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1.  Determining the prevalence and predictors of sleep disordered breathing in patients with chronic heart failure: rationale and design of the SCHLA-HF registry 
Background
The objective of the SCHLA-HF registry is to investigate the prevalence of sleep-disordered breathing (SDB) in patients with chronic heart failure with reduced left ventricular systolic function (HF-REF) and to determine predictors of SDB in such patients.
Methods
Cardiologists in private practices and in hospitals in Germany are asked to document patients with HF-REF into the prospective SCHLA-HF registry if they meet predefined inclusion and exclusion criteria. Screening was started in October 2007 and enrolment was completed at the end of May 2013. After enrolment in the registry, patients are screened for SDB. SDB screening is mainly undertaken using the validated 2-channel ApneaLink™ device (nasal flow and pulse oximetry; ResMed Ltd., Sydney, Australia). Patients with a significant number of apneas and hypopneas per hour recording time (AHI ≥15/h) and/or clinical symptoms suspicious of SDB will be referred to a cooperating sleep clinic for an attended in-lab polysomnography with certified scoring where the definite diagnosis and, if applicable, the differentiation between obstructive and central sleep apnea will be made. Suggested treatment will be documented.
Discussion
Registries play an important role in facilitating advances in the understanding and management of cardiovascular disease. The SCHLA-HF registry will provide consistent data on a large group of patients with HF-REF that will help to answer questions on the prevalence, risk factors, gender differences and stability of SDB in these patients by cross-sectional analyses. Further insight into the development of SDB will be gained by extension of the registry to include longitudinal data.
doi:10.1186/1471-2261-14-46
PMCID: PMC3983862  PMID: 24716484
Registry; Prevalence; Heart failure; Sleep-disordered breathing; Obstructive sleep apnea; Central sleep apnea; Cheyne-Stokes respiration; Predictors
2.  Acute oxygenation changes on ischemic foot of a novel intermittent pneumatic compression device and of an existing sequential device in severe peripheral arterial disease 
Background
Intermittent pneumatic compression (IPC) improves haemodynamics in peripheral arterial disease (PAD), but its effects on foot perfusion were scarcely studied. In severe PAD patients we measured the foot oxygenation changes evoked by a novel intermittent IPC device (GP), haemodynamics and compliance to the treatment. Reference values were obtained by a sequential foot-calf device (SFC).
Methods
Twenty ischemic limbs (Ankle-Brachial Index = 0.5 ± 0.2) of 12 PAD patients (7 male, age: 74.5 ± 10.8 y) with an interval of 48 ± 2 hours received a 35 minute treatment in supine position with two IPC devices: i) a Gradient Pump (GP), which slowly inflates a single thigh special sleeve and ii) an SFC (ArtAssist®, ACI Medical, San Marcos, CA, USA), which rapidly inflates two foot-calf sleeves. Main outcome measure: changes of oxygenated haemoglobin at foot (HbO2foot) by continuous near-infrared spectroscopy recording and quantified as area-under-curve (AUC) for periods of 5 minutes. Other measures: haemodynamics by echo-colour Doppler (time average velocity (TAV) and blood flow (BF) in the popliteal artery and in the femoral vein), patient compliance by a properly developed form.
Results
All patients completed the treatment with GP, 9 with SFC. HbO2foot during the working phase, considered as average value of the 5 minutes periods, increased with GP (AUC 458 ± 600 to 1216 ± 280) and decreased with SFC (AUC 231 ± 946 to −1088 ± 346), significantly for most periods (P < 0.05). The GP treatment was associated to significant haemodynamic changes from baseline to end of the treatment (TAV = 10.2 ± 3.3 to 13.5 ± 5.5 cm/sec, P = 0.004; BF = 452.0 ± 187.2 to 607.9 ± 237.8 ml/sec, P = 0.0001), not observed with SFC (TAV = 11.2 ± 3.4 to 11.8 ± 4.3 cm/sec; BF = 513.8 ± 203.7 to 505.9 ± 166.5 ml/min, P = n.s.). GP obtained a higher score of patient compliance (P < 0.0001).
Conclusions
A novel IPC thigh device, unlike a traditional SFC device, increased foot oxygenation in severe PAD, together with favourable haemodynamic response and high compliance to the treatment under the present experimental conditions.
doi:10.1186/1471-2261-14-40
PMCID: PMC3978124  PMID: 24684834
Intermittent pneumatic compression devices; Near-infrared spectroscopy; Peripheral vascular disease; Perfusion; Critical limb ischemia
3.  Pattern of blood pressure distribution and prevalence of hypertension and prehypertension among adults in Northern Ethiopia: disclosing the hidden burden 
Background
Hypertension is the 3rd cause of death accounting for one in eight deaths worldwide. Hypertension was thought to be rare in Africa, but it is now recognized as one of the most important cerebrovascular diseases contributing to about 40% of these diseases in the continent.
The aims of this study were to describe the pattern of blood pressure distribution among adults, and determine prevalence of prehypertension and hypertension among adults in Northern Ethiopia.
Method
The study was done on a community-based sample of 1183 adults of 697 (58.8%) urban and 486 (41.1%) rural residents using statistical multistage sampling procedures. The study was based on the recent WHO and JNC-7 classification of blood pressure. Multi-item structured questionnaires were also developed to elicit additional information on the subjects.
Results
The overall prevalence of hypertension and prehypertension in the study population was 18.1% and 37.2%, respectively. The prevalence of hypertension positively correlated with body mass index and age in both urban and rural residents (P = 0.001). Sex and age adjusted mean systolic blood pressure (SBP) was statistically higher in urban than in rural population (P = 0.001).
Conclusion
Hypertension was found to have high prevalence in the study region. However, people’s awareness and control of hypertension was found to be very poor. Lack of a clear hypertension prevention guidelines and strategies nationwide can aggravate the impact of cardiovascular diseases.
doi:10.1186/1471-2261-14-33
PMCID: PMC3973867  PMID: 24592854
Blood pressure; Prehypertension; Hypertension
4.  Genetic and ElectroNic medIcal records to predict oUtcomeS in Heart Failure patients (GENIUS-HF) - design and rationale 
Background
Studies adopting electronic medical records and genomic information are becoming widespread. Through this new modality in research, it is possible to study how genetic variants influence susceptibility towards chronic conditions and can improve patient care.
Our aim is to develop a biobank with 2,000 heart failure patients treated in a tertiary cardiology hospital containing electronic medical records data and biologic samples for performing genome-wide association studies for validation and development of medical decision routines aimed at helping the clinical management of patients.
Methods/Design
Patients between 18 and 80 years old with heart failure diagnosis of different etiologies and left ventricular ejection fraction ≤ 50% in the past 2 years will be eligible for enrollment on the cohort. After consent, patients will be submitted to clinical baseline, echocardiography, cardiograph impedance and biochemical evaluation. Study data will be collected and managed using Research Electronic Data Capture tools. The follow up will take place every 6 months to assess cardiovascular outcomes (all-cause mortality, cardiovascular mortality, hospitalization for worsening heart failure and current medication use). Initial analytical strategy will focus on the establishment of the accuracy of electronic medical records extraction protocols for main predictor factors of morbidity and mortality in heart failure.
Discussion
Building a biobank with biologic samples and clinical data of 2,000 heart failure patients we will perform genome-wide association studies. By this way, we pretend to study how genetic variants influence susceptibility towards chronic conditions. Besides, it will be created a working group focused on the development and implementation of algorithms for validation and application of medical routines using the electronic medical records of the Heart Institute (InCor - HCFMUSP).
Trial registration
Current Controlled Trials NTC02043431.
doi:10.1186/1471-2261-14-32
PMCID: PMC3975857  PMID: 24592820
Biobank; Genome-wide association; Electronic data; Cardiovascular outcomes
5.  Comparative effects of recombinant human brain natriuretic peptide and dobutamine on acute decompensated heart failure patients with differsent blood BNP levels 
Background
Recombinant human B-type natriuretic peptide (rhBNP) has been indicated for the treatment of acute decompensated heart failure (ADHF). However, the therapeutic efficacy of intravenous rhBNP is not always satisfactory in patients with extremely high blood BNP levels. In this study, we evaluated the effects of rhBNP on patients with different BNP levels.
Methods
One hundred and five patients with ADHF whose left ventricular ejection fraction (LVEF) was <40%, were assigned to a high BNP group (BNP ≤ 3000 pg/mL) or an extra-high BNP group (BNP > 3000 pg/mL) , depending on their admission plasma BNP levels. Each group was then subdivided into rhBNP or dobutamine subgroups according to intravenous administration with either rhBNP or dobutamine for 24-72h. In the high BNP group, 58 patients were randomized to subgroup rhBNP (n = 28) and subgroup dobutamine (n = 30). In the extra-high BNP group, 47 patients were randomized to subgroup rhBNP (n = 24) and subgroup dobutamine (n = 23). The effects of rhBNP and dobutamine on patients in the high and extra-high BNP groups were compared.
Results
In the high BNP group, rhBNP was more efficient than dobutamine at improving NYHA classification (P < 0.05), decreasing plasma BNP levels (P < 0.05), increasing LVEF (P < 0.05), and reducing hospital length of stay (P < 0.05). However, rhBNP displayed no superior therapeutic efficacy to dobutamine in the extra-high BNP group. Adverse cardiovascular events in patients treated with rhBNP were similar to adverse events in patients treated with dobutamine in both the high and extra-high BNP groups.
Conclusions
rhBNP was more efficient than dobutamine at improving heart function in patients with ADHF when plasma BNP was ≤3000 pg/mL. However, rhBNP treatment showed no advantages over dobutamine when plasma BNP reached extremely high levels (>3000 pg/mL).
Trial registration
ClinicalTrials.gov Identifier: NCT01837849.
doi:10.1186/1471-2261-14-31
PMCID: PMC3975880  PMID: 24593826
Acute decompensated heart failure; Recombinant human brain natriuretic peptide; Dobutamine
6.  Routine angiography in survivors of out of hospital cardiac arrest with return of spontaneous circulation: a single site registry 
Background
Coronary revascularization in resuscitated out of hospital cardiac arrest (OOHCA) patients has been associated with improved survival.
Methods
This was a retrospective review of patients with OOHCA between 01/07/2007 and 31/03/2009 surviving to hospital admission. Cardiac risk factors, demographics, treatment times, electrocardiogram (ECG), angiographic findings and in-hospital outcomes were recorded.
Results
Of the 78 patients, 63 underwent coronary angiography. Traditional cardiac risk factors were common in this group. Chest pain occurred in 33.3% pre-arrest, 59.0% were initially treated at a peripheral hospital, 83.3% had documented ventricular tachycardia or ventricular fibrillation, 55.1% had specific ECG changes, 65.4% had acute myocardial infarction (AMI) as the cause of OOHCA and the majority had multi-vessel disease. ST elevation strongly predicted AMI. The in-hospital survival was 67.9% with neurological deficit in 13.2% of survivors. The group of patients who had an angiogram were more likely to have AMI as a cause of cardiac arrest (71.4% vs 40.0%, p = 0.01) and more likely to have survived to discharge (74.6% vs 40.0%, p < 0.01). Poor outcome was associated with older age, cardiogenic shock, longer transfer times, diabetes, renal impairment and a long duration to return of spontaneous circulation.
Conclusions
Acute myocardial infarction was the commonest cause of OOHCA and a high rate of survival to discharge was seen with a strategy of routine angiography and revascularization.
doi:10.1186/1471-2261-14-30
PMCID: PMC3944915  PMID: 24580723
Cardiac arrest; Myocardial infarction; OOHCA; Angiography; Therapeutic hypothermia
7.  Manipulation of valve composition to elucidate the role of collagen in aortic valve calcification 
Background
Extracellular matrix (ECM) disarray is found in calcific aortic valvular disease (CAVD), yet much remains to be learned about the role of individual ECM components in valvular interstitial cell (VIC) function and dysfunction. Previous clinical analyses have shown that calcification is associated with decreased collagen content, while previous in vitro work has suggested that the presence of collagen attenuates the responsiveness of VICs to pro-calcific stimuli. The current study uses whole leaflet cultures to examine the contributions of endogenous collagen in regulating the phenotype and calcification of VICs.
Methods
A “top-down” approach was used to characterize changes in VIC phenotype in response to collagen alterations in the native 3D environment. Collagen-deficient leaflets were created via enzymatic treatment and cultured statically for six days in vitro. After culture, leaflets were harvested for analysis of DNA, proliferation, apoptosis, ECM composition, calcification, and gene/protein expression.
Results
In general, disruption of collagen was associated with increased expression of disease markers by VICs in whole organ leaflet culture. Compared to intact control leaflets, collagen-deficient leaflets demonstrated increased VIC proliferation and apoptosis, increased expression of disease-related markers such as alpha-smooth muscle actin, alkaline phosphatase, and osteocalcin, and an increase in calcification as evidenced by positive von Kossa staining.
Conclusions
These results indicate that disruption of the endogenous collagen structure in aortic valves is sufficient to stimulate pathological consequences in valve leaflet cultures, thereby highlighting the importance of collagen and the valve extracellular matrix in general in maintaining homeostasis of the valve phenotype.
doi:10.1186/1471-2261-14-29
PMCID: PMC3946110  PMID: 24581344
Valvular interstitial cells; Calcific aortic valve disease; Collagen; Extracellular matrix
8.  Rheumatic heart disease in Uganda: the association between MHC class II HLA DR alleles and disease: a case control study 
Background
Rheumatic heart disease (RHD), the only long term consequence of acute rheumatic fever, remains a leading cause of morbidity and mortality among young adults in Uganda. An inherited susceptibility to acute rheumatic fever centers around the major histocompatibility class II human leucocyte antigens. However, there is paucity of data from sub-Saharan Africa. This study compares the frequency of HLA class II DR alleles between RHD cases and normal controls in Uganda.
Methods
One hundred ninety-nine participants including 96 established RHD cases aged 5–60 years and 103 age and sex matched normal controls were recruited for participation. DNA was manually extracted from buffy coat samples and HLA analysis was performed. HLA-DR allelic frequency comparison between cases and controls were estimated using conditional logistic regression with 95% confidence intervals. P -values were corrected for multiple hypothesis testing.
Results
199 participants (103 female, 51.8%) completed the study. The mean (SD) age in years for cases and controls were 29.6 (10.2) and 29(18), respectively. After conditional logistic regression and multiple hypothesis testing, HLA-DR1was associated with a decreased risk of RHD (OR = 0.42, CI 0.21-085, P = 0.01, Corrected P value (PC) = 0.09,) while HLA-DR11 was associated with increased risk of RHD (OR = 3.31, CI 1.57-6.97, P = <0.001, Pc < 0.001). No other significant associations were found.
Conclusion
In this first study of HLA genetic susceptibility to RHD in Uganda, HLA- DR1 was more common in normal controls while HLA- DR11 was more common among RHD cases suggesting a disease susceptibility association. In future studies, high resolution HLA analysis and genome wide studies should be carried out to confirm this pattern.
doi:10.1186/1471-2261-14-28
PMCID: PMC3943278  PMID: 24581333
Rheumatic heart disease; HLA-DR1; HLA-DRB11; MHC- major histocompatibility complex
9.  Validation of continuous clinical indices of cardiometabolic risk in a cohort of Australian adults 
Background
Indicators of cardiometabolic risk typically include non-clinical factors (e.g., smoking). While the incorporation of non-clinical factors can improve absolute risk prediction, it is impossible to study the contribution of non-clinical factors when they are both predictors and part of the outcome measure. Metabolic syndrome, incorporating only clinical measures, seems a solution yet provides no information on risk severity. The aims of this study were: 1) to construct two continuous clinical indices of cardiometabolic risk (cCICRs), and assess their accuracy in predicting 10-year incident cardiovascular disease and/or type 2 diabetes; and 2) to compare the predictive accuracies of these cCICRs with existing risk indicators that incorporate non-clinical factors (Framingham Risk Scores).
Methods
Data from a population-based biomedical cohort (n = 4056) were used to construct two cCICRs from waist circumference, mean arteriole pressure, fasting glucose, triglycerides and high density lipoprotein: 1) the mean of standardised risk factors (cCICR-Z); and 2) the weighted mean of the two first principal components from principal component analysis (cCICR-PCA). The predictive accuracies of the two cCICRs and the Framingham Risk Scores were assessed and compared using ROC curves.
Results
Both cCICRs demonstrated moderate accuracy (AUCs 0.72 – 0.76) in predicting incident cardiovascular disease and/or type 2 diabetes, among men and women. There were no significant differences between the predictive accuracies of the cCICRs and the Framingham Risk Scores.
Conclusions
cCICRs may be useful in research investigating associations between non-clinical factors and health by providing suitable alternatives to current risk indicators which include non-clinical factors.
doi:10.1186/1471-2261-14-27
PMCID: PMC3976083  PMID: 24571233
Cardiometabolic; Cardiovascular disease; Type 2 diabetes; Risk scores; ROC; AUC; Validation
10.  Association between serum uric acid levels and cardiovascular disease in middle-aged and elderly Chinese individuals 
Background
A link between uric acid (UA) levels and cardiovascular diseases has been previously reported. However, its importance as a risk factor is still controversial. This study sought to determine whether elevated serum uric acid levels are associated with cardiovascular disease (CVD) in middle-aged and elderly Chinese individuals.
Methods
We conducted a population-based cross-sectional study in Shanghai, with a total of 8510 participants aged ≥40 years. The CVD included diagnosed coronary heart disease (CHD) and stroke. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans.
Results
Uric acid levels were positively associated with BMI, waist circumference, triglycerides, systolic blood pressure, diastolic blood pressure, glycohemoglobin, fasting plasma glucose, postprandial 2-hour plasma glucose (all P < 0.05), and negatively associated with HDL-cholesterol (P < 0.001). The prevalence of CVD significantly increased with increasing quartiles of UA in those without MetS group (p trend < 0.001), but not necessarily increased in those with MetS. After adjustment for metabolic syndrome and other cardiovascular risk factors, multivariate logistic regression analysis showed that odds ratios (OR) for CHD, stroke, and CVD in those in the fourth quartiles were 2.34 (95% confidence interval [CI] 1.73 to 3.45), 2.18 (95% CI 1.86 to 3.28), and 2.16 (95% CI 1.80 to 3.29), respectively, compared with those in the first quartile of UA.
Conclusions
Elevated serum uric acid level was associated with CVD, independent of conventional cardiovascular disease risk factors and metabolic syndrome.
doi:10.1186/1471-2261-14-26
PMCID: PMC3974065  PMID: 24568132
Uric acid; Cardiovascular disease; Metabolic syndrome; Stroke; Coronary heart disease
11.  C-reactive protein levels in patients at cardiovascular risk: EURIKA study 
Background
Elevated C-reactive protein (CRP) levels are associated with high cardiovascular risk, and might identify patients who could benefit from more carefully adapted risk factor management. We have assessed the prevalence of elevated CRP levels in patients with one or more traditional cardiovascular risk factors.
Methods
Data were analysed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov Identifier: NCT00882336), which included patients (aged ≥50 years) from 12 European countries with at least one traditional cardiovascular risk factor but no history of cardiovascular disease. Analysis was also carried out on the subset of patients without diabetes mellitus who were not receiving statin therapy.
Results
In the overall population, CRP levels were positively correlated with body mass index and glycated haemoglobin levels, and were negatively correlated with high-density lipoprotein cholesterol levels. CRP levels were also higher in women, those at higher traditionally estimated cardiovascular risk and those with greater numbers of metabolic syndrome markers. Among patients without diabetes mellitus who were not receiving statin therapy, approximately 30% had CRP levels ≥3 mg/L, and approximately 50% had CRP levels ≥2 mg/L, including those at intermediate levels of traditionally estimated cardiovascular risk.
Conclusions
CRP levels are elevated in a large proportion of patients with at least one cardiovascular risk factor, without diabetes mellitus who are not receiving statin therapy, suggesting a higher level of cardiovascular risk than predicted according to conventional risk estimation systems.
Trial registration
ClinicalTrials.gov Identifier: NCT00882336
doi:10.1186/1471-2261-14-25
PMCID: PMC3943833  PMID: 24564178
C-reactive protein; Cardiovascular disease; Epidemiology; Risk factors/global assessment
12.  Worsened arterial stiffness in high-risk cardiovascular patients with high habitual carbohydrate intake: a cross-sectional vascular function study 
Background
Previous studies suggested that high dietary carbohydrate intake is associated with increased cardiovascular risk through raised triglyceride and decreased high-density lipoprotein-cholesterol levels. However, the relation between carbohydrate intake and arterial stiffness has not been established. The purpose of this study was to examine this relation among high-risk cardiovascular patients.
Methods
We studied the relation between dietary macronutrient intake and arterial stiffness in 364 patients with documented cardiovascular diseases or risk equivalent (coronary artery diseases 62%, ischemic stroke 13%, diabetes mellitus 55%) and in 93 age-and-sex matched control subjects. Dietary macronutrient intake was assessed using a validated food-frequency questionnaire (FFQ) for Chinese. Heart-ankle pulse wave velocity (PWV) was measured non-invasively with a Vascular Profiling System (VP2000, Colin Corp. USA). A dietary pattern with ≥60% total energy intake derived from carbohydrates was defined as a high-carbohydrate diet according to the Dietary Reference Intakes (DRI) for Chinese.
Results
Subjects who consumed a high-carbohydrate diet had significantly higher mean PWV than those who did not consume a high-carbohydrate diet (P = 0.039). After adjustment for potential confounders, high-carbohydrate diet was associated with significantly increased PWV [B = 73.50 (10.81 to 136.19), P = 0.022]. However, there was no significant association between high-carbohydrate diet and PWV in controls (P = 0.634).
Conclusions
High-carbohydrate diet is associated with increased arterial stiffness in patients with established cardiovascular disease or risk equivalent.
doi:10.1186/1471-2261-14-24
PMCID: PMC3948104  PMID: 24559092
Macronutrient; Carbohydrate intake; Arterial stiffness; Pulse wave velocity; Secondary prevention
13.  Differential associations of central and brachial blood pressure with carotid atherosclerosis and microvascular complications in patients with type 2 diabetes 
Background
We examined the relationship between central blood pressure (BP), brachial BP with carotid atherosclerosis and microvascular complications in type 2 diabetes mellitus (T2DM).
Methods
We recruited 201 patients who were evaluated for central BP, brachial BP, carotid ultrasonography, brachial-ankle pulse wave velocity (baPWV), ankle-brachial index (ABI) and microvascular complications. Central BP were calculated using a radial automated tonometric system.
Results
Agreement between central BP and brachial BP was very strong (concordance correlation coefficient between central and brachial SBP = 0.889, between central and brachial PP = 0.816). Central pulse pressure (PP) was correlated with mean carotid intima-media thickness (CIMT), baPWV and ABI, whereas brachial PP was borderline significantly correlated with CIMT. The prevalence of nephropathy(DN) and retinopathy(DR) according to the brachial PP tertiles increased, the prevalences of microvascular complications were not different across central PP tertiles. In multivariate analysis, the relative risks (RRs) for the presence of DR were 1.2 and 4.6 for the brachial PP tertiles 2 and 3 when compared with the first tertile. Also, the RRs for the presence of DN were 1.02 and 3 for the brachial PP tertiles 2 and 3 when compared with the first tertile.
Conclusions
Agreement of central BP and brachial BP was very strong. Nonetheless, this study showed that higher brachial PP levels are associated with increased probability for the presence of microvascular complications such as DR/DN. However, there are no associations with central SBP and central PP with microvascular complications. Central BP levels than brachial BP are correlated with surrogate marker of macrovascular complications.
doi:10.1186/1471-2261-14-23
PMCID: PMC3936908  PMID: 24555866
Central blood pressure; Brachial blood pressure; Microvascular complications; Carotid atherosclerosis; Type 2 diabetes
14.  Phenotype, origin and estimated prevalence of a common long QT syndrome mutation: a clinical, genealogical and molecular genetics study including Swedish R518X/KCNQ1 families 
Background
The R518X/KCNQ1 mutation is a common cause of autosomal recessive (Jervell and Lange Nielsen Syndrome- JLNS) and autosomal dominant long QT syndrome (LQTS) worldwide. In Sweden p.R518X accounts for the majority of JLNS cases and is the second most common cause of LQTS. Here we investigate the clinical phenotype and origin of Swedish carriers of the p.R518X mutation.
Methods
The study included 19 Swedish p.R518X index families, ascertained by molecular genetics methods (101 mutation-carriers, whereof 15 JLNS cases and 86 LQTS cases). In all families analyses included assessment of clinical data (symptoms, medications and manually measured electrocardiograms), genealogy (census records), haplotype (microsatellite markers) as well as assessment of mutation age and associated prevalence (ESTIAGE and DMLE computer software).
Results
Clinical phenotype ranged from expectedly severe in JLNS to surprisingly benign in LQTS (QTc 576 ± 61 ms vs. 462 ± 34 ms, cumulative incidence of (aborted) cardiac arrest 47% vs. 1%, annual non-medicated incidence rate (aborted) cardiac arrest 4% vs. 0.04%).
A common northern origin was found for 1701/1929 ancestors born 1650-1950. Historical geographical clustering in the coastal area of the Pite River valley was shown. A shared haplotype spanning the KCNQ1 gene was seen in 17/19 families. Mutation age was estimated to 28 generations (95% CI 19;41). A high prevalence of Swedish p.R518X heterozygotes was suggested (~1:2000-4000).
Conclusions
R518X/KCNQ1 occurs as a common founder mutation in Sweden and is associated with an unexpectedly benign phenotype in heterozygous carriers.
doi:10.1186/1471-2261-14-22
PMCID: PMC3942207  PMID: 24552659
Long QT Syndrome; Genotype-phenotype correlations; Clinical phenotype; Founder mutation; Mutation age; Prevalence estimate
15.  Duration of dual antiplatelet therapy following percutaneous coronary intervention on re-hospitalization for acute coronary syndrome 
Background
The optimal duration of dual antiplatelet therapy after percutaneous coronary intervention (PCI) remains uncertain. The objective of this study was to examine the association between duration of dual antiplatelet therapy and re-hospitalization for acute coronary syndrome (ACS) in ACS patients who underwent PCI.
Methods
We identified 975 newly diagnosed ACS patients who underwent PCI between July, 2007 and June, 2009, at a medical center in Taiwan. Cox proportional hazard models were used to examine the association between duration of dual antiplatelet therapy (9 months, 12 months and 15 months) and risks of re-hospitalization for ACS.
Results
At a mean follow-up of 2.3 years, we found that use of clopidogrel for ≥ 12 months was associated with a decreased risk of re-hospitalization for ACS (adjusted HR 0.59, 95% CI 0.36-0.95; p = 0.03). However, use of clopidogrel for ≥ 15 months was not associated with a decreased risk of re-hospitalization for ACS (adjusted HR 0.57, 95% CI 0.29-1.13; p = 0.11). Similar results were found in patients who implanted drug-eluting stents (DES), for whom at least 12 months of clopidogrel therapy is especially critical.
Conclusion
The benefit of ≥ 12 months of clopidogrel use in reducing the risk of re-hospitalization for ACS was significant among ACS patients who underwent PCI and was especially critical for those who implanted DES.
doi:10.1186/1471-2261-14-21
PMCID: PMC3974105  PMID: 24533683
Acute coronary syndrome (ACS); Percutaneous coronary intervention (PCI); Clopidogrel; Dual antiplatelet therapy; Drug eluting stent (DES)
16.  Obstacles and alternative options for cardiac rehabilitation in Nanjing, China: an exploratory study 
Background
Coronary heart disease (CHD) is a major cause of morbidity and mortality, and cardiac rehabilitation (CR) is still not well developed in mainland China. The objective of this study is to investigate the barriers associated with those seeking cardiac rehabilitation (CR) and to explore appropriate secondary prevention modalities tailored to the needs of Chinese patients with coronary heart disease (CHD).
Methods
A consecutive series of eligible patients was recruited from the cardiac department of a teaching hospital in Nanjing, located in southeast China. Structured face-to-face interviews were conducted with 328 patients prior to hospital discharge. Patient preferences for seeking an outpatient CR program or an alternative outpatient self-choice, minimal-cost educational program were evaluated. Socio-demographic characteristics and clinical data were assessed. Additionally, patients were asked to provide the reasons affecting their choice.
Results
Overall, only 14.3% patients preferred the standard CR program. Factors associated with non-participating were female gender (odds ratios [ORs], 6.05, 95% CI, 1.30-28.19), older age (ORs, 1.11, 95% CI, 1.04-1.19, per year), less education (ORs, 8.13, 95% CI, 2.83-23.38), low income (ORs, 3.26, 95% CI, 1.24-8.54), and having either basic medical care or a lack of health insurance (ORs, 10.01, 95% CI, 3.90-25.68). The most common reason for refusing to participate in CR was that patients could not afford it. Of the remaining patients, 65.8% patients chose self-choice educational programs, especially for female (ORs, 5.84, 95% CI, 2.67-12.79), older (ORs, 1.06, 95% CI, 1.02-1.11, per year), and low income (ORs, 2.14, 95% CI, 1.12-4.10) patients. The main reasons for their preferences were their desires for more information about disease and risk factors, the low cost, feasibility, and saving time.
Conclusions
Multiple barriers, which may occur at the patient, health system, and societal levels, have prevented eligible patients from participating in CR programs. Self-choice educational programs, an alternative model incorporating more information, would strongly meet the needs of most patients. A feasible delivery format for secondary prevention should be provided for all CHD patients.
doi:10.1186/1471-2261-14-20
PMCID: PMC3930547  PMID: 24533661
Coronary heart disease; Secondary prevention; Cardiac rehabilitation; Health education
17.  Serum TGF-β1 and SMAD3 levels are closely associated with coronary artery disease 
Background
Coronary artery disease (CAD) is one of the most common diseases leading to mortality and morbidity worldwide. There is considerable debate on whether serum transforming growth factor β1 (TGF-β1) levels are associated with long-term major adverse cardiovascular events in patients with CAD, and to date, no study has specifically addressed levels in patients with different degrees of CAD severity.
Methods
Serum TGF-β1 and mothers against decapentaplegic homolog 3 (SMAD3) concentrations were evaluated in 279 patients with CAD and 268 controls without CAD. The clinical and biochemical characteristics of all subjects were also determined and analyzed.
Results
TGF-β1 and SMAD3 concentrations in CAD patients were significantly higher than those in the controls. The serum TGF-β1 level in acute myocardial infarction (AMI) was significantly higher than that in both stable angina pectoris (SAP) and unstable angina pectoris (UAP) (p < 0.05), while there was no marked difference between levels in SAP and UAP (p > 0.05). SMAD3 levels showed no obvious difference among AMI, SAP, and UAP. TGF-β1 and SMAD3 are potential biomarkers for CAD, and may be more accurate than Lpa, ApoA1, uric acid, BUN, or triglycerides (TG).
Conclusions
Serum TGF-β1 and SMAD3 levels are closely associated with CAD, and may become useful biomarkers for diagnosis and risk stratification.
doi:10.1186/1471-2261-14-18
PMCID: PMC3936998  PMID: 24533640
Coronary artery disease; TGF-β1; SMAD3 protein; Human; Biomarkers
18.  Impact of renal insufficiency on mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention 
Background
Chronic kidney disease is associated with increased risk of mortality. We examined the impact of moderate and severe renal insufficiency (RI) on short- and long-term mortality among unselected patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).
Methods
From January 1, 2002 to December 31, 2010 all patients with STEMI treated with primary PCI were identified. The hazard ratio (HR) for death was estimated using a Cox regression model, controlling for potential confounders. RI was defined as creatinine clearance (CrCl) < 60 mL/min (moderate RI: CrCl ≤30 < 60 mL/min and severe RI: CrCl < 30 mL/min).
Results
The study cohort consisted of 4,116 patients of whom 898 (21.8%) had RI and 3,218 (78.2%) had a CrCl ≥ 60 mL/min. Compared to patients without RI, patients with RI were older, more often female and more likely to have diabetes mellitus, hypertension and to present with a higher Killip class.
Among patients with a preserved kidney function and patients with RI, 30-day all-cause mortality was 3.5% vs. 20.9% (log-rank p < 0.001); 1-year all-cause mortality was 5.7% vs. 29.4% (log-rank p < 0.001); 5-year all-cause mortality was 13.4% vs. 47.4% (log-rank p < 0.001). Moderate and severe RI were associated with higher 1-year mortality compared to patients with a preserved renal function (CrCl ≤30 < 60 mL/min: adjusted HR 2.71 [95% CI 2.09-3.51], p < 0.001), and (CrCl < 30 mL/min: adjusted HR 7.09 [4.82-10.44], p < 0.001).
Conclusion
In unselected STEMI patients treated with primary PCI, moderate and severe RI were associated with increased risk of mortality.
doi:10.1186/1471-2261-14-15
PMCID: PMC3922030  PMID: 24506974
ST-segment elevation myocardial infarction; Renal insufficiency; Mortality
19.  Aspirin use and knowledge in the community: a population- and health facility based survey for measuring local health system performance 
Background
Little is known about the relationship between cardiovascular risk, disease and actual use of aspirin in the community.
Methods
The Measuring Disparities in Chronic Conditions (MDCC) study is a community and health facility-based survey designed to track disparities in the delivery of health interventions for common chronic diseases. MDCC includes a survey instrument designed to collect detailed information about aspirin use. In King County, WA between 2011 and 2012, we surveyed 4633 white, African American, or Hispanic adults (45% home address-based sample, 55% health facility sample). We examined self-reported counseling on, frequency of use and risks of aspirin for all respondents. For a subgroup free of CAD or cerebral infarction that underwent physical examination, we measured 10-year coronary heart disease risk and blood salicylate concentration.
Results
Two in five respondents reported using aspirin routinely while one in five with a history of CAD or cerebral infarction and without contraindication did not report routine use of aspirin. Women with these conditions used less aspirin than men (65.0% vs. 76.5%) and reported more health problems that would make aspirin unsafe (29.4% vs. 21.2%). In a subgroup undergoing phlebotomy a third of respondents with low cardiovascular risk used aspirin routinely and only 4.6% of all aspirin users had no detectable salicylate in their blood.
Conclusions
In this large urban county where health care delivery should be of high quality, there is insufficient aspirin use among those with high cardiovascular risk or disease and routine aspirin use by many at low risk. Further efforts are needed to promote shared-decision making between patients and clinicians as well as inform the public about appropriate use of routine aspirin to reduce the burden of atherosclerotic vascular disease.
doi:10.1186/1471-2261-14-16
PMCID: PMC3922250  PMID: 24507089
Aspirin; Prevention; Coronary disease
20.  Impact of self-management interventions on stable angina symptoms and health-related quality of life: a meta-analysis 
Background
Chronic stable angina (CSA) has a major negative impact on health-related quality of life (HRQL) including poor general health status, psychological distress, and inability to self-manage.
Methods
We used meta-analysis to assess the effectiveness of self-management interventions for improving stable angina symptoms, HRQL and psychological well-being. Nine trials, involving 1,282 participants in total, were included. We used standard inverse-variance random-effects meta-analysis to combine the trials. Heterogeneity between trials was evaluated using chi-square tests for the tau-squared statistic and quantified using the I2 statistic.
Results
There was significant improvement in the frequency of angina symptoms (Seattle Angina Questionnaire [SAQ], symptom diary) across trials, standardized mean difference (SMD): 0.30 (95% Confidence interval [CI] 0.14, 0.47), as well as reduction in the use of sublingual (SL) nitrates, SMD: -0.49 (95% CI -0.77, -0.20). Significant improvements for physical limitation (SAQ), SMD: 0.38 (95% CI 0.20, 0.55) and depression scores (Hospital Anxiety and Depression Scale), SMD: -1.38 (95% CI -2.46, -0.30) were also found. The impact of SM on anxiety was uncertain due to statistical heterogeneity across trials for this outcome, I2 = 98%. SM did not improve other HRQL dimensions including angina stability, disease perception, and treatment satisfaction.
Conclusions
SM interventions significantly improve angina frequency and physical limitation; they also decrease the use of SL nitrates and improve depression in some cases. Further work is needed to make definitive conclusions about the impact of SM on cardiac-specific anxiety.
doi:10.1186/1471-2261-14-14
PMCID: PMC3945741  PMID: 24483947
Stable angina; Self-management; Health-related quality of life
21.  Self-reported recall and daily diary-recorded measures of weight monitoring adherence: associations with heart failure-related hospitalization 
Background
Weight monitoring is an important element of HF self-care, yet the most clinically meaningful way to evaluate weight monitoring adherence is uncertain. We conducted this study to evaluate the association of (1) self-reported recall and (2) daily diary-recorded weight monitoring adherence with heart failure-related (HF-related) hospitalization.
Methods
We conducted a prospective cohort study among 216 patients within a randomized trial of HF self-care training. All patients had an initial self-care training session followed by 15 calls (median) to reinforce educational material; patients were also given digital scales, instructed to weigh daily, record weights in a diary, and mail diaries back monthly. Weight monitoring adherence was assessed with a self-reported recall question administered at 12 months and dichotomized into at least daily versus less frequent weighing. Diary-recorded weight monitoring was evaluated over 12 months and dichotomized into ≥80% and <80% adherence. HF-related hospitalizations were ascertained through patient report and confirmed through record review.
Results
Over 12 months in 216 patients, we identified 50 HF-related hospitalizations. Patients self-reporting daily or more frequent weight monitoring had an incidence rate ratio of 1.34 (95% CI 0.24-7.32) for HF-related hospitalizations compared to those reporting less frequent weight monitoring. Patients who completed ≥80% of weight diaries had an IRR of 0.37 (95% CI 0.18-0.75) for HF-related hospitalizations compared to patients who completed <80% of weight diaries.
Conclusions
Self-reported recall of weight monitoring adherence was not associated with fewer HF hospitalizations. In contrast, diary-recorded adherence ≥80% of days was associated with fewer HF-related hospitalizations. Incorporating diary-based measures of weight monitoring adherence into HF self-care training programs may help to identify patients at risk for HF-related hospitalizations.
doi:10.1186/1471-2261-14-12
PMCID: PMC3912256  PMID: 24483776
Heart failure; Patient compliance; Monitoring; Physiologic
22.  Atrial fibrillation alters the microRNA expression profiles of the left atria of patients with mitral stenosis 
Background
Structural changes of the left and right atria associated with atrial fibrillation (AF) in mitral stenosis (MS) patients are well known, and alterations in microRNA (miRNA) expression profiles of the right atria have also been investigated. However, miRNA changes in the left atria still require delineation. This study evaluated alterations in miRNA expression profiles of left atrial tissues from MS patients with AF relative to those with normal sinus rhythm (NSR).
Methods
Sample tissues from left atrial appendages were obtained from 12 MS patients (6 with AF) during mitral valve replacement surgery. From these tissues, miRNA expression profiles were created and analyzed using a human miRNA microarray. Results were validated via reverse-transcription and quantitative PCR for 5 selected miRNAs. Potential miRNA targets were predicted and their functions and potential pathways analyzed via the miRFocus database.
Results
The expression levels of 22 miRNAs differed between the AF and NSR groups. Relative to NSR patients, in those with AF the expression levels of 45% (10/22) of these miRNAs were significantly higher, while those of the balance (55%, 12/22) were significantly lower. Potential miRNA targets and molecular pathways were identified.
Conclusions
AF alters the miRNA expression profiles of the left atria of MS patients. These findings may be useful for the biological understanding of AF in MS patients.
doi:10.1186/1471-2261-14-10
PMCID: PMC3909014  PMID: 24461008
Atrial fibrillation; Microrna; Mitral stenosis; Microarray; Mirfocus
23.  Continuing decrease in coronary heart disease mortality in Sweden 
Background
Deaths from coronary heart disease (CHD) have been decreasing in most Western countries over the last few decades. In contrast, a flattening of the decrease in mortality has been recently reported among younger age groups in some countries. We aimed to determine whether the decrease in CHD mortality is flattening among Swedish young adults.
Methods
We examined trends in CHD mortality in Sweden between 1987 and 2009 among persons aged 35 to 84 years using CHD mortality data from the Swedish National Register on Cause of Death. Annual percent changes in rates were examined using Joinpoint software.
Results
Overall, CHD mortality rates decreased by 67.4% in men and 65.1% in women. Among men aged 35–54 years, there was a modest early attenuation from a marked initial decrease. In the oldest women aged 75–84 years, an attenuation in the mortality decrease was observed from 1989 to 1992, followed by a decrease, as in all other age groups.
Conclusions
In Sweden, coronary heart disease deaths are still falling. We were unable to confirm a flattening of the decline in young people. Death rates continue to decline in men and women across all age groups, albeit at a slower pace in younger men since 1991. Continued careful monitoring of CHD mortality trends in Sweden is required, particularly among young adults.
doi:10.1186/1471-2261-14-9
PMCID: PMC3930358  PMID: 24447603
Myocardial ischemia; Mortality; Risk factors; Coronary heart disease
24.  A Cross-sectional study of stand-alone Percutaneous Coronary Intervention in a Nigerian Cardiac Catheterization Laboratory 
Background
There is a paucity of diagnostic and therapeutic facilities in Nigeria to confirm coronary artery disease and offer appropriate interventional therapy. There is now a private cardiac catheterization laboratory in Lagos but as there are no sustained Open Heart Surgery programmes, percutaneous coronary interventions are currently being performed without surgical backup. This study was designed to assess results of stand-alone percutaneous coronary intervention (PCI) as currently practiced in Lagos, Nigeria.
Methods
This cross-sectional study was conducted between July 2009 and July 2012. The study included all patients that underwent PCI in Lagos. Data was extracted from a prospectively maintained database.
Results
Coronary artery disease was confirmed in 80 (52.6%) of 152 Nigerians referred with a diagnosis of Ischaemic Heart Disease. There were 53 males (66.2%) and 27 females (33.8%). The average age was 60.3 +/−9.6 years and average euroscore was 4.5 +/−3.1. Of the 80 patients, 77 (96.3%) had significant stenoses and were candidates for revascularization. Distribution of significant stenoses was one in 32 patients (41.5%), two in 11 patients (14.3%), three in 19 patients (24.7%), four in 13 patients (16.9%) and five in 2 patients (2.6%). PCI was performed in 48 (62.3%) of the patients eligible for revascularization as the coronary anatomy in the remaining patients was not suitable for PCI. The indication for PCI was for myocardial infarction or unstable angina in 39 patients (81.2%). PCI was performed with PTCA plus stenting in 41 patients (85.4%) and with PTCA alone in 7 patients (14.6%) with good angiographic results. Overall 29 of the 48 patients (60.4%) had complete revascularization of significant stenoses. Complications of PCI were bleeding that required blood transfusion in 1 patient (2.1%), minor femoral haematomas in 2 patients (4.2%), and a major adverse clinical event in 1 patient (2.1%).
Conclusion
A stand-alone PCI programme has been developed in Lagos, Nigeria. Both elective and urgent PCIs have been performed with no mortalities and a low complication rate. Increased volumes will however accrue and complete revascularization rates would be improved with the establishment of Open Heart Surgery programmes to provide CABG as back-up for PCI and alternate therapy for more complex lesions.
doi:10.1186/1471-2261-14-8
PMCID: PMC3897932  PMID: 24433419
25.  Lipid, adipokine and ghrelin levels in myocardial infarction patients with insulin resistance 
Background
Insulin resistance (IR) is a risk factor for ischaemic heart disease and myocardial infarction (MI). IR often manifests in MI and is regarded as an independent predictor of in-hospital mortality, which can provide early risk stratification for recurrent acute coronary events.
Methods
The study enrolled 200 patients (130 males and 70 females aged 61.4 ± 1.12 years) diagnosed with ST elevation MI. At days 1 and 12 from the MI onset, IR levels and lipid profiles, as well as serum glucose, insulin, adipokine and ghrelin levels, were measured.
Results
Free fatty acid (FFA) levels had the most pronounced changes: IR patients had a 9-fold increase in FFA levels at day 1, and patients without IR had a 6-fold increase. Leptin levels at days 1 and 12, in IR patients were, on average, 1.5- and 2-fold higher compared to the controls and patients with no IR (р < 0.05). Leptin levels in IR patients were increased throughout the entire hospital stay. Resistin levels in IR patients were, on average, 1.4-fold higher throughout the entire hospital stay, while in non-IR patients, resistin levels were similar to the controls. Adiponectin levels in IR patients were decreased compared to the controls, while in patients with IR, they were similar to the controls. Both IR and non-IR MI patients had 3-fold and 3.7-fold lower ghrelin levels at day 1, respectively, compared to the controls. The correlation analysis showed a negative correlation between ghrelin and FFA (r = −0.48 р = 0.007), ghrelin and leptin (r = −0.4 р = 0.003), ghrelin and insulin (r = −0.54 р = 0.002), and ghrelin and glucose (r = −0.31 р = 0.002) in MI patients.
Conclusion
Dyslipidaemia, along with insulinaemia and glycaemia, is one of the most significant IR risk factors in the acute and early recovery phases of MI. Dyslipidaemia is characterised by a high FFA level; an imbalance of leptin, resistin, and adiponectin; and a deficiency of ghrelin in the acute and early recovery periods of MI. FFA and ghrelin can be used as promising molecular markers to stratify the risk of recurrent acute coronary events and diabetes mellitus in MI patients.
doi:10.1186/1471-2261-14-7
PMCID: PMC3898041  PMID: 24433403
Insulin resistance; Myocardial infarction; Free fatty acids; Adipokines; Ghrelin

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