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1.  Percutaneous treatment of spontaneous left main coronary artery dissection using drug-eluting stent 
Background
Spontaneous coronary artery dissection is a rare cause of ischemic heart disease and sudden death. Prompt diagnosis is of paramount importance, especially in cases when it manifests with ST elevation myocardial infarction (STEMI).
Case presentation
We report a case of a 42 year-old woman, who presented with an anterior STEMI in a hospital without on-site percutaneous coronary intervention (PCI) facilities. She was transferred to our hospital and coronary angiography revealed a spontaneous dissection of the left main stem coronary artery (LM). The dissection was successfully managed with PCI.
Conclusion
PCI appears to be a potential option, for the treatment of selected cases with spontaneous LM dissection, presenting with an acute coronary syndrome.
doi:10.1186/1471-2261-14-191
PMCID: PMC4279601  PMID: 25519008
Spontaneous coronary artery dissection; Left main; Percutaneous coronary intervention
2.  Endurance training or beta-blockade can partially block the energy metabolism remodeling taking place in experimental chronic left ventricle volume overload 
Background
Patients with chronic aortic valve regurgitation (AR) causing left ventricular (LV) volume overload can remain asymptomatic for many years despite having a severely dilated heart. The sudden development of heart failure is not well understood but alterations of myocardial energy metabolism may be contributive. We studied the evolution of LV energy metabolism in experimental AR.
Methods
LV glucose utilization was evaluated in vivo by positron emission tomography (microPET) scanning of 6-month AR rats. Sham-operated or AR rats (n = 10-30 animals/group) were evaluated 3, 6 or 9 months post-surgery. We also tested treatment intervention in order to evaluate their impact on metabolism. AR rats (20 animals) were trained on a treadmill 5 times a week for 9 months and another group of rats received a beta-blockade treatment (carvedilol) for 6 months.
Results
MicroPET revealed an abnormal increase in glucose consumption in the LV free wall of AR rats at 6 months. On the other hand, fatty acid beta-oxidation was significantly reduced compared to sham control rats 6 months post AR induction. A significant decrease in citrate synthase and complex 1 activity suggested that mitochondrial oxidative phosphorylation was also affected maybe as soon as 3 months post-AR.
Moderate intensity endurance training starting 2 weeks post-AR was able to partially normalize the activity of various myocardial enzymes implicated in energy metabolism. The same was true for the AR rats treated with carvedilol (30 mg/kg/d). Responses to these interventions were different at the level of gene expression. We measured mRNA levels of a number of genes implicated in the transport of energy substrates and we observed that training did not reverse the general down-regulation of these genes in AR rats whereas carvedilol normalized the expression of most of them.
Conclusion
This study shows that myocardial energy metabolism remodeling taking place in the dilated left ventricle submitted to severe volume overload from AR can be partially avoided by exercise or beta-blockade in rats.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-14-190) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2261-14-190
PMCID: PMC4279960  PMID: 25518920
3.  Proprotein convertase subtilisin/kexin type 9 expression is transiently up-regulated in the acute period of myocardial infarction in rat 
Background
The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been confirmed as a major factor regulating cholesterol homeostasis and has low-density lipoprotein receptor (LDLR) independent effects. In addition, the pathogenesis of acute myocardial infarction (AMI) involves lipids alteration and other acute phase responses. It remains unknown whether the PCSK9 expression is influenced by the impact of AMI. The present study aimed to investigate the changes of PCSK9 concentration using AMI rat model.
Methods
AMI (n = 6-8 at each time point) or sham operated (n = 6) adult male rats model were used. Whole blood and liver tissue were collected at 1, 3, 6, 9, 12, 24, 48, and 96 hour (h) post infarction. The plasma PCSK9 concentration was measured by ELISA and lipid profiles were measured by enzymatic assay. The liver mRNA levels of PCSK9, LDLR, sterol response element binding protein-2 (SREBP-2) and hepatocyte nuclear factor 1α (HNF1α) were measured by quantitative real-time PCR.
Results
The plasma PCSK9 concentration was increased from 12 h to 96 h (P < 0.05 vs. control). Paralleled with the enhanced plasma PCSK9 concentration, the hepatic PCSK9 mRNA expression was up-regulated by 2.2-fold at 12 h and 4.1-fold at 24 h. Hepatic mRNA levels of LDLR, SREBP-2 and HNF1α were all increased and lipid profiles underwent great changes at this acute period.
Conclusions
We firstly demonstrated that PCSK9 was transiently up-regulated in the acute period of AMI, which is also driven by transcriptional factors, SREBP-2 and HNF1α, suggesting that the role of PCSK9 in myocardial injury may be needed further study.
doi:10.1186/1471-2261-14-192
PMCID: PMC4279995  PMID: 25519174
Acute myocardial infarction; PCSK9; Rat
4.  A pharmacodynamic comparison of 5 anti-platelet protocols in patients with ST-elevation myocardial infarction undergoing primary PCI 
Background
Despite advances in anti-platelet treatments, there still exists an early increase in both ischemic as well as bleeding events following primary PCI in patients with ST-elevation myocardial infarction (STEMI). Platelet inhibition data of different anti-platelet treatments in the acute phase of a myocardial infarction might offer some insight into these problems. The aim of this study was to evaluate the pharmacodynamic profile of 5 different anti-platelet treatments in the acute phase of STEMI in patients undergoing primary PCI.
Methods
A total of 223 STEMI patients undergoing primary PCI were prospectively included. Patients received either pre-hospital clopidogrel only, pre-hospital clopidogrel followed by prasugrel switch in the cath lab, prasugrel treatment only, pre-hospital clopidogrel followed by ticagrelor switch in the cath lab or pre-hospital ticagrelor only. Platelet reactivity was measured serially using vasodilator-stimulated phosphoprotein (VASP).
Results
Patients receiving pre-hospital clopidogrel followed by prasugrel switch showed similar platelet inhibition data as patients receiving prasugrel only, with more than 90% being good responders the day after PCI. Average time from prasugrel administration to a VASP value of <50% was 1.5 hours. In patients receiving pre-hospital ticagrelor, 50% were good responders at completion of PCI and average time to a VASP-value of <50% was 2.3 hours. Only 32% of patients receiving clopidogrel only were responders the day after PCI.
Conclusions
Switching from an upstream bolus dose of clopidogrel to prasugrel at the time of PCI, appeared as a safe and feasible option with no tendency for overshoot or attenuation of platelet inhibition. Pre-hospital administration of ticagrelor was associated with a 50% good responder rate at completion of PCI.
doi:10.1186/1471-2261-14-189
PMCID: PMC4274705  PMID: 25516485
Prasugrel; Ticagrelor; Clopidogrel; Upstream; STEMI
5.  Visit-to-visit blood pressure variability is a marker of cardiac diastolic function and carotid atherosclerosis 
Background
The associations between visit-to-visit blood pressure (BP) variability and cardiac function and carotid atherosclerosis is not clear.
Methods
Study subjects were 144 subjects (80 were female, aged 73 ± 9 years) who underwent echocardiography and cervical ultrasonography. The ratio of early ventricular filling velocity to early diastolic mitral annular velocity (E/e’), ejection fraction, left ventricular mass index (LVMI), and maximum intima-media thickness (max-IMT) of the carotid artery were compared between the highest (high variability) and lowest (low variability) tertiles of the standard deviation of systolic BP (9.9 ± 3.5 mmHg).
Results
E/e’ and max-IMT were significantly greater in the high variability group than in the low variability group after adjusting for age, sex, baseline systolic BP, and other covariates (high variability vs. low variability; E/e’: 13.03 ± 5.33 vs. 10.66 ± 3.30, multivariate-adjusted difference (β) = 1.82, 95% confidence interval 0.06–3.58; max-IMT: 1.65 ± 0.43 mm vs. 1.42 ± 0.46 mm, β = 0.20 mm, 95% confidence interval 0.03–0.36 mm). There were no significant differences in LVMI or ejection fraction.
Conclusion
These results indicate that high visit-to-visit BP variability is associated with diastolic function and carotid atherosclerosis, and is a possible risk factor for diastolic dysfunction and atherosclerosis.
doi:10.1186/1471-2261-14-188
PMCID: PMC4273455  PMID: 25510736
6.  Metformin use in patients with type 2 diabetes mellitus is associated with reduced risk of deep vein thrombosis: a non-randomized, pair-matched cohort study 
Background
Metformin, an insulin-sensitizer, may correct several physiologic abnormalities owing to insulin resistance in patients with type 2 diabetes mellitus (DM). The effects of metformin on venous thrombosis in patient with type 2 DM have not been reported. Our study strived to explore the relationship of metformin therapy and the subsequent development of deep vein thrombosis (DVT) using a nationwide, population-based database.
Methods
From 1997 to 2003, we identified a study cohort consisting of patients with type 2 DM using metformin 7154 cases in the National Health Insurance Research Database. A control cohort without metformin, matched for age, sex, comorbidities, and medications was selected for comparison.
Results
Of the 14945 patients (7167 patients with metformin vs. 7778 control), 60 (0.40%) patients developed DVT during a mean follow-up period of 3.74 years, including 16 (0.21%) from the cohort with metformin and 44 (0.56%) from the control group. Subjects with metformin experienced a 0.427 fold (95% confidence interval 0.240-0.758; P = 0.004) changes of risk reduction in development of DVT, which was independent of age, sex and co-morbidities. Kaplan-Meier analysis also revealed metformin therapy is associated with lower occurrence of DVT (log-rank test, P = 0.001).
Conclusions
Metformin may have protective effect in patients with type 2 DM for DVT.
doi:10.1186/1471-2261-14-187
PMCID: PMC4274716  PMID: 25510597
Deep vein thrombosis; Metformin; Type 2 diabetes mellitus
7.  Retrospective review of superficial femoral artery stenting in diabetic patients: thiazolidinedione use may decrease reinterventions 
Background
Diabetics are known to have inferior outcomes following peripheral vascular interventions. Thiazolidinediones are oral diabetic agents which improve outcomes following coronary bare metal stenting. No studies have been performed evaluating thiazolidinedione use and outcomes following lower extremity endovascular interventions. We hypothesize that diabetic patients taking thiazolidinediones at the time of primary superficial femoral artery (SFA) stenting have fewer reinterventions.
Methods
A retrospective review was performed to identify diabetic patients undergoing primary SFA stenting. The unit of analysis was the extremity. The primary outcome was freedom from target lesion revascularization stratified by thiazolidinedione use, evaluated by Kaplan Meier curves and a log rank test. A Cox proportional hazards model was constructed to determine variables associated with freedom from target lesion revascularization.
Results
SFA stents were placed in 138 extremities in 128 diabetic patients between August 1, 2001 and July 15, 2012. Twenty-four patients were taking thiazolidinediones at the time of SFA stenting. All patients taking thiazolidinediones had TASC A or B lesions. Twenty-seven extremities in the non-thiazolidinedione group had TASC C or D lesions and were excluded to control for disease severity. Freedom from target lesion revascularization was significantly higher in diabetics taking thiazolidinediones at 2 years, 88.5% vs. 59.4%, P = 0.02, SE < 10%. Cox modeling identified a protective trend for thiazolidinedione use (thiazolidinedione use HR 0.33, 95% CI 0.09-1.13), whereas critical limb ischemia and insulin use were associated with trends for worse freedom from target lesion revascularization.
Conclusions
This pilot, translation study demonstrates that diabetic patients taking thiazolidinediones at the time of primary SFA stenting have decreased reintervention rates at 2 years. These results may be explained by higher adiponectin levels or other anti-inflammatory effects in patients taking thiazolidinedione. National and regional quality improvement registries should consider collecting information regarding specific diabetic regimens and use of PPAR agonists such as cilostazol and fibrates.
doi:10.1186/1471-2261-14-184
PMCID: PMC4269962  PMID: 25495345
Adiponectin; Diabetes; Peripheral arterial disease; Thiazolidinediones; Endovascular
8.  Implication of plasma intermedin levels in patients who underwent first-time diagnostic coronary angiography: a single centre, cross-sectional study 
Background
Intermedin (IMD) is involved in the prevention of atherosclerotic plaque progression, possessing cardioprotective effects from hypertrophy, fibrosis and ischemia-reperfusion injury. Elevated plasma IMD levels have been demonstrated in patients with acute coronary syndromes. No human study has examined the role of IMD in stable patients who underwent diagnostic coronary angiography with suspicion of coronary artery disease (CAD). Thus we investigated the role of IMD as a biomarker to discriminate patients with CAD and predict those with severe disease who require early and intensive therapeutic intervention before presenting with acute coronary syndrome.
Methods
Eligible two hundred and thirty-eight consecutive patients (123 males, mean age 58.4 ± 10.0 years) who underwent first-time diagnostic coronary angiography were included in this study. Plasma concentrations of IMD were measured from arterial blood samples by the enzyme-linked immunosorbent assay. Patients were divided into three groups according to the presence and degree of CAD, consisting of 48 patients with normal coronary anatomy (Group 1), 111 patients with < 50% coronary stenosis (Group 2), and 79 patients with ≥ 50% stenosis in at least one of the major coronary arteries (group 3). The severity and extent of CAD was evaluated by calculations of the vessel, Gensini, and SYNTAX scores.
Results
Circulating plasma IMD levels in patients with CAD were significantly higher than those in patients without CAD (157.7 ± 9.6, 134.8 ± 11.9, and 117.6 ± 7.9 pg/mL in groups 3, 2 and 1 respectively; p < 0.001). Besides, plasma IMD levels were correlated with Gensini and SYNTAX scores (rs = 0.742, and rs = 0.296, respectively; p < 0.05). The presence of ≥50% coronary artery stenosis could be predicted if a cut-off value of 147.7 pg/mL for plasma IMD was used with 88.6% sensitivity and 88.7% specificity. Moreover, a plasma IMD level of <126.6 pg/mL could discriminate a patient with normal coronary arteries from patients with angiographically proven CAD with a sensitivity and specificity of 84.7%, and 83.3% respectively.
Conclusions
We demonstrated that IMD might be used as a biomarker to predict CAD and its severity in patients who underwent first time diagnostic coronary angiography.
doi:10.1186/1471-2261-14-182
PMCID: PMC4271361  PMID: 25495100
Intermedin; Coronary artery disease; Diagnostic coronary angiography
9.  Echocardiographic evaluation of thalassemia intermedia patients in Duhok, Iraq 
Background
Cardiac complications are among the most serious problems of thalassemia intermedia patients. The current study was initiated to address the latter issue through the study of the echocardiographic findings and correlate it with clinical characteristics of thalassemia intermedia patients in Duhok, Kurdistan region, Iraq.
Methods
An echocardiographic assessment of 61beta-thalassemia intermedia cases was performed. It included 30 males and 31 females, with a mean age 19.6 ± 7.5 years. The standard echostudy of two-dimension and M-mode measurements of cardiac chambers were done. The continuous doppler regurgitant jet of tricuspid and pulmonary valves were recorded. Left ventricle diastolic function was assessed by pulsed doppler of mitral valve inflow. To correlate the clinical with echocardiographic findings, patients were divided, according to tricuspid regurgitant velocity, into three groups (<2.5 m/sec, 2.5-2.9 m/sec and ≥3 m/sec).
Results
Tricuspid regurgitant velocity <2.5 m/sec, 2.5-2.9 m/sec and ≥3 m/sec occurred in 42(69%), 11(18%) and 8(13%) respectively. Comparing to other groups patients with tricuspid regurgitant velocity ≥3 m/sec were older and included more males. They had lower hemoglobin levels, but higher ferritin levels. Their age at diagnosis and the age of the initiation of blood transfusion were later. Most of them had significant exertional dyspnea. They also had relatively lower left ventricle ejection fraction values. Right ventricular diameter and right atrial size were larger in the same group. Tricuspid regurgitant velocity as a continuous predictor was associated positively with age, cardiac volumes and pulmonary regurgitation though negatively associated with ejection fraction.
Conclusions
Echo-derived right and left side cardiac complications are not uncommon in thalassemia intermedia patients. Therapeutic trails targeting these complications are indicated, and echocardiographic assessment is necessary to be offered early for thalassemia intermedia.
doi:10.1186/1471-2261-14-183
PMCID: PMC4272797  PMID: 25495194
Thalassemia intermedia; Tricuspid velocity jet; Pulmonary hypertension; Iraq
10.  Cardiovascular autonomic dysfunction and oxidative stress induced by fructose overload in an experimental model of hypertension and menopause 
Background
Metabolic syndrome is characterized by the association of 3 or more risk factors, including: abdominal obesity associated with an excess of abdominal fat, insulin resistance, type 2 diabetes, dyslipidemia and hypertension. Moreover, the prevalence of hypertension and metabolic dysfunctions sharply increases after the menopause. However, the mechanisms involved in these changes are not well understood. Thus, the aim of this study was to assess the effects of fructose overload on cardiovascular autonomic modulation, inflammation and cardiac oxidative stress in an experimental model of hypertension and menopause.
Methods
Female SHR rats were divided into (n = 8/group): hypertensive (H), hypertensive ovariectomized (HO) and hypertensive ovariectomized undergoing fructose overload (100 g/L in drinking water) (FHO). Arterial pressure (AP) signals were directly recorded. Cardiac autonomic modulation was evaluated by spectral analysis. Oxidative stress was evaluated in cardiac tissue.
Results
AP was higher in the FHO group when compared to the other groups. Fructose overload promoted an increase in body and fat weight, triglyceride concentration and a reduction in insulin sensitivity. IL-10 was reduced in the FHO group when compared to the H group. TNF-α was higher in the FHO when compared to all other groups. Lipoperoxidation was higher and glutathione redox balance was reduced in the FHO group when compared to other groups, an indication of increased oxidative stress. A negative correlation was found between IL-10 and adipose tissue.
Conclusion
Fructose overload promoted an impairment in cardiac autonomic modulation associated with inflammation and oxidative stress in hypertensive rats undergoing ovarian hormone deprivation.
doi:10.1186/1471-2261-14-185
PMCID: PMC4279597  PMID: 25495455
Menopause; Metabolic syndrome; Heart rate variability; Blood pressure variability; Inflammation; Oxidative stress
11.  Finger volume pulse waveforms facilitate reliable assessment of heart rate variability, but not blood pressure variability or baroreflex function 
Background
We sought to determine whether heart rate variability (HRV), blood pressure (BP) variability, and baroreceptor-heart rate reflex sensitivity can be reliably assessed using finger volume pulse waveforms obtained from the commercially available EndoPAT device.
Methods
Non-invasive BP (Finometer Pro as a non-invasive standard) and finger volume (EndoPAT) waveforms were recorded in 65 adults (37 ± 14 years; 60% female) and systolic BP and heart rate (HR) time series were derived after calibrating the EndoPAT signal based on systolic and diastolic BP values obtained by a sphygomomanometer. Transfer function analyses were performed to test for coherence between systolic BP and HR time series derived from the Finometer and EndoPAT devices. Time-domain HRV parameters, frequency domain HR and systolic BP variability parameters, and baroreflex sensitivity (sequence technique) were computed from Finometer- and EndoPAT-derived time series and intraclass correlation coefficients (ICC) were calculated.
Results
Squared coherence between systolic BP time series derived from the Finometer and EndoPAT devices was low, suggesting poor correlation. In contrast, squared coherence between HR time series derived from the two devices was excellent [High Frequency (HF) = 0.80, Low Frequency (LF) = 0.81], with gain values close to 1.0. ICC values for time- and frequency-domain HRV parameters were excellent (>0.9 except for relative HF HRV, which was 0.77), while ICC values for frequency-domain BP variability parameters and baroreceptor-HR reflex sensitivity were low.
Conclusions
Finger volume pulse waveforms can be used to reliably assess both time-domain and frequency-domain HR variability. However, frequency domain BP variability parameters cannot be reliably assessed from finger volume pulse waveforms using the simple calibration technique used in this study.
doi:10.1186/1471-2261-14-180
PMCID: PMC4269858  PMID: 25487432
EndoPAT; Finometer Pro; Cardiovascular function; Device validation
12.  Analysis of risk factors of ST-segment elevation myocardial infarction in young patients 
Background
Acute myocardial infarction (AMI) is often present in old populations and rare in young people. Its incidence significantly increased recent years. The mechanism and disease course of AMI in young people are probably different from that in old population. The aim of this study was to analyze clinical risk factors of STEMI in young patients.
Methods
Data was collected from consecutive patients ≤ 44 years of age (young; n = 86) and 60–74 years of age (old; n = 65) diagnosed with STEMI, and 79 young age-matched patients without coronary artery disease (CAD), hospitalized between January 2009 and June 2013.
Results
The young STEMI group had a significantly higher proportion of males (88.37 vs. 53.16%; P < 0.01), smokers (82.56 vs. 49.37%; P < 0.01) and patients with a family history of early CAD (54.65 vs. 32.91%; P < 0.05) than age-matched controls. Young STEMI patients also had significantly higher levels of fasting blood sugar (6.39 vs. 5.25 mmol/L; P < 0.001), glycated hemoglobin (HbA1c) (6.26 vs. 5.45%; P < 0.05), total cholesterol (5.14 vs. 4.65 mmol/L, P < 0.05), and fibrinogen (Fib) (3.39 vs. 2.87; P < 0.01). Compared with the old STEMI group, young STEMI patients had significantly higher proportions of males (88.37 vs. 63.08%; P < 0.01) smokers (82.56 vs. 41.54%; P < 0.01), and those with a family history of early CAD (54.65 vs. 18.46%; P < 0.01). Young STEMI patients also lower Fib (3.39 vs. 3.88 g/L; P < 0.01), less frequent occurrence of angina pectoris before STEMI (13.95 vs. 29.23%; P < 0.05) compared with the old STEMI group. Logistic regression analysis indicated that male sex (OR = 5.891), smoking (OR = 3.500), family history of early CAD (OR = 3.194), Fib (OR = 2.414) and HbA1c (OR = 1.515) are associated with STEMI in young patients.
Conclusion
In addition to previously recognized risk factors (male sex, smoking and family history of early CAD), Fib and HbA1c are associated with STEMI in individuals ≤ 44 years of age without antecedent angina pectoris.
doi:10.1186/1471-2261-14-179
PMCID: PMC4271480  PMID: 25487289
Antecedent angina pectoris; Fibrinogen; Glycated hemoglobin; Risk factors; ST-segment elevation myocardial infarction; Young patients
13.  The correlation between serum lipid profile with carotid intima-media thickness and plaque 
Background
It is indicated that non-HDL cholesterol and lipid ratios, including total/HDL cholesterol and LDL/HDL cholesterol ratios, are risk indicators with greater predictive value for coronary atherosclerotic progression or regression compared with conventional lipid profile. However, there have been few reports about the correlation between serum lipid profile with carotid intima-media thickness (IMT) and plaque in Chinese general people.
Methods
We examined 402 subjects without apparent diseases in a cross-sectional study (mean age 50.16 years; 36.07% female). Demographics, anthropometrics, and laboratory data were collected. The presence of carotid plaque and intima-media thickness were evaluated by ultrasonography.
Results
Univariate correlations showed carotid IMT was correlated with LDL-C (r = 0.137, p = 0.009), non-LDL-C levels (r = 0.140, p = 0.008) and LDL-C/HDL-C ratio (r = 0.169, p = 0.001). After adjustment for potential covariates, LDL-C/HDL-C ratio (β = 0.132, p < 0.001) were independent variables that interacted on carotid IMT. Other risk factors including age and systolic blood pressure were independently associated with carotid IMT. LDL-C levels, non-HDL-C levels, TC/HDL-C and LDL-C/HDL-C ratios were significantly higher, but HDL-C levels were significantly lower in subjects with carotid plaque than those without it. The subsequent multiple logistic regression analysis showed that LDL-C (OR; 1.325, 95% CI; 1.046-1.821, p = 0.033) and HDL-C levels (OR; 0.093, 95% CI; 0.038-0.227, p < 0.001) were significantly associated with the presence of carotid plaque after adjustment of age. Furthermore, LDL-C combined with HDL-C levels showed the highest area under the curve (0.788, 95% CI; 0.740–0.837, p < 0.001).
Conclusions
Serum LDL-C/HDL-C ratio represents as an independent index associated with increased carotid IMT and LDL-C combined with HDL-C levels may be useful markers for predicting the presence of carotid plaque in the Chinese general population.
doi:10.1186/1471-2261-14-181
PMCID: PMC4272763  PMID: 25491329
Subclinical atherosclerosis; Lipid ratio; Intima-media thickness; Plaque
14.  Metabolic syndrome among hypertensive patients at University of Gondar Hospital, North West Ethiopia: a cross sectional study 
Background
Data is sparse concerning the magnitude of metabolic syndrome (MetS) in developing countries like Ethiopia whose major health problem had long been under-nutrition and infectious diseases rather than non-communicable diseases (NCDs) including hypertension, obesity and MetS. However, it is obvious that the NCDs are recently taking over and becoming the major health care concerns in the developing countries. This pattern could be partly explained by the nation’s sustained economical growth in the last few decades in addition to the increasing globalization related adoption of western lifestyle. The aim of this study was to assess the prevalence of metabolic syndrome and associated factors among hypertensive patients in North West Ethiopia.
Method
A cross sectional study was conducted on 300 hypertensive individuals who get follow-up care at University of Gondar Hospital after diagnosed as hypertensive. The WHO STEP-wise approach to surveillance of NCD was used. Fasting blood glucose level, triglyceride and high density lipoprotein cholesterol were determined using standardized laboratory procedures.
Result
The prevalence of metabolic syndrome was 40.7% and 39.3% according to the modified NCEP-ATP III and IDF criteria respectively. Low HDL-c was found to be the most frequently encountered (81.3%) component of MetS other than the hypertension. Being female was significantly associated with MetS (AOR = 4.34; 95% CI: 2.09, 8.99) using IDF and (AOR = 3.30; 95% CI: 1.66, 6.58) using NCEP-ATP III criteria. Abnormal BMI which included both high and low BMI was found to have significant association with MetS (AOR = 3.10; 95% CI: 1.73, 5.58) using IDF and (AOR = 1.84; 95% CI: 1.05, 3.22) as diagnosed using the NCEP-ATP III criteria.
Conclusion
We recommend a comprehensive medical care approach to hypertensive patients to adequately assess and address the additional components of MetS which are known to potentiate the risks of cardiovascular diseases among hypertensive patients.
doi:10.1186/1471-2261-14-177
PMCID: PMC4273452  PMID: 25481843
Hypertension; Metabolic syndrome; Cardiovascular risk; Dyslipidemia; Insulin resistance
15.  Biatrial myxoma and multiple organ infarctions combined with Leriche syndrome in a female patient 
Background
Multiple organ infarctions combined with Leriche syndrome due to embolic particles of myxoma are very rare. There is no definite guideline for immediate medical treatment.
Case presentation
A 36-year-old married female was referred to the emergency department (ED) with severe pain of both lower extremities and gradual decreased mental status. Brain magnetic resonance imaging (MRI) and computed tomography angiography (CTA) revealed acute multiple organ infarctions including the brain, spleen, and bilateral kidneys combined with Leriche syndrome. To evaluate the embolic source, echocardiography was performed and it revealed biatrial myxoma. Because of the risk of progression in systemic embolic events, surgical excision and embolectomy were performed urgently. After the operation, renal function was recovered, and the pain of both limbs was relieved. However, the visual field defect due to the brain infarction remained. She was discharged uneventfully on the fourteenth postoperative day.
Conclusion
This was an extremely rare case of multiple organ infarctions combined with Leriche syndrome as the initial presentation of biatrial myxoma. The treatment of choice for myxoma is surgical excision, but the optimal timing of operations is still controversial in patients who have had recent neurological insults. Echocardiography was useful to clarify the diagnosis and decide on the proper treatment modality: surgical treatment or thrombolysis.
doi:10.1186/1471-2261-14-175
PMCID: PMC4267151  PMID: 25480676
Myxoma; Heart atria; Cerebrovascular accident; Leriche syndrome; Echocardiography
16.  Population risk factor estimates for abdominal aortic aneurysm from electronic medical records: a case control study 
Background
Using abdominal aortic aneurysm (AAA) as a model, this case–control study used electronic medical record (EMR) data to assess known risk factors and identify new associations.
Methods
The study population consisted of cases with AAA (n =888) and controls (n =10,523) from the Geisinger Health System EMR in Central and Northeastern Pennsylvania. We extracted all clinical and diagnostic data for these patients from January 2004 to December 2009 from the EMR. From this sample set, bootstrap replication procedures were used to randomly generate 2,500 iterations of data sets, each with 500 cases and 2000 controls. Estimates of risk factor effect sizes were obtained by stepwise logistic regression followed by bootstrap aggregation. Variables were ranked using the number of inclusions in iterations and P values.
Results
The benign neoplasm diagnosis was negatively associated with AAA, a novel finding. Similarly, type 2 diabetes, diastolic blood pressure, weight and myelogenous neoplasms were negatively associated with AAA. Peripheral artery disease, smoking, age, coronary stenosis, systolic blood pressure, age, height, male sex, pulmonary disease and hypertension were associated with an increased risk for AAA.
Conclusions
This study utilized EMR data, retrospectively, for risk factor assessment of a complex disease. Known risk factors for AAA were replicated in magnitude and direction. A novel negative association of benign neoplasms was identified. EMRs allow researchers to rapidly and inexpensively use clinical data to expand cohort size and derive better risk estimates for AAA as well as other complex diseases.
doi:10.1186/1471-2261-14-174
PMCID: PMC4269847  PMID: 25475588
Aortic Aneurysm; Abdominal; Electronic medical record; Neoplasms; Benign; Risk factors; Blood pressure; Diabetes mellitus; Type 2; Case–control studies
17.  Trial of a family-based education program for heart failure patients in rural Thailand 
Background
Heart failure (HF) significantly impacts on the daily lives of patients and their carers. In Western society HF education programs have increased patient and carer knowledge and improved health-related quality of life. However, there is a paucity of such evidence in Asia. For example, to date no studies have been conducted in Thailand to investigate the potential benefits of a family-based education program on the health outcomes of HF patients and carers.
Methods
This randomised controlled trial will evaluate the effectiveness of an education program on knowledge, self-care and health-related quality of life of Thai HF patients and their carers. Assessments will be conducted at baseline, three and six months. Participants will be assigned by independent random allocation to an intervention (family-based education plus usual care) or a control (usual care) group. Analyses will be conducted on an intention-to-treat basis.
Discussion
This trial will be the first to evaluate the effectiveness of family-based education for HF patients and carers residing in rural Thailand. It attempts to advance understanding of family-based HF education and address the gap in service provision.
Trial registration
Thai Clinical Trial Registry TCTR20140506003
doi:10.1186/1471-2261-14-173
PMCID: PMC4265427  PMID: 25475489
Family; Education; Self-care; Health-related quality of life; Heart failure; Thailand
18.  Self-rated health is associated with the length of stay at the intensive care unit and hospital following cardiac surgery 
Background
Recently, a considerable amount of evidence suggested that anxiety, depression and other psychosocial variables might influence the outcomes of cardiac surgery. This study investigated the relationship between length of stay at the intensive care unit (ICU) and hospital after surgery and different psychosocial variables (e.g. depression, anxiety, self rated health, happiness, satisfaction).
Methods
We enrolled prospective patients who were waiting for elective cardiac surgery (N = 267) and consented to take part in the study. We collected data of sociodemographic, medical and perioperative factors as well as psychosocial questionnaires completed 1.56 days (standard deviation [SD] = 0.7) before surgery. The primary clinical endpoint was an ICU stay of at least 3 days and the secondary was hospital stay of at least 10 days.
Results
Two hundred sixty-seven patients participated in this study. Four patients (1.5%) died in the hospital and 38 patients (14.5%) spent more than 3 days in the ICU and 62 patients (23.2%) spent more than 10 days in the hospital. After controlling for medical and sociodemographic factors, lower self rated health (Adjusted Odds Ratio [AOR]: 0.51, 95% confidence interval [CI]: 0.28-0.95; p = 0.03), lower rate of happiness (AOR: 0.76, 95% CI: 0.59-0.97, p = 0.03), postoperative cardiac failure (AOR: 7.09, 95% CI:1.21-41.54; p = 0.03) and postoperative complications (AOR: 9.52, 95% CI: 3.76-24.11; p < 0.001) were associated with longer ICU stay. More than 10 days of hospital stay was associated with higher occurrence of COPD (AOR 4.56, CI: 1.95-10.67, p < 0.001), NYHA stage (AOR 6.76, CI: 2.57-17.79, p < 0.001), operation time (AOR 1.45, CI: 1.19-1.76, p < 0.001), female gender (AOR 2.16, CI: 1.06-4.40, p = 0.034) and lower self-rated health (AOR 0.63, CI: 0.41-0.99, p = 0.044).
Conclusions
Lower happiness and self-rated health may influence the outcome of cardiac surgery. Therefore, these variables should be assessed in patients.
doi:10.1186/1471-2261-14-171
PMCID: PMC4258288  PMID: 25432074
ICU stay; Happiness; Self-rated health; Cardiac surgery; Risk stratification
19.  Study of adherence to exercise in heart failure: the HEART camp trial protocol 
Background
Adherence to the Heart Failure Society of America (HFSA) 2010 guidelines recommending 30 minutes of supervised moderate intensity exercise five days per week is difficult for patients with heart failure (HF). Innovative programs are needed to assist HF patients to adhere to long-term exercise. The objective of this prospective randomized two-group repeated measures experimental design is to determine the efficacy of a behavioral exercise training intervention on long-term adherence to exercise at 18 months in patients with heart failure.
Methods/Design
A sample size of 246 subjects with heart failure will be recruited over a 3 year period. All subjects receive a cardiopulmonary exercise test and 9 supervised exercise training sessions during a 3 week run-in period prior to randomization. Subjects completing at least 6 of 9 training sessions are randomized to the HEART Camp Intervention group (HC) or to a standard care (SC) exercise group. The HC intervention group receives cognitive-behavioral strategies that address the intervention components of knowledge, attitudes, self-efficacy, behavioral self-management skills and social support. The SC group is provided access to the exercise facility and regular facility staff for the 18 month study period. The primary aim is to evaluate the effect of HEART Camp on adherence to exercise, with our central hypothesis that the HC group will have significantly better adherence to exercise at 18 months. Secondary aims include evaluating which components of the HEART Camp intervention mediate the effects of the intervention on adherence; evaluating the effect of HEART Camp on specific health outcomes; exploring selected demographic variables (race, gender, age) as potential moderators of the effect of the HEART Camp intervention on adherence; and exploring the perceptions and experiences that contextualize exercise adherence.
Discussion
The HEART Camp intervention is the first to test a multi-component intervention designed to improve long-term adherence to exercise behavior in patients with HF. Improving long-term adherence to exercise is the logical first step to ensure the required dose of exercise that is necessary to realize beneficial health outcomes and reduce costs in this burdensome chronic illness.
Trial registration
Clincaltrials.gov NCT01658670.
doi:10.1186/1471-2261-14-172
PMCID: PMC4280683  PMID: 25433674
Heart failure; Exercise adherence; Moderate intensity exercise; HEART camp; Heart failure society of America guidelines
20.  Interaction of type 2 diabetes mellitus with Chromosome 9p21 rs10757274 polymorphism on the risk of myocardial infarction: a case–control study in Chinese population 
Background
Myocardial infarction (MI) is a serious complication of Coronary Artery Disease (CAD). Previous studies have identified genetic variants on chromosome 9p21 and 6p24 that are associated with CAD, but further studies need to be conducted to investigate whether these genetic variants are associated with the pathogenesis of MI. We therefore performed this study to assess the association between the risk of MI and SNP rs10757274 on chromosome 9p21 and SNP rs6903956 on chromosome 6p24, and to explore the gene-environment interactions in a Chinese population.
Methods
A hospital-based case–control study, consisting of 502 MI patients and 308 controls, was conducted in a Chinese population. Demographic, behavioral information and clinical characteristics were collected, and genotyping of the two SNPs was performed using single base primer extension genotyping technology. The unconditional logistic regression (ULR) method was adopted to assess the association of the two SNPs with MI risk. Both generalized multifactor dimensionality reduction (GMDR) and ULR methods were applied to explore the effect of gene-environment interactions on the risk of MI.
Results
After adjusting for covariates, it was observed that SNP rs10757274 on chromosome 9p21 was significantly associated with MI. Compared with subjects carrying the AA genotype, subjects carrying the GA or GG genotypes had a higher MI risk (ORa = 1.52, 95% CI:1.06–2.19, pa = 0.0227; ORa = 2.40, 95% CI:1.51–3.81, pa = 0.0002, respectively). Furthermore, a two-factor gene-environment interaction model of CDKN2A/B (rs10757274) and type 2 diabetes mellitus (T2DM) was identified to be the best model by GMDR (p = 0.0107), with a maximum prediction accuracy of 59.18%, and a maximum Cross-validation Consistency of 10/10. By using the ULR method, additive interaction analysis found that the combined effect resulted in T2DM-positive subjects with genotype GG/GA having an MI risk 4.38 times that of T2DM-negative subjects with genotype AA (ORadd = 4.38, 95% CI:2.56–7.47, padd < 0.0001).
Conclusions
These results show that gene polymorphism of CDKN2A/B (rs10757274) is associated with MI risk in a Chinese population. Furthermore, T2DM is likely to have an interaction with CDKN2A/B (rs10757274) that contributes to the risk of MI.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-14-170) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2261-14-170
PMCID: PMC4255939  PMID: 25430018
21.  Increased expression of NF-AT3 and NF-AT4 in the atria correlates with procollagen I carboxyl terminal peptide and TGF-β1 levels in serum of patients with atrial fibrillation 
Background
Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Unfortunately, the precise mechanisms and sensitive serum biomarkers of atrial remodeling in AF remain unclear. The aim of this study was to determine whether the expression of the transcription factors NF-AT3 and NF-AT4 correlate with atrial structural remodeling of atrial fibrillation and serum markers for collagen I and III synthesis.
Methods
Right and left atrial specimens were obtained from 90 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (n = 30), paroxysmal atrial fibrillation (n = 30), and persistent atrial fibrillation (n = 30) groups. NF-AT3, NF-AT4, and collagen I and III mRNA and protein expression in atria were measured. We also tested the levels of the carboxyl-terminal peptide from pro-collagen I, the N-terminal type I procollagen propeptides, the N-terminal type III procollagen propeptides, and TGF-β1 in serum using an enzyme immunosorbent assay.
Results
NF-AT3 and NF-AT4 mRNA and protein expression were increased in the AF groups, especially in the left atrium. NF-AT3 and NF-AT4 expression in the right atrium was increased in the persistent atrial fibrillation group compared the sinus rhythm group with similar valvular disease. In patients with AF, the expression levels of nuclear NF-AT3 and NF-AT4 correlated with those of collagens I and III in the atria and with PICP and TGF-β1 in blood.
Conclusions
These data support the hypothesis that nuclear NF-AT3 and NF-AT4 participates in atrial structural remodeling, and that PICP and TGF-β1 levels may be sensitive serum biomarkers to estimate atrial structural remodeling with atrial fibrillation.
doi:10.1186/1471-2261-14-167
PMCID: PMC4251842  PMID: 25422138
Atrial fibrillation; Atrial fibrosis; Transcription factor; NF-AT3; NF-AT4; Carboxyl terminal peptide from pro-collagen I; N-terminal type I procollagen propeptides; N-terminal type III procollagen propeptides
22.  Glucose–insulin–potassium therapy in patients with acute coronary syndrome: a meta-analysis of randomized controlled trials 
Background
Glucose-insulin-potassium (GIK) has been advocated in the setting of acute coronary syndrome (ACS) to reduce ischemia-related arrhythmias and myocardial injury. We conducted a meta-analysis of randomized controlled trials (RCTs) to assess whether the use of GIK infusions >3 or <3 hours after the onset of symptoms reduce mortality or cardiac arrest.
Methods
Electronic databases (Medline, EMBASE, and Cochrane Central Register of Controlled Trials) and references of retrieved articles were searched for RCTs evaluating the effect of GIK infusions, <3 hours or >3 hours after the onset of symptoms, on mortality and/or cardiac arrest. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each outcome.
Results
Nine trials were identified and eligible for review. The summary OR for in-hospital mortality was 1.01 (95% CI 0.94 to 1.09), based on 2,542 deaths among 27,294 patients. The subgroup analysis according to the study enrollment time (within 3 hours [OR, 0.77, 95% CI 0.50-1.16], vs. >3 hours [OR, 0.90; 95% CI, 0.67-1.21]) did not reveal any difference in mortality.
Conclusions
Administration of GIK in ACS patients does not significantly reduce mortality whether or not GIK administration >3 or <3 hours after the onset of symptoms.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-14-169) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2261-14-169
PMCID: PMC4256054  PMID: 25425404
Glucose–insulin–potassium; Acute coronary syndrome; Meta-analysis
23.  Prolonged P wave duration predicts stroke mortality among type 2 diabetic patients with prevalent non-major macrovascular disease 
Background
Prolonged P wave duration is a marker of delayed inter-atrial conduction which may predict cardiovascular disease (CVD). Type 2 diabetes is a risk factor for all atherosclerotic manifestations including stroke. We evaluated the prognostic significance of prolonged P wave duration among middle-aged Finnish type 2 diabetes patients with and without prevalent non-major macrovascular disease (PNMMVD) with respect to total and stroke mortality.
Methods
We followed up for 18 years 739 type 2 diabetic patients without previous major CVD event at baseline. Participants were stratified according to P wave duration (<114 or ≥114 ms) and PNMMVD (i.e. coronary heart disease defined as ischaemic ECG changes and typical symptoms of angina pectoris, or claudication; yes or no). The Cox proportional hazards model was used to estimate the joint association between P wave duration, PNMMVD and the mortality risk.
Results
During the follow-up, 509 patients died, and 59 of them died from stroke. Those who had prolonged P wave duration had 2.45 (95% confidence interval: 1.11-5.37) increased stroke mortality among PNMMVD patients. In patients without PNMMVD, there was no relationship between P wave duration and stroke mortality.
Conclusions
As an easily measurable factor P wave duration merits further studies with higher number of patients to evaluate its importance in the estimation of stroke risk in type 2 diabetic patients with PNMMVD.
doi:10.1186/1471-2261-14-168
PMCID: PMC4280689  PMID: 25425321
Type 2 diabetes; Cardiovascular disease; ECG; P wave duration; Stroke mortality
24.  Cigarette smoke increases cardiomyocyte ceramide accumulation and inhibits mitochondrial respiration 
Background
Cigarette smoking is a common and lethal worldwide habit, with considerable mortality stemming from its deleterious effects on heart function. While current theories posit altered blood lipids and fibrinogen metabolism as likely mediators, none have explored the role of the sphingolipid ceramide in exacerbating heart function with smoke exposure. Ceramide production is a consequence of cigarette smoke in the lung, and considering ceramide’s harmful effects on mitochondrial function, we sought to elucidate the role of ceramide in mediating smoke-induced altered heart mitochondrial respiration.
Methods
Lung cells (A549) were exposed to cigarette smoke extract (CSE) and heart cells (H9C2) were exposed to the lung-cell conditioned medium. Adult male mice were exposed sidestream cigarette smoke for 8 wk with dietary intervention and ceramide inhibition. Ceramides and heart cell or myocardial mitochondrial respiration were determined.
Results
Lung cell cultures revealed a robust response to cigarette smoke extract in both production and secretion of ceramides. Heart cells incubated with lung-cell conditioned medium revealed a pronounced inhibition of myocardial mitochondrial respiration, though this effect was mitigated with ceramide inhibition via myriocin. In vivo, heart ceramides increased roughly 600% in adult mice with long-term sidestream cigarette smoke exposure. This resulted in a significant ceramide-dependent reduction in left myocardial mitochondrial respiration, as heart mitochondria from the mice exposed to both smoke and myriocin injections respired normally.
Conclusions
These results suggest ceramide to be an important mediator of altered myocardial mitochondrial function with cigarette smoke exposure. Thus, anti-ceramide therapies might be considered in the future to protect heart mitochondrial function with smoke exposure.
doi:10.1186/1471-2261-14-165
PMCID: PMC4247675  PMID: 25416336
25.  Stable phase post-MI patients have elevated VEGF levels correlated with inflammation markers, but not with atherosclerotic burden 
Background
The role of vascular endothelial growth factor (VEGF) in patients in the stable phase after myocardial infarction (MI) has not yet been explored. Therefore, we compared the values of VEGF in post-MI patients with those obtained in healthy controls. Furthermore, we investigated whether the values of VEGF correlate to either inflammation markers or the atherosclerotic burden.
Methods
41 male patients (on average 44 years old) in the stable phase after MI (on average 20.5 months after MI) were recruited, while 25 healthy age-matched males served as controls. Plasma levels of VEGF and several markers of inflammation were measured by standard procedures. The atherosclerotic burden was determined by the angiographic severity of coronary atherosclerosis, endothelial dysfunction (measured by ultrasound measurement of the flow mediated dilation of the brachial artery), the intima-media thickness of the common carotid artery and the ankle-brachial pressure index.
Results
VEGF values were significantly elevated in post-MI patients compared to the controls (53.8 ± 42.7 pg/ml vs. 36.3 ± 8.9 pg/ml, p = 0.014). The elevated VEGF values significantly correlated to the (increased) values of the inflammatory molecules interleukin 6 and 8 (r = 0.37, p = 0.017; and r = 0.45, p = 0.003; respectively). In contrast, no correlation was found between VEGF and the parameters of the atherosclerotic burden, although FMD and IMT were significantly impaired in patients.
Conclusions
We found that plasma levels of VEGF are increased in the stable phase after MI and correlate with inflammation cytokines, but not with the atherosclerotic burden. Thus, this suggests that increased levels of VEGF are a part of ongoing inflammatory activity. Since VEGF in these patients stimulates neovascularization of inflamed plaques and induces their destabilization, the VEGF level can have an important negative prognostic value. Clearly, further studies are needed to clarify the role of VEGF as a prognostic marker.
doi:10.1186/1471-2261-14-166
PMCID: PMC4251840  PMID: 25417001
Vascular endothelial growth factor; Inflammation markers; Interleukin 6; Interleukin 8; Endothelial dysfunction; Myocardial infarction; Young adult patients

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