Association of Thrombin Generation Potential with Platelet PAR-1 Regulation and P-Selectin Expression in Patients on Dual Antiplatelet Therapy

We studied the association of thrombin generation potential with platelet protease activated receptor (PAR)-1 regulation and platelet activation in 52 stable coronary artery disease patients on continuous therapy with aspirin and clopidogrel (n?=?42) or prasugrel (n?=?10). Compared to controls, peak thrombin generation potential was elevated in only 11 patients (p?>?0.05), while F1.2 was elevated in 26 patients (p?<?0.0001). PAR-1 and thrombin inducible P-selectin expression were significantly elevated in patients compared to controls (p?<?0.001). There were no significant correlations between levels of thrombin generation potential or F1.2 and PAR-1 regulation. However, there was a significant inverse correlation between levels of peak thrombin generation potential and in vitro thrombin-inducible expression of P-selectin (p?=?0.002), suggesting in vivo depletion of platelet alpha granules due to ongoing platelet activation.     

Cystatin C is better than albuminuria as a predictor of pulse wave velocity in hypertensive patients

Introduction: Arterial stiffness is important in the evaluation of the cardiovascular risk in both general population and hypertensive patients. In this study, we aimed to investigate the associations of both serum cystatin C levels and albuminuria with arterial stiffness in healthy controls and hypertensive patients.

Patients and methods: Seventy-six healthy controls (male/female?=?44/32) and 76 hypertensive patients (male/female?=?43/33) were enrolled. Arterial stiffness parameters such as augmentation index (AIx) and pulse wave velocity (PWV) were non-invasively measured with the Arteriograph (Tensiomed Ltd., Budapest, Hungary).

Results: AIx (31.92?±?14.31 vs. 27.95?±?11.03, p?=?0.03) and PWV (9.84?±?1.62 vs. 8.87?±?2.04, p?p?=?0.002) and higher serum cystatin C levels [0.76 (0.67–0.95) vs. 0.68 (0.62–0.78) mg/L, p?=?0.03]. In the hypertensive group, AIx was significantly correlated with PWV (r?=?0.519, p?r?=?–0.438, p?=?0.003), mean arterial pressure (MAP) (r?=?0.288, p?=?0.015) and urinary albumin–creatinine ratio (ACR) (r?=?0.386, p?=?0.004). PWV was associated with serum cystatin C (r?=?0.442, p?=?0.003) and MAP (r?=?0.377, p?=?0.001). In the linear regression analysis (model r?=?0.577, p?=?0.006) for the prediction of PWV in hypertensive patients, MAP, urinary ACR, age and serum cystatin C levels were included as independent variables. Cystatin C was found to be the significant determinant of PWV in hypertensive patients.

Conclusion: Multivariate analysis revealed that serum cystatin C but not albuminuria was significantly associated with PWV in hypertensive patients. Serum cystatin C may be better than albuminuria as a predictor of arterial stiffness in hypertensive patients.     

Prognostic value of uric acid in patients with ST-elevated myocardial infarction undergoing primary coronary intervention

Elevated uric acid (UA) levels have been associated with cardiovascular disease in epidemiologic studies. The relation between UA levels and long-term outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention is not known. Data from 2,249 consecutive patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention were evaluated. Patients were divided into 2 groups with high or low UA using upper limits of normal of 6 mg/dl for women and 7 mg/dl for men. There were 1,643 patients in the low-UA group (mean age 55.9 ± 11.6 years, 85% men) and 606 patients in the high-UA group (mean age 60.5 ± 12.6 years, 76% men). Serum UA levels were 8.0 ± 1.5 mg/dl in the high-UA group and 5.2 ± 1.0 mg/dl in the low-UA group (p <0.001). The in-hospital mortality rate was significantly higher in patients with high UA levels (9% vs 2%, p <0.001), as was the rate of adverse outcomes in patients with high UA. The mean follow-up time was 24.3 months. Cardiovascular mortality, reinfarction, target vessel revascularization, heart failure, and major adverse cardiac events were all significantly higher in the high-UA group. In a multivariate analyses, high plasma UA levels were an independent predictor of major adverse cardiac events in the hospital (odds ratio 2.03, 95% confidence interval 1.25 to 3.75, p = 0.006) and during long-term follow-up (odds ratio 1.64, 95% confidence interval 1.05 to 2.56, p = 0.03). In conclusion, high UA levels on admission are independently associated with in-hospital and long-term adverse outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention.     

Relation of Neutrophil/Lymphocyte Ratio to Coronary Flow to In-Hospital Major Adverse Cardiac Events in Patients With ST-Elevated Myocardial Infarction Undergoing Primary Coronary Intervention

With the growing understanding of the role of inflammation in patients with atherosclerotic disease, studies have focused on high-sensitivity C-reactive protein (hs-CRP) and other inflammatory markers in their association with outcomes in ST-segment elevation myocardial infarction. The goal of this study was to investigate the association of the neutrophil/lymphocyte (N/L) ratio and in-hospital major adverse cardiac events (MACEs) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). The association of hs-CRP and N/L ratio on admission with Thrombolysis In Myocardial Infarction (TIMI) flow grade after PCI was assessed in 418 consecutive primary patients with PCI. The N/L ratio was significantly higher in the no-reflow group (TIMI grade 0/1/2 flow, n = 158) compared to that of the normal-flow group (TIMI grade 3 flow, n = 260, 4.6 ± 1.7 vs 3.1 ± 1.9, p <0.001). In-hospital MACEs were significantly higher in patients with no reflow (23% vs 7%, p <0.001). There was a significant and positive correlation between hs-CRP and N/L ratio (r = 0.657, p <0.001). In receiver operating characteristic analysis, N/L ratio >3.3 predicted no reflow with 74% sensitivity and 83% specificity. In a multivariate regression model, N/L ratio remained an independent correlate of no reflow (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.34 to 1.76, p <0.001) and in-hospital MACEs (OR 1.14, 95% CI 0.98 to 1.32, p = 0.043). The N/L ratio, an inexpensive and easily measurable laboratory variable, is independently associated with the development of no reflow and in-hospital MACEs in patients with ST-segment elevation myocardial infarction undergoing primary PCI.     

The effect of local corticosteroid injection on F-wave conduction velocity and sympathetic skin response in carpal tunnel syndrome

The aim of this study was to evaluate the efficacy of steroid injection for the treatment of the carpal tunnel syndrome (CTS), with F-wave parameters and sympathetic skin response (SSR). Seventeen hands of 10 women patients were treated with local steroid injection with 2-month follow-up. All patients underwent single injection into the carpal tunnel. Response to injection was measured nerve conduction studies (NCSs), median nerve F waves, and SSR before and after treatment. To determine the normal values, 42 hands of 21 healthy women were also studied. There was a significant improvement of sensory and motor nerve conduction values when compared to baseline values (P < 0.01). At the end of follow-up period, the median sensory distal latency and the sensory latency differences between the median and the ulnar nerve were improved 35 and 65%, respectively. The maximum, mean F-wave amplitudes and chronodispersion showed a slight improvement with respect to baseline values and controls, but statistical significance was not achieved after treatment. Although no statistically significant improvements were observed in SSR parameters, slightly decreased amplitudes and increased habituation of SSR were noted at the end of the treatment. The present study shows that the local steroid injection results in improvement in NCSs values, but the F-wave parameters were not effectual in short-term outcome of CTS treatment. These findings suggest that the sensory latency differences between the median and the ulnar wrist-to-digit 4 are better parameters in the median nerve recovery after treatment than the median sensory distal latency. Furthermore, the SSR does not seem to be a sensitive method in follow-up of CTS treatment.     

S100A8/A9 aggravates post-ischemic heart failure through activation of RAGE-dependent NF-κB signaling

The extracellular heterodimeric protein S100A8/A9 activates the innate immune system through activation of the receptor of advanced glycation end products (RAGE) and Toll-like receptors. As activation of RAGE has recently been associated with sustained myocardial inflammation and heart failure (HF) we studied the role of S100A8/A9 in the development of post-ischemic HF. Hypoxia led to sustained induction of S100A8/A9 accompanied by increased nuclear factor (NF-)κB binding activity and increased expression of pro-inflammatory cytokines in cardiac fibroblasts and macrophages. Knockdown of either S100A8/A9 or RAGE rescued the induction of pro-inflammatory cytokines and NF-κB activation after hypoxia. In a murine model of post-ischemic HF both cardiac RNA and protein levels of S100A8/A9 were elevated as soon as 30 min after hypoxia with sustained activation up to 28 days after ischemic injury. Treatment with recombinant S100A8/A9 resulted in reduced cardiac performance following ischemia/reperfusion. Chimera experiments after bone marrow transplantation demonstrated the importance of RAGE expression on immune cells for their recruitment to the injured myocardium aggravating post-ischemic heart failure. Signaling studies in isolated ventricles indicated that MAP kinases JNK, ERK1/2 as well as NF-κB mediate signals downstream of S100A8/A9-RAGE in post-ischemic heart failure. Interestingly, cardiac performance was not affected by administration of S100A8/A9 in RAGE^?/?-mice, which demonstrated significantly improved cardiac recovery compared to WT-mice. Our study provides evidence that sustained activation of S100A8/A9 critically contributes to the development of post-ischemic HF driving the progressive course of HF through activation of RAGE.