Levels of Selenium, Zinc, Copper, and Cardiac Troponin I in Serum of Patients with Acute Coronary Syndrome

The aim of this study was to assess the levels of selenium (Se), zinc (Zn), copper (Cu), and troponin I (TnI) in patients with acute coronary syndrome (ACS) on admission to our emergency department in comparison to healthy control subjects. Patients with diagnosed ACS (n?=?100) were included in the study group. Control subjects (n?=?100) were selected from healthy volunteers in the same age range. Venous blood samples were obtained to evaluate the levels of Se, Zn, Cu, and TnI (on admission for the ACS group). Serum Se, Zn, and Cu levels were significantly less in the ACS group compared to the control group (p <0.001, p <0.01, and p <0.001, respectively). The serum TnI level was significantly greater in the ACS group compared to the control group (p <0.05). The serum Se level in the ACS group correlated significantly with the TnI level (r?=??0.211, p?=?0.035). These results indicate that Se, Zn, and Cu deficiencies may be risk factors for ACS, and a decreased serum Se level in patients with ACS might reflect the degree of myocardial necrosis.     

Butyrylcholinesterase Predicts Cardiac Mortality in Young Patients with Acute Coronary Syndrome

Background

The incidence of acute coronary syndrome (ACS) in young people (≤65 years) is continuously rising. While prognostic factors in ACS are well-investigated less attention has been paid to their age-dependent prognostic value and their particular relevance in younger patients. The aim of our study was to assess the age-dependent prognostic impact of butyrylcholinesterase (BChE).

Methods

Retrospective cohort study including 624 patients with ACS. Patients were stratified by age into equal groups (n = 208) corresponding to “young patients” (45–64 years), "middle-aged patients” (65–84 years) and “old patients” (85–100 years). Cox regression hazard analysis was used to assess the influence of BChE on survival.

Results

After a mean follow-up time of 4.0 (interquartile range [IQR] 2.0–6.4) years, 154 patients (24.7%) died due to a cardiac cause. In the overall cohort, BChE was indirectly associated with cardiac mortality-free survival (adjusted hazard ratio (HR): 0.70 (95% confidence interval [CI] 0.53–0.93, p = 0.01). The primary-analysis of BChE by age strata showed the strongest effect in the age group 45–64 years with an adjusted HR per 1-SD of 0.28 (95% CI 0.12–0.64, p = 0.003), a weaker association with mortality in middle aged (65–84 years: adjusted HR per 1-SD 0.66 [95% CI: 0.41–1.06], p = 0.087), and no association in older patients (85–100 years: adjusted HR per 1-SD 0.89 [95% CI: 0.58–1.38], p = 0.613).

Conclusion

BChE is a strong predictor for cardiac mortality specifically in younger patients with ACS aged between 45 and 64 years. No significant association of BChE with cardiac-mortality was detected in other age classes.     

慢性肾脏病患者心脏结构与功能变化的超声心动图研究

目的:研究慢性肾脏病(CKD)患者心脏结构及功能的变化.方法:选择我院肾内科175例慢性肾脏病未透析患者,按照2003年美国国家肾脏基金会-肾脏病转归质量(NKF-K/DOQI)指南的标准进行分期,观察所有患者心脏结构及功能在超声中的变化.结果:慢性肾脏病患者随着肾功能的恶化,各组之间比较,室间隔厚度(IVST)、左心室后壁厚度(LVPW)、左心室心肌重量指数(LVMI)、左心室舒张末期内径(LVDd)、左心房内径(LAD)具有升高的趋势(P＜0.05,P＜0.01);但E/A比值未出现伴随着肾功能恶化而逐渐减低的趋势(P＞0.05);射血分数(EF)、短轴缩短卒(FS)在各期之间无明显变化(P＞0.05);而TVI技术测定的Em、Em/Am具有显著减低的趋势(P＜0.05,P＜0.01);瓣膜返流以二尖瓣返流为主.结论:慢性肾脏病患者心脏结构与功能随肾功能减退而加重,超声心动图检查结合组织速度显像(TVI)技术能更好地检测心脏结构和功能变化,尤其是检测左心室舒张功能障碍.     

NT-proBNP与急性冠脉综合征患者冠脉病变程度及预后的关系

目的:探讨N末端脑钠肽原(NT-pro BNP)与急性冠脉综合征(ACS)患者冠脉病变程度及预后的关系。方法:选择2012年1月至2015年6月我院收治的ACS患者400例为研究对象,根据病情症状的不同将患者分为不稳定心绞痛(UA)组和急性心肌梗死(AMI)组,各200例,另选同期200例非ACS患者作为对照组,比较各组患者的NT-pro BNP水平及ACS患者的心功能情况,并比较ACS患者的冠脉造影结果,通过Syntax评分系统评价冠脉病变,随访6-12个月,对比各组患者的主要心血管不良事件(MACE)发生率,通过上述比较及分析,研究ACS患者NT-pro BNP与冠脉病变程度及预后的关系。结果:AMI组及UA组患者的NT-pro BNP水平明显高于对照组,且AMI组患者的NT-pro BNP水平明显高于UA组,差异有统计学意义(P0.05);AMI组患者的冠脉病变Syntax积分高于UA组,差异有统计学意义(P0.05);冠脉病变Syntax积分≥33分的ACS患者的NT-pro BNP水平高于Syntax积分0-22分的患者,差异有统计学意义(P0.05);同时双支病变和三支病变患者的Syntax积分及NT-pro BNP水平高于单支病变患者,差异有统计学意义(P0.05);随访6-12个月发生MACE患者的NT-pro BNP水平明显高于未发生MACE者,差异有统计学意义(P0.05)。Pearson相关性分析显示,患者的冠脉病变程度与NT-pro BNP及Syntas积分均呈正相关(r=0.667,0.842;P0.05)。患者随访6-12个月MACE发生率与NT-pro BNP及Syntas积分也呈正相关(r=0.708,0.821;P0.05)。结论:ACS患者的冠脉病变程度及预后与其NT-pro BNP水平具有较好的相关性,值得临床关注。     

Effects of Clopidogrel on Mortality,Cardiovascular and Bleeding Outcomes in Patients with Chronic Kidney Disease - Data from Taiwan Acute Coronary Syndrome Full Spectrum Registry

Background

The efficacy of clopidogrel is inconclusive in the chronic kidney disease (CKD) population with acute coronary syndrome (ACS). Furthermore, CKD patients are prone to bleeding with antiplatelet therapy. We investigated the efficacy and safety of clopidogrel in patients with ACS and CKD.

Methods

In a Taiwan national-wide registry, 2819 ACS patients were enrolled. CKD is defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m². The primary endpoints are the combined outcomes of death, non-fatal myocardial infarction and stroke at 12 months.

Results

Overall 949 (33.7%) patients had CKD and 2660 (94.36%) patients received clopidogrel treatment. CKD is associated with increased risk of the primary endpoint at 12 months (HR 2.39, 95% CI 1.82 to 3.15, p<0.01). Clopidogrel use is associated with reduced risk of the primary endpoint at 12 months (HR 0.42, 95% CI: 0.29–0.60, p<0.01). Cox regression analysis showed that clopidogrel reduced death and primary endpoints for CKD population (HR 0.35, 95% CI: 0.21–0.61 and HR 0.48, 95% CI: 0.30–0.77, respectively, both p<0.01). Patients with clopidogrel(−)/CKD(−), clopidogrel(+)/CKD(+) and clopidogrel(−)/CKD(+) have 2.4, 3.0 and 10.4 fold risk to have primary endpoints compared with those receiving clopidogrel treatment without CKD (all p<0.01). Clopidogrel treatment was not associated with increased in-hospital Thrombolysis In Myocardial Infarction (TIMI) bleeding in CKD population.

Conclusion

Clopidogrel could decrease mortality and improve cardiovascular outcomes without increasing risk of bleeding in ACS patients with CKD.     

Pericardial Fat Is Associated with Coronary Artery Calcification in Non-Dialysis Dependent Chronic Kidney Disease Patients

Pericardial fat (PF) a component of visceral adipose tissue has been consistently related to coronary atherosclerosis in the general population. This study evaluated the association between PF and coronary artery calcification (CAC) in non-dialysis dependent chronic kidney disease (CKD) patients. This is a post-hoc cross sectional analysis of the baseline of a prospective cohort of 117 outward CKD patients without manifest coronary artery disease (age, 56.9±11.0 years, 64.1% males, 95.1% hypertensives, 25.2% diabetics, 15.5% ever smokers, CKD stage 2 to 5 with estimated glomerular filtration rate 36.8±18.1 ml/min). CAC scores, PF volume and abdominal visceral fat (AVF) areas were measured by computed tomography. The association of PF as a continuous variable with the presence of CAC was analyzed by multivariate logistic regression. CAC (calcium score >0) was present in 59.2% patients. Those presenting CAC were on average 10 years older, had a higher proportion of male gender (78.7% vs. 42.9%, p<0.001), and had higher values of waist circumference (95.9±10.7 vs. 90.2±13.2 cm, p = 0.02), PF volumes (224.8±107.6 vs. 139.1±85.0 cm³, p<0.01) and AVF areas (109.2±81.5 vs. 70.2±62.9 cm², p = 0.01). In the multivariate analysis, adjusting for age, gender, diabetes, smoking and, left ventricular concentric hypertrophy, PF was significantly associated with the presence of CAC (OR: 1.88 95% CI: 1.03–3.43 per standard deviation). PF remained associated with CAC even with additional adjustments for estimated glomerular filtration rate or serum phosphorus (OR: 1.85 95% CI: 1.00–3.42, p = 0.05). PF is independently associated with CAC in non-dialysis dependent CKD patients.     

非透析慢性肾脏病患者心脏功能生物标记物的临床价值比较

目的:比较非透析慢性肾脏病患者心脏功能生物标记物的临床应用价值。方法:选取122例非透析且无急性冠脉综合征(ACS)的慢性肾脏病患者(CKD),将其分为CKD1-2期组、CKD3-4期组和CKD5期组,同时选择同期确诊急性冠脉综合征的慢性肾脏病患者20例作为对照组,观察并比较各组患者室间隔厚度(IVST)、左室后壁厚度(LVPWT),检测血液中血肌酐(Scr)、尿素氮(BUN)、心型脂肪酸结合蛋白(HFABP)、心肌钙蛋白(cTnI)以及肌酸激酶同功酶(CK-MB)。结果:非ACS的CKD患者HFABP、cTnI、CK-MB水平均呈不同程度增高,且各CKD组中这三个指标的阳性率存在显著差异,其中HFABP阳性率最高(P0.05)。cTnI与e GFR、Scr及年龄无显著相关性(P0.05),但与IVST、LVPWT呈显著正相关(P0.05);CK-MB与e GFR、Scr、年龄、IVST、LVPWT均无相关性(P0.05);HFABP与e GFR呈负相关(P0.05),与Scr和BUN正相关(P0.05),与年龄、IVST、LVPWT无相关性(P0.05)。结论:在非ACS的CKD患者中,HFABP可能不是一个可靠的反映心脏功能的生物标记物,cTnI及CK-MB对于CKD患者而言是较为可靠的心脏标记物。     

高敏肌钙蛋白预测急性冠脉综合征的价值分析

目的:研究早期检测高敏肌钙蛋白对预测及诊断急性冠脉综合征的价值。方法:以2012年1月至2014年07月于我院就诊的82例疑似急性冠脉综合征患者为研究对象,采集血液标本,均分为两组,一组行血清常规肌钙蛋白T(c Tn T)检测,结果归入对照组;一组行血清高敏肌钙蛋白(hs-c Tn I)检测,结果归入观察组。同时行心肌酶谱及心电图检查,以其动态演变为金标准,评价两组敏感度、特异度,绘制ROC曲线。结果:金标准提示共64例阳性患者。观察组检测hs-c Tn I阳性62例,敏感度92.2%(59/64),特异度88.9%(16/18);对照组检查c Tn T阳性59例,敏感度79.7%(51/64),特异度55.6%(10/18),观察组ROC曲线优于对照组(P=0.000)。健康人群肌钙蛋白含量显著性低于急性冠脉综合征患者,差异具备统计学意义(P0.05)。结论:hs-c Tn I检测有助于预测急性冠脉综合征,其诊断敏感度及特异度均较高,可满足现阶段诊治需求。     

Basal and Ischemia-Induced Transcardiac Troponin Release into the Coronary Circulation in Patients with Suspected Coronary Artery Disease

Background

Cardiac troponin is a specific biomarker for cardiomyocyte necrosis in acute coronary syndromes. Troponin release from the coronary circulation remains to be determined because of the lower sensitivity of the conventional assay. We sought to determine basal and angina-induced troponin release using a highly sensitive troponin assay.

Methods and Results

The cardiac troponin T levels in serum sampled from the peripheral vein (PV), the aortic root (AO), and the coronary sinus (CS) were measured in 105 consecutive stable patients with coronary risk factor(s) and suspected coronary artery disease (CAD) and in 33 patients without CAD who underwent an acetylcholine provocation test. At baseline, there was a significant increase in the troponin levels from AO [9.0 (6.4, 13.1) pg/mL for median (25^th, 75^th percentiles)] to CS [10.3 (7.3, 15.5) pg/mL, p<0.001] in 96 (91.4%) patients and the difference was 1.1 (0.4, 2.1) pg/mL, which reflected basal transcardiac troponin release (TTR). TTR was positively correlated with PV levels (r = 0.22, p = 0.03). Male sex, left ventricular hypertrophy determined by echocardiography, T-wave inversion, and CAD correlated with elevated TTR defined as above: median, 1.1 pg/mL. A significant increase in TTR was noted in 17 patients with coronary spasms [0.6 (0.2, 1.2) pg/mL, p<0.01] but not in 16 patients without spasms [0.0 (−0.5, 0.9) pg/mL, p = 0.73] after the acetylcholine provocation.

Conclusion

Basal TTR in the coronary circulation was observed in most of the patients with suspected CAD and risk factor(s). This sensitive assay detected myocardial ischemia-induced increases in TTR caused by coronary spasms.     

Relation between Mild to Moderate Chronic Kidney Disease and Coronary Artery Disease Determined with Coronary CT Angiography

Background

Both end-stage and milder stages of chronic kidney disease (CKD) are associated with an increased risk of adverse cardiovascular events. Several studies found an association between decreasing renal function and increasing coronary artery calcification, but it remains unclear if this association is independent from traditional cardiovascular risk factors. Therefore, the aim of this study was to investigate whether mild to moderate CKD is independently associated with coronary plaque burden beyond traditional cardiovascular risk factors.

Methods

A total of 2,038 patients with symptoms of chest discomfort suspected for coronary artery disease underwent coronary CT-angiography. We assessed traditional risk factors, coronary calcium score and coronary plaque characteristics (morphology and degree of luminal stenosis). Patients were subdivided in three groups, based on their estimated glomerular filtration rate (eGFR) Normal renal function (eGFR ≥90 mL/min/1.73 m²); mild CKD (eGFR 60–89 mL/min/1.73 m²); and moderate CKD (eGFR 30–59 mL/min/1.73 m²).

Results

Coronary calcium score increased significantly with decreasing renal function (P<0.001). Coronary plaque prevalence was higher in patients with mild CKD (OR 1.83, 95%CI 1.52–2.21) and moderate CKD (OR 2.46, 95%CI 1.69–3.59), compared to patients with normal renal function (both P<0.001). Coronary plaques with >70% luminal stenosis were found significantly more often in patients with mild CKD (OR 1.67 (95%CI 1.16–2.40) and moderate CKD (OR2.36, 95%CI 1.35–4.13), compared to patients with normal renal function (both P<0.01). After adjustment for traditional cardiovascular risk factors, the association between renal function and the presence of any coronary plaque as well as the association between renal function and the presence of coronary plaques with >70% luminal stenosis becomes weaker and were no longer statistically significant.

Conclusion

Although decreasing renal function is associated with increasing extent and severity of coronary artery disease, mild to moderately CKD is not independently associated with coronary plaque burden after adjustment for traditional cardiovascular risk factors.     

Low-Dose Aspirin for Prevention of Cardiovascular Disease in Patients with Chronic Kidney Disease

Background

Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD). Previous trials have investigated the effects of low-dose aspirin on CVD prevention in patients with diabetes; however, patients with CKD were not examined. The role of aspirin in diabetics is controversial, and the available literature is contradictory. Therefore, we studied whether low-dose aspirin would be beneficial for patients with CKD, a group that is at high risk for CVD.

Method

From a total of 25340 patients with CKD, 1884 recipients of low-dose aspirin (100 mg/day) were paired 1∶1 with non-recipients for analysis using propensity score matching. The primary endpoint was the development of atherosclerotic CVD, including coronary arterial disease, stroke, and peripheral arterial disease. Secondary endpoints included death from any cause, bleeding events, doubling of serum creatinine, and renal death.

Results

The incidence of a primary endpoint of any atherosclerotic CVD was significantly higher in the aspirin users than in the non-users (P<0.001). Secondary endpoints, including all-cause mortality and composite bleeding events, were not significantly different between the aspirin users and the non-users. However, the doubling of serum creatinine levels (P = 0.001) and renal death (P = 0.042) were significantly associated with the use of aspirin.

Conclusion

These results suggest that the use of low-dose aspirin in patients with CKD may have harmful consequences related to the development of CVD and renal progression.     

Efficacy of Benzbromarone in Hyperuricemic Patients Associated with Chronic Kidney Disease

We have retrospectively evaluated the uric acid control status and renal function changes over a period of up to 7 years in 35 patients with renal impairment who had stage 3 or higher chronic kidney disease (CKD; stage 3 in 32 patients, stage 4 in 2 patients, and stage 5 in 1 patient) associated with hyperuricemia and were receiving monotherapy with benzbromarone as an antihyperuricemic drug. Serum uric acid levels significantly decreased from 8.5 ± 0.9 to 6.1 ± 0.8 mg/dL at 6 months and were subsequently controlled at less than 7.0 mg/dL in most patients. Most patients received benzbromarone at a dose of 25–50 mg/day, whereas 150–200 mg/day was used in some patients with stage 4 or 5 CKD. No significant changes in estimated glomerular filtration rate (eGFR) from the baseline value of 46.2 ± 11.5 mL/minute/1.73 m² were found after benzbromarone therapy. Although the renal function impairment did not improve by reducing the serum uric acid levels with benzbromarone, the renal function did not deteriorate further on the therapy. These results suggest that benzbromarone is applicable to the management of hyperuricemia associated with renal impairment.     

Precipitating Factors of Acute Illness in Patients with Chronic Disease

The precipitating causes of acute illness in patients with chronic organic disease can often be prevented, reversed or controlled. The various kinds of precipitating factors are described, and their anticipation and the prompt institution of remedial measures are emphasized.     

Chronic Kidney Disease and Diabetic Retinopathy in Patients with Type 2 Diabetes

Purpose

To explore the relationship between chronic kidney disease (CKD) and diabetic retinopathy (DR) in a representative population of type 2 diabetes mellitus (DM2) patients in Catalonia (Spain).

Methods

This was a population-based, cross-sectional study. A total of 28,344 patients diagnosed with DM2 who had recorded ophthalmologic and renal functional examinations were evaluated. Data were obtained from a primary healthcare electronic database of medical records. CKD was defined as an estimated glomerular filtration ratio (eGFR) of <60 ml/min/1.73m² and/or urine albumin to creatinine ratio (UACR) ≥30 mg/g. DR was categorized as non-vision threatening diabetic retinopathy and vision threatening diabetic retinopathy.

Results

CKD was associated with a higher rate of DR [OR], 95% confidence interval [CI], 1.5 (1.4–1.7). When we analyzed the association between different levels of UACR and DR prevalence observed that DR prevalence rose with the increase of UACR levels, and this association was significant from UACR values ≥10 mg/g, and increased considerably with UACR values ≥300mg/g (Odds ratio [OR], 95% confidence interval [CI], 2.0 (1.6–2.5). This association was lower in patients with eGFR levels 44 to 30 mL/min/1.73m² [OR], 95% confidence interval [CI], 1.3 (1.1–1.6).

Conclusions

These results show that CKD, high UACR and/or low eGFR, appear to be associated with DR in this DM2 population.     

Leukocyte Proliferation and Immune Modulator Production in Patients with Chronic Kidney Disease

Introduction

In Chronic Kidney Disease (CKD), immune cells are affected by uremic retention toxins. Given this effect, we analyzed lymphocyte proliferative response and immune modulators production following in vitro stimulation.

Methods

Whole blood was drawn from healthy controls, patients with eGFR <20 ml/min/1.73 m² (Pre-dialysis, CKD stages 4 and 5) and hemodialysis patients (stage 5D). Peripheral cells were incubated for six days with pokeweed mitogen, concanavalin A, Staphylococcus enterotoxin A or influenza A vaccine. Peripheral lymphocyte proliferation was then analyzed by the “Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood” (FASCIA) method, and cytokine profile in the cell supernatants was analyzed by the Milliplex multi-array method.

Results

The absolute number of lymphoblasts in response to mitogenic stimulation and the number of cells in each CD4+ and CD8+ subpopulation were similar comparing the three groups, except for a single decline in number of lymphoblasts after stimulation with Staphylococcus enterotoxin A, comparing dialysis patients with healthy controls. Levels of interleukin (IL)-2 (p=0.026), -10 (p=0.019) and -15 (p=0.027) in the Staphylococcus enterotoxin A-stimulated supernatant were lower in hemodialysis patients compared to healthy controls. Levels of IL-15 (p=0.017) from pre-dialysis patients and levels of IL-5 (p=0.019) from hemodialysis patients in influenza A vaccine-stimulated supernatants were also lower compared to controls. In pokeweed mitogen–stimulated supernatant, IL-2 levels (p=0.013) were lower in hemodialysis patients compared to pre-dialysis patients. TNF-α, IL-10, IL-12, IL-15, IL-8, MCP-1, IP-10, IFN-α2, IL-1α and eotaxin levels were all significantly higher in plasma obtained from CKD patients.

Conclusion

Our results suggest that T-cells from CKD patients have similar proliferative response to stimulation compared with healthy individuals. Moreover, however the immune cells show inability to produce selected cytokines, most likely due to the uremic milieu or dialysis procedure.     

Impact of Coronary Dominance on In-Hospital Outcomes after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome

Objective

This study evaluated the manner in which coronary dominance affects in-hospital outcomes of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).

Background

Previous studies have shown that left dominant coronary anatomies are associated with worse prognoses in patients with coronary artery disease.

Methods

Data were analyzed from 4873 ACS patients undergoing PCI between September 2008 and April 2013 at 14 hospitals participating in the Japanese Cardiovascular Database Registry. The patients were grouped based on diagnostic coronary angiograms performed prior to PCI; those with right- or co-dominant anatomy (RD group) and those with left-dominant anatomy (LD group).

Results

The average patient age was 67.6±11.8 years and both patient groups had similar ages, coronary risk factors, comorbidities, and prior histories. The numbers of patients presenting with symptoms of heart failure, cardiogenic shock, or cardiopulmonary arrest were significantly higher in the LD group than in the RD group (heart failure: 650 RD patients [14.7%] vs. 87 LD patients [18.8%], P = 0.025; cardiogenic shock: 322 RD patients [7.3%] vs. 48 LD patients [10.3%], P = 0.021; and cardiopulmonary arrest: 197 RD patients [4.5%] vs. 36 LD patients [7.8%], P = 0.003). In-hospital mortality was significantly higher among LD patients than among RD patients (182 RD patients [4.1%] vs. 36 LD patients [7.8%], P = 0.001). Multivariate logistic regression analysis revealed that LD anatomy was an independent predictor for in-hospital mortality (odds ratio, 1.75; 95% confidence interval, 1.06–2.89; P = 0.030).

Conclusion

Among ACS patients who underwent PCI, LD patients had significantly worse in-hospital outcomes compared with RD patients, and LD anatomy was an independent predictor of in-hospital mortality.     

Inflammation Activation Contributes to Adipokine Imbalance in Patients with Acute Coronary Syndrome

Inflammation can be activated as a defensive response by the attack of acute coronary syndrome (ACS) for ischemic tissue injury. The aim of the present study was to investigate the impact of ACS-activated inflammation on adipokine imbalance and the effects of statins on the crosstalk between inflammation and adipokine imbalance during ACS. In this study, 586 subjects were categorized into: (1) control group; (2) SA (stable angina) group; and (3) ACS group. Circulating levels of hs-CRP, adiponectin and resistin were measured by ELISA. Furthermore, forty C57BL/6 mice were randomized into: sham, AMI, low-statin (atorvastatin, 2 mg/kg/day) and high-statin (atorvastatin, 20 mg/kg/day) group. After 3 weeks, AMI models were established by surgical coronary artery ligation. Circulating levels and adipose expressions of adiponectin and resistin were assessed in animals. Besides, we investigate the effects of atorvastatin on ox-LDL-induced adipokine imbalance in vitro. As a result, we found that ACS patients had higher hs-CRP and resistin levels and lower adiponectin levels. Our correlation analysis demonstrated hs-CRP concentrations were positively correlated with resistin but negatively with adiponectin levels in humans. Our animal findings indicated higher circulating hs-CRP and resistin levels and lower adiponectin levels in AMI mice. Atorvastatin pre-treatment dose-dependently decreased hs-CRP and resistin levels but increased adiponectin levels in mice. The consistent findings were observed about the adipose expressions of resistin and adiponectin in mice. In study in vitro, ox-LDL increased cellular resistin expressions and otherwise for adiponectin expressions, which dose-dependently reversed by the addition of atorvastatin. Therefore, our study indicates that the ACS attack activates inflammation leading to adipokine imbalance that can be ameliorated by anti-inflammation of atorvastatin.     

电阻抗法在急性冠脉综合征患者中的应用

目的:探讨电阻抗法测定血小板聚集功能在冠心病患者中的应用。方法:通过电阻抗法对486名急性冠脉综合征的患者检测,所有患者分别于服药前和服药后第4天抽取肘静脉血,采血后1小时内用全血阻抗法测定三磷酸腺苷(ADP)和花生四烯酸(AA)诱导的血小板聚集率;其中50例患者出现氯吡格雷抵抗,28例患者出现阿司匹林抵抗。结果:通过电阻抗法测定的抗血小板药物抵抗的发生率(10.29%)与文献报道的一致;在原来抗血小板药物基础增加西洛他唑或者增加氯吡格雷的剂量都能明显改善血小板药物抵抗,随着服药时间的增加血小板药物抵抗呈下降趋势;大剂量氯吡格雷组相比西洛他唑组在改善氯吡格雷抵抗更明显,差异有统计学意义(P0.05)。结论:电阻抗法测定血小板聚集功能方便快捷、安全可靠,更方便指导临床用药。     

Mutual Rescues between Two Dominant Negative Mutations in Cardiac Troponin I and Cardiac Troponin T

Troponin T (TnT) and troponin I (TnI) are two evolutionarily and functionally linked subunits of the troponin complex that regulates striated muscle contraction. We previously reported a single amino acid substitution in the highly conserved TnT-binding helix of cardiac TnI (cTnI) in wild turkey hearts in concurrence with an abnormally spliced myopathic cardiac TnT (cTnT) (Biesiadecki, B. J., Schneider, K. L., Yu, Z. B., Chong, S. M., and Jin, J. P. (2004) J. Biol. Chem. 279, 13825–13832). To investigate the functional effect of this cTnI mutation and its potential value in compensating for the cTnT abnormality, we developed transgenic mice expressing the mutant cTnI (K118C) in the heart with or without the deletion of the endogenous cTnI gene to mimic the homozygote and heterozygote of wild turkeys. Double and triple transgenic mice were created by crossing the cTnI-K118C lines with transgenic mice overexpressing the myopathic cTnT (exon 7 deletion). Functional studies of ex vivo working hearts found that cTnI-K118C alone had a dominantly negative effect on diastolic function and blunted the inotropic responses of cardiac muscle to β-adrenergic stimuli without abolishing the protein kinase A-dependent phosphorylation of cTnI. When co-expressed with the cTnT mutation, cTnI-K118C corrected the significant depression of systolic function caused by cTnT exon 7 deletion, and the co-existence of exon 7-deleted cTnT minimized the diastolic abnormality of cTnI-K118C. Characterization of this naturally selected pair of mutually rescuing mutations demonstrated that TnI-TnT interaction is a critical link in the Ca²⁺ signaling and β-adrenergic regulation in cardiac muscle, suggesting a potential target for the treatment of troponin cardiomyopathies and heart failure.     

Assessment of Vascular Function in Patients With Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this is only partially explained by traditional CVD risk factors. Vascular dysfunction is an important non-traditional risk factor, characterized by vascular endothelial dysfunction (most commonly assessed as impaired endothelium-dependent dilation [EDD]) and stiffening of the large elastic arteries. While various techniques exist to assess EDD and large elastic artery stiffness, the most commonly used are brachial artery flow-mediated dilation (FMD_BA) and aortic pulse-wave velocity (aPWV), respectively. Both of these noninvasive measures of vascular dysfunction are independent predictors of future cardiovascular events in patients with and without kidney disease. Patients with CKD demonstrate both impaired FMD_BA, and increased aPWV. While the exact mechanisms by which vascular dysfunction develops in CKD are incompletely understood, increased oxidative stress and a subsequent reduction in nitric oxide (NO) bioavailability are important contributors. Cellular changes in oxidative stress can be assessed by collecting vascular endothelial cells from the antecubital vein and measuring protein expression of markers of oxidative stress using immunofluorescence. We provide here a discussion of these methods to measure FMD_BA, aPWV, and vascular endothelial cell protein expression.