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1.  Prevalence of hypertension among federal ministry civil servants in Addis Ababa, Ethiopia: a call for a workplace-screening program 
Background
The prevalence of hypertension (HTN) is increasing rapidly in Ethiopia, but data are limited on hypertension prevalence in specific workplaces. Therefore, the aim of this study was to assess the prevalence and associated factors of hypertension among federal ministry civil servants.
Methods
Institutional based cross sectional study was conducted from February to April 2014. Simple random sampling technique was used to select 655study participants. A standardized questionnaire adapted from The World Health Organization’s (WHO) STEP tool was used to collect the data. In this study, HTN was defined as mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 140/90 mmHg and above, and patients on regular drug therapy for H. Data were entered into EPI-Info 3.5.2 and analyzed by SPSS version 20. Binary logistic regression model was used to identify associated factors. Odds ratio with 95 % CI was computed to assess the strength of the association and significant level.
Result
The prevalence of hypertension was found to be 27.3 % (95 % CI 23.3 – 31 %). Civil servants of age 48 years and above [AOR = 5.88, 95 % CI: 2.36-14.67], age 38-47 years [AOR = 2.80, 95 % CI: 1.18-6.60] and age 28-37 years [AOR = 2.35, 95 % CI: 1.00-5.56]) were more likely to be hypertensive. Similarly, ever cigarette smoking [AOR =2.34(1.31-4.17), family history of hypertension [AOR = 3.26, 95 % CI 1.96-5.40], self-reported Diabetes Mellitus (DM) [AOR = 13.56, 95 % CI: 6.91-26.6], and body mass index (BMI > 25 kg/m2) [AOR = 7.36, 95 % CI: 2.36-14.67] were found to be significantly associated with hypertension.
Conclusion
The prevalence of hypertension among federal ministry civil servants was found to be high; which is an indication for institution based hypertension-screening programs especially focusing on those aged 28 years and above, obese, DM patients and cigarette smokers.
doi:10.1186/s12872-015-0062-9
PMCID: PMC4511244  PMID: 26197712
Hypertension; Ministries civil servants; Ethiopia
2.  Ability of ambulatory ECG-based T-wave alternans to modify risk assessment of cardiac events: a systematic review 
Background
Exercise-based spectral T-wave alternans (TWA) has been proposed as a noninvasive tool-identifying patients at risk of sudden cardiac death (SCD) and cardiac mortality. Prior studies have indicated that ambulatory electrocardiogram (AECG)-based TWA is an important alternative platform to exercise for risk stratification of cardiac events. This study sought to review data regarding 24-hour AECG-based TWA and to discuss its potential role in risk stratification of fatal cardiac events across a series of patient risk profiles.
Methods
Prospective clinical studies of the predictive value of AECG-based TWA obtained with daily activity published between January 1990 and November 2014 were retrieved. Major endpoints included composite endpoint of SCD, cardiac mortality, and severe arrhythmic events.
Results
Data were accumulated from 5 studies involving a total of 1,588 patients, including 317 positive and 1,271 negative TWA results. Compared with the negative group, positive group showed increased rates of SCD (hazard ratio [HR]: 7.49, 95% confidence interval [CI]: 2.65 to 21.15), cardiac mortality (HR: 4.75, 95% CI: 0.42 to 53.55), and composite endpoint (SCD, cardiac mortality, and severe arrhythmic events, HR: 5.94, 95% CI: 1.80 to 19.63). For the 4 studies evaluating TWA measured using the modified moving average method, the HR associated with a positive versus negative TWA result was 9.51 (95% CI: 4.99 to 18.11) for the composite endpoint.
Conclusions
The positive group of AECG-based TWA has a nearly six-fold risk of severe outcomes compared with the negative group. Therefore, AECG-based TWA provides an accurate means of predicting fatal cardiac events.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-14-198) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2261-14-198
PMCID: PMC4289555  PMID: 25528490
T-wave alternans; Ambulatory electrocardiogram; Sudden cardiac death; Cardiac event
3.  Role of SIRT3 in Angiotensin II-induced human umbilical vein endothelial cells dysfunction 
Background
SIRT3, a member of the sirtuin family of NAD+-dependent deacetylases, resides primarily in the mitochondria and has been shown to deacetylate several metabolic and respiratory enzymes that regulate important mitochondrial functions. Previous researches show an important role of SIRT3 in regulating the production of reactive oxygen species (ROS), and highlight the ability of SIRT3 to protect cells from oxidative damage. A key substance of renin-angiotensin-aldosterone system (RAAS), Angiotensin II (AngII) can induce cells dysfunction by increasing the production of ROS. In this paper, we focus on the role of SIRT3 in AngII-induced human umbilical vein endothelial cells (HUVECs) dysfunction.
Methods
To study the influence of AngII on SIRT3 expression, HUVECs were treated with AngII of 10−7, 10−6, 10−5 mol/L for 24 h. SIRT3 expression was detected by wester-blotting analysis and RT-PCR. In addition, to research the role of SIRT3 in AngII-induced HUVECs,we used SIRT3 siRNA to knock down SIRT3 expression in HUVECs. Cells pretreated with negative control siRNA or SIRT3 siRNA were exposed to AngII for 24 h, and endothelial nitric oxide synthase (eNOS) expression, eNOS activity, total level of nitric oxide (NO) and ROS generation of each group were detected.
Results
Here we show that AngII treatment could increase generation of ROS, and decrease eNOS activity and total level of NO, while upregulated eNOS expression as a compensatory mechanism. The stimulation of AngII upregulated the expression of SIRT3 in HUVECs. SIRT3 siRNA worsen the AngII-induced effects above, besides, downregulated eNOS protein expression.
Conclusion
These data suggest that SIRT3 plays a role of protection in AngII-induced HUVECs dysfunction via regulation of ROS generation.
doi:10.1186/s12872-015-0075-4
PMCID: PMC4520206
SIRT3; Endothelial dysfunction; AngII; Reactive oxygen species; HUVECs
4.  Prevalence and factors associated with inappropriate use of treadmill exercise stress test for coronary artery disease: a cross-sectional study 
Background
In some countries, the public health system has less availability when compared to the population covered by health insurance. In addition, inappropriate referrals for treadmill exercise stress test increase spending and lead to unnecessary interventions. We aim to determine the prevalence and characteristics of inappropriate referrals for treadmill exercise stress tests in the assessment of coronary artery disease (CAD), considering public and private health systems scenarios.
Methods
A cross-sectional design was used to describe the frequency of inappropriate use of exercise testing in the diagnosis of CAD and to determine its predictors. We consecutively enrolled 191 patients from two outpatient facilities in Northeast Brazil. For inclusion, the exercise testing should be referred for the assessment of CAD. We performed logistic regression models to identify independent predictors of inappropriate use.
Results
Treadmill exercise stress tests were rated as inappropriate in 150 (78 %) patients. The majority of patients had low or very low pre-test probability of CAD. Presence of hypertension, diabetes and dyslipidemia were more frequent in the appropriate than inappropriate indications (71 %, 19 % and 29 % versus 43 %, 8 % and 16 %, respectively). Tests performed both at the public and private system showed high prevalence of inappropriate examinations, higher in the latter (57 % versus 87 %, P < 0.001). The private health system was the major independent predictor of inappropriate referral, consistent in all regression models (when adjusting for clinical variables, OR = 4.3; P < 0.001).
Conclusion
The vast majority of treadmill exercise stress test referrals in the assessment of CAD were inappropriate. The availability of the method and not the estimate probability of CAD appear to be the underlying condition for a treadmill test referral.
doi:10.1186/s12872-015-0048-7
PMCID: PMC4467076  PMID: 26078052
Exercise testing; Treadmill test; Coronary artery disease; Appropriateness criteria
6.  Noncompaction cardiomyopathy: a substrate for a thromboembolic event 
Background
Noncompaction cardiomyopathy (NCC) is a rare genetic cardiomyopathy characterized by a thin, compacted epicardial layer and an extensive noncompacted endocardial layer. The clinical manifestations of this disease include ventricular arrhythmia, heart failure, and systemic thromboembolism.
Case presentation
A 43-year-old male was anticoagulated by pulmonary thromboembolism for 1 year when he developed progressive dyspnea. Cardiovascular magnetic resonance imaging showed severe biventricular trabeculation with an ejection fraction of 15%, ratio of maximum noncompacted/compacted diastolic myocardial thickness of 3.2 and the presence of exuberant biventricular apical thrombus.
Conclusion
Still under discussion is the issue of which patients and when they should be anticoagulated. It is generally recommended to those presenting ventricular systolic dysfunction, antecedent of systemic embolism, presence of cardiac thrombus and atrial fibrillation. In clinical practice the patients with NCC and ventricular dysfunction have been given oral anticoagulation, although there are no clinical trials showing the real safety and benefit of this treatment.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-15-7) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2261-15-7
PMCID: PMC4407327  PMID: 25618133
Cardiomyopathy; Echocardiography; Magnetic resonance; Noncompaction; Thromboembolism
7.  The in vivo blood compatibility of bio-inspired small diameter vascular graft: effect of submicron longitudinally aligned topography 
Background
Cardiovascular disease is the leading cause of deaths worldwide and the arterial reconstructive surgery remains the treatment of choice. Although large diameter vascular grafts have been widely used in clinical practices, there is an urgent need to develop a small diameter vascular graft with enhanced blood compatibility. Herein, we fabricated a small diameter vascular graft with submicron longitudinally aligned topography, which mimicked the tunica intima of the native arterial vessels and were tested in Sprague–Dawley (SD) rats.
Methods
Vascular grafts with aligned and smooth topography were prepared by electrospinning and were connected to the abdominal aorta of the SD rats to evaluate their blood compatibility. Graft patency and platelet adhesion were evaluated by color Doppler ultrasound and immunofluorescence respectively.
Results
We observed a significant higher patency rate (p = 0.021) and less thrombus formation in vascular graft with aligned topography than vascular graft with smooth topography. However, no significant difference between the adhesion rates on both vascular grafts (smooth/aligned: 0.35‰/0.12‰, p > 0.05) was observed. Moreover, both vascular grafts had few adherent activated platelets on the luminal surface.
Conclusion
Bionic vascular graft showed enhanced blood compatibility due to the effect of surface topography. Therefore, it has considerable potential for using in clinical application.
doi:10.1186/1471-2261-13-79
PMCID: PMC3850682  PMID: 24083888
Vascular grafts; Electrospinning; Aligned topography; Thrombosis; Platelet adhesion
8.  Evaluation of a self-management patient education program for patients with chronic heart failure undergoing inpatient cardiac rehabilitation: study protocol of a cluster randomized controlled trial 
Background
Chronic heart failure requires a complex treatment regimen on a life-long basis. Therefore, self-care/self-management is an essential part of successful treatment and comprehensive patient education is warranted. However, specific information on program features and educational strategies enhancing treatment success is lacking. This trial aims to evaluate a patient-oriented and theory-based self-management educational group program as compared to usual care education during inpatient cardiac rehabilitation in Germany.
Methods/Design
The study is a multicenter cluster randomized controlled trial in four cardiac rehabilitation clinics. Clusters are patient education groups that comprise HF patients recruited within 2 weeks after commencement of inpatient cardiac rehabilitation. Cluster randomization was chosen for pragmatic reasons, i.e. to ensure a sufficient number of eligible patients to build large-enough educational groups and to prevent contamination by interaction of patients from different treatment allocations during rehabilitation. Rehabilitants with chronic systolic heart failure (n = 540) will be consecutively recruited for the study at the beginning of inpatient rehabilitation. Data will be assessed at admission, at discharge and after 6 and 12 months using patient questionnaires. In the intervention condition, patients receive the new patient-oriented self-management educational program, whereas in the control condition, patients receive a short lecture-based educational program (usual care). The primary outcome is patients’ self-reported self-management competence. Secondary outcomes include behavioral determinants and self-management health behavior (symptom monitoring, physical activity, medication adherence), health-related quality of life, and treatment satisfaction. Treatment effects will be evaluated separately for each follow-up time point using multilevel regression analysis, and adjusting for baseline values.
Discussion
This study evaluates the effectiveness of a comprehensive self-management educational program by a cluster randomized trial within inpatient cardiac rehabilitation in Germany. Furthermore, subgroup-related treatment effects will be explored. Study results will contribute to a better understanding of both the effectiveness and mechanisms of a self-management group program as part of cardiac rehabilitation.
Trial registration
German Clinical Trials Register: DRKS00004841; WHO International Clinical Trials: = DRKS00004841
doi:10.1186/1471-2261-13-60
PMCID: PMC3765303  PMID: 23968340
Chronic heart failure; Patient education; Self-management; Evaluation; Cluster-RCT; Cardiac rehabilitation
9.  Trans-subclavian approach for radiofrequency ablation of premature ventricular contractions originating from subtricuspid annulus: a case report 
Background
Catheter ablation has been established as a curative treatment strategy for ventricular arrhythmias. The standard procedure of most ventricular arrhythmias originating from the right ventricle is performed via the femoral vein. However, a femoral vein access may not achieve a successful ablation in some patients.
Case presentation
We reported a case of a 29-year old patient with symptomatic premature ventricular contractions was referred for catheter ablation. Radiofrequency energy application at the earliest endocardial ventricular activation site via the right femoral vein could not eliminate the premature ventricular contractions. Epicardial mapping could not obtain an earlier ventricular activation when compared to the endocardial mapping, and at the earliest epicardial site could not provide an identical pace mapping. Finally, we redeployed the ablation catheter via the right subclavian vein by a long sheath. During mapping of the subvalvular area of the right ventricle, a site with a good pace mapping and early ventricular activation was found, and premature ventricular contractions were eliminated successfully.
Conclusion
Ventricular arrhythmias originating from the subtricuspid annulus may be successfully abolished via a trans-subclavian approach and a long sheath. Although access via the right subclavian vein for mapping and ablation is an effective alternative, it is not a routine approach.
doi:10.1186/1471-2261-13-7
PMCID: PMC3582537  PMID: 23419096
Premature ventricular contractions; Tricuspid annulus; Radiofrequency catheter ablation
10.  Coronary artery fistula between single right coronary artery and right pulmonary artery: a case report and literature review 
Background
Coronary artery fistula and single coronary artery are two different rare congenital anomalies. The cases with co-existed the two anomalies are more rare. To the best of our knowledge with literature review, the coronary artery fistula between single right coronary artery and right pulmonary artery has not been previously reported.
Case presentation
In the present article, we report a Chinese patient (a 8-month-old male) who presented cyanosis when cried and heart murmur. The cardiac angiography confirmed coronary artery fistula between single coronary artery arising from the right aortic sinus and right pulmonary artery. Furthermore, the right pulmonary artery was interrupted with main pulmonary artery and the pulmonary blood supplied by single right coronary artery. Following the surgical procedure, the anomalous fistula vessel was cut and sutured. The right pulmonary artery was reconstructed to connect with main pulmonary artery. The patient had an uneventful postoperative course and discharged. Then we reviewed the related literature with Medline and Pubmed databases for further details.
Conclusion
We believe our patient is the very particular case about coronary artery fistula combined with single coronary artery, and it is first reported with our literature review. As other coronary anomalies, coronary or aortic root angiography is the gold standard method for the diagnosis. Furthermore, early surgery is an optimal treatment in our case.
Electronic supplementary material
The online version of this article (doi:10.1186/s12872-015-0166-2) contains supplementary material, which is available to authorized users.
doi:10.1186/s12872-015-0166-2
PMCID: PMC4681080  PMID: 26674589
Coronary artery fistula; Single coronary artery; Angiography
11.  Admission hypoxia-inducible factor 1α levels and in-hospital mortality in patients with acute decompensated heart failure 
Background
Hypoxia-inducible factor 1 (HIF-1) is a critical regulator for cellular oxygen balance. Myocardial hypoxia can induce the increased expression of HIF-1α. Our goals were to evaluate the value of HIF-1α in predicting death of patients with acute decompensated heart failure (ADHF) and describe the in vivo relationship between serum HIF-1α and N-terminal–pro-brain natriuretic peptide (NT-proBNP) levels.
Method
We included 296 patients who were consecutively admitted to the emergency department for ADHF. The primary end point was in-hospital death. The patients were categorized as HFrEF (patients with reduced systolic function) and HFpEF (patients with preserved systolic function) groups.
Results
In our patients, the median admission HIF-1α level was 2.95 ± 0.85 ng/ml. The HIF-1α level was elevated significantly in HFrEF patients and deceased patients compared with HFpEF patients and patients who survived. The HIF-1α level was positively correlated with NT-proBNP and cardiac troponin T levels, and negatively correlated with left ventricular ejection fraction and systolic blood pressure. Kaplan–Meier curves revealed a significant increase in in-hospital mortality in ADHF patients with higher HIF-1α levels. Multivariable Cox regression analysis showed that HIF-1α levels were not correlated with the short-term prognosis of ADHF patients.
Conclusions
This is the first study to evaluate the circulating levels of HIF-1α in ADHF patients. Serum HIF-1α levels may reflect a serious state in patients with ADHF. Due to the limitations of the study, serum HIF-1α levels were not correlated with the in-hospital mortality based on regression analysis. Further studies are needed to demonstrate the diagnostic and/or prognostic role of HIF-1α as a risk biomarker in patients with ADHF.
doi:10.1186/s12872-015-0073-6
PMCID: PMC4518524
Hypoxia-inducible factor 1α; Acute decompensated heart failure; N-terminal–pro-brain natriuretic peptide; In-hospital mortality
12.  FGF21 protects against ox-LDL induced apoptosis through suppressing CHOP expression in THP1 macrophage derived foam cells 
Background
FGF21,as a member of the fibroblast growth factor superfamily, is an important endogenous regulator to systemic glucose and lipid metabolism. Elevated serum FGF21 levels have been reported in subjects with coronary heart disease and carotid artery plaques. The formation and apoptosis of foam cell, induced by ox-LDL and oxysterols, are key steps in the development of atherosclerosis.
Methods
In this study, THP1 derived macrophages were induced into foam cells by ox-LDL or sterols. The formation and apoptosis of foam cells treated with or without FGF21 were analyzed.
Results
We demonstrated that the accumulation of cholesterol was decreased after FGF21 treatment in THP1 macrophage derived foam cells. Consistently, the apoptosis of macrophage was alleviated dramatically with FGF21 treatment. ERK1/2 knockdown didn’t abrogate the effect of FGF21 on THP1 macrophage derived foam cells. However, FGF21 suppressed the induced expression of CHOP and DR5 in THP1 macrophage derived foam cells.
Conclusion
FGF21 protects against the formation and apoptosis of THP1 macrophages derived foam cells through suppressing the expression of CHOP.
doi:10.1186/s12872-015-0077-2
PMCID: PMC4518604
Macrophage; ER stress; FGF21; Foam cell; CHOP
13.  Preconditioning offers cardioprotection in hyperlipidemic rat hearts: possible role of Dopamine (D2) signaling 
Background
Ischemic preconditioning (IPC) induced cardioprotection has been reported to be blunted in hyperlipidemic subjects. Dopamine, via its D2 receptor signaling, appears to mimic the signaling cascade involved in myocardial preconditioning and is also involved in the inhibition of hyperlipidemia induced mediators. The present study was designed to investigate the possible involvement of D2 receptors in IPC and to see whether dopamine preconditioning can offer cardioprotection in hyperlipidemic rat hearts.
Methods
Wistar albino rats were divided into 8 groups and fed on normal or high fat diet for 4 weeks. Hyperlipidemia was confirmed after 4 weeks by serum lipid estimations. Isolated perfused hearts were subjected to ischemic preconditioning or dopamine induced pharmacological preconditioning followed by 30-min ischemic insult and 60-min reperfusion. Clozapine was administered as D2 antagonist. Coronary perfusate (basal and post-ischemic) was collected for the estimations of LDH (Lactate dehydrogenase) and CKMB (Creatine kinase MB). Hearts were then removed and frozen for infarct size measurement.
Results
A significant increase body weight, serum lipids except HDL was noted in high fat diet fed rats, as compared to normal rats. The level of LDH, CKMB in coronary effluent and infarct size were found to be decreased in preconditioned normal hearts, as compared to hearts treated with ischemia reperfusion. This effect was found to be blunted in hyperlipidemic animals. Dopamine (10 μM) alone and in combination with ischemic preconditioning significantly reduced the levels of LDH, CKMB and infarct size in hyperlipidemic hearts, as compared to preconditioned and non-preconditioned hyperlipidemic hearts. This effect was abolished significantly by Clozapine (D2 antagonist).
Conclusion
The present study reveals possible involvement of D2 receptors in ischemic preconditioning and suggests that dopamine preconditioning may offer significant cardioprotection in hyperlipidemic rat hearts.
doi:10.1186/s12872-015-0071-8
PMCID: PMC4515884  PMID: 26216101
Dopamine; Preconditioning; Hyperlipidemia; Infarct
14.  Feasibility of a new method using two-dimensional transesophageal echocardiography for aortic annular sizing in patients undergoing transcatheter aortic valve implantation; a case–control study 
Background
Accurate preoperative assessment of the aortic annulus dimension is crucial for successful transcatheter aortic valve implantation (TAVI). In this study we validated a new method using two-dimensional transesophageal echocardiography (2D-TEE) for measurement of the aortic annulus prior to TAVI.
Methods
We analysed 124 patients who underwent successful TAVI using a self-expandable prosthesis, divided equally into two groups; in the study group we used the cross sectional short axis 2D-TEE for measurement of the aortic annulus and in the control group we used the long axis 2D-TEE.
Results
Both groups were comparable regarding the clinical parameters. On the other hand, patients in the study group had less left ventricular ejection fraction (38.9 % versus 45.6 %, p = 0.01). The aortic valve annulus was, although not statistically significant, smaller in the study group (21.58 versus 23.28 mm, p = 0.25).
Post procedural quantification of the aortic regurgitation revealed that only one patient in both groups had severe aortic regurgitation (AR), in this patient the valve was implanted deep. The incidence of significant AR was higher in the control group (29.0 % versus 12.9 %, p = 0.027).
Conclusions
Sizing of the aortic valve annulus using cross-sectional 2D-TEE offers a safe and plausible method for patients undergoing TAVI using the self-expandable prosthesis and is significantly superior to using long axis 2D-TEE.
doi:10.1186/s12872-015-0072-7
PMCID: PMC4517415  PMID: 26216218
TAVI; Sizing; Echocardiography
15.  Risk factors and in-hospital outcome of acute ST segment elevation myocardial infarction in young Bangladeshi adults 
Background
South Asians have a higher overall incidence rate and younger age of onset for acute myocardial infarction (AMI) compared to Western populations. However, limited information is available on the association of preventable risk factors and outcomes of AMI among young individuals in Bangladesh. The aim of this study was to determine the risk factors and in-hospital outcome of AMI among young (age ≤40 years) adults in Bangladesh.
Methods
We conducted a prospective observational study among consecutive 50 patients aged ≤40 years and 50 patients aged >40 years with acute ST Segment Elevation Myocardial Infarction (STEMI) and followed-up in-hospital at the National Institute of Cardiovascular Diseases (NICVD). Clinical characteristics, biochemical findings, diet, echocardiography and in-hospital outcomes were compared between the two groups. Multivariate logistic regression was performed to assess the association between risk factors and in-hospital outcome in young patients adjusting for other confounding variables.
Results
The mean age of the young and older patient groups was 36.5 ± 4.6 years and 57.0 ± 9.1 years respectively. Male sex (OR 3.4, 95 % CI 1.2 − 9.75), smoking (OR 2.4, 95 % CI 1.04 − 5,62), family history of MI (OR 2.4, 95 % CI 1.11 − 5,54), homocysteine (OR 1.2, 95 % CI 1.08 − 1.36), eating rice ≥2 times daily (OR 3.5, 95 % CI 1.15 − 10.6) and eating beef (OR 4.5, 95 % CI 1.83 − 11.3) were significantly associated with the risk of AMI in the young group compared to older group. In multivariate analysis, older patients had significantly greater chance of developing heart failure (OR 7.5, 95 % CI 1.51 to 37.31), re-infarction (OR 7.0, 95 % CI 1.08 − 45.72), arrhythmia (OR 15.3, 95 % CI 2.69 − 87.77) and cardiogenic shock (OR 69.0, 95 % CI 5.81 − 85.52) than the younger group.
Conclusion
Younger AMI patients have a different risk profile and better in-hospital outcomes compared to the older patients. Control of preventable risk factors such as smoking, unhealthy diet, obesity and dyslipidemia should be reinforced at an early age in Bangladesh.
doi:10.1186/s12872-015-0069-2
PMCID: PMC4509563  PMID: 26197888
16.  Functional capacity and heart rate response: associations with nocturnal hypertension 
Background
Absences of normative, 10–20 % declines in blood pressure (BP) at night, termed nocturnal non-dipping, are linked to increased cardiovascular mortality risks. Current literature has linked these absences to psychological states, hormonal imbalance, and disorders involving hyper-arousal. This study focuses on evaluating associations between nocturnal non-dipping and indices of functional cardiac capacity and fitness.
Methods
The current study was a cross-sectional evaluation of the associations between physical capacity variables e.g. Metabolic Equivalent (MET) and Maximum Heart Rate (MHR), Heart rate reserve (HRR), and degree of reduction in nocturnal systolic blood pressure (SBP) or diastolic blood pressure (DBP), also known as ‘dipping’. The study sample included 96 cardiac patient participants assessed for physical capacity and ambulatory blood pressure monitoring. In addition to evaluating differences between groups on nocturnal BP ‘dipping’, physical capacity, diagnoses, and medications, linear regression analyses were used to evaluate potential associations between nocturnal SBP and DBP ‘dipping’, and physical capacity indices.
Results
45 males and 14 females or 61.5 % of 96 consented participants met criteria as non-dippers (<10 % drop in nocturnal BP). Although non-dippers were older (p = .01) and had a lower maximum heart rate during the Bruce stress test (p = .05), dipping was only significantly associated with Type 2 Diabetes co-morbidity and was not associated with type of medication. Within separate linear regression models controlling for participant sex, MHR (β = 0.26, p = .01, R2 = .06), HRR (β = 0. 19, p = .05, R2 = .05), and METs (β = 0.21, p = .04, R2 = .04) emerged as significant but small predictors of degree of nighttime SBP dipping. Similar relationships were not observed for DBP.
Conclusions
Since the variables reflecting basic heart function and fitness (MHR and METs), did not account for appreciable variances in nighttime BP, nocturnal hypertension appears to be a complex, multi-faceted phenomena.
doi:10.1186/s12872-015-0064-7
PMCID: PMC4511245  PMID: 26197812
Ambulatory blood pressure monitoring; Abnormal nocturnal blood pressure; Nocturnal non-dipping
17.  Specific inhibition of bile acid transport alters plasma lipids and GLP-1 
Background
Elobixibat is a minimally absorbed ileal bile acid (BA) transporter (IBAT) inhibitor in development against chronic constipation (CC) and constipation-predominant Irritable Bowel Syndrome (IBS-C). CC is associated with an increased risk for cardiovascular disease and type2 diabetes mellitus. The objectives of this study were to evaluate metabolic effects of elobixibat. Effects on plasma lipids and BA synthesis were evaluated utilizing a 4-week, placebo-controlled study in patients with dyslipidemia while changes of glucagon-like peptide-1 (GLP-1) by elobixibat was assayed in samples from a 14 day high-dose elobixibat study in patients with CC.
Methods
Thirty-six dyslipidemic patients, 21 females, mean age 63 years, were randomized to 2.5 mg or 5 mg elobixibat or placebo once daily for four weeks. The primary endpoint was the change in low density lipoprotein (LDL) cholesterol. Secondary endpoints included other lipid parameters and serum 7α-hydroxy-4-cholesten-3-one (C4), a marker of BA (bile acid) synthesis. Another study, in 36 patients with CC treated with high dose elobixibat; 15 mg or 20 mg/day or placebo for 14 days, was evaluated for changes in GLP-1.
Results
In the dyslipidemia study LDL cholesterol was reduced by 7.4 % (p = 0.044), and the LDL/HDL ratio was decreased by 18 % (p = 0.004). Serum C4 increased, indicating that BA synthesis was induced. No serious adverse events were recorded. In the CC study, GLP-1 increased significantly in both the 15 mg (20.7 ± 2.4 pmol/L; p = 0.03) and the 20 mg group (25.6 ± 4.9 pmol/L; p = 0.02).
Conclusions
Elobixibat reduces LDL cholesterol and LDL/HDL ratio and increase circulating peak GLP-1 levels, the latter in line with increased intestinal BA mediated responses in humans.
Trial registrations
ClinicalTrial.gov: NCT01069783 and NCT01038687.
doi:10.1186/s12872-015-0070-9
PMCID: PMC4511433  PMID: 26197999
Dyslipidemia; Elobixibat; Glucagon-like peptide-1 (GLP-1); Ileal bile acid (BA) transporter (IBAT) inhibitor
18.  Troponin in diabetic patients with and without chronic coronary artery disease 
Background
Cardiac-specific troponin detected with the new high-sensitivity assays can be chronically elevated in response to cardiovascular comorbidities and confer important prognostic information, in the absence of unstable coronary syndromes. Both diabetes mellitus and coronary artery disease are known predictors of troponin elevation. It is not known whether diabetic patients with coronary artery disease have different levels of troponin compared with diabetic patients with normal coronary arteries. To investigate this question, we determined the concentrations of a level 1 troponin assay in two groups of diabetic patients: those with multivessel coronary artery disease and those with angiographically normal coronary arteries.
Methods
We studied 95 diabetic patients and compared troponin in serum samples from 50 patients with coronary artery disease (mean age = 63.7, 58 % male) with 45 controls with angiographically normal coronary arteries. Brain natriuretic peptide and the oxidative stress biomarkers myeloperoxidase, nitrotyrosine and oxidized LDL were also determined.
Results
Diabetic patients with coronary artery disease had higher levels of troponin than did controls (median values, 12.0 pg/mL (95 % CI:10–16) vs 7.0 pg/mL (95 % CI: 5.9-8.5), respectively; p = 0.0001). The area under the ROC curve for the diagnosis of CAD was 0.712 with a sensitivity of 70 % and a specificity of 66 %. Plasma BNP levels and oxidative stress variables (myeloperoxidase, nitrotyrosine, and oxidized LDL) were not different between the two groups. In a multivariate analysis, gender (p = 0.04), serum glucose (0.03) and Troponin I (p = 0.01) had independent statistical significance.
Conclusion
Troponin elevation is related to the presence of chronic coronary artery disease in diabetic patients with multiple associated cardiovascular risk factors. Troponin may serve as a biomarker in this high-risk population.
Trial registration
http://www.controlled-trials.com Registration number:ISRCTN26970041
doi:10.1186/s12872-015-0051-z
PMCID: PMC4508806  PMID: 26195004
Biological markers; Troponin; Diabetes mellitus; Coronary artery disease
19.  The impact of social deprivation on mortality following acute myocardial infarction, stroke or subarachnoid haemorrhage: A record linkage study 
Background
The impact of social deprivation on mortality following acute myocardial infarction (AMI), stroke and subarachnoid haemorrhage (SAH) is unclear. Our objectives were, firstly, to determine, for each condition, whether there was higher mortality following admission according to social deprivation and secondly, to determine how any higher mortality for deprived groups may be correlated with factors including patient demographics, timing of admission and hospital size.
Methods
Routinely collected, linked hospital inpatient, mortality and primary care data were analysed for patients admitted as an emergency to hospitals in Wales between 2004 and 2011 with AMI (n = 30,663), stroke (37,888) and SAH (1753). Logistic regression with Bonferroni correction was used to examine, firstly, any significant increases in mortality with social deprivation quintile and, secondly, the influence of patient demographics, timing of admission and hospital characteristics on any higher mortality among the most socially deprived groups.
Results
Mortality was 14.3 % at 30 days for AMI, 21.4 % for stroke and 35.6 % for SAH. Social deprivation was significantly associated with higher mortality for AMI (25 %; 95 % CI = 12 %, 40 %) higher for quintile V compared with I), stroke (24 %; 14 %, 34 %), and non-significantly for SAH (32 %; −7 %, 87 %).
The higher mortality at 30 days with increased social deprivation varied significantly according to patient age for AMI patients and time period for SAH. It was also highest for both AMI and stroke patients, although not significantly for female patients, for admissions on weekdays and during autumn months.
Conclusions
We have demonstrated a positive association between social deprivation and higher mortality following emergency admissions for both AMI and stroke. The study findings also suggest that the influence of patient demographics, timing of admission and hospital size on social inequalities in mortality are quite similar for AMI and stroke.
Electronic supplementary material
The online version of this article (doi:10.1186/s12872-015-0045-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s12872-015-0045-x
PMCID: PMC4506594  PMID: 26187051
Mortality; Social deprivation; Risk factors; Acute myocardial infarction; Stroke; Subarachnoid haemorrhage
20.  Serum S-100β and NSE levels after off-pump versus on-pump coronary artery bypass graft surgery 
Background
We aimed to evaluate serum levels of S-100 beta (S-100β) and neuron specific enolase (NSE) in patients with coronary heart disease (CHD) after off-pump versus on-pump coronary artery bypass graft (CABG) surgery.
Methods
The PubMed (~2013) and the Chinese Biomedical Database (CBM) (1982 ~ 2013) were searched without language restrictions. After extraction of relevant data from selected studies, meta-analyses were conducted using STATA software (Version 12.0, Stata Corporation, College Station, Texas USA). Possible sources of heterogeneity were examined through univariate and multivariate meta-regression analyses and verified by Monte Carlo Simulation.
Results
Eleven studies with a total of 411 CHD patients met the inclusion criteria. Our meta-analysis showed no significant difference in serum S-100β and NSE levels between the on-pump group and the off-pump group before surgery. In the on-pump group, there was a significant difference in serum S-100β levels of CHD patients between before and after surgery, especially within the first 24 h after surgery. Furthermore, in the on-pump group, there was a significant difference in serum NSE levels of CHD patients between before and after surgery, particularly at 0 h after surgery. In the off-pump group, there was an obvious difference in serum S-100β levels between before and after surgery, especially within 24 h after surgery. Our results also demonstrated that serum S-100β and NSE levels of CHD patients in the on-pump group were significantly higher than those of patients in the off-pump group, especially within 24 h after surgery.
Conclusions
Our findings provide empirical evidence that off-pump and on-pump CABG surgeries may increase serum S-100β and NSE levels in CHD patients, which was most prominent within 24 h after on-pump CABG surgery.
doi:10.1186/s12872-015-0050-0
PMCID: PMC4504080  PMID: 26179379
S-100β; NSE; Coronary heart disease; Coronary artery bypass grafting; Meta-analysis
21.  Cathether-based interventional strategies for cor triatriatum in the adult – feasibility study through a hybrid approach 
Background
Cor triatriatum is a rare congenital cardiac abnormality, consisting of an obstructing membrane between the pulmonary veins and the mitral valve in varying patterns. The entitiy can mimick the pathophysiology of mitral stenosis, necessitating surgical resection. Occasionally, percutaneous balloon dilatation of the membrane has been successfully performed.
Case presentation
We report two cases with cor triatriatum where intraoperative balloon dilatation of the membrane was attempted followed by surgical resection, to explore the feasibility of cathether-based interventional strategies for cor triatriatum.
Conclusions
Various anatomical variations exist of cor triatriatum, depending on the drainage of the pulmonary veins and the drainage of the proximal chamber in the right or left atrium. Only isolated forms of cor triatriatum where all pulmonary veins ultimately drain into the left atrium can be recommended for percutaneous strategies. In addition, several anatomical characteristics should be considered to predict technical success of cathether-based interventional strategies, such as the location of the membrane, the degree of pulmonary vein stenosis, the extent of calcification, and the presence of other (congenital) cardiovascular abnormalities. Furthermore, long-term efficacy of these strategies remains to be confirmed. As such, surgical treatment of cor triatriatum remains the mainstay of treatment in adult patients, especially when other cardiovascular anomalies are present which require surgical correction.
doi:10.1186/s12872-015-0067-4
PMCID: PMC4499942  PMID: 26169911
Congenital heart disease; Cardiovascular intervention; Cardiac surgery
22.  Performance of Sokolow-Lyon index in detection of echocardiographically diagnosed left ventricular hypertrophy in a normal Eastern German population - results of the CARLA study 
Background
Arterial hypertension is a common disease with high prevalence in the general population. Left ventricular hypertrophy (LVH) is an independent risk factor in arterial hypertension. Electrocardiographic indices like the Sokolow-Lyon index (SLI) are recommended as diagnostic screening methods for LVH.
We assessed the diagnostic performance of the SLI in a cohort of a large general population.
Methods
We used electrocardiographic and echocardiographic data from the prospective, population-based cohort study CARdio-vascular Disease, Living and Ageing in Halle (CARLA). Linear and logistic regression models were used to assess the association of SLI with LVH. To assess the impact of the body-mass-index (BMI), we performed interaction analyses.
Results
AUC of SLI to predict LVH was 55.3 %, sensitivity of the SLI was 5 %, specificity 97 %. We found a significant association of SLI after covariate-adjustment with echocardiographically detected LVH (increase of left-ventricular mass index, LVMI 7.0 g/m2 per 1 mV increase of SLI, p < 0.0001). However, this association was mainly caused by an association of SLI with the left-ventricular internal diameter (LVIDd, increase of 0.06 cm/m2 per 1 mV increase of SLI, p < 0.0001). In obese (BMI > 30 kg/m2) we found the strongest association with an increase of 9.2 g/m2 per 1 mV.
Conclusions
Although statistically significant, relations of SLI and echocardiographic parameters of LVH were weak and mainly driven by the increase in LVIDd, implicating a more eccentric type of LVH in the collective. The relations were strongest when obese subjects were taken into account. Our data do not favour the SLI as a diagnostic screening test to identify patients at risk for LVH, especially in non-obese subjects without eccentric LVH.
doi:10.1186/s12872-015-0066-5
PMCID: PMC4501293  PMID: 26169782
Left ventricular hypertrophy; Hypertrophy; ECG; Sokolow-Lyon index; Sokolow; Obesity
23.  Lack of “obesity paradox” in patients presenting with ST-segment elevation myocardial infarction including cardiogenic shock: a multicenter German network registry analysis 
Background
Studies have associated obesity with better outcomes in comparison to non-obese patients after elective and emergency coronary revascularization. However, these findings might have been influenced by patient selection. Therefore we thought to look into the obesity paradox in a consecutive network STEMI population.
Methods
The database of two German myocardial infarction network registries were combined and data from a total of 890 consecutive patients admitted and treated for acute STEMI including cardiogenic shock and cardiopulmonary resuscitation according to standardized protocols were analyzed. Patients were categorized in normal weight (≤24.9 kg/m2), overweight (25-30 kg/m2) and obese (>30 kg/m2) according to BMI.
Results
Baseline clinical parameters revealed a higher comorbidity index for overweight and obese patients; 1-year follow-up comparison between varying groups revealed similar rates of all-cause death (9.1 % vs. 8.3 % vs. 6.2 %; p = 0.50), major adverse cardiac and cerebrovascular [MACCE (15.1 % vs. 13.4 % vs. 10.2 %; p = 0.53)] and target vessel revascularization in survivors [TVR (7.0 % vs. 5.0 % vs. 4.0 %; p = 0.47)] with normal weight when compared to overweight or obese patients. These results persisted after risk-adjustment for heterogeneous baseline characteristics of groups. An analysis of patients suffering from cardiogenic shock showed no impact of BMI on clinical endpoints.
Conclusion
Our data from two network systems in Germany revealed no evidence of an “obesity paradox”in an all-comer STEMI population including patients with cardiogenic shock.
doi:10.1186/s12872-015-0065-6
PMCID: PMC4498506  PMID: 26162888
Coronary stent; Obesity paradox; Mortality; Cardiogenic shock
24.  Influence of glycemic control on gain in VO2 peak, in patients with type 2 diabetes enrolled in cardiac rehabilitation after an acute coronary syndrome. The prospective DARE study 
Background
Gain in VO2 peak after cardiac rehabilitation (CR) following an acute coronary syndrome (ACS), is associated with reduced mortality and morbidity. We have previously shown in CR, that gain in VO2 peak is reduced in Type 2 diabetic patients and that response to CR is impaired by hyperglycemia.
Methods
We set up a prospective multicenter study (DARE) whose primary objective was to determine whether good glycemic control during CR may improve the gain in VO2 peak. Sixty four type 2 diabetic patients, referred to CR after a recent ACS, were randomized to insulin intensive therapy or a control group with continuation of the pre-CR antidiabetic treatment. The primary objective was to study the effect of glycemic control during CR on the improvement of peak VO2 by comparing first the 2 treatment groups (insulin intensive vs. control) and second, 2 pre-specified glycemic control groups according to the final fructosamine level (below and above the median).
Results
At the end of the CR program, the gain in VO2 peak and the final fructosamine level (assessing glycemic level during CR) were not different between the 2 treatment groups. However, patients who had final fructosamine level below the median value, assessing good glycemic control during CR, showed significantly higher gain in VO2 peak (3.5 ± 2.4 vs. 1.7 ± 2.4 ml/kg/min,p = 0.014) and ventilatory threshold (2.7 ± 2.5 vs. 1.2 ± 1.9 ml/kg/min,p = 0.04) and a higher proportion of good CR-responders (relative gain in VO2 peak ≥ 16 %): 66 % vs. 36 %, p = 0.011. In multivariate analysis, gain in VO2 peak was associated with final fructosamine level (p = 0.010) but not with age, gender, duration of diabetes, type of ACS, insulin treatment or basal fructosamine.
Conclusions
The DARE study shows that, in type 2 diabetes, good glycemic control during CR is an independent factor associated with gain in VO2 peak. This emphasizes the need for good glycemic control in CR for type 2 diabetic patients.
Trial registration
Trial registered as NCT00354237 (19 July 2006).
doi:10.1186/s12872-015-0055-8
PMCID: PMC4495681  PMID: 26152221
Diabetes; Cardiac rehabilitation; Myocardial infarction; Hyperglycemia
25.  Neither endothelial function nor carotid artery intima-media thickness predicts coronary computed tomography angiography plaque burden in clinically healthy subjects: a cross-sectional study 
Background
Cardiovascular risk assessment is usually based on traditional risk factors and risk assessment algorithms. However, a number of risk markers that might provide additional predictive power have been identified. Endothelial function determined by digital reactive hyperemia peripheral arterial tonometry (RH-PAT) and carotid artery intima-media thickness (IMT) have both been proposed as surrogate markers for coronary artery disease (CAD). We aimed to examine the ability of RH-PAT and IMT to predict coronary computed tomography angiography (CTA) plaque burden in clinically healthy subjects.
Methods
Fifty-eight clinically healthy volunteers (50–73 years old) underwent testing for RH-PAT and IMT as well as coronary CTA, including coronary artery calcium (CAC) scoring. Coronary CTA was analyzed with respect to any atheromatous plaques, stenotic as well as non-stenotic. The Mann–Whitney U-test was used to compare the groups with and without CAD and the Spearman test was used to test for correlation between variables.
Results
Twenty-five (43 %) subjects had normal coronary arteries, without any signs of atherosclerosis. The median (range) number of diseased segments was 1 (0–10), RH-PAT index 2.2 (1.4-4.9), IMT 0.70 (0.49-0.99) mm and CAC 4 (0–1882). There was no association between presence or extent of CAD and RH-PAT index (Spearman correlation coefficient rs = 0.13) or IMT (rs = 0.098). As expected, CAC was strongly correlated to presence and extent of CAD by coronary CTA (rs =0.86; p < 0.0001).
Conclusions
Neither evaluation of endothelial function by RH-PAT nor assessment of carotid artery IMT can reliably be used to predict coronary CTA plaque burden in clinically healthy subjects.
doi:10.1186/s12872-015-0061-x
PMCID: PMC4494716  PMID: 26148508
CAD; Coronary artery disease; RH-PAT; PAT; Endothelial function; IMT; CIMT; Intima-media thickness; Coronary CTA; Coronary computed tomography angiography

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