;lt; 2 mg/L (Table). For individuals with ASCVD and CKD, the following factors were characteristic of systemic inflammation: female sex, smoking, younger age, higher BMI, lower eGFR and high-density lipoprotein cholesterol levels, and higher levels of low-density lipoprotein (LDL) cholesterol, triglycerides and glycated haemoglobin (HbA1c) (Table). Conclusion In these large, ongoing phase 3 trials, systemic inflammation, defined as hsCRP levels ≥ 2 mg/L, was present at baseline in &amp;gt; 55% of individuals with ASCVD and CKD. CV risk factors were more prevalent among individuals with hsCRP ≥ 2 mg/L than in those with hsCRP &amp;lt; 2 mg/L. Interventional studies are warranted to assess to what extent anti-inflammatory agents can address the associated ASCVD risk.Table

Associations of C-reactive protein with depressive symptoms over time after mild to moderate ischemic stroke in the PROSCIS-B cohort

Background and purposeC-reactive protein serves as a marker of inflammation and is linked to depression in the general population. We aimed to assess whether elevated baseline levels of high-sensitivity C-reactive protein (hs-CRP) are associated with depressive symptoms over time in a prospective cohort of mild-to-moderate first-ever ischemic stroke patients.MethodsData were obtained from the Prospective Cohort with Incident Stroke Berlin (NCT01363856). Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) at three annual follow-up points. We assessed the association of elevated levels of hs-CRP with CES-D scores over time via linear mixed models. In a subgroup analysis, we explored an interaction effect with sex.ResultsWe included 585 ischemic stroke patients with baseline data on CRP levels. The mean age was 67 (13 SD), 39% (n = 226) were female, and the median National Institutes of Health Stroke Scale (NIHSS) was 3 (IQR 1–4). Twenty percent of survivors showed evidence for depressive symptoms one year after stroke with CES-D ≥ 16, 21% at year two, and 17% at year three. Higher log-transformed baseline hs-CRP levels were associated with higher CES-D Scores over time in the adjusted linear mixed model (β = 1.28; (95% CI 0.22–2.34)). The subgroup analysis revealed an interaction effect of hs-CRP on depressive symptoms in women (β = 2.33; (95% CI 0.71–3.95)).ConclusionIn our cohort with mild-to-moderate first-ever ischemic stroke patients, hs-CRP levels were associated with more depressive symptoms over time, with an interaction effect for the female sex.Study registrationhttps://clinicaltrials.gov; Unique identifier: NCT01363856.

Baseline High-Sensitivity C-Reactive Protein as a Predictor of Adverse Clinical Events in Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Meta-Analysis.

Inflammation in patients with coronary artery disease (CAD) has been linked to adverse clinical outcomes. A useful biomarker for measuring inflammation levels, high-sensitivity C-reactive protein (hs-CRP) in the blood can be used to detect the presence of low-grade inflammation. This study sought to assess the predictive value of baseline hs-CRP levels for adverse clinical events in CAD patients undergoing percutaneous coronary intervention (PCI). To investigate this topic, a meta-analysis was performed. We conducted a systematic search of PubMed, Embase, and the Cochrane Library for original articles reporting the correlation between hs-CRP levels and adverse clinical events in CAD patients undergoing PCI. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and conducted a meta-analysis by extracting relevant data. Our pooled calculations yielded hazard ratios or odds ratios with 95% confidence intervals. A total of 28 studies comprising 60544 patients were included in this analysis. High baseline hs-CRP levels predicted increased risk for major adverse cardiac events (P = 0.037), major adverse cardiac and cerebrovascular events (P = 0.020), all-cause mortality (P = 0.001), cardiovascular mortality (P < 0.001), death and/or myocardial infarction (P = 0.017) in patients, as well as restenosis (P < 0.001). However, there was no association between elevated baseline hs-CRP levels and thrombosis. In conclusion, in CAD patients undergoing PCI, baseline hs-CRP levels are reliable predictors of major adverse cardiac events, major adverse cardiac and cerebrovascular events, all-cause mortality, cardiovascular mortality, death and/or myocardial infarction, and restenosis. Therefore, hs-CRP can effectively assist in prognosis determination for CAD patients undergoing PCI.

Peripheral inflammation associated with depression and reduced weight loss: a longitudinal study of bariatric patients.

Research implicates inflammation in the vicious cycle between depression and obesity, yet few longitudinal studies exist. The rapid weight loss induced by bariatric surgery is known to improve depressive symptoms dramatically, but preoperative depression diagnosis may also increase the risk for poor weight loss. Therefore, we investigated longitudinal associations between depression and inflammatory markers and their effect on weight loss and clinical outcomes in bariatric patients. This longitudinal observational study of 85 patients with obesity undergoing bariatric surgery included 41 cases with depression and 44 controls. Before and 6 months after surgery, we assessed depression by clinical interview and measured serum high-sensitivity C-reactive protein (hsCRP) and inflammatory cytokines, including interleukin (IL)-6 and IL-10. Before surgery, depression diagnosis was associated with significantly higher serum hsCRP, IL-6, and IL-6/10 ratio levels after controlling for confounders. Six months after surgery, patients with pre-existing depression still had significantly higher inflammation despite demonstrating similar weight loss to controls. Hierarchical regression showed higher baseline hsCRP levels predicted poorer weight loss (β = -0.28, p = 0.01) but had no effect on depression severity at follow-up (β = -0.02, p = 0.9). Instead, more severe baseline depressive symptoms and childhood emotional abuse predicted greater depression severity after surgery (β = 0.81, p < 0.001; and β = 0.31, p = 0.001, respectively). Depression was significantly associated with higher inflammation beyond the effect of obesity and other confounders. Higher inflammation at baseline predicted poorer weight loss 6 months after surgery, regardless of depression diagnosis. Increased inflammation, rather than depression, may drive poor weight loss outcomes among bariatric patients.

High sensitivity C reactive protein levels and atrial fibrillation recurrence after catheter ablation for atrial fibrillation: A systematic review and meta-analysis.

Atrial fibrillation (AF) recurrence after AF ablation is not uncommon. High sensitivity C reactive protein (hs-CRP) is a widely used inflammatory marker with a potential property to predict AF recurrence. We conducted a systematic review and a meta-analysis to find an association between hs-CRP levels and AF recurrence after ablation. We searched PubMed, Embase, and Wiley-Cochrane Library from inception to January 2022 for studies that reported hs-CRP levels in patients who underwent AF ablation. Weighted mean difference (WMD) was used to evaluate the difference between hs-CRP levels in post-ablation AF recurrent and non-recurrent group. Also, the difference between hs-CRP levels in pre- and post-ablation was determined. We identified 10 studies, and a total of 789 patients were included (299 recurrent vs. 490 non-recurrent patients). The mean age was 57.7 years (76.4% male). There was no difference in baseline hs-CRP levels between AF recurrent and non-recurrent group (WMD = 0.05, 95% CI = -0.04 to 0.15, p = 0.045). However, higher hs-CRP levels post-ablation were found in AF recurrent group (WMD = 0.09, 95% CI = 0.03-0.15, p < 0.001). There is no significant difference in baseline hs-CRP levels between AF recurrent and non-recurrent patients after AF ablation. However, higher post-ablation hs-CRP level was found in AF recurrent group. High Sensitivity C reactive protein may play a role as a predictor of AF recurrence.

856-P: Long-Term Safety and Efficacy Evaluation of Hydroxychloroquine in T2D

This prospective, multicentric, phase 4 study enrolled 747 T2D patients uncontrolled (A1c≥7) on Metformin+SU combination to receive add on HCQ 400 mg/day for 52 weeks. Primary outcome measure was, long term safety of HCQ evaluated in ITT population (n=747). Secondary outcomes were post treatment changes in glycemic, lipids and inflammatory parameters. Total of 191 AEs were reported in 111 patients, most were GI related (26.2%), mild in intensity (85%) and unlikely related (70%) to HCQ. Level 1 hypoglycemia was reported in 6.8% patients and mild NPDR in 11 patients. Of the 9 SAEs reported, 8 were unrelated and 1 (anemia) was probably related to HCQ. In mITTc population, the overall fall in A1c, FBG and PPG at week 12, 24 and 52 was significant from baseline. Additionally, a significant fall in TC, LDL-C, non-HDL-C was reported at week 24 and 52 from baseline. Patients were divided in two subgroups based on their baseline hsCRP levels (≤3 or ≥3). Of the 52% females enrolled, more than 60 % had high inflammatory load at baseline. There was significant fall in A1c, FBG, PPG, LDL-C, TC, and non-HDL-C at week 24 and 52 irrespective of baseline hsCRP. However, fall in A1C was significantly more at week 12 and 24 in patients with higher inflammatory load (hsCRP: ≥3) at baseline (p&amp;lt;0.0001). T2D is characterized by chronic low grade inflammation (meta-inflammation). HCQ has significantly reduced glycemic parameters with added benefits on lipids Disclosure A.Pareek: None. N.Chandurkar: None. K.B.Naidu: None. P.Dicholkar: None.

#2959 EFFICACY AND SAFETY OF ROXADUSTAT IN PATIENTS WITH ANEMIA OF DIALYSIS-DEPENDENT CKD WITH OR WITHOUT INFLAMMATION: A POOLED ANALYSIS OF 4 PHASE 3 STUDIES

Abstract Background and Aims Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia of chronic kidney disease (CKD). ESA hyporesponsiveness is prevalent in a significant portion of patients with CKD, especially those with end-stage renal disease on dialysis. Inflammation has been reported to contribute to ESA hyporesponsiveness and is associated with poor outcomes in patients with CKD. Roxadustat, an oral medication, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has previously demonstrated efficacy in patients with anemia of CKD. This pooled analysis evaluated the efficacy and safety of roxadustat in correcting hemoglobin (Hb) levels in subgroups of patients with dialysis-dependent (DD) CKD with or without inflammation at baseline. Method Data for this analysis were pooled from four phase 3, randomized, open-label, active comparator−controlled studies (HIMALAYAS [NCT02052310], ROCKIES [NCT02174731], PYRENEES [NCT02278341], SIERRAS [NCT02273726]) in patients with DD CKD. Outcomes evaluated were mean Hb change from baseline to Weeks 28−52 and mean weekly roxadustat dose (mg/kg) at Week 24 in patients with or without baseline inflammation (as determined by high-sensitivity C-reactive protein [hsCRP] level, divided into quintiles). Data were analyzed with an analysis of covariance model with baseline Hb as a covariate. Adjusted least-squares means, their difference, and corresponding confidence intervals were generated from datasets where missing data were imputed using missing at random-based multiple imputation, by treatment group, with baseline Hb, cardiovascular/cerebrovascular/thromboembolic history, geographical region (United States vs non-United States) and incident vs stable dialysis (≤4 vs &amp;gt;4 months) as predictor variables. Safety data were summarized descriptively. Results In total, 4072 patients with DD CKD (roxadustat N = 2022; ESA N = 2050) were evaluated. At baseline, mean Hb levels (g/dL [SD]) were similar in the roxadustat (9.80 [1.29]) and ESA (9.83 [1.29]) groups, regardless of baseline hsCRP levels (roxadustat hsCRP quintiles 1−5: 9.72 [1.43], 9.78 [1.27], 9.80 [1.32], 9.90 [1.18], and 9.79 [1.23], respectively; ESA hsCRP quintiles 1−5: 9.75 [1.34], 9.92 [1.23], 9.90 [1.23], 9.96 [1.23], and 9.62 [1.38], respectively). Hb change from baseline was greater in patients treated with roxadustat compared with ESA, regardless of baseline hsCRP levels (Fig. 1). At Week 24, patients with higher baseline hsCRP levels did not require higher doses of roxadustat compared to patients with lower baseline hsCRP levels (Fig. 2). The overall percentages of patients with at least one treatment-emergent adverse event were similar for patients treated with roxadustat (hsCRP quintiles 1−5: 86.7, 88.1, 86.6, 88.7, and 90.0, respectively) or ESA (hsCRP quintiles 1−5: 83.5, 84.6, 90.5, 88.2, and 87.9, respectively) across hsCRP quintiles. Conclusion In patients with anemia of DD CKD, roxadustat increased Hb levels without requiring increased doses of roxadustat in patients with or without baseline inflammation. Results from the current analysis suggest that roxadustat is effective, with a comparable safety profile to ESA, regardless of inflammation status.

Role of High-Sensitivity C-reactive Protein Levels in Predicting the Risk of Six-Month Event Rates in Patients With Chronic Stable Angina Undergoing Percutaneous Transluminal Coronary Angioplasty With a Drug-Eluting Stent.

Introduction This prospective observational study reports the association between baseline high-sensitivity C-reactive protein (hs-CRP) levels and adverse events at six months in patients who were diagnosed with symptomatic chronic stable angina and then underwent percutaneous transluminal coronary angioplasty (PTCA) with a drug-eluting stent (DES). Methods A total of 104 patients were examined with chronic stable angina over a period of six months. Before conducting percutaneous coronary intervention (PCI), the baseline levels of hs-CRP were measured, and based on the levels, the patients were grouped into high and low hs-CRP groups. Results The primary causes of death or the need for repeat revascularization or myocardial infarction or angina were concluded after assessing the patients for six months. A total of 104 patients were studied, amongwhich 72 (69.23%) had low hs-CRP and 32 (30.77%) had high hs-CRP levels. The number of males in this study was 68 (65.38%) and females were 36 (34.62%). The mean age of the patients was 55.26 ± 10.31 years. There were no significant differences among the groups in terms of gender, age, comorbidities, and risk factors except for certain predisposing factors like dyslipidemia and smoking. Moreover, we did not find any significant difference amongthe groups in the cause of death and myocardial infarction after a follow-up of six months. However, we observed a higher need for revascularization and angina outcomes in the group with high hs-CRP compared to low hs-CRP. Conclusion It can be concluded that a higher risk of angina and repeat revascularization is related to a high baseline hs-CRP but there is no evidence whether it is somehow linked to myocardial infarction and mortality or not.

The Role of High-sensitive C-Reactive Protein in predicting Severity of Coronary Artery Disease in Patients with Acute Coronary Syndromes

Objectives: We investigated the correlation between baseline C-reactive protein (Hs-CRP) levels and severity of coronary artery disease (CAD), measured in terms of Syntax Score (SScore), among patients presenting with acute coronary syndromes (ACS). Methodology: This cross-sectional study was conducted at the Armed Forces Institute of Cardiology (AFIC), Rawalpindi, from April 2022 to October 2022. Baseline Hs-CRP levels were obtained for all the patients. Patients were divided into three groups as per the SScore as low (≤ 22), intermediate (≥ 23), and high (≥ 33) burden of CAD. Results: Out of the 200 patients studied, 82.5% (165) were males, and mean age was 60.16±10.66 years. Diabetics were 50% (100) of the sample, 48.5% (97) were hypertensive, and smokers were 17.5% (35). Median Hs-CRP was 4.0 mg/L [2.0-12.5 mg/L], and median left ventricular ejection fraction (LVEF) was 45% [40-55%]. Median SScore was 23.5 [14.5-30.0], with 44.5% (89) categorized as low, 36.5% (73) as intermediate, and 19% (38) as high burden of CAD. The correlation between Hs-CRP and SScore was 0.236 (p=0.001) and -0.229 (p=0.001) with LVEF. A significant increase in Hs-CRP was observed in relation to the burden of CAD (p&lt;0.001) with median of 2.0 mg/L [1.0-4.2 mg/L], 6.0 mg/L [3.1-15.7 mg/L], and 12.5 mg/L [5.8-20.7 mg/L] for low, intermediate, high burden of CAD, respectively. Conclusion: Admission Hs-CRP was found to be positively correlated with the burden of CAD and negatively correlated with LVEF in patients with ACS.

Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors versus erythropoiesis-stimulating agents on iron metabolism and inflammation in patients undergoing dialysis: A systematic review and meta-analysis

AimsThis study aimed to evaluate the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) on iron metabolism and inflammation in dialysis-dependent chronic kidney disease (DD-CKD) patients. MethodsPubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov websites were searched for randomized controlled trials (RCTs) investigating HIF-PHIs versus ESAs for DD-CKD patients. Key findingsTwenty studies with 14,737 participants were included in the meta-analysis, which demonstrated no significant difference in the effect of transferrin saturation and ferritin between HIF-PHIs and the ESAs group (MD, 0.65; 95%CI, −0.45 to 1.75; very low certainty; SMD, −0.03; 95% CI, −0.13 to 0.07; low certainty). However, HIF-PHIs significantly increased the iron (MD, 2.30; 95% CI, 1.40 to 3.20; low certainty), total iron-binding capacity (SMD, 0.82; 95% CI, 0.66 to 0.98; low certainty), and transferrin (SMD, 0.90; 95%CI, 0.74 to 1.05; moderate certainty) levels when compared with the ESAs group. In contrast, the hepcidin level and dosage of intravenous iron were significantly decreased in the HIF-PHIs group compared with the ESAs group (MD, −15.06, 95%CI, −21.96 to −8.16; low certainty; MD, −18.07; 95% CI, −30.05 to −6.09; low certainty). The maintenance dose requirements of roxadustat were independent of baseline CRP or hsCRP levels with respect to the effect on inflammation. SignificanceHIF-PHIs promote iron utilization and reduce the use of intravenous iron therapy. Furthermore, HIF-PHIs, such as roxadustat, maintain the erythropoietic response independent of the inflammatory state. Thus, HIF-PHIs may be an alternative treatment strategy for anemia in DD-CKD patients, where ESA is hyporesponsive due to iron deficiency and inflammation.