Cheng-An Chiu

Serum levels of total p-cresylsulphate are associated with angiographic coronary atherosclerosis severity in stable angina patients with early stage of renal failure

OBJECTIVE p-Cresylsulphate (PCS), a protein-bound uraemic retention solute, is known to cause endothelial dysfunction and possibly plays a role in coronary atherosclerosis. We aimed to investigate the relationship of total PCS with traditional biomarkers associated with chronic coronary atherosclerosis. In addition, the relationship between serum total PCS levels and the severity of coronary artery stenosis was also explored. METHODS AND RESULTS Serum total PCS concentrations were measured by using the Ultra Performance LC System in 202 consecutive stable angina patients, and their associations with angiographic indexes of the number of diseased vessels and modified Gensini score were estimated. Patients with significant coronary artery stenosis have higher median serum total PCS levels than patients with normal coronary arteries. Statistically significant associations were observed between the serum total PCS levels and the number of diseased vessels (beta=0.261, p=0.0002), and modified Gensini score (beta=0.171, p=0.016). Using multivariate analysis, serum total PCS level was independently associated with the presence and severity of CAD. CONCLUSIONS This study indicates that serum total PCS levels are significantly higher in the presence of CAD and are correlated with the severity of the disease, which suggest that increased serum total PCS may be involved in the pathogenesis of coronary atherosclerosis.

Elevated Visfatin/Pre-B-cell Colony-enhancing Factor Plasma Concentration in Ischemic Stroke

BACKGROUND Visfatin/pre-B-cell colony-enhancing factor is a cytokine that is expressed as a protein in several tissues (e.g., liver, skeletal muscle, immune cells), including adipose tissue, and is reported to stimulate inflammatory cytokine expressions and promote vascular smooth cell maturation. Visfatin may act as a proinflammatory cytokine and be involved in the process of atherosclerosis. In this study, we investigated whether plasma visfatin levels were altered in patients with ischemic stroke. METHODS Plasma visfatin concentrations were measured through enzyme immunoassays in patients with ischemic stroke and in control subjects without stroke. RESULTS The mean plasma concentration of visfatin in the 120 patients with ischemic stroke was significantly higher than that of the 120 control subjects without stroke (51.5 +/- 48.4 v 23.0 +/- 23.9 ng/mL, P < .001). Multiple logistic regression analysis confirmed plasma visfatin to be an independent factor associated with ischemic stroke. Increasing concentrations of visfatin were independently and significantly associated with a higher risk of ischemic stroke when concentrations were analyzed as both a quartile and a continuous variable. The multiple logistic regression analysis-adjusted odds ratios and 95% confidence intervals for ischemic stroke in the second, third, and fourth quartiles were 2.3 (0.7-7.7), 6.9 (2.2-23.3), and 20.1 (4.9-97.7), respectively. Plasma visfatin concentration was positively associated with high-sensitivity C-reactive protein levels and negatively associated with low-density lipoprotein cholesterol. CONCLUSIONS Our results indicate that higher visfatin levels are associated with ischemic stroke in the Chinese population.

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.

Interpretation of elevated plasma visfatin concentrations in patients with ST-elevation myocardial infarction

Visfatin is a cytokine that is expressed in many tissues, including the heart, and has been proposed to play a role in plaque destabilization leading to acute myocardial injury. The present study evaluates plasma levels of visfatin in acute ST-elevation myocardial infarction (STEMI) patients and examines the temporal changes in visfatin levels from the acute period to the subacute period to determine a correlation with the degree of myocardial ischemia. We evaluated 54 patients with STEMI. Circulating levels of visfatin and brain natriuretic peptide (BNP) were measured by ELISA. In addition, local expression of visfatin and BNP were detected by quantitative real-time polymerase chain reaction and immunohistochemical (IHC) analysis of left ventricular myocytes in a mouse model of myocardial infarction (MI). Plasma levels of visfatin were significantly increased in patients with STEMI on admission, relative to controls (effort angina patients and individuals without coronary artery disease). The visfatin levels reached a peak 24h after percutaneous coronary intervention (PCI) and then decreased toward the control range during the first week after PCI. The basal plasma visfatin levels were found to correlate with peak troponin-I, peak creatine kinase-MB, total white blood cell count, and BNP levels. Trend analyses confirmed that visfatin levels correlated with the number of diseased coronary arteries. Further, in MI mice, mRNA levels of visfatin and BNP were found to be higher than in sham-treated mice. IHC analysis showed that visfatin and BNP immunoreactivity was diffusely observable in left ventricular myocytes of the MI mice. This study indicates that plasma visfatin levels are significantly higher in STEMI patients and that these higher visfatin levels correlate with elevated levels of cardiac enzymes, suggesting that increased plasma visfatin may be closely related to the degree of myocardial damage.

Brachial-Ankle Pulse Wave Velocity as an Early Indicator of Left Ventricular Diastolic Function Among Hypertensive Subjects

While increased arterial stiffness is a known risk of cardiovascular disease, pulse wave velocity (PWV) is a conventionally adopted index of arterial stiffness. However, the relationship between PWV and left ventricular functions are not thoroughly evaluated. This cross-sectional study investigated whether PWV measurement is an early indicator of left ventricular (LV) dysfunction. A noninvasive, volume-plethysmographic apparatus was used to determine blood pressure, electrocardiogram, heart sounds, and PWV in 42 consecutively diagnosed subjects with hypertension, and 42 sex- and age-matched nonhypertension subjects were studied. Arterial stiffness and aortic stiffness were evaluated by brachial-ankle (b-a) PWV, heart-carotid (h-c) PWV, heart-femoral (h-f) PWV, carotid-femoral (c-f) PWV, and femoral-ankle (f-a) PWV. Function of LV was estimated by tissue Doppler imaging (TDI) echocardiography. Hypertension subjects exhibited higher b-a PWV and late diastolic mitral flow velocity values than those of nonhypertensive subjects. Pearson correlation analysis revealed that LV diastolic function (Emav) negatively correlated with c-f PWV and b-a PWV. Multiple linear regression analysis indicated that b-a PWV was independently and negatively associated with LV diastolic function (Emav). Further analysis by stratified hypertensive status, the b-a PWV were independently and negatively associated with Emav in hypertensive subjects (p = 0.004) only. In conclusion, the b-a PWV, but not c-f PWV, h-c PWV, h-f PWV, or f-a PWV, is significantly correlated with LV diastolic function in hypertensive subjects, indicating that b-a PWV involving both central and peripheral components of arterial stiffness may be an early indicator of LV dysfunction.

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.

Medical Treatment of a Salmonella-infected Left Ventricular Pseudoaneurysm: A Case Report

Here, we present a case of Salmonella infection in a post‐myocardial infarction patient with a left ventricular aneurysm and mural thrombus. This is a rare case that was successfully treated with medicinal therapy alone. Our experience with this case documents the early spontaneous drainage of the myocardial abscess by 8 weeks of antibiotic therapy under serial two‐ and three‐dimensional echocardiography to monitor the clinical outcomes and guide the decision‐making process. This approach may be a viable alternative for intolerant, high‐risk surgical aneurysmectomy patients.