Chia-Chang Hsu

Increased levels of total P-Cresylsulphate and indoxyl sulphate are associated with coronary artery disease in patients with diabetic nephropathy.

BACKGROUND Indoxyl sulphate (IS) and p-cresylsulphate (PCS) are uremic toxins with similar protein-binding, dialytic clearance, and proinflammatory features. Few studies have evaluated the possible associations between these solutes and coronary artery disease (CAD) in type 2 diabetes (T2D) patients. METHODS A hospital-based case control study was performed. A total of 209 T2D patients were divided into two groups based on the presence/absence of significant CAD (≥50% luminal reduction). Serum total PCS and IS levels were measured using the Ultra Performance LC System. The relationship between total PCS and IS levels were investigated. Coronary calcium scores and the modified Gensini score were analyzed. RESULTS Serum total PCS and IS levels were significantly higher in patients with both T2D and significant CAD, than in non-diabetic control subjects and T2D patients without CAD (all p < 0.05). Logistic regression analysis revealed independent and significant associations between the two solutes and CAD status. Serum total PCS, IS, and numbers of diseased vessels were elevated in groups with estimated glomerular filtration rate (eGFR) of 60-89 ml/min/1.73 m2 and below. Also, serum total PCS and IS levels were significantly associated with eGFR, coronary calcium scores, Gensini score, adipocytokines (adiponectin, visfatin, and leptin), and total white blood cell count. CONCLUSIONS Serum total PCS and IS levels were elevated in patients with T2D and CAD. These increases were associated with renal function deterioration, inflammation, and coronary atherosclerosis.

Circulating secreted frizzled-related protein 5 (Sfrp5) and wingless-type MMTV integration site family member 5a (Wnt5a) levels in patients with type 2 diabetes mellitus

Secreted frizzled‐related protein 5 (Sfrp5), an endogenous inhibitor of wingless‐type MMTV integration site family (Wnt) signalling, is an anti‐inflammatory adipokine whose expression is perturbed in models of obesity and type 2 diabetes mellitus (T2DM). Wnt member 5a (Wnt5a) is a representative ligand, and recent reports suggest that Wnt5a is involved in inflammatory diseases and metabolic disorders. The aim of this study was to investigate whether plasma Wnt5a and Sfrp5 levels are altered in patients with T2DM.

Associations among chronic kidney disease, high total p-cresylsulfate and major adverse cardiac events

BACKGROUND Cardiovascular disease is prevalent among patients with chronic kidney disease (CKD). Patients with CKD have elevated levels of p-cresylsulfate (PCS), which has been linked with cardiovascular mortality in this population. The aim of this study was to evaluate the clinical significance of CKD in coronary artery disease (CAD) patients and to investigate whether a significant correlation exists between CKD, total PCS and poor clinical outcomes in CAD patients. METHODS We assessed the occurrence of major adverse cardiac events (MACEs) among 340 consecutive CAD patients who enrolled in a disease management program after the patients were discharged from the hospital. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 ml/min per 1.73 m(2). RESULTS Kaplan-Meier analysis revealed that CKD and high total PCS levels (>1.66 mg/L) were significantly associated with the occurrence of MACE. A multivariate Cox hazard regression model revealed that the predictive independent risk factor for the occurrence of MACE was high total PCS level (relative risk = 1.387). We divided the patients with or without CKD and high or low total PCS levels into 4 groups according to their eGFR and total PCS levels, respectively. The hazard ratio for MACE in the group with both CKD and high total PCS level was 1.721, relative to the group without CKD that had low total PCS level (p=0.005). CONCLUSIONS A high serum level of total PCS may be a predictor of elevated risk of MACE in CAD patients with low eGFR.

Relationship between shift work and peripheral total and differential leukocyte counts in Chinese steel workers

Relationship between shift work and peripheral total and differential leukocyte counts in Chinese steel workers: Li‐Fen Lu, et al. Division of Cardiac Surgery, Department of Surgery, E‐Da Hospital, I‐Shou University, Taiwan

Associations among chronic kidney disease, high total p-cresylsulfate and left ventricular systolic dysfunction.

BACKGROUND A significant number of patients with chronic kidney disease (CKD) have cardiac abnormalities, and left ventricular systolic dysfunction (LVSD) is a common manifestation. p-Cresylsulfate (PCS), a protein-bound uraemic retention solute, is known to cause endothelial dysfunction and possibly plays a role in coronary atherosclerosis. Furthermore, the associations among serum total PCS, major adverse cardiovascular events, all-cause mortality, and QTc prolongation have also been found in previous studies. We thus investigated the association of total PCS and CKD with LVSD in the clinical setting. METHODS We included 403 consecutive patients with stable angina. To evaluate LV function, all patients underwent echocardiography. To measure the serum total PCS concentrations and estimated glomerular filtration rate (eGFR), blood samples were obtained. RESULTS Multiple regression analysis showed that left atrium diameter, left ventricular mass index, end diastolic interventricular septal thickness, left ventricular end-systolic diameter, left ventricular end-systolic volume, stroke volume, left ventricular end-systolic volume index, left ventricular ejection fraction (LVEF), and the interventricular septum/posterior wall of the left ventricle were independently associated with total PCS (all p<0.05). In addition, a significantly decreased LVEF was present in patients with lower and higher serum total PCS and with CKD, and with higher serum total PCS and without CKD than from those with lower serum total PCS concentrations and without CKD (p=0.004). In the multivariate logistic regression analysis, when patients without CKD and lower PCS were used as reference group, patients with the higher total PCS concentration and without CKD had an odds ratio of 3.59 for the risk of LVSD, the lower total PCS concentration and with CKD had an odds ratio of 3.89 for the risk of LVSD, and the higher total PCS concentration and with CKD had an odds ratio of 4.04 for the risk of LVSD (p=0.039, p=0.038, and p=0.020, respectively). CONCLUSIONS High serum concentrations of total PCS or CKD, or both, represent an increased risk of impaired LV systolic function in stable angina patients.

Increased Expression of Visfatin in Monocytes and Macrophages in Male Acute Myocardial Infarction Patients

We demonstrated that visfatin expressed in monocytes and neutrophils and increased their reactivity in male acute ST-segment elevation myocardial infarction patients. Furthermore, visfatin was strongly appeared in lipid rich coronary rupture plaques and macrophages. These results suggest another explanation about leukocytes mediated visfatin that may play a pathogenesis role in coronary vulnerable plaques rupture.

Circulating visfatin level is associated with hepatocellular carcinoma in chronic hepatitis B or C virus infection

Abstract Adipocytokines play an important role in adipose tissue homeostasis, especially in obesity‐associated disorders such as non‐alcoholic fatty liver and their complications including hepatocellular carcinoma (HCC). Although visfatin is an adipocytokine highly expressed in visceral fat that has been demonstrated to play a critical role in the progression of human malignancies, little is known about the role of visfatin in HCC associated with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. In this study, we investigated whether plasma visfatin levels were altered in patients with HCC and the association between plasma visfatin levels and pretreatment hematologic profiles. Plasma visfatin levels were measured by enzyme‐linked immunosorbent assays in 193 patients with different stages of HBV or HCV infection, and 92 healthy control subjects. The patients with HCC and chronic HCV or HBV infection had higher levels of visfatin than patients with HBV, HCV, and cirrhosis. In multivariate logistic regression analysis, levels of alpha‐fetoprotein (AFP) (OR: 1.13, p = 0.003), and plasma visfatin (OR: 1.17, p = 0.046) were independently associated with HCC. Multiple stepwise regression analysis showed that plasma visfatin level was positively associated with age, aspartate aminotransferase to platelet ratio index (APRI), and AFP. Trend analyses confirmed that plasma visfatin concentration was associated with AFP > 8 ng/mL, cirrhosis, HCC, tumor size > 5 cm, and Barcelona Clinic Liver Cancer‐C stage. These results suggested that the plasma visfatin level is associated with the presence of HCC, and that a higher plasma visfatin level may be important in the pathogenesis of HCC. Visfatin may act as both a protective and pro‐inflammatory factor. Plasma visfatin concentration may serve as an additional tool to identify patients with more advanced necroinflammation.

Increased Levels of Total p-Cresylsulfate Are Associated with Pruritus in Patients with Chronic Kidney Disease

Background: Pruritus is a common and distressing symptom that affects patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and p-cresylsulfate (PCS) are uremic toxins with similar protein binding, dialytic clearance, and proinflammatory features. Pruritus in CKD may correlate better with uremic toxins than the glomerular filtration rate (GFR), suggesting that uremic toxins either in the central nervous system or peripherally may play an important role in the pathophysiology. Objective: We sought to investigate the potential contribution of serum total IS and PCS to the pathogenesis of pruritus. Methods: The serum levels of total IS and PCS concentrations were measured in all patients by using the Ultra Performance LC System. The characteristics of pruritus were assessed using a visual analog scale score and an interview questionnaire. Results: Among the 320 CKD patients, 35% had pruritus. The patients with pruritus were older and had a higher frequency of diabetes mellitus, higher uric acid, calcium, phosphorus, creatinine, high-sensitivity C-reactive protein, and total IS and PCS levels, and lower albumin concentrations and estimated GFR (eGFR) than those without pruritus. Increasing concentrations of total PCS were independently and significantly associated with pruritus. Multiple logistic regression analysis revealed total PCS as an independent association factor for pruritus, even after full adjustment of known biomarkers. Furthermore, serum total PCS levels were positively associated with calcium, phosphorus, blood urea nitrogen, creatinine, and white blood cell count, and negatively associated with eGFR, hemoglobin, and hematocrit. Conclusion: Our results indicate that total PCS may play a role in the pathogenesis of pruritus.

Circulating secreted frizzled-related protein 5 and chronic kidney disease in patients with acute ST-segment elevation myocardial infarction

HighlightsWe evaluate patients with acute STEMI who did or did not have CKD.We examine whether plasma Sfrp5 levels were altered in patients with CKD.With increasing Sfrp5, the patients had higher frequency of stage 4 or 5 CKD.Plasma Sfrp5 level was associated with CKD for patients >65 years old.Sfrp5 may play a role in the pathogenesis of CKD in older acute STEMI patients. &NA; Secreted frizzled‐related protein‐5 (Sfrp5) known as secreted antagonist binds to Wnt protein. It has been shown to be downregulated by histone acetylation and promoter methylation, and to function as a tumor suppressor gene by inducing apoptosis in renal cell cancer cells. However, its relationship with chronic kidney disease (CKD) has not been well studied. Our objective was to investigate the effect of plasma Sfrp5 levels in subjects with and without CKD. Plasma Sfrp5 levels were determined by enzyme‐linked immunosorbent assays in 196 consecutive patients with acute ST‐segment elevation myocardial infarction (STEMI). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. For the purpose of this study, stage 1 or 2 CKD patients (eGFR ≥ 60 ml/min per 1.73 m2) were classified as not having CKD. With increasing Sfrp5 tertiles, the patients had higher frequencies of hypertension, stage 4 or 5 CKD, and waist‐to‐hip ratio, incrementally lower eGFRs and serum hemoglobin levels, and higher levels of blood urine nitrogen (BUN), creatinine, and adiponectin. Multivariate logistic regression analysis showed that an increased plasma Sfrp5 level was independently associated with CKD for all subjects (adjusted odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02–1.14; p = 0.011). Sfrp5 was also significantly positively related to BUN, creatinine, and adiponectin, and significantly negatively related to eGFR and hemoglobin. When the patients were stratified by age, plasma Sfrp5 level was independently related to CKD for patients >65 years old (adjusted OR, 1.10; 95% CI, 1.00–1.20; p = 0.045), however, the association was not significant for those <65 years old. In addition, Sfrp5 was significantly positively related to BUN, creatinine, and adiponectin, and significantly negatively related to eGFR and hemoglobin in patients >65 years old. Our results suggest that Sfrp5 may play a role in the pathogenesis of CKD in acute STEMI patients who are older than 65 years.