High sensitivity C-reactive protein (hsCRP): Its relationship with metabolic syndrome and Framingham Risk Score

@#Introduction: Cardiovascular disease (CVD) remains the leading cause of death in Malaysia. Identification of asymptomatic at-risk individuals is often achieved by means of a risk prediction algorithm. Traditional CVD risk factors and their associated algorithms are, however, limited by residual CVD risk. High sensitivity C-reactive protein (hsCRP) has emerged as a novel CVD risk factor. This study aimed to evaluate hsCRP as an adjunct CVD risk marker among the adult Malaysian population by determining its correlation with the Framingham Risk Score (FRS). Comparison analyses were done according to sociodemographic, clinical and laboratory factors and between subjects with and without Metabolic Syndrome (MetS). Method: This cross-sectional study involved eighty-three (n=83) adults attending a health screening program at Universiti Putra Malaysia (UPM). Demographic data, anthropometric measurements and blood samples for fasting blood glucose (FBG), fasting lipid profile (FSL), glycated haemoglobin (HbA1c) and hsCRP were taken. Respondents were grouped according toFRSand the Joint Interim Statementinto 10-year CVD risk categories (low, intermediate and high) and MetS, respectively. Results: hsCRP was significantly increased in patients with high body mass index (BMI) (p=0.001), at-risk waist circumference (WC) (p=0.001) and MetS (p=0.009). Spearman’s correlation coefficient showed a significant positive correlation between hsCRP level and total FRS score (r=0.26, p<0.05) and HDL-C score (r=0.22, p<0.05). Conclusion: The significant difference of hsCRP levels across obesity levels and MetS with its modest correlation with FRS scores supported the adjunctive role of hsCRP in CVD risk prediction, most likely capturing the inflammatory pathological aspect and thus partly accounting for the residual CVD risk.

Postoperative day 3 drain amylase versus fistula risk score: predicting clinically relevant postoperative pancreatic fistula following pancreatico-duodenectomy

Background: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains the most common cause of perioperative morbidity following pancreatico-duodenectomy (PD). Early and accurate prediction of CR-POPF can be helpful in postoperative drain management as well as stratifying patients for enhanced recovery protocol after surgery. Both fistula risk score (FRS) and postoperative drain amylase levels have been analyzed in past. However, currently there is no clear consensus regarding the ideal predictor. Present study sought to assess the utility of postoperative day 3 drain amylase (POD-3DA) level as a predictor of CR-POPF in comparison with FRS.Methods: A retrospective analysis was done on 57 patients who underwent PD at our institute between 2014 to 2018. POPF was defined and graded in accordance with ISGPF definition. Receiver operating characteristic (ROC) analysis predicted a threshold of POD3DA >486 IU/l associated with CR-POPF. Sensitivity, specificity and odds ratios with 95%CI calculated and ROC curves were plotted for POD3DA of ≥500 IU/l and FRS (negligible/low vs. moderate/ high) as predictors of CR-POPF.Results: Incidence of POPF and CR-POPF was 63% and 32% respectively. Sensitivity and specificity of POD3DA ≥500 and moderate/high FRS for predicting CR-POPF were 83%, 79% & 78%, 51% respectively. Difference between ROC area under the curve (AUC) for POD3DA ≥500 IU/l (0.868) and FRS (0.692) was significant (p=0.028). Combining FRS and POD3DA ≥500 IU/l improved specificity (87%) at the cost of sensitivity (67%). The negative predictive value of POD3DA <500 IU/l and negligible/low FRS were 91.2% and 83.3% respectively.Conclusions: POD3DA level greater than 5 times of upper normal range is more precise at predicting CR-POPF, hence clinically more reliable for drain and postoperative management.

Fibroblast growth factor receptor-1 is essential for regulation of mitochondrial biogenesis via control of microRNA let-7b / 中华内分泌代谢杂志

Objective To explore the role of fibroblast growth factor receptor ( FGFR ) 1 in endothelial homeostasis via an induction of microRNA let-7s, with effects on AcSDKP(N-acetyl-seryl-aspartyl-lysyl-proline) and associated mitochondrial biogenesis. Methods Blocking FGFR1 signaling pathway, Western blot and immunofluorescence staining were used to measure mitochondrial fusion ( mitofusin-2, MFN2;optic atrophy protein 1, OPA1 ) and fission ( dynamin-related protein-1, DRP1 ) proteins and mitochondrial biogenesis by MitoTraker Green. Also real-time quantitative PCR(qPCR) was performed to test microRNA let-7' expression. Results FGFR1 signaling pathway was critical for AcSDKP maintaining mitochondrial biogenesis through induction of microRNA let-7b. In endothelial cells, the AcSDKP restored the triple[TGF-β2, interleukin (IL)-1β, tumor necrosis factor (TNF)-α]-suppressed microRNA let-7b-5p expression and associated with mitochondrial biogenesis. Such effect of AcSDKP was lost in either fibroblast growth factor receptor substrate 2 (FRS2) siRNA or neutralizing FGFR1 treated-cells. Similarly, AcSDKP lost its effect on mitochondrial biogenesis in microRNA let-7b-5p inhibitor-treated-cells. In addition, microRNA let-7b-5p mimic reversed the FRS2 siRNA-suppressed mitochondrial biogenesis in endothelial cells. Conclusion These findings demonstrated that FGFR1 is critical for maintaining mitochondrial biogenesis through control of microRNA let-7b-5p in endothelial cells.

Association between kidney function and Framingham risk score in an admixed population of Brazil

ABSTRACT Chronic kidney disease (CKD) increases cardiovascular disease (CVD) risk development. However, the mechanisms of reduced kidney function with CVD risk are unclear. This study aimed to investigate the association between kidney function and Framingham risk score (FRS) in participants with traditional cardiovascular risk factors and normal estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m² in an admixed population of Brazil. The participants were divided into three groups according to FRS: low risk group with 0% to <10%, moderate risk group with ≥10% to 20% and high risk group with >20%. The eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Data from participants were collected by questionnaire, and blood and urine samples were collected to analyze biochemical markers. A total of 214 subjects aged 53±10 years old was collected. There were 77 individuals in low risk group, 59 in moderate risk group and 78 in high-risk group. Mean eGFRCKD-EPI was 89.39±15.05 mL/min/1.73 m² and 90.74±16.17 mL/min/1.73 m2 when race adjustment. The results indicated that there is an increasing the cardiovascular risk with a decreased of eGFR, conforming to a significant inverse correlation observed between eGFR and FRS with Spearman correlation (R²=-0.256, p<0.001; R²=-0.224, p=0.001, when adjusted for race). There was a statistically significant difference in eGFRCKD-EPI (p<0.001) and eGFRCKD-EPI with race adjustment (p=0.002) among risk groups. The data suggests that the reduction eGFR is associated with elevated FRS among Brazilian adults without CKD. Furthermore, the results suggest that race adjustment it's not necessary in Brazilian population.

Expression and significance of Maspin and IKKα in sinusoidal mucosa of rats with fungal rhinosinusitis / 中国比较医学杂志

Objective To investigate the expression and significance of Maspin and IKKα in nasosinusoidal mucosa of rats with fungal rhinosinusitis (FRS).Methods A total of 40 SD rats were used to establish the FRS model, and randomly divided into nasal obstruction group, FRS group, immunosuppressive group and invasive FRS group, 10 rats in each group.Another 10 normal rats were used as control group.Mice in the control group were fed with normal diet.In the nasal obstruction group, the mice had only hemostatic cotton stuffed in the nasal cavity and injection of 0.9% NaCl in the abdominal and nasal cavities.In the FRS group, the mice were injected Aspergillus fumigatus spore suspension into the nasal cavity and 0.9% NaCl i.p.The mice of the immunosuppressive group were given cyclophosphamide i.p.and 0.9% NaCl injection into the nasal cavity.The invasive FRS group was injected with cyclophosphamide i.p.and Aspergillus fumigatus spore suspension into the nasal cavity.The serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA).The expression of Maspin and IKKα in nasosinusoidal mucosa was detected by immunohistochemical staining.The expression of Maspin mRNA and IKKα mRNA in the nasosinusoidal mucosa was detected by fluorescence quantitative PCR.Results The serum levels of IL-6 and TNF-α in different groups were significantly different (P 0.05).Theresult of immunohistochemical staining showed that the protein expression of Maspin in the FRS group and invasive FRS group was significantly lower than that in the control group, nasal obstruction group and immunosuppressive group, while the expression of IKKα protein was significantly higher than that of control group, nasal obstruction group and immunosuppressive group (P< 0.05).The protein expression of Maspin in the invasive FRS group was significantly lower than that in the FRS group, by contrast, the expression of IKKα protein was significantly higher (P< 0.05).The PCRresult revealed that the expression levels of Maspin and IKKα mRNA were (0.217 ± 0.013) and (0.193 ± 0.012), significantly lower than that in the control, obstruction and immunosuppressive groups [(0.309 ± 0.021), (0.302 ± 0.017), and (0.293 ± 0.02)] (P< 0.05), while the expressions level of IKKα mRNA were significantly higher [(0.319 ± 0.043), (0.384 ± 0.048) vs (0.169 ± 0.015), (0.171 ± 0.018), and (0.175 ± 0.019)] (P< 0.05).Conclusions Down-regulation of Maspin expression after IKKα activation is the main cause of the onset of FRS, which may also be one of the mechanisms of invasive FRS.