High-sensitivity C-reactive Protein Levels Research Articles

Evaluating the effect of the antiPCSK9 vaccine on systemic inflammation and oxidative stress in CFA-challenged albino mice

Abstract Background Besides effective lipid lowering therapy aimed to reduce LDL-C, one should always look at other risk factors that may essentially increase the risk of residual cardiovascular disease risk, including diabetes, thrombotic factors and inflammation. Purpose To find whether the antiPCSK9 vaccine can affect the serum C-reactive protein (CRP) and oxidative stress during acute systemic inflammation. Methods Male albino mice were randomly divided into three groups, including non-treated mice (the sham group), mice treated with Freund's complete adjuvant (CFA) (the CFA group), and vaccinated mice treated with CFA (the vaccine group). The vaccine group was subcutaneously immunized with the antiPCSK9 formulation, four times in bi-weekly intervals. To induce inflammation, all mice were subjected to the CFA challenge after the vaccination plan. To determine the efficacy of the antiPCSK9 vaccine in albino mice, plasma antiPCSK9 antibody titer, plasma PCSK9 concentration, and PCSK9/LDLR interaction were assayed. The serum level of high-sensitive CRP (hs-CRP) and oxidative stress status were evaluated by a mouse CRP ELISA kit and the pro-oxidant antioxidant balance (PAB) assay, respectively. Results Upon three boosters, the vaccine induced a high-titer IgG antiPCSK9 antibody in albino mice, which was accompanied with a significant reduction in the plasma level of the free PCSK9 (-24.7% and -28.5% compared with the sham and CFA group, respectively), and the inhibition of PCSK9/LDLR interaction (-27.8% and -29.4% compared with the sham and CFA group, respectively). In addition, the serum level of hs-CRP was significantly increased in the vaccine and CFA groups by 225% and 274%, respectively, when compared with the sham group; however, it was non-significantly decreased (-18%) in the vaccine group in comparison with the CFA group (Figure 1A). Moreover, the PAB values indicated that oxidative stress was significantly increased in the CFA group (by 72.7%) and the vaccine group (by 76%) when compared to the sham group; however, there was no significant difference in the PAB values between the vaccine and CFA groups (Figure 1B). Conclusion Our results indicate that, despite inducing the production of the functional antiPCSK9 antibodies, the antiPCSK9 vaccine failed to significantly reduce the serum hs-CRP and oxidative stress induced in the CFA-challenged albino mice. Figure 1. The effect of the antiPCSK9 vaccine on (A) the serum level of hs-CRP in albino mice and (B) the serum PAB in albino mice. The sham group involved non-treated mice, the CFA group involved the CFA-treated mice, and the vaccine group involved mice who after vaccination were treated with the CFA. Pooling of samples was performed to obtain sufficient sample volume for assay, when needed. The PAB values were expressed in an arbitrary HK (Hamidi-Koliakos). Data are expressed as mean ±SD (10 mice per group). Statistical differences at a p-value <0.05 were considered as significant.Figure 1.

Abstract 15908: A Meta-Analysis Revealing an Association Between High Sensitivity C-Reactive Protein Levels and Cognitive Impairment After 3-Months of Ischemic Stroke

Introduction: Cognitive impairment has a significant impact on functional recovery and quality of life in stroke patients. Given the emerging role of high sensitivity C-reactive protein (hs-CRP) as a biomarker for predicting post-stroke cognitive decline, we conducted a meta-analysis to investigate this association. Methods: We systematically searched SCOPUS, PubMed, and Google Scholar databases until May 2023 using relevant keywords. Pooled effect sizes were estimated using a random-effects model, and I2 statistics and leave-one-out sensitivity analysis were performed to assess heterogeneity and robustness, respectively (p-value < 0.05 considered significant). Results: The final analysis included five studies spanning the years 2018-2023, with a total sample size of 9,625 patients, all from China, and predominantly male (57.85%). The median follow-up period was 3 months. Patients with higher hs-CRP levels had a higher burden of smoking, alcohol consumption, hypertension, diabetes, hyperlipidemia, and lower education levels. The meta-analysis revealed an increased risk of cognitive impairment after ischemic stroke associated with higher hs-CRP levels (adjusted odds ratio [aOR] 1.15; 95% CI: 1.01-1.30, p - 0.03). Substantial heterogeneity was observed among the studies (I2 = 79.23%; p < 0.01). However, a leave-one-out sensitivity analysis confirmed the robustness of the findings, indicating that no single study strongly influenced the overall results. Conclusion: This meta-analysis provides evidence of an association between elevated hs-CRP levels and cognitive impairment following ischemic stroke. However, the limited number of studies, mainly from a specific population, highlights the need for further research to enhance the generalizability of these findings.

Abstract 12389: Predictors of Elevated High-Sensitivity C-reactive Protein in a US Population With Atherosclerotic Cardiovascular Disease: Results From the National Health and Nutrition Examination Survey

Introduction: Evidence suggests that inflammation is causally related to ASCVD. Elevated levels of high-sensitivity C-reactive protein (hsCRP) may identify individuals most likely to benefit from emerging anti-inflammatory therapies but hsCRP is not measured routinely in clinical practice. Aims: To identify potential risk factors indicating elevated hsCRP in patients with ASCVD. Methods: This cross-sectional study using data from the 1999–2010 and 2015–2018 NHANES cycles included adults (≥ 20 years old) with self-reported ASCVD and available hsCRP levels, plus sex and race/ethnicity data. Elevated hsCRP was defined as hsCRP 2–10 mg/L. Following weighting towards the US population, risk factors were assessed using multivariate logistic regression. Results: In total, 3415 individuals with ASCVD were included. In the weighted population (n = 13,008,371), 54.5% had elevated hsCRP. Median hsCRP levels increased with increasing numbers of risk factors ( Figure 1 ). Characteristics of groups with and without elevated hsCRP are shown in Table 1 . Smoking (OR 1.78 [95% CI: 1.11, 2.87]; p = 0.018) and BMI (OR per unit increase: 1.10 [1.06, 1.15]; p < 0.001) were associated with higher odds of elevated hsCRP; receipt of metabolic medication (OR 0.55 [0.39–0.77]; p < 0.001) and male sex (OR 0.60 [0.44–0.83]; p = 0.002) were associated with lower odds of elevated hsCRP. Conclusion: In this analysis of US NHANES data, smoking, BMI and female sex were linked to elevated hsCRP. The greater the number of risk factors, the higher the hsCRP level. Targeted hsCRP screening should be considered to identify those most likely to benefit from emerging anti-inflammatory therapies.

Abstract 16779: Tirzepatide Reduces High-Sensitivity C-reactive Protein in Patients With Type 2 Diabetes and High Cardiovascular Risk: A Post Hoc Analysis of the SURPASS-4 Trial

Background: People with type 2 diabetes (T2D) who have elevated levels of high-sensitivity C-reactive protein (hsCRP) face a greater risk of myocardial infarction and coronary death. Early data for tirzepatide (TZP), a GIP/GLP-1 receptor agonist, suggest a hsCRP lowering effect. Here, we compare the effect of TZP and insulin glargine (iGlar) on hsCRP in patients with T2D and established or high risk for cardiovascular (CV) disease. Methods: hsCRP concentration was quantified by immunoassay (Roche, Indianapolis, IN) with lower limits of detection at concentrations of 0.15 mg/L. Plasma was collected from 1995 fasted participants at baseline (329, 328, 338, and 1000 on 5, 10, 15 mg TZP and on iGlar, respectively) and 52 weeks in SURPASS-4. The % changes of hsCRP from baseline were estimated by mixed model with repeated measures. The shifts in hsCRP risk categories (hsCRP >3 mg/L or 1-3 mg/L versus <1 mg/L) from baseline to 52 weeks are reported. The linear relationship between % change from baseline of hsCRP and change in body mass index (BMI) was analyzed using Pearson correlation coefficient. Results: Baseline hsCRP (mean ± SD, 5.6 ± 12.5 mg/L) was elevated in this study population. Among the participants, 48%, 36%, and 16% were in the >3, 1-3 and <1 mg/L hsCRP categories, respectively. Participants in the elevated hsCRP categories had higher body weight and BMI at baseline. After 52 weeks of treatment, the 5, 10, 15 mg TZP and iGlar groups resulted in -38.0%, -44.2%, -47.8%, and 0.6% changes in the concentration of hsCRP, respectively. More TZP-treated patients improved their hsCRP categories when compared with iGlar-treated participants (Table). The reduction in hsCRP in the pooled TZP groups correlated with the reduction of BMI (r=0.07, p=0.049). Conclusions: Tirzepatide treatment significantly lowers hsCRP in patients with T2D and increased CV risk versus baseline and iGlar. Substantially more participants shift to a lower hsCRP category when compared with insulin glargine.

Abstract 11734: Allopurinol & Plaque Stabilization in Patients With Acute Coronary Syndrome: A Randomized Clinical Trial

Background: Allopurinol, a xanthine inhibitor that lowers uric acid (UA) concentration, has been proven to reduce inflammation and oxidative stress in patients with cardiovascular disease. However, it is unknown whether these beneficial effects translate into favorable plaque modification in acute coronary syndromes (ACS). Aims: This study aimed to investigate whether allopurinol therapy could improve plaque stabilization in ACS patients using coronary computed tomography angiography (CCTA). Methods: This was a prospective, single-center, randomized, double-blind clinical trial began in March 2019 (clinical trial.gov identifier NCT03745729). A total of 162 acute coronary syndromes (ACS) patients aged 18-80 years with a blood level of high-sensitivity C-reactive protein (hsCRP) > 2 mg/L were included. The subjects were randomly assigned in a 1:1 ratio to receive either allopurinol sustained-release capsules (at a dose of 0.25 g once daily) or placebo for 12 months. The primary efficacy endpoint was the change in low-attenuation plaque volume (LAPV) from baseline to the 12-month follow-up. Results: Among 162 patients, 54 in allopurinol group and 51 in placebo group completed the study. There were no significant differences between the allopurinol and placebo groups in terms of baseline data for age (58.5±10.2 years vs. 56.8±10.0 years, P=0.392) and sex (male/female, 40/14 vs. 40/11, P=0.600). The median follow-up duration was 14 months in both groups. Compared with placebo, allopurinol therapy did not significantly alter LAPV (-13.4±3.7% vs. -17.8±3.6%, P=0.390), intermediate attenuation plaque volume (-16.1±3.0% vs. -16.2±2.9%, P=0.992), dense calcified plaque volume (12.2±13.7% vs. 9.7±13.0%, P=0.894), total atheroma volume (-15.2±3.2% vs. -16.4±3.1%, P=0.785), remodeling index (2.0±3.9% vs. 5.4±3.8%, P=0.536) or hsCRP levels (-73.6 [17.9-91.6] % vs. -81.2 [47.7-95.4] %, P=0.286). Conclusions: Our findings suggest, for the first time, that allopurinol therapy does not improve atherosclerotic plaque instability or inflammation in ACS.

Abstract 17772: The Relationship Between Renin-Angiotensin System Inhibition and Coronary Artery Calcification Evaluated by Intravascular Ultrasound

Introduction: Coronary artery calcification is significantly associated with major adverse cardiac events in patients with coronary artery disease (CAD), and severely calcified lesions are significantly associated with poor outcomes after percutaneous coronary intervention (PCI). Hypothesis: The relationship between renin-angiotensin system inhibition and coronary artery calcification is unknown. Methods: Five hundred stable CAD patients undergoing PCI were divided into none/mild and moderate/severe calcification groups according to the grade of calcification in the target lesion evaluated by intravascular ultrasound (IVUS). Calcification with a calcium arch >180° and calcium length >5 mm in the target lesion was defined as moderate/severe calcification. We examined the association between patient’s characteristics and morphology in target lesions assessed by IVUS. Results: One hundred ninety of the 500 patients (38%) showed moderate/severe calcification of the culprit lesion. In the moderate/severe calcification group, the survival rate was significantly lower, and cumulative incidence of major cardiovascular and cerebrovascular events (MACCE) was higher than in the none/mild calcification group after PCI (p=0.015 and p=0.003, respectively). Age, body mass index, hypertension, use of angiotensin-converting enzyme inhibitor (ACEI), hemodialysis, high-sensitivity C-reactive protein levels, low-density lipoprotein cholesterol levels, serum albumin levels were associated with moderate/severe calcification lesion in univariate logistic analysis, but the use of angiotensin II receptor blocker was not. Multivariate logistic analysis identified age [odds ratio (OR); 1.05, 95% confidence interval (CI): 1.02-1.08, p<0.001], use of ACEI (OR; 0.46, 95% CI: 0.23-0.91, p=0.025), and hemodialysis (OR; 6.07, 95% CI: 2.39-15.42, p<0.001) as independent factors of moderate/severe calcification lesions. A comparison of P-value for interaction of use of ACEI and hemodialysis was p=0.51. Conclusions: Using of ACEI was negatively associated with moderate/severe calcification in target lesions assessed by IVUS. ACEI may have a potential for inhibitory effect on coronary artery calcification.

Abstract 15093: Serum Apolipoprotein-A2 Levels Are a Stronger Predictor of the Residual Cardiovascular Event Risk After Percutaneous Coronary Intervention

Introduction and Aim: Apolipoprotein-A2 (apoA2) is the second major apolipoprotein that constitutes high-density lipoprotein cholesterol (HDL-C) particles, following apolipoprotein-A1 (apoA1). HDL-C can be divided into two main subfractions: those containing both apoA1 and apoA2, and those containing only apoA1. It is believed that HDL-C particles with apoA2 exhibit superior functionality in lipid metabolism compared to those without apoA2. However, the clinical impact of apoA2 on future cardiovascular events in patients who have undergone percutaneous coronary intervention (PCI) remains unclear. The aim of our study is to test the hypothesis that apoA2 would be a stronger predictor of residual cardiovascular risk compared to other apolipoproteins in the statin era. Methods: We examined 638 patients who underwent PCI with a second-generation drug-eluting stent for acute or chronic coronary syndrome and had their apolipoproteins measured between 2016 and 2021 (median follow-up period of 17.7 months). The patients were divided into two groups based on the median serum apoA2 values. We assessed the incidence of major adverse cardiovascular events (MACEs), including cardiovascular death, non-fatal acute coronary syndrome, ischemic stroke, exacerbation of heart failure, or target vessel revascularization. Results: A total of 563 patients (88%) received statin treatment, and the median serum low-density lipoprotein cholesterol was 93 mg/dL. A total of 138 patients (21.6%) experienced MACEs, and Kaplan-Meier analysis revealed that the lower apoA2 group had a significantly higher incidence of MACEs compared to the higher apoA2 group (23.6% vs. 19.7%, p=0.036). However, the other apolipoproteins, including apolipoprotein-A1, B, C2, C3, or E, showed no significant difference in MACEs. Multivariate Cox hazard analysis indicated that apoA2 was an independent predictor of MACEs (hazard ratio 1.51; 95% confidence interval 1.06-2.14, p = 0.022). Furthermore, apoA2 levels exhibited the strongest inverse association with high-sensitivity C-reactive protein levels (ρ= -0.48, p<0.0001). Conclusions: Serum apoA2 level may be the strongest predictor of residual cardiovascular event risk after PCI among apolipoproteins.

Abstract 13581: Effect of Lipoprotein(a) on Long-Term Outcomes at Different LDL-C and hs-CRP Status in Patients With Percutaneous Coronary Intervention

Background: Although some studies have shown that the risk of adverse events associated with lipoprotein (a) [Lp(a)] are influenced by low-density lipoprotein cholesterol (LDL-C) or high-sensitivity C-reactive protein (hs-CRP) levels, results on whether hs-CRP and LDL-C jointly mediate the effect of Lp(a) on long-term outcomes are unknown. Aim: To investigate the effect of Lp(a) on long-term clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) according to LDL-C levels and further hs-CRP levels. Methods: This prospective study consecutively enrolled 10,724 patients with PCI in the year 2013. The primary endpoint was all-cause death. The secondary endpoint was cardiac death. Results: There were 10,000 patients with available baseline data included in final analysis (Age 58.33±10.26 years, 77.27% Male). During a median follow-up of 5.1 years, 358 patients developed all-cause death and 217 cardiac death. After the multi-variable Cox analysis, in the overall population, Lp(a) ≥ 30 mg/dL was an independent risk factor of all-cause death and cardiac death. Further analysis showed that, in patients with LDL-C < 70 mg/dL, Lp(a) ≥ 30 mg/dL was not an independent risk factor of all-cause death and cardiac death regardless of hs-CRP < 2 or ≥ 2 mg/L. However, when LDL-C ≥ 70 mg/dL, in the setting of hs-CRP ≥ 2 mg/L, Lp(a) ≥ 30 mg/dL was an independent risk factor of all-cause death and cardiac death; in the setting of hs-CRP < 2 mg/L, Lp(a) ≥ 30 mg/dL was only the independent risk factor of cardiac death. Conclusions: The current study first reported that LDL-C and hs-CRP jointly affected the long-term outcomes associated with Lp(a) in PCI patients. When LDL-C < 70 mg/dL, Lp(a) ≥ 30 mg/dL was not associated with the risk of all-cause death and cardiac death irrespective of hs-CRP levels. Our finding may be instructive for the management and treatment of Lp(a) in the future.

Abstract 15680: Serum High-Sensitivity C-reactive Protein Levels Throughout Early Adulthood and Subclinical Atherosclerosis in Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Introduction: Single measures of high sensitivity C-reactive protein (hs-CRP) have been associated with atherosclerosis. However, trajectories of hs-CRP through young adulthood and their associations with mid-life coronary artery calcification (CAC) are poorly characterized. Methods: We examined longitudinal data from 4681 participants in the CARDIA study, including men and women aged 18-30 years at baseline followed for 25 years. We included participants with >3 hs-CRP measurements and a CAC score measured at year 25. We also examined cardiovascular (CV) risk factor trajectories through young adulthood in parallel with hs-CRP. Multivariable logistic regression models were used to assess association between hs-CRP trajectories and CAC >0 status at year 25. Results: We identified 5 discrete trajectories in hs-CRP from young adulthood to middle age according to measured hs-CRP levels and time course: low-stable (56%, n=1364), low-early rise (18%, n=432), low-late rise (7%, n=155), elevated-stable (6%, n=136), and elevated-decline (13%, n=308) (Figure 1). Compared with the low-stable group, trajectories with early, but not later elevations of hs-CRP levels had significantly higher odds of CAC score > 0 at year 25. Odds ratios (OR; adjusted for age, sex, race and education) were 1.71 (95% CI, 1.11-2.64) for the elevated-stable group and 1.98 (1.49-2.65) for elevated-decline group. After adjustment for all CV risk factors, only the elevated-decline group retained significance (OR 1.46, 1.06-2.02). Trajectories of CV risk factors, especially BMI, through young adulthood were highly correlated with hs-CRP trajectories, and attenuated associations of hs-CRP with CAC. Conclusions: Trajectories with early elevations in hs-CRP in young adulthood are associated with mid-life CAC. CV risk factor trajectories correlate with hs-CRP over time, suggesting that hs-CRP trajectory may integrate data from other risk factors and provide information about CAC risk.

Response to interleukin-1 blockade with anakinra in women and men with ST-segment elevation myocardial infarction.

Interleukin-1 blockade with anakinra reduces high-sensitivity C-reactive protein (hsCRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). Sex-based differences in STEMI patients have been reported, but no data are available regarding response to anakinra. We analyzed the systemic inflammation and composite end-point of new-onset HF or death in women and men with STEMI treated with anakinra from three different Virginia Commonwealth University Anakinra Response Trial (VCUART) randomized clinical trials. We analyzed 139 patients, 29 (21%) were women while 110 (79%) were men. Baseline hsCRP was higher in women compared to men (8.9 [5.2-13.5] vs. 4.2 [2.1-7.7] mg/L, P<0.001). Eighty-four patients were treated with anakinra (22 [75%] women and 62 [56%] men). The area under the curve of hsCRP (hsCRP-AUC) after 14 days was numerically lower in patients receiving anakinra versus placebo both in men (86 [37-130] vs. 223 [119-374] mg day/L) and in women (73 [46-313] vs. 242 [102-988] mg day/L) (P<0.001 for multiple groups, P for interaction 0.22). The incidence of the composite endpoint was also numerically lower in the anakinra group compared to placebo, both in men (4 [6.4%] vs. 14 [29.1%]) and in women (3 [13.6%] vs. 2 [28.5%]) (P=0.019 for multiple groups, P for interaction 0.44). There were no statistically significant differences between women and men in hsCRP-AUC and death or HF events when comparing separately the anakinra and placebo groups (all P>0.05). Women were underrepresented in the VCUART trials, they appeared to have higher hsCRP levels at time of presentation, yet to benefit similar to men by treatment with anakinra in STEMI.

Maternal inflammation during pregnancy is associated with risk of ADHD in children at age 10

IntroductionMaternal inflammation during pregnancy may affect early neurodevelopment in offspring as suggested by preclinical and register data. However, clinical evidence for risk of aberrant neurodevelopment later in childhood is scarce. In the population-based COPSAC2010 mother–child cohort, we investigated associations between maternal inflammation levels during pregnancy and the risk of a diagnosis of ADHD as well as the load of ADHD symptoms in the children at age 10. MethodsThe COPSAC2010 cohort consists of 700 mother–child pairs followed prospectively since pregnancy week 24.Maternal high-sensitivity C-Reactive Protein (hs-CRP) level at week 24 of gestation was investigated in relation to child neurodevelopment by age 10 using logistic and linear regression models with extensive confounder adjustment, including socioeconomic status and maternal polygenic risk of ADHD. The children completed a comprehensive examination of neurodevelopment including categorical (i.e., diagnostic) and dimensional (i.e., symptom load) psychopathology using the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) and parental rated ADHD-Rating Scale (ADHD-RS). ResultsA total of 604 (86 %) of the 700 children in the COPSAC2010 cohort participated in the COPSYCH visit at age 10. Sixty-five (10.8 %) fulfilled a research diagnosis of ADHD (16 girls and 49 boys). Higher maternal hs-CRP level in pregnancy at week 24 (median 5.4 mg/L) was significantly associated with increased risk for a diagnosis of ADHD, adjusted OR 1.40, 95 %CI (1.16–1.70), p = 0.001. Additionally, higher maternal hs-CRP was associated with increased ADHD symptom load in the entire cohort, reflected by ADHD-RS raw scores. DiscussionThese clinical data demonstrated a robust association of prenatal maternal inflammation assessed by hs-CRP with a diagnosis of ADHD by age 10. Moreover, maternal inflammation was associated with ADHD symptom load in the complete cohort. Identifying inflammation as an important marker will provide a potential target for future increased awareness and prevention during pregnancy thereby ultimately improving neurodevelopmental outcomes in children.

Extraction of mandibular third molars: relationship of preoperative anxiety with body mass index, serum high-sensitivity C-reactive protein levels, and visual analog scale scores and predictors of postoperative complications

Extraction of mandibular third molars: relationship of preoperative anxiety with body mass index, serum high-sensitivity C-reactive protein levels, and visual analog scale scores and predictors of postoperative complications

Exercise training decreases the load and changes the content of circulating SDS-resistant protein aggregates in patients with heart failure with reduced ejection fraction

BackgroundHeart failure (HF) often disrupts the protein quality control (PQC) system leading to protein aggregate accumulation. Evidence from tissue biopsies showed that exercise restores PQC system in HF; however, little is known about its effects on plasma proteostasis.AimTo determine the effects of exercise training on the load and composition of plasma SDS-resistant protein aggregates (SRA) in patients with HF with reduced ejection fraction (HFrEF).MethodsEighteen patients with HFrEF (age: 63.4 ± 6.5 years; LVEF: 33.4 ± 11.6%) participated in a 12-week combined (aerobic plus resistance) exercise program (60 min/session, twice per week). The load and content of circulating SRA were assessed using D2D SDS-PAGE and mass spectrometry. Cardiorespiratory fitness, quality of life, and circulating levels of high-sensitive C-reactive protein, N-terminal pro-B-type natriuretic peptide (NT-proBNP), haptoglobin and ficolin-3, were also evaluated at baseline and after the exercise program.ResultsThe exercise program decreased the plasma SRA load (% SRA/total protein: 38.0 ± 8.9 to 36.1 ± 9.7%, p = 0.018; % SRA/soluble fraction: 64.3 ± 27.1 to 59.8 ± 27.7%, p = 0.003). Plasma SRA of HFrEF patients comprised 31 proteins, with α-2-macroglobulin and haptoglobin as the most abundant ones. The exercise training significantly increased haptoglobin plasma levels (1.03 ± 0.40 to 1.11 ± 0.46, p = 0.031), while decreasing its abundance in SRA (1.83 ± 0.54 × 1011 to 1.51 ± 0.59 × 1011, p = 0.049). Cardiorespiratory fitness [16.4(5.9) to 19.0(5.2) ml/kg/min, p = 0.002], quality of life, and circulating NT-proBNP [720.0(850.0) to 587.0(847.3) pg/mL, p = 0.048] levels, also improved after the exercise program.ConclusionExercise training reduced the plasma SRA load and enhanced PQC, potentially via haptoglobin-mediated action, while improving cardiorespiratory fitness and quality of life of patients with HFrEF.

Cross-sectional analysis of depressive symptom profiles and serum C-reactive protein levels: data from the Northern Finland 1966 birth cohort

Purpose Individuals with depression exhibit significantly higher levels of systemic inflammation than those without depression, particularly among those with atypical depression. However, this association has been less convincing at the population level among individuals without a formal depression diagnosis but with suggestive symptoms. Our aim was to clarify this association. Materials and methods In a large birth cohort sample of the Finnish general population, we examined the cross-sectional association between high-sensitivity C-reactive protein (hsCRP) levels in venous blood samples and atypical/non-atypical depressive symptoms using the Beck Depression Inventory-II to screen 5443 middle-aged participants. Results As expected, depressive symptoms associated to elevated hsCRP-levels compared to non-depressed. Participants with the atypical subtype of depressive symptoms (n = 84) had an odds ratio (OR) of 2.59 (95% CI 1.40–4.81) for elevated hsCRP levels compared to the non-depressed group. Similarly, our findings indicate that participants with non-atypical symptoms (n = 440) also showed an OR of 1.42 (95% CI 1.05–1.92) when compared to the non-depressed group (n = 4919). Conclusions These results provide additional support for previous research linking depression and inflammation and add to the field with a unique and sizeable study population. Furthermore, the current results support the notion that different types of depressive symptoms may be associated with inflammatory markers in slightly different ways.

Obesity, diabetes and their metabolic correlates in middle-aged adults with Down syndrome.

Obesity in adults without Down syndrome is associated with an adverse metabolic profile including high prevalence of pre-diabetes and diabetes, high levels of insulin, non-high-density lipoprotein (HDL) cholesterol, leptin and high-sensitivity C-reactive protein (hsCRP) and low levels of HDL and adiponectin. We examined whether obesity in middle-aged adults with Down syndrome is also related to an adverse metabolic profile. This cross-sectional study included 143 adults with Down syndrome, with a mean age of 55.7±5.7years and 52.5% women. Body mass index (BMI) was classified as underweight (BMI<18.5kg/m2 ), normal (BMI 18.5-24.9kg/m2 ), overweight (BMI 25-29.9kg/m2 ) and obese (BMI≥30kg/m2 ). Diabetes was ascertained by history or by haemoglobin A1c (HbA1c) as normal glucose tolerance (HbA1c<5.7%), pre-diabetes (HbA1c 5.7-6.4%) and diabetes (HbA1c≥6.5%). We measured non-fasting lipids, hsCRP, insulin, adiponectin and leptin. The majority of the sample had an overweight (46.9%) or obesity (27.3%) status. However, there was a relatively low prevalence of pre-diabetes (9.8%) and diabetes (6.9%). Overweight and obesity status were not associated with lower HDL and adiponectin and higher insulin, non-HDL cholesterol and hsCRP as expected in adults without Down syndrome. However, overweight and obesity were strongly associated with higher leptin (P<0.001). The only metabolic correlate of obesity in middle-aged adults with Down syndrome was high leptin levels. Our findings are limited by non-fasting laboratory tests but suggest that middle-aged adults with Down syndrome do not have the adverse metabolic profile related to obesity found in adults without Down syndrome.

Prevalence, clinical profile, and risk factors of peripheral artery disease in an Iraqi cohort of chronic kidney disease.

Peripheral artery disease (PAD) is prevalent in patients with chronic kidney disease (CKD) and is associated with substantial morbidity, mortality, and a lower quality of life. This study aimed to determine the prevalence of PAD, clinical profile, and related risk factors among patients with CKD in Iraq (a low-to middle-income country). A cross sectional study comprised 175 CKD patients, of them 60% were male, their mean age was 56 ± 12.5 years, attending Nephrology unit, Hawler Teaching Hospital, Erbil, Iraq between march 2022 and November 2022. Data on demographic and baseline characteristics were collected. Laboratory tests were performed. All participants underwent a detailed history and clinical examination. Vascular lesions in the lower limbs were assessed using the ankle-brachial index. PAD was diagnosed based on an ankle-brachial index value ˂ 0.9, relevant symptoms, and clinical findings. Forty-nine patients (28%) had PAD, and only 17 (34.7%) were symptomatic. PAD was significantly associated with older age (P = .008), male sex (P = .039), diabetes (P = .012), and hypertension (P = .023). In addition, PAD prevalence was significantly higher in patients with prior coronary artery disease (P < .001), advanced CKD stages (P .032), low estimated glomerular filtration rate (P .03), albuminuria (P .002), elevated glycated hemoglobin (P .04), and high sensitive C-reactive protein (P < .001). No significant association was detected between PAD and body mass index, smoking, CKD duration, cerebrovascular disease, dyslipidemia, albumin, creatinine, hemoglobin, total PTH, and phosphate. Peripheral artery disease was prevalent in patients with CKD in Iraq, and the most affected patients were asymptomatic. Older age, male sex, hypertension, diabetes, prior coronary artery disease, advanced CKD stages, albuminuria, higher glycated hemoglobin level, and increased high-sensitivity C-reactive protein level were identified as risk factors. Early detection of occult PAD might enhance efforts toward proper prevention and treatment.

Assessment of selected biomarkers of bone healing and inflammation among subjects with fracture on traditional and conventional treatment methods

Abstract &#x0D; &#x0D; Fractures have significant implications for health. Treatment approaches vary, including traditional and conventional methods. This study in Ekpoma, Nigeria assessed biomarkers in fracture healing through a cross-sectional random sampling. Blood samples from 60 subjects were analyzed for hydroxyproline, creatinine, calcium, alkaline phosphatase, and C-reactive protein. The aim was to evaluate treatment effectiveness and improvement in patient outcomes by monitoring bone remodeling. Statistical analysis utilized is the SPSS software version 21.0 software (SPSS Inc., Chicago, IL, USA). Biochemical marker analysis revealed that serum alkaline phosphatase activity, calcium, and creatinine did not significantly differ between subjects without fractures and those with fractures (p&gt;0.05). However, hydroxyproline levels exhibited a significant difference (p&lt;0.05), with higher values observed in subjects with fractures. Additionally, C-reactive protein levels showed significant variations (p&lt;0.05), indicating increased inflammation in fracture patients. High-sensitive C-reactive protein levels also displayed significant differences (p&lt;0.05). Further analysis comparing male and female subjects without fractures and those with fractures revealed no significant variations in serum alkaline phosphatase, calcium, and creatinine levels (p&gt;0.05). However, hydroxyproline levels demonstrated significant variations (p&lt;0.05) between males and females in the fracture group, suggesting gender-specific differences in bone metabolism. C-reactive protein and High-sensitive C-reactive protein levels exhibited significant variations (p&lt;0.05) between males and females in the fracture group. Furthermore, a comparison between patients on traditional and conventional treatment methods indicated significant variations in serum alkaline phosphatase activity and calcium levels (p&lt;0.05), suggesting distinct effects of the treatment modalities on these markers. However, no significant differences were observed in creatinine, C-reactive protein, and high-sensitive C-reactive protein levels (p&gt;0.05). Traditional and conventional fracture treatment methods may affect biochemical markers differently, with gender-specific variations in hydroxyproline, C-reactive protein, and high-sensitive C-reactive protein levels. Further research is needed to understand the clinical implications and underlying mechanisms of these findings.

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.

Relationship between C-reactive protein level and periodontitis and systemic diseases.

Periodontitis affects systemic disease risk, although the relationship thereof in the context of different C-reactive protein (CRP) levels is not clear. This study investigated the association of periodontitis with systemic diseases according to high-sensitivity CRP (hs-CRP) level and sought to identify the risk of systemic diseases in patients with periodontitis. We used data from the seventh (2016-2018) Korea National Health and Nutrition Examination Survey. In a total of 16,489 subjects, the hs-CRP group was classified into the hs-CRP low-risk group and the hs-CRP high-risk group. Propensity score matching (PSM) is used for 1:1 matching of confounding variables (e.g., age, gender, income, and education) between hs-CRP low-risk and hs-CRP at-risk groups to analyze the final 5316 subjects. The association between general characteristics and prevalence of systemic diseases was analyzed using descriptive statistics and the chi-squared test. The associations between hs-CRP level and systemic and periodontitis were analyzed using logistic regression analyses. Within the hs-CRP group, the presence of periodontitis was associated with a significantly increased prevalence of hypertension, diabetes mellitus, and stroke. In the hs-CRP risk group, periodontitis significantly increased the risk of hypertension and diabetes mellitus by 2.1 and 2.4 times, respectively. The presence of periodontitis significantly increases the prevalence of systemic diseases and more so in individuals with higher hs-CRP levels. This indicates the significance of maintaining oral health in reducing the risk of systemic diseases.

Investigations of leukocyte and inflammatory markers in pregnancies complicated by preeclampsia

ObjectivesPreeclampsia is a frequent and potentially fatal pregnancy complication. It can be challenging to make a timely diagnosis. Identifying clinically useful biochemical markers would be a remedying tool to support the diagnosis of preeclampsia. The aim was to investigate differential cell counts and acute phase reactants as diagnostic markers of preeclamptic third-trimester pregnancies and in relation to pregnancy term, gravidity and the severity of hypertension. MethodsBased on a cohort of 421 pregnant women, we included 174 participants (case n = 84, control n = 90) during the third trimester. Peripheral blood was sampled to measure differential white blood cell counts and acute phase reactants on the day of inclusion. ResultsThe neutrophil-to-lymphocyte ratio and plasma haptoglobin levels were significantly increased in healthy pregnancies compared with preeclamptic pregnancies. Plasma ferritin levels and albumin levels were respectively increased and decreased in cases of preeclampsia compared with controls. Albumin was specific among multigravida. Plasma transferrin and high-sensitivity C-reactive protein (hs-CRP) levels were significantly decreased and increased, respectively, in cases with preterm preeclampsia compared with term preeclampsia. ConclusionPlasma ferritin and albumin levels reflected higher inflammation in cases with preeclampsia compared with healthy pregnancies; the same did plasma transferrin and hs-CRP levels in preterm versus term preeclampsia. When considering the normal ranges plasma albumin and hs-CRP levels identified preeclamptic from healthy third-trimester pregnancies and preterm from term preeclampsia cases, respectively, with near-acceptable diagnostic performances. Further validation of the diagnostic value will require larger sample-sized studies with paired plasma and serum samples.