CHADS2 and CHA2DS2-VASc scores as predictors of platelet reactivity in acute coronary syndrome

BackgroundPlatelet function testing (PFT) in patients treated with P2Y₁₂ inhibitors has been widely evaluated for the prediction of stent thrombosis, myocardial infarction, and bleeding events following percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS). Thus, PFT-guided treatment could positively affect patient outcomes. Data regarding clinical parameters for predicting platelet reactivity in ACS patients are limited. Therefore, our study aims to evaluate CHADS2 and CHA2DS2-VASc scores as predictors for platelet reactivity in ACS patients.MethodsTwo hundred and ninety-one consecutive patients who underwent PCI and were treated with aspirin and clopidogrel due to ACS were tested for their CHADS2, CHA2DS2-VASc scores and platelet reactivity using adenosine diphosphate (ADP)-induced aggregation (conventional aggregometry). Patients were classified into groups according to their CHADS2 and CHA2DS2-VASc scores. Low-risk group (0–1 score) for CHADS2 and CHA2DS2-VASc scores and high-risk group (2–6, 2–9) for CHADS2 and CHA2DS2-VASc scores, respectively. Furthermore, platelet reactivity in each group were compared (low CHADS2 group vs high CHADS2 group, and low CHA2DS2-VASc vs high CHA2DS2-VASc). Platelet reactivity was defined as low platelet reactivity (<19 U), optimal platelet reactivity [(OPR); 19–46 U], and high on-treatment platelet reactivity [(HPR); >46 U]. Thereafter receiver operating characteristic curve analysis was conducted to verify whether CHADS2 and CHA2DS2-VASc scores could predict platelet reactivity.ResultsLow CHADS2 and CHA2DS2-VASc scores were significantly correlated with lower mean platelet ADP-induced aggregation as compared with high CHADS2 and CHA2DS2-VASc scores [45.5 U (± 16) vs. 54.8 U (±15) and 44.2 U (±16) vs. 51.0 U (±17), respectively, p = 0.01 for both].ConclusionIn ACS patients treated with clopidogrel following PCI, high CHADS2 and CHA2DS2-VASc scores correlated with HPR and lower scores correlated with OPR. Further studies are needed to evaluate our findings’ clinical implications.     

Association of left ventricular hypertrophy with high-sensitive C-reactive protein in hemodialysis patients

Background

Micro inflammation and cardiovascular disease such as left ventricular hypertrophy (LVH) are common in hemodialysis (HD) patients. Hence, we have evaluated the relationship between high-sensitive C-reactive protein (hs-CRP), as an inflammation marker, and left ventricular mass index (LVMi) and left ventricular mass (LVM) in HD patients.

Methods

An analytical cross-sectional study was performed in 104 HD patients. Serum hs-CRP, LVMi, LVM, and blood pressure were evaluated; demographic data and duration of HD were also recorded. Finally, results were analyzed by using Student’s t test, Pearson’s correlation coefficient, one-way ANOVA and multiple regression to determine the relationship between LVMi and other variables.

Results

A total of 66 male patients (63.46 %) and 38 female patients, with a mean age of 51.75 ± 15.98 years-old, participated in this study. Hypertension was the most common underlying disease (65.4 %). The mean LVMi was 366.98 ± 120.89 g/m² and the mean hs-CRP was 8.55 mg/l. Eighty-nine percent of patients had LVH. The hs-CRP level was significantly associated with age and with LVM (P = 0.0001, P = 0.039, respectively). On multivariate analysis, hs-CRP and systolic blood pressure were found to be independent predictors of LVM and LVMi.

Conclusions

This study shows that hs-CRP and systolic BP are independent predictors of LVH in HD patients.     

Expression of Salivary S100A7 Levels in Stage I Oral Submucous Fibrosis: A Clinical and Laboratory Study

Background: Oral submucous fibrosis (OSF) is a chronic debilitating condition characterized by juxta-epithelial fibrosis. The main etiological agent associated with the high-risk precancerous condition is areca nut use. S100A7 is a member of the largest calcium-binding proteins exclusively found in vertebrates and are associated with the regulation of numerous intracellular and extracellular functions. The aim of this study was to investigate the expression of protein S100A7 in salivary samples of individuals with stage I OSF and healthy controls. Methods: This study included 63 participants, 30 of whom had OSF stage I and 33 healthy controls. Nonprobability quota sampling technique was utilized for recruitment of the study participants. A structured baseline questionnaire was used to collect demographic data. Saliva samples were collected by passive droll technique in a sterile container. Salivary levels of S100A7 were quantified by enzyme-linked immunosorbent assay. For the normality of the data Shapiro Wilk test was performed. Student t-test was commuted to evaluate the expression of S100A7 protein expression between both the study groups. Results: The mean salivary S100A7 value for stage I OSF group was 0.334 ng/ml, compared to 0.172 ng/ml for healthy controls. Student t-test reported a statistically significant difference, indicating higher levels of S100A7 in stage I OSF group than in healthy controls (p < 0.001). In the individual group analysis, a significant negative correlation was found between salivary S100A7 and duration of areca nut use (r = –0.45, p = 0.009) and gutka chewing (r = –0.20, p = 0.03), while a significant positive correlation was found between salivary S100A7 and mouth opening (r = 0.03, p = 0.04). Conclusions: Higher levels of S100A7 protein level was seen in stage I OSF group in comparison to the healthy individuals. Results of our study suggest that S100A7 could be used as a surrogate assessment to identify patients at risk of OSF development.     

Neuregulin‐1 positively modulates glial response and improves neurological recovery following traumatic spinal cord injury

Spinal cord injury (SCI) results in glial activation and neuroinflammation, which play pivotal roles in the secondary injury mechanisms with both pro‐ and antiregeneration effects. Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin‐1 (Nrg‐1) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg‐1 dysregulation on glial and immune cell reactivity following SCI. Using complementary in vitro approaches and a clinically‐relevant model of severe compressive SCI in rats, we demonstrate that immediate delivery of Nrg‐1 (500 ng/day) after injury enhances a neuroprotective phenotype in inflammatory cells associated with increased interleukin‐10 and arginase‐1 expression. We also found a decrease in proinflammatory factors including IL‐1β, TNF‐α, matrix metalloproteinases (MMP‐2 and 9) and nitric oxide after injury. In addition, Nrg‐1 modulates astrogliosis and scar formation by reducing inhibitory chondroitin sulfate proteoglycans after SCI. Mechanistically, Nrg‐1 effects on activated glia are mediated through ErbB2 tyrosine phosphorylation in an ErbB2/3 heterodimer complex. Furthermore, Nrg‐1 exerts its effects through downregulation of MyD88, a downstream adaptor of Toll‐like receptors, and increased phosphorylation of Erk1/2 and STAT3. Nrg‐1 treatment with the therapeutic dosage of 1.5 μg/day significantly improves tissue preservation and functional recovery following SCI. Our findings for the first time provide novel insights into the role and mechanisms of Nrg‐1 in acute SCI and suggest a positive immunomodulatory role for Nrg‐1 that can harness the beneficial properties of activated glia and inflammatory cells in recovery following SCI.     

Effects of combination of cyclosporine with losartan or enalapril on kidney function in uremic rats

Long-term treatment with cyclosporine in solid organ transplantation has been shown to be associated with the development of hypertension and nephrotoxicity. Angiotensin-converting enzyme inhibitors have well-known nephroprotective properties and may prevent cyclosporine A (CYA)-induced hypertension. Angiotensin receptor 1 antagonists have similar properties. The purpose of this study was to investigate if losartan or enalapril could be administered with CYA to reduce its nephrotoxic effect in uremic rats. The studies were performed on the following groups of rats: group I--control; group II--control rats + losartan; group III--control rats + CYA; group IV uremic rats; group V--uremic rats + losartan; group VI--uremic rats + CYA; group VII--uremic rats + losartan + CYA, group VIII--control rats + enalapril; group IX--control rats + enalapril + CYA; group X - uremic rats + enalapril; group XI--uremic rats + enalapril + CYA. Pretreatment with CYA, losartan or enalapril in uremic rats resulted in a significant increase in urea and creatinine levels and a decrease in hematocrit. The same effect was observed when uremic rats were given CYA + losartan or CYA + enalapril. Pretreatment with losartan was associated with the increase in the level of CYA much higher than with CYA treatment alone. Similarly, pretreatment with enalapril resulted in a significant increase in CYA concentration in both groups of rats given CYA: uremic and non-uremic. Results of our study show that the treatment with cyclosporine and a combination of losartan or enalapril results in an increase in creatinine and urea levels and a decrease in hematocrit. Therefore, physicians should exercise caution, when they give losartan and enalapril to kidney allograft recipients treated with cyclosporine, particularly with impaired allograft function.