Dachun Xu

Sensitivity and specificity of the ankle—brachial index to diagnose peripheral artery disease: a structured review

The ankle—brachial index (ABI) is a simple, inexpensive diagnostic test for peripheral artery disease (PAD). However, it has shown variable accuracy for identification of significant stenosis. The authors performed a structured review of the sensitivity and specificity of ABI ≤ 0.90 for the diagnosis of PAD. MEDLINE, EMBASE, Cochrane databases, Science Citation Index database, and Biological Abstracts database were searched for studies of the sensitivity and specificity of using ABI ≤ 0.90 for the diagnosis of PAD. Eight studies comprising 2043 patients (or limbs) met the inclusion criteria. The result indicated that, although strict inclusion criteria on studies were formulated, different reference standards were found in these studies, and methods of ABI determination and characteristics of populations varied greatly. A high level of specificity (83.3—99.0%) and accuracy (72.1—89.2%) was reported for an ABI ≤ 0.90 in detecting ≥ 50% stenosis, but there were different levels of sensitivity (15—79%). Sensitivity was low, especially in elderly individuals and patients with diabetes. In conclusion, the test of ABI ≤ 0.90 can be a simple and useful tool to identify PAD with serious stenosis, and may be substituted for other non-invasive tests in clinical practice.

Diagnostic Value of Ankle-Brachial Index in Peripheral Arterial Disease: A Meta-analysis

BACKGROUND In a previous review, we reported that ankle brachial index (ABI) ≤ 0.90 could reliably identify patients with peripheral artery disease (PAD). Since then, more studies have been published which may extend the power of a meta-analysis of studies of diagnostic accuracy of the ABI. MEDLINE and several other databases were searched for studies on sensitivity and specificity of using ABI ≤ 0.90 for PAD diagnosis compared with angiography. METHODS Quality of each study was assessed by standards for reporting diagnostic accuracy initiative and quality assessment for studies of diagnostic accuracy tool. Heterogeneity was assessed using the Cochran Q statistic, χ(2), and inconsistency index. The area under the curve and Q* were estimated using summary receiver operator curve. The pooled diagnostic odds ratio (DOR), sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of ABI ≤ 0.90 to diagnose PAD were estimated using Meta-DiSc software (Meta-DiSc, Madrid, Spain). RESULTS Four studies comprising 569 patients (922 limbs) met inclusion criteria. Significant heterogeneity among these studies was not detected in DOR but was evident in pooled sensitivity, specificity, PLR, and NLR. The area under the curve under the summary receiver operator curve is 0.87 (standard error = 0.02) and diagnostic accuracy (Q*) is 0.80 (standard error = 0.02). Additionally, DOR was 15.33 with corresponding 95% confidence intervals of 9.39-25.02. The pooled sensitivity and specificity of ABI ≤ 0.90 for PAD diagnosis were 75% and 86% and the pooled PLR and NLR were 4.18 and 0.29, respectively. CONCLUSIONS We conclude that test of ABI ≤ 0.90 can be a useful tool to identify PAD with serious stenosis in clinical practice.

Prognostic Significance of Visit-to-Visit Systolic Blood Pressure Variability: A Meta-Analysis of 77,299 Patients

In recent clinical investigations, visit‐to‐visit systolic blood pressure (SBP) variability was proven as a predictor of cardiovascular events and all‐cause mortality. However, inconsistent results exist in this association. A meta‐analysis of 13 prospective studies was conducted to evaluate the prognostic value of visit‐to‐visit SBP variability by different parameters in 77,299 patients with a mean follow‐up of 6.3 years. The pooled age‐ and mean SBP‐adjusted hazard ratios (HRs) for all‐cause mortality were 1.03 (95% confidence interval [CI], 1.02–1.04; P<.001) per 1‐mm Hg increase in SBP standard deviation (SD) and 1.04 (1.02–1.06, P<.001) per 1% in SBP coefficient of variation, and the corresponding values of cardiovascular mortality were 1.10 (1.02–1.17, P<.001) and 1.01 (0.99–1.03, P=.32), respectively. Moreover, a 1‐mm Hg increase in SD was significantly associated with stroke, with an HR of 1.02 (1.01–1.03, P<.001). Visit‐to‐visit SBP variability, independent of age and mean SBP, is a predictor of cardiovascular and all‐cause mortality and stroke.

Circular RNAs in Cardiovascular Disease: An Overview

Circular RNA (circRNA), a novel type of endogenous noncoding RNA (ncRNA), has become a research hotspot in recent years. CircRNAs are abundant and stably exist in creatures, and they are found with covalently closed loop structures in which they are quite different from linear RNAs. Nowadays, an increasing number of scientists have demonstrated that circRNAs may have played an essential role in the regulation of gene expression, especially acting as miRNA sponges, and have described the potential mechanisms of several circRNAs in diseases, hinting at their clinical therapeutic values. In this review, the authors summarized the current understandings of the biogenesis and properties of circRNAs and their functions and role as biomarkers in cardiovascular diseases.

Different β-Blockers and Initiation Time in Patients Undergoing Noncardiac Surgery: A Meta-analysis

Abstract:The effects of differences among &bgr;-blockers and initiation times in patients undergoing noncardiac surgery (NCS) remain unknown. On June 1, 2012, the authors searched PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to identify all trials of perioperative &bgr;-blockers in patients undergoing NCS published between January 1960 and June 2012. The authors included only randomized, double-blind and placebo-controlled trials of perioperatively administered &bgr;-blockers (ie, during the pre-, intra- and/or postoperative period) in patients with at least 1 risk factor for coronary artery disease undergoing NCS. The endpoints of these trials had to include all-cause mortality, myocardial infarction (MI) and/or stroke. The authors identified 8 English-language publications, involving 11,180 patients, which fulfilled our inclusion criteria. Perioperative &bgr;-blocker therapy was associated with a significant decrease in patient risk of developing MI (relative risk [RR] = 0.73; 95% confidence interval [CI], 0.61–0.86) but a significant increase in risk of developing stroke (RR = 2.17; 95% CI, 1.35–3.50) versus placebo, resulting in a nonsignificant decrease in overall mortality (RR = 0.91; 95% CI, 0.60–1.36). Indirect comparisons demonstrated that perioperative atenolol therapy was associated with lower mortality and incidence of MI. &bgr;-blocker therapy initiated >1 week before surgery was associated with improved postoperative mortality. Perioperative &bgr;-blocker treatment of patients undergoing NCS increases the incidence of stroke but decreases the incidence of MI, leading to a nonsignificant decrease in mortality. The authors also observed that atenolol treatment or &bgr;-blocker therapy initiated >1 week before NCS was associated with improved outcomes.

Effect of asymmetric dimethylarginine (ADMA) on heart failure development

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases that limits nitric oxide bioavailability and can increase production of NOS derived reactive oxidative species. Increased plasma ADMA is a one of the strongest predictors of mortality in patients who have had a myocardial infarction or suffer from chronic left heart failure, and is also an independent risk factor for several other conditions that contribute to heart failure development, including hypertension, coronary artery disease/atherosclerosis, diabetes, and renal dysfunction. The enzyme responsible for ADMA degradation is dimethylarginine dimethylaminohydrolase-1 (DDAH1). DDAH1 plays an important role in maintaining nitric oxide bioavailability and preserving cardiovascular function in the failing heart. Here, we examine mechanisms of abnormal NO production in heart failure, with particular focus on the role of ADMA and DDAH1.

A comparison of 2 devices for radial artery hemostasis after transradial coronary intervention.

Background and Objective:Transradial access is an attractive approach for angiography or percutaneous coronary intervention. Different devices have been used to apply pressure locally at the site of arterial entry for achieving hemostasis. The aim of this study was to evaluate the effect of 2 different hemostatic devices on radial artery outcomes after transradial coronary intervention. Subjects and Methods:This study included 600 patients who had undergone transradial coronary intervention who were randomized into 2 groups after the procedure: 300 were treated with a radial compression device (TR Band, Terumo Medical, Tokyo, Japan) (CD group) and the other 300 patients were treated using a chitosan-based pad (Anscare, Daxon, Taoyuan, Taiwan) (CS group). Compression time, major and minor access site bleeding complications, and incidence of radial artery occlusion were recorded. Results:There were no statistical differences in the baseline clinical characteristics of the patients between the 2 groups. Compression time in the CS group was significantly shorter than that in the CD group (P < .001). Although no major access site bleeding complications were observed in either group, 6 patients in each group experienced minor access site bleeding complications. At the same time, 61 patients in the CD group and 21 patients in the CS group experienced errhysis (20% vs 7%, respectively; P < .001). Early radial artery occlusion (24 hours) occurred in 11.7% of the patients in the CD group and 5.4% of the patients in the CS group (P < .05). Chronic radial artery occlusion (30 days) occurred in 10% of the patients in the CD group and 5% of the patients in the CS group (P < .05). Conclusion:The application of the chitosan-based pad showed better hemostatic efficacy and a lower incidence of radial artery occlusion after transradial coronary intervention compared with the compression device.

Growth Arrest–Specific 6 Exacerbates Pressure Overload–Induced Cardiac Hypertrophy

Growth arrest–specific 6 (GAS6) is a member of the vitamin K–dependent protein family that is involved in the regulation of the cardiovascular system, including vascular remodeling, homeostasis, and atherosclerosis. However, there is still no study that systemically elucidates the role of GAS6 in cardiac hypertrophy. Here, we found that GAS6 was upregulated in human dilated cardiomyopathic hearts, hypertrophic murine hearts, and angiotensin II–treated cardiomyocytes. Next, we examined the influence of GAS6 expression in response to a cardiac stress by inducing chronic pressure overload with aortic banding in wild-type and GAS6-knockout mice or cardiac-specific GAS6 overexpressing mice. Under basal conditions, the GAS6-knockout mice had normal left ventricular structure and function but after aortic banding, the mice demonstrated less hypertrophy, fibrosis, and contractile dysfunction when compared with wild-type mice. Conversely, cardiac-specific overexpression of GAS6 exacerbated aortic banding–induced cardiac hypertrophy, fibrosis, and dysfunction. Furthermore, we demonstrated that GAS6 activated the mitogen-activated protein kinase kinase 1/2–extracellular signal-regulated kinase 1/2 pathway during pressure overload–induced cardiac hypertrophy, and the pharmacological mitogen-activated protein kinase kinase 1/2 inhibitor U0126 almost completely reversed GAS6 overexpression–induced cardiac hypertrophy and fibrosis, resulting in improved cardiac function. Collectively, our data support the notion that GAS6 impairs ventricular adaptation to chronic pressure overload by activating mitogen-activated protein kinase kinase 1/2–extracellular signal-regulated kinase 1/2 signaling. Our findings suggest that strategies to reduce GAS6 activity in cardiac tissue may be a novel approach to attenuate the development of congestive heart failure.

Bleeding Risk and Mortality of Edoxaban: A Pooled Meta-Analysis of Randomized Controlled Trials

Objective(s) Edoxaban, a factor Xa inhibitor, is a new oral anticoagulant that has been developed as an alternative to vitamin K antagonists. However, its safety remains unexplored. Methods Medline, Embase and Web of Science were searched to March 8, 2014 for prospective, randomized controlled trials (RCTs) that assessed the safety profile of edoxaban with warfarin. Safety outcomes examined included bleeding risk and mortality. Results Five trials including 31,262 patients that met the inclusion criteria were pooled. Overall, edoxaban was associated with a significant decrease in major or clinically relevant nonmajor bleeding events [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.74 to 0.82, p<0.001] and any bleeding events [RR 0.82, 95% CI 0.79 to 0.85, p<0.001]. Edoxaban also showed superiority to warfarin both in all-cause mortality [RR 0.92, 95% CI0.85 to0.99, p = 0.02] and cardiovascular mortality [RR 0.87, 95% CI0.79 to 0.96, p = 0.004]. Subgroup analyses indicated that RRs of edoxaban 30, 60 or 120 mg/d were 0.67 (p<0.001), 0.87 (p<0.001) and 3.3 (p = 0.004) respectively in major or clinically relevant nonmajor bleeding; 0.71 (p<0.001), 0.89 (p<0.001) and 2.29 (p = 0.002) respectively in any bleeding; as well as 0.86 (p = 0.01), 0.87 (p = 0.01) and 0.28 (p = 0.41) respectively in cardiovascular death… Meanwhile, paramount to note that pooled results other than the largest trial showed edoxaban was still associated with a decrease in the rate of major or clinically relevant nonmajor bleeding event (p = 0.02) and any bleeding (p = 0.002), but neither in all-cause death (p = 0.66) nor cardiovascular death (p = 0.70). Conclusions Edoxaban, a novel orally available direct factor Xa inhibitor, seems to have a favorable safety profiles with respect to bleeding risk and non-inferior in mortality when compared to warfarin. Further prospective RCTs are urgently needed to confirm the results of this meta-analysis.

Factors Associated with Blood Pressure Control in Hypertensive Patients with Coronary Heart Disease: Evidence from the Chinese Cholesterol Education Program

Blood pressure (BP) remains poorly controlled among hypertensive patients with coronary heart disease (CHD) in China. Improvement of its management will require an understanding of the patient characteristics and treatment factors associated with uncontrolled hypertension. A cross-sectional survey of 3,279 patients from 52 centers in China was performed to examine potential barriers to adequate blood pressure control of hypertensive patients with CHD. Uncontrolled hypertension was defined as blood pressure ≥130/or 80 mmHg. Multivariable logistic regression was used to identify factors associated with poor blood pressure control. Mean age of the patients was 65 years, 40% were women, and mean BMI was 25 kg/m2. Mean systolic blood pressure was 136±18 mmHg and mean diastolic blood pressure was 80±11 mmHg. Only 18% of patients had a mean blood pressure <130/80 mmHg during the study period. Multivariate analysis revealed several independent factors of poor blood pressure control: body mass index ≥23 kg/m2, the presence of stable angina pectoris (SAP), family history of diabetes, and use of calcium channel blockers (CCB). Further analysis showed that non-dihydropyridine calcium antagonist was significantly correlated with low BP control rate. Some of these may be amenable to modification. The results of our study suggest that overweight, the presence of SAP and family history of diabetes are important factors for tight BP control in primary care. In addition, non-dihydropyridine calcium channel blockers appear less effective than other therapies in control of blood pressure and should not be the first choice among hypertensive patients with CHD. Further identification of patients at risk of poor BP control can lead to targeted interventions to improve management.