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1.  Abdominal aortic calcification quantified by the Morphological Atherosclerotic Calcification Distribution (MACD) index is associated with features of the metabolic syndrome 
Background
Abdominal aortic calcifications (AAC) predict cardiovascular mortality. A new scoring model for AAC, the Morphological Atherosclerotic Calcification Distribution (MACD) index may contribute with additional information to the commonly used Aortic Calcification Severity (AC24) score, when predicting death from cardiovascular disease (CVD). In this study we investigated associations of MACD and AC24 with traditional metabolic-syndrome associated risk factors at baseline and after 8.3 years follow-up, to identify biological parameters that may account for the differential performance of these indices.
Methods
Three hundred and eight healthy women aged 48 to 76 years, were followed for 8.3 ± 0.3 years. AAC was quantified using lumbar radiographs. Baseline data included age, weight, blood pressure, blood lipids, and glucose levels. Pearson correlation coefficients were used to test for relationships.
Results
At baseline and across all patients, MACD correlated with blood glucose (r2 = 0.1, P< 0.001) and to a lesser, but significant extent with traditional risk factors (p < 0.01) of CVD. In the longitudinal analysis of correlations between baseline biological parameters and the follow-up calcification assessment using radiographs we found LDL-cholesterol, HDL/LDL, and the ApoB/ApoA ratio significantly associated with the MACD (P< 0.01). In a subset of patients presenting with calcification at both baseline and at follow-up, all cholesterol levels were significantly associated with the MACD (P< 0.01) index. AC24 index was not correlated with blood parameters.
Conclusion
Patterns of calcification identified by the MACD, but not the AC24 index, appear to contain useful biological information perhaps explaining part of the improved identification of risk of cardiovascular death of the MACD index. Correlations of MACD but not the AC24 with glucose levels at baseline suggest that hyperglycemia may contribute to unique patterns of calcification indicated by the MACD.
doi:10.1186/1471-2261-11-75
PMCID: PMC3258192  PMID: 22185588
Cardiovascular disease; aortic calcification; risk factors; AAC24
2.  Systematic review: comparative effectiveness of adjunctive devices in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention of native vessels 
Background
During percutaneous coronary intervention (PCI), dislodgement of atherothrombotic material from coronary lesions can result in distal embolization, and may lead to increased major adverse cardiovascular events (MACE) and mortality. We sought to systematically review the comparative effectiveness of adjunctive devices to remove thrombi or protect against distal embolization in patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI of native vessels.
Methods
We conducted a systematic literature search of Medline, the Cochrane Database, and Web of Science (January 1996-March 2011), http://www.clinicaltrials.gov, abstracts from major cardiology meetings, TCTMD, and CardioSource Plus. Two investigators independently screened citations and extracted data from randomized controlled trials (RCTs) that compared the use of adjunctive devices plus PCI to PCI alone, evaluated patients with STEMI, enrolled a population with 95% of target lesion(s) in native vessels, and reported data on at least one pre-specified outcome. Quality was graded as good, fair or poor and the strength of evidence was rated as high, moderate, low or insufficient. Disagreement was resolved through consensus.
Results
37 trials met inclusion criteria. At the maximal duration of follow-up, catheter aspiration devices plus PCI significantly decreased the risk of MACE by 27% compared to PCI alone. Catheter aspiration devices also significantly increased the achievement of ST-segment resolution by 49%, myocardial blush grade of 3 (MBG-3) by 39%, and thrombolysis in myocardial infarction (TIMI) 3 flow by 8%, while reducing the risk of distal embolization by 44%, no reflow by 48% and coronary dissection by 70% versus standard PCI alone. In a majority of trials, the use of catheter aspiration devices increased procedural time upon qualitative assessment.
Distal filter embolic protection devices significantly increased the risk of target revascularization by 39% although the use of mechanical thrombectomy or embolic protection devices did not significantly impact other final health outcomes. Distal balloon or any embolic protection device increased the achievement of MBG-3 by 61% and 20% and TIMI3 flow by 11% and 6% but did not significantly impact other intermediate outcomes versus control. Upon qualitative analysis, all device categories, with exception of catheter aspiration devices, appear to significantly prolong procedure time compared to PCI alone while none appear to significantly impact ejection fraction. Many of the final health outcome and adverse event evaluations were underpowered and the safety of devices overall is unclear due to insufficient amounts of data.
Conclusions
In patients with STEMI, for most devices, few RCTs evaluated final health outcomes over a long period of follow-up. Due to insufficient data, the safety of these devices is unclear.
doi:10.1186/1471-2261-11-74
PMCID: PMC3313863  PMID: 22185559
3.  COPE-ICD: A randomised clinical trial studying the effects and meaning of a comprehensive rehabilitation programme for ICD recipients -design, intervention and population 
Background
Growing evidence exists that living with an ICD can lead to fear and avoidance behaviour including the avoidance of physical activity. It has been suggested that psychological stress can increase the risk of shock and predict death. Small studies have indicated a beneficial effect arising from exercise training and psychological intervention, therefore a large-scale rehabilitation programme was set up.
Methods/Design
A mixed methods embedded experimental design was chosen to include both quantitative and qualitative measures. A randomised clinical trial is its primary component. 196 patients (power-calculated) were block randomised to either a control group or intervention group at a single centre. The intervention consists of a 1-year psycho-educational component provided by two nurses and a 12-week exercise training component provided by two physiotherapists. Our hypothesis is that the COPE-ICD programme will reduce avoidance behaviour, sexual dysfunction and increase quality of life, increase physical capability, reduce the number of treatment-demanding arrhythmias, reduce mortality and acute re-hospitalisation, reduce sickness leading to absence from work and be cost-effective. A blinded investigator will perform all physical tests and data collection.
Discussion
Most participants are men (79%) with a mean age of 58 (range 20-85). Most ICD implantations are on primary prophylactic indication (66%). 44% is NYHA II. Mean walk capacity (6MWT) is 417 m. Mean perception of General Health (SF-36) is PCS 42.6 and MCS 47.1.
A large-scale ICD rehabilitation trial including psycho-educational intervention and exercise training has been initiated and will report findings starting in 2011.
Trial Registration
ClinicalTrials.gov: NCT00569478
doi:10.1186/1471-2261-11-33
PMCID: PMC3131243  PMID: 21682864
4.  C-reactive protein is an independent predictor for carotid artery intima-media thickness progression in asymptomatic younger adults (from the Bogalusa Heart Study) 
Background
Conflicting information exists regarding the association between hsCRP and the progression of early stages of atherosclerosis. The purpose of the study was to investigate the association of high sensitiviy c-reactive protein (hsCRP) along with major cardiovascular (CV) risk factors on early carotid atherosclerosis progression in a large, population-based cohort study.
Methods
The study cohort included 839 young adults (aged 24 to 43 years, 70% white, 42% men) enrolled in Bogalusa Heart Study, who in 2001-2002 attended baseline examination with measurements of CV risk factors. Progression of carotid artery intima-media thickness (IMT) was assessed during a mean follow-up of 2.4 years.
Results
Carotid artery IMT progression rates were as follows: composite carotid artery = 9.2 ± 52 μm/y, common carotid artery = 0.0 ± 51 μm/y, carotid bulb = 8.8 ± 103 μm/y, and internal carotid artery = 18.9 ± 81 μm/y. Elevated baseline hsCRP, reflecting an inflammatory state, showed independent association with composite carotid artery IMT progression. Increased age, systolic blood pressure, fasting glucose, LDL cholesterol, and current smoking were other risk associates of carotid artery IMT progression in young adults, indicating an underlying burden on the CV system by multiple risk factors.
Conclusion
In this population-based study, we observed independent categorical association of increased hsCRP with carotid artery IMT progression in young adults. This study underlines the importance of assesssing hsCRP levels along with smoking and traditional CV risk factor profiles in asymptomatic young adults.
doi:10.1186/1471-2261-11-78
PMCID: PMC3264529  PMID: 22208681
Carotid artery intima-media thickness progression; cardiovascular risk; c-reactive protein; epidemiology; young adults
5.  Novel association patterns of cardiac remodeling markers in patients with essential hypertension and atrial fibrillation 
Background
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are essential for the cardiac extracellular matrix (ECM) remodeling. We investigated differences in serum levels of these markers between patients with atrial fibrillation (AF) and sinus rhythm (SR).
Methods
Serum levels of MMP-2, MMP-3, MMP-9 and TIMP-1 were measured in 86 patients: 27 on SR without any AF history, 33 with paroxysmal and 26 with permanent AF. All subjects had essential hypertension, normal systolic function and no coronary artery disease.
Results
Patients with AF had higher MMP-2, MMP-3 and MMP-9 and lower TIMP-1 compared to SR subjects (all p < 0.001). Paroxysmal AF was associated with higher MMP-2 levels compared to permanent AF (p < 0.001). Matrix metalloproteinase-9 but not MMP-3 was higher in permanent compared to paroxysmal AF group (p < 0.001). Patients with AF had lower levels of TIMP-1 compared to those with SR while permanent AF subjects had lower TIMP-1 levels than those with paroxysmal AF (p < 0.001 for both comparisons). Lower TIMP-1 was the only independent factor associated with AF (OR: 0.259, 95%CI: 0.104-0.645, p = 0.004).
Conclusions
In hypertensives, paroxysmal AF and permanent AF differ with respect to serum MMPs. Increased MMP-2 is associated with paroxysmal, whereas increased MMP-9 with permanent AF. Additionally, lower levels of TIMP-1 had a strong association with AF incidence.
doi:10.1186/1471-2261-11-77
PMCID: PMC3276440  PMID: 22204652
6.  Needs and barriers to improve the collaboration in oral anticoagulant therapy: a qualitative study 
Background
Oral anticoagulant therapy (OAT) involves many health care disciplines. Even though collaboration between care professionals is assumed to improve the quality of OAT, very little research has been done into the practice of OAT management to arrange and manage the collaboration. This study aims to identify the problems in collaboration experienced by the care professionals involved, the solutions they proposed to improve collaboration, and the barriers they encountered to the implementation of these solutions.
Methods
In the Netherlands, intensive follow-up of OAT is provided by specialized anticoagulant clinics (ACs). Sixty-eight semi-structured face-to-face interviews were conducted with 103 professionals working at an AC. These semi-structured interviews were transcribed verbatim and analysed inductively. Wagner's chronic care model (CCM) and Cabana's framework for improvement were used to categorize the results.
Results
AC professionals experienced three main bottlenecks in collaboration: lack of knowledge (mostly of other professionals), lack of consensus on OAT, and limited information exchange between professionals. They mentioned several solutions to improve collaboration, especially solutions of CCM's decision support component (i.e. education, regular meetings, and agreements and protocols). Education is considered a prerequisite for the successful implementation of other proposed solutions such as developing a multidisciplinary protocol and changing the allocation of tasks. The potential of the health care organization to improve collaboration seemed to be underestimated by professionals. They experienced several barriers to the successful implementation of the proposed solutions. Most important barriers were the lack motivation of non-AC professionals and lack of time to establish collaboration.
Conclusions
This study revealed that the collaboration in OAT is limited by a lack of knowledge, a lack of consensus, and a limited information exchange. Education was identified as the best way to improve collaboration and considered a prerequisite for a successful implementation of other proposed solutions. Hence, the implementation sequence is of importance in order to improve the collaboration successfully. First step is to establish alignment regarding collaboration with all involved professionals to encounter the lack of motivation of non-AC professionals and lack of time.
doi:10.1186/1471-2261-11-76
PMCID: PMC3268100  PMID: 22192088
7.  Evaluation of coronary blood flow velocity during cardiac arrest with circulation maintained through mechanical chest compressions in a porcine model 
Background
Mechanical chest compressions (CCs) have been shown capable of maintaining circulation in humans suffering cardiac arrest for extensive periods of time. Reports have documented a visually normalized coronary blood flow during angiography in such cases (TIMI III flow), but it has never been actually measured. Only indirect measurements of the coronary circulation during cardiac arrest with on-going mechanical CCs have been performed previously through measurement of the coronary perfusion pressure (CPP). In this study our aim was to correlate average peak coronary flow velocity (APV) to CPP during mechanical CCs.
Methods
In a closed chest porcine model, cardiac arrest was established through electrically induced ventricular fibrillation (VF) in eleven pigs. After one minute, mechanical chest compressions were initiated and then maintained for 10 minutes upon which the pigs were defibrillated. Measurements of coronary blood flow in the left anterior descending artery were made at baseline and during VF with a catheter based Doppler flow fire measuring APV. Furthermore measurements of central (thoracic) venous and arterial pressures were also made in order to calculate the theoretical CPP.
Results
Average peak coronary flow velocity was significantly higher compared to baseline during mechanical chests compressions and this was observed during the entire period of mechanical chest compressions (12 - 39% above baseline). The APV slowly declined during the 10 min period of mechanical chest compressions, but was still higher than baseline at the end of mechanical chest compressions. CPP was simultaneously maintained at > 20 mmHg during the 10 minute episode of cardiac arrest.
Conclusion
Our study showed good correlation between CPP and APV which was highly significant, during cardiac arrest with on-going mechanical CCs in a closed chest porcine model. In addition APV was even higher during mechanical CCs compared to baseline. Mechanical CCs can, at minimum, re-establish coronary blood flow in non-diseased coronary arteries during cardiac arrest.
doi:10.1186/1471-2261-11-73
PMCID: PMC3297515  PMID: 22182425
8.  Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into foods from the Indian subcontinent - a blinded, randomised, placebo controlled trial 
Background
Coronary heart disease (CHD) is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA) and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk.
Methods/Design
The Diabetes Health, Residence & Metabolism in Asians (DHRMA) study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI) staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI) supply of chapatti (bread), stone ground, high protein wheat flour and white basmati rice (high bran, unpolished) or commercially available (leading brand) versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner.
Discussion
It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive) for South Asian ethnic communities.
Trial registration
Current Controlled Trials ISRCTN02839188
doi:10.1186/1471-2261-11-70
PMCID: PMC3259037  PMID: 22136261
9.  The higher exercise intensity and the presence of allele I of ACE gene elicit a higher post-exercise blood pressure reduction and nitric oxide release in elderly women: an experimental study 
Background
The absence of the I allele of the angiotensin converting enzyme (ACE) gene has been associated with higher levels of circulating ACE, lower nitric oxide (NO) release and hypertension. The purposes of this study were to analyze the post-exercise salivary nitrite (NO2-) and blood pressure (BP) responses to different exercise intensities in elderly women divided according to their ACE genotype.
Methods
Participants (n = 30; II/ID = 20 and DD = 10) underwent three experimental sessions: incremental test - IT (15 watts workload increase/3 min) until exhaustion; 20 min exercise 90% anaerobic threshold (90% AT); and 20 min control session without exercise. Volunteers had their BP and NO2- measured before and after experimental sessions.
Results
Despite both intensities showed protective effect on preventing the increase of BP during post-exercise recovery compared to control, post-exercise hypotension and increased NO2- release was observed only for carriers of the I allele (p < 0.05).
Conclusion
Genotypes of the ACE gene may exert a role in post-exercise NO release and BP response.
doi:10.1186/1471-2261-11-71
PMCID: PMC3261092  PMID: 22136292
10.  Role of aldosterone on lung structural remodelling and right ventricular function in congestive heart failure 
Background
The mechanisms of benefit of mineralocorticoid receptors antagonists in congestive heart failure (CHF) are still debated. We hypothesized that aldosterone contributes to pulmonary remodelling and right ventricular (RV) dysfunction associated with CHF by stimulation of lung myofibroblasts (MYFs) proliferation.
Methods
Rats with moderate to large myocardial infarcts (MI) and CHF were studied. Two weeks after MI, spironolactone 100 mg/kg/day (n = 21) or no treatment (n = 24) were given for 3 weeks and compared to sham (n = 8).
Results
Infarct size was similar by ultrasound and pathologic measures in both MI groups.
The MI-untreated group developed important lung remodelling with nearly doubling of dry lung weight (p < 0.01), reduced left ventricular (LV) fractional shortening (16 ± 2% vs. 53 ± 1%; mean ± SEM, p < 0.0001), pulmonary hypertension (RV systolic pressure: 40 ± 3 mmHg vs. 27 ± 1 mmHg, p < 0.01) and RV hypertrophy (RV/(LV + septum): 38 ± 3% vs. 24 ± 1%, p < 0.05). Spironolactone had no effect on these parameters and did not improve LV or RV performance (tricuspid annular plane systolic excursion and RV myocardial performance index) measured by echocardiography. CHF induced a restrictive respiratory syndrome with histological lung fibrosis: this was also unaffected by spironolactone. Finally, isolated lung MYFs did not proliferate after exposure to aldosterone.
Conclusion
Aldosterone does not significantly contribute to pulmonary remodelling and RV dysfunction associated with CHF. Other mechanisms are responsible for the beneficial effects of spironolactone in CHF.
doi:10.1186/1471-2261-11-72
PMCID: PMC3297512  PMID: 22136321
spironolactone; pulmonary heart disease; pulmonary hypertension; myofibroblasts
11.  Prevalence of major infections and adverse outcomes among hospitalized. ST-elevation myocardial infarction patients in Florida, 2006 
Background
ST-elevation myocardial infarction (STEMI) patients have risk factors and co-morbidities and require procedures predisposing to healthcare acquired infections (HAIs). As few data exist on the extent and consequences of infections among these patients, the prevalence, predictors, and potential complications of major infections among hospitalized STEMI patients at all Florida acute care hospitals during 2006 were analyzed.
Methods
Sociodemographic characteristics, risk factors, co-morbidities, procedures, complications, and mortality were analyzed from hospital discharge data for 11, 879 STEMI patients age ≥18 years. We used multivariable logistic regression modeling to examine and adjust for multiple potential predictors of any infection, bloodstream infection (BSI), pneumonia, surgical site infection (SSI), and urinary tract infection (UTI).
Results
There were 2, 562 infections among 16.6% of STEMI patients; 6.2% of patients had ≥2 infections. The most prevalent HAIs were UTIs (6.0%), pneumonia (4.6%), SSIs (4.1%), and BSIs (2.6%). Women were at 29% greater risk, Blacks had 23% greater risk, and HAI risk increased 11% with each 5 year increase in age. PCI was the only protective major procedure (OR 0.81, 95% CI, 0.69-0.95, p < .05). HAI lengthened hospital stays. STEMI patients with a BSI were almost 5 times more likely (31.3% vs. 6.5%, p < .0001), and those with pneumonia were 3 times more likely (19.6% vs. 6.5%, p < .0001) to die before discharge.
Conclusions
The protective effect of PCI on risk of infection is likely mediated by its many benefits, including reduced length of hospitalizations.
doi:10.1186/1471-2261-11-69
PMCID: PMC3252246  PMID: 22108297
12.  Adherence to the European Society of Cardiology (ESC) guidelines for chronic heart failure - A national survey of the cardiologists in Pakistan 
Background
The aims of this study were to evaluate the awareness of and attitudes towards the 2005 European Society of Cardiology (ESC) guidelines for Heart Failure (HF) of the cardiologists in Pakistan and assess barriers to adherence to guidelines.
Methods
A cross-sectional survey was conducted in person from March to July 2009 to all cardiologists practicing in 4 major cities in Pakistan (Karachi, Lahore, Quetta and Peshawar). A validated, semi-structured questionnaire assessing ESC 2005 Guidelines for HF was used to obtain information from cardiologists. It included questions about awareness and relevance of HF guidelines (See Additional File 1). Respondents' management choices were compared with those of an expert panel based on the guidelines for three fictitious patient cases. Cardiologists were also asked about major barriers to adherence to guidelines.
Results
A total of 372 cardiologists were approached; 305 consented to participate (overall response rate, 82.0%). The survey showed a very high awareness of CHF guidelines; 97.4% aware of any guideline. About 13.8% considered ESC guidelines as relevant or very relevant for guiding treatment decisions while 92.8% chose AHA guidelines in relevance. 87.2% of respondents perceived that they adhered to the HF guidelines. For the patient cases, the proportions of respondents who made recommendations that completely matched those of the guidelines were 7% (Scenario 1), 0% (Scenario 2) and 20% (Scenario 3). Respondents considered patient compliance (59%) and cost/health economics (50%) as major barriers to guideline implementation.
Conclusion
We found important self reported departures from recommended HF management guidelines among cardiologists of Pakistan.
doi:10.1186/1471-2261-11-68
PMCID: PMC3250933  PMID: 22093082
Heart failure; cardiologist; guidelines; awareness
13.  Association between carotid area calcifications and periodontal risk: a cross sectional study of panoramic radiographic findings 
Background
The aim was to investigate the extent to which it is possible to diagnose suspected carotid calcification from dental panoramic radiography (PR) and to establish an association to periodontal risk.
Methods
824 PRs from one dental practice were investigated. Parameters considered were gender, age, bone loss - age index, tooth loss, periodontal risk and suspected carotid calcification (left, right, both sides). Periodontal risk was classified: low risk (under 4 missing teeth, bone loss - age index under 0.5), moderate risk (5 to 8 missing teeth and/or bone loss - age index 0.5 to 1.0) and high risk (more than 9 missing teeth and or bone loss - age index greater than 1.0).
Results
Of 824 patients, 349 were male (42.4%) and 475 female (57.6%); the mean age was 48.32 ± 16.52 years. In 9.0% (n = 74) of PRs, suspected carotid calcification was diagnosed (right: 5.5%, left: 2.3%, both sides: 1.2%). The mean tooth loss was 4.16 ± 5.39 teeth. In the case of 282 patients (34.2%), there was a low, in 335 patients (40.7%) a moderate, and in 207 patients (25.1%) a high periodontal risk. There was a significant correlation found between number of cases of suspected carotid calcification and periodontal risk, tooth loss and age (p = 0.0001). However, only age showed a significant association (OR: 4.9; CI: 2.4-9.8; p < 0.0001) in contrast to periodontal risk (OR 1.4; CI: 0.9-2.4).
Conclusion
PR can provides indication of carotid calcification as a secondary (chance) finding. In addition, periodontal risk may be correlated with positive findings of carotid calcification.
doi:10.1186/1471-2261-11-67
PMCID: PMC3224751  PMID: 22070470
14.  Genotype-informed estimation of risk of coronary heart disease based on genome-wide association data linked to the electronic medical record 
Background
Susceptibility variants identified by genome-wide association studies (GWAS) have modest effect sizes. Whether such variants provide incremental information in assessing risk for common 'complex' diseases is unclear. We investigated whether measured and imputed genotypes from a GWAS dataset linked to the electronic medical record alter estimates of coronary heart disease (CHD) risk.
Methods
Study participants (n = 1243) had no known cardiovascular disease and were considered to be at high, intermediate, or low 10-year risk of CHD based on the Framingham risk score (FRS) which includes age, sex, total and HDL cholesterol, blood pressure, diabetes, and smoking status. Of twelve SNPs identified in prior GWAS to be associated with CHD, four were genotyped in the participants as part of a GWAS. Genotypes for seven SNPs were imputed from HapMap CEU population using the program MACH. We calculated a multiplex genetic risk score for each patient based on the odds ratios of the susceptibility SNPs and incorporated this into the FRS.
Results
The mean (SD) number of risk alleles was 12.31 (1.95), range 6-18. The mean (SD) of the weighted genetic risk score was 12.64 (2.05), range 5.75-18.20. The CHD genetic risk score was not correlated with the FRS (P = 0.78). After incorporating the genetic risk score into the FRS, a total of 380 individuals (30.6%) were reclassified into higher-(188) or lower-risk groups (192).
Conclusion
A genetic risk score based on measured/imputed genotypes at 11 susceptibility SNPs, led to significant reclassification in the 10-y CHD risk categories. Additional prospective studies are needed to assess accuracy and clinical utility of such reclassification.
doi:10.1186/1471-2261-11-66
PMCID: PMC3269823  PMID: 22151179
15.  Awareness, treatment and control of hypertension among the elderly living in their home in Tunisia 
Background
Hypertension is a cardiovascular disorder rapidly emerging as a major public health problem in developing countries. However, the acknowledgement of the prevalence and the significant impact of hypertension in elderly are very important for health policy. The objective of the present investigation was to evaluate the prevalence, awareness and treatment of hypertension among the elderly living in their home in Tunisia at Monastir City. We also examined the impact of socio-demographic characteristics and known risk factors for high blood pressure.
Methods
A community based sample of 598 non-institutionalized elderly (age ≥ 65 years), was selected using probabilistic multistage cluster sampling.
Results
There was a predominance of female (66%) and mean age was 72.3 ± 7.4 years. The prevalence of hypertension was 52% (n = 311), awareness (81%, n = 252), treatment (78.4%, n = 244) and only 30.7% (n = 75) are correctly treated. The prevalence of hypertension was higher for the female population (55.5%) when compared to males (45%). No urban/rural differences were observed and no difference was observed by educational level. Multiple logistic regression analyses identified a higher body mass index, diabetes mellitus and disability as important correlates of the prevalence of hypertension.
Conclusion
These findings provide important information on the prevalence, awareness and control of hypertension in Monastir City and confirm their association with other cardio-vascular risk factors. Effective public health measures and strategies are needed to improve prevention, diagnosis and access to treatment of this elderly population.
doi:10.1186/1471-2261-11-65
PMCID: PMC3234182  PMID: 22044442
Hypertension; Elderly; Prevalence; Awareness; Tunisia; Home living
16.  Giant pulmonary artery aneurysm in a patient with vasoreactive pulmonary hypertension: a case report 
Background
Pulmonary artery aneurysms are a rare condition, frequently associated with pulmonary hypertension. However, the evolution and treatment of this pathology is still not clear.
Case Presentation
The authors report a case of a 65-year old patient with pulmonary artery aneurysm associated with pulmonary arterial hypertension. Due to a positive vasoreactivity test, treatment with calcium channel blockers was started with near normalization of the right cardiac pressures. Nevertheless, after 20 months of treatment, the pulmonary artery aneurysm size remained unchanged with an associated severe pulmonary regurgitation and causing extrinsic compression of the main left coronary artery. Surgical correction was successfully performed.
Conclusions
This is the first case report of a pulmonary artery aneurysm described to be associated with vasoreactive pulmonary hypertension in a living patient. Although medical therapy for pulmonary hypertension was started, surgical correction of the aneurysm was executed in order to prevent its future complications.
doi:10.1186/1471-2261-11-64
PMCID: PMC3228743  PMID: 22018102
17.  Variation of mortality after coronary artery bypass surgery in relation to hour, day and month of the procedure 
Background
Mortality and complications after percutaneous coronary intervention is higher when performed after regular duty hours due to challenging patient characteristics, inferior processes of care and limited resources. Since these challenges are also encountered during coronary artery bypass graft (CABG) surgery that is performed after regular work hours, we assessed whether hour and day of procedure influenced mortality after CABG.
Methods
We studied 4,714 consecutive patients who underwent CABG at the Minneapolis Veterans Administration (VA) Medical Center between 1987 and 2009. We compared postoperative (30-day) mortality rates in relation to hour and day in which the operation was performed.
Results
Operations performed on weekends and after 4 PM had higher risk patients (p < 0.0001) and were more likely to be emergent (p < 0.0001), require intra-aortic balloon pump support (p < 0.0001) and result in postoperative complications (p < 0.0001) compared to those at regular work hours. Mortality was significantly higher when CABG was performed on weekends compared to weekdays (9.4% versus 2.5%; odds ratio (OR) 4.1, 95% confidence interval (CI) 1.6 to 10.4, p = 0.003), and after 4 PM compared to between 7 AM-4 PM (6.2% versus 2.2%; OR 2.9, 95% CI 1 to 8, p = 0.049). In multivariable analysis, when adjusted for the urgency of the operation and the VA estimated mortality risk score, these associations were no longer statistically significant.
Conclusions
Mortality after CABG is higher when surgery is performed on the weekends and after 4 PM. These variations in mortality were related to higher patient risk, and urgency of the operation rather than external factors.
doi:10.1186/1471-2261-11-63
PMCID: PMC3206827  PMID: 22014242
coronary artery bypass surgery; mortality
18.  Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice 
Background
Cardiac inflammation and generation of oxidative stress are known to contribute to trastuzumab (herceptin) induced cardiac toxicity. Toll-like receptors (TLRs) are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signaling, we investigated whether or not TLR4 is involved in trastuzumab induced cardiotoxicity.
Methods
Seven days after a single injection of herceptin (2 mg/kg; i.p.), left ventricular pressure volume loops were measured in HeN compotent (TLR4+/+) and HeJ mutant (TLR4-/-) treated with trastuzumab and control mice. Immunofluorescent staining for monocyte infiltration and analyses of plasma by (ELISAs) for different chemokines including: MCP-1and tumor necrosis factor-α (TNF-α), Western immunoblotting assay for ICAM-1, and used troponin I for cardiac injury marker.
Results
Trastuzumab injection resulted in an impairment of left ventricular function in TLR-4 competent (HeN), in contrast TLR4-/- trastuzumab mice showed improved left ventricular function EF%, CO; p < 0.05, attenuation of mononuclear cell infiltration in TLR4 -/-; p < 0.05 vs.TLR-4 competent (HeN), reduced level of cytokines TNF-α, MCP-1 and ICAM-1 expression in TLR4-/-, marked reduction of myocardial troponin-I levels in TLR4-deficient mice. Data are presented as means ± SE; n = 8 in each group p < 0.05 vs.TLR-4 competent (HeN).
Conclusions
Treatment with trastuzumab induces an inflammatory response that contributes to myocardial tissue TLR4 mediates chemokine expression (TNF-α, MCP-1and ICAM-1), so in experimental animals TLR4 deficiency improves left ventricular function and attenuates pathophysiological key mechanisms in trastuzumab induced cardiomyopathy.
doi:10.1186/1471-2261-11-62
PMCID: PMC3209438  PMID: 21999911
Toll Like Receptor 4; cardiac-toxicity; Inflammation; trastuzumab
19.  Improving interMediAte Risk management. MARK study 
Background
Cardiovascular risk functions fail to identify more than 50% of patients who develop cardiovascular disease. This is especially evident in the intermediate-risk patients in which clinical management becomes difficult. Our purpose is to analyze if ankle-brachial index (ABI), measures of arterial stiffness, postprandial glucose, glycosylated hemoglobin, self-measured blood pressure and presence of comorbidity are independently associated to incidence of vascular events and whether they can improve the predictive capacity of current risk equations in the intermediate-risk population.
Methods/Design
This project involves 3 groups belonging to REDIAPP (RETICS RD06/0018) from 3 Spanish regions. We will recruit a multicenter cohort of 2688 patients at intermediate risk (coronary risk between 5 and 15% or vascular death risk between 3-5% over 10 years) and no history of atherosclerotic disease, selected at random. We will record socio-demographic data, information on diet, physical activity, comorbidity and intermittent claudication. We will measure ABI, pulse wave velocity and cardio ankle vascular index at rest and after a light intensity exercise. Blood pressure and anthropometric data will be also recorded. We will also quantify lipids, glucose and glycosylated hemoglobin in a fasting blood sample and postprandial capillary glucose. Eighteen months after the recruitment, patients will be followed up to determine the incidence of vascular events (later follow-ups are planned at 5 and 10 years). We will analyze whether the new proposed risk factors contribute to improve the risk functions based on classic risk factors.
Discussion
Primary prevention of cardiovascular diseases is a priority in public health policy of developed and developing countries. The fundamental strategy consists in identifying people in a high risk situation in which preventive measures are effective and efficient. Improvement of these predictions in our country will have an immediate, clinical and welfare impact and a short term public health effect.
Trial Registration
Clinical Trials.gov Identifier: NCT01428934
doi:10.1186/1471-2261-11-61
PMCID: PMC3207912  PMID: 21992621
Risk assessment; cardiovascular diseases; primary prevention; primary health care.
20.  The effect of an educational intervention on coronary artery bypass graft surgery patients' participation rate in cardiac rehabilitation programs: a controlled health care trial 
Background
Cardiac rehabilitation has a beneficial effect on the prognosis and quality of life of cardiac patients, and has been found to be cost-effective. This report describes a comprehensive and low cost educational intervention designed to increase the attendance at cardiac rehabilitation programs of patients who have undergone coronary artery bypass graft surgery.
Methods/Design
A controlled prospective intervention trial. The control arm comprised 520 patients who underwent coronary artery bypass graft surgery between January 2004 and May 2005 in five medical centers across Israel. This group received no additional treatment beyond usual care. The intervention arm comprised 504 patients recruited from the same cardiothoracic departments between June 2005 and November 2006. This group received oral and written explanations about the advantages of participating in cardiac rehabilitation programs and a telephone call two weeks after hospital discharge intended to further encourage their enrollment. The medical staff attended a one-hour seminar on cardiac rehabilitation. In addition, it was recommended that referral to cardiac rehabilitation be added to the letter of discharge from the hospital. Both study groups were interviewed before surgery and one-year post surgery. A one-year post-operative interview assessed factors affecting patient attendance at cardiac rehabilitation programs, as well as the structure and content of the cardiac rehabilitation programs attended. Anthropometric parameters were measured at pre- and post-operative interviews;- and medical information was obtained from patient medical records. The effect of cardiac rehabilitation on one- and three-year mortality was assessed.
Discussion
We report a low cost yet comprehensive intervention designed to increase cardiac rehabilitation participation by raising both patient and medical staff awareness to the potential benefits of cardiac rehabilitation.
Trial registration
ClinicalTrials.gov: NCT00356863
doi:10.1186/1471-2261-11-60
PMCID: PMC3214809  PMID: 21982052
coronary artery disease; educational program; patient rights; tertiary prevention; intervention
21.  Prevalence of peripheral arterial disease in subjects with moderate cardiovascular risk: Italian results from the PANDORA study Data from PANDORA (Prevalence of peripheral Arterial disease in subjects with moderate CVD risk, with No overt vascular Diseases nor Diabetes mellitus) 
Background
The PANDORA study has recently examined the prevalence of low ankle brachial index (ABI) in subjects with moderate risk of cardiovascular disease. This sub-analysis of the PANDORA study examines the prevalence of asymptomatic peripheral arterial disease (PAD), as determined by ABI, in Italian subjects presenting with moderate cardiovascular risk, in the absence of diabetes or overt vascular disease.
Methods
PANDORA is a non-interventional, cross-sectional study that was performed in 6 European countries, involving subjects with at least one cardiovascular (CV) risk factor. The primary objective was to evaluate the prevalence of asymptomatic PAD using ABI. For this post-hoc sub-analysis, data were extracted for subjects enrolled in Italy, comprising 51.5% (n = 5298) of subjects from the original PANDORA study. Secondary objectives were to establish the prevalence and treatment of CV risk factors.
Results
The mean age was 63.9 years and 22.9% (95% CI 21.7-24.0) of subjects presented with asymptomatic PAD. A range of risk factors comprising smoking, hypertension, low HDL-cholesterol, family history of coronary heart disease and habit of moderate-high alcohol intake were significantly associated with asymptomatic PAD (p < 0.0001). Statin treatment had the lowest incidence in Italian subjects. Furthermore, patients treated with statins were significantly less likely to have asymptomatic PAD than those who were not (p = 0.0001).
Conclusions
Asymptomatic PAD was highly prevalent in Italian subjects, the majority of whom were not candidates for ABI assessment according to current guidelines. Findings from this study suggest that these patients should be carefully examined in clinical practice and ABI measured so that therapeutic interventions known to decrease their CV risk may be offered.
Trial registration number
ClinicalTrials.gov: NCT00689377
doi:10.1186/1471-2261-11-59
PMCID: PMC3198689  PMID: 21981988
Peripheral vascular disease; ankle-brachial index; atherosclerosis; risk factors; prevention
22.  A Retrospective Cohort Study of the Potency of lipid-lowering therapy and Race-gender Differences in LDL cholesterol control 
Background
Reasons for race and gender differences in controlling elevated low density lipoprotein (LDL) cholesterol may be related to variations in prescribed lipid-lowering therapy. We examined the effect of lipid-lowering drug treatment and potency on time until LDL control for black and white women and men with a baseline elevated LDL.
Methods
We studied 3,484 older hypertensive patients with dyslipidemia in 6 primary care practices over a 4-year timeframe. Potency of lipid-lowering drugs calculated for each treated day and summed to assess total potency for at least 6 and up to 24 months. Cox models of time to LDL control within two years and logistic regression models of control within 6 months by race-gender adjust for: demographics, clinical, health care delivery, primary/specialty care, LDL measurement, and drug potency.
Results
Time to LDL control decreased as lipid-lowering drug potency increased (P < 0.001). Black women (N = 1,440) received the highest potency therapy (P < 0.001) yet were less likely to achieve LDL control than white men (N = 717) (fully adjusted hazard ratio [HR] 0.66 [95% CI 0.56-0.78]). Black men (N = 666) and white women (N = 661) also had lower adjusted HRs of LDL control (0.82 [95% CI 0.69, 0.98] and 0.75 [95% CI 0.64-0.88], respectively) than white men. Logistic regression models of LDL control by 6 months and other sensitivity models affirmed these results.
Conclusions
Black women and, to a lesser extent, black men and white women were less likely to achieve LDL control than white men after accounting for lipid-lowering drug potency as well as diverse patient and provider factors. Future work should focus on the contributions of medication adherence and response to treatment to these clinically important differences.
doi:10.1186/1471-2261-11-58
PMCID: PMC3197552  PMID: 21961563
dyslipidemia; anticholesterolemic agents; healthcare disparities; survival analysis
23.  B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina 
Background
Several mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS.
Methods
We included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses.
Results
119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively.
The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients.
Conclusion
BNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS.
Trial Registration
ClinicalTrials.gov Identifier: NCT01377402.
doi:10.1186/1471-2261-11-57
PMCID: PMC3199275  PMID: 21958326
24.  Cardiac medication prescribing and adherence after acute myocardial infarction in Chinese and South Asian Canadian patients 
Background
Failure to adhere to cardiac medications after acute myocardial infarction (AMI) is associated with increased mortality. Language barriers and preference for traditional medications may predispose certain ethnic groups at high risk for non-adherence. We compared prescribing and adherence to ACE-inhibitors (ACEI), beta-blockers (BB), and statins following AMI among elderly Chinese, South Asian, and Non-Asian patients.
Methods
Retrospective-cohort study of elderly AMI survivors (1995-2002) using administrative data from British Columbia. AMI cases and ethnicity were identified using validated ICD-9/10 coding and surname algorithms, respectively. Medication adherence was assessed using the 'proportion of days covered' (PDC) metric with a PDC ≥ 0.80 indicating optimal adherence. The independent effect of ethnicity on adherence was assessed using multivariable modeling, adjusting for socio-demographic and clinical characteristics.
Results
There were 9926 elderly AMI survivors (258 Chinese, 511 South Asian patients). More Chinese patients were prescribed BBs (79.7% vs. 73.1%, p = 0.04) and more South Asian patients were prescribed statins (73.5% vs. 65.2%, p = 0.001). Both Chinese (Odds Ratio [OR] 0.53; 95%CI, 0.39-0.73; p < 0.0001) and South Asian (OR 0.78; 95%CI, 0.61-0.99; p = 0.04) patients were less adherent to ACEI compared to Non-Asian patients. South Asian patients were more adherent to BBs (OR 1.3; 95%CI, 1.04-1.62; p = 0.02). There was no difference in prescribing of ACEI, nor adherence to statins among the ethnicities.
Conclusion
Despite a higher likelihood of being prescribed evidence-based therapies following AMI, Chinese and South Asian patients were less likely to adhere to ACEI compared to their Non-Asian counterparts.
doi:10.1186/1471-2261-11-56
PMCID: PMC3189887  PMID: 21923931
medication adherence; acute myocardial infarction; ethnicity
25.  HYPEST study: profile of hypertensive patients in Estonia 
Background
More than one third of adult population in Estonia has problems with elevated blood pressure (BP). The Hypertension in Estonia (HYPEST) study represents the country's first hypertension-targeted sample collection aiming to examine the epidemiological and genetic determinants for hypertension (HTN) and related cardiovascular diseases (CVD) in Estonian population. The HYPEST subjects (n = 1,966) were recruited across Estonia between 2004-2007 including clinically diagnosed HTN cases and population-based controls. The present report is focused on the clinical and epidemiological profile of HYPEST cases, and gender-specific effects on the pathophysiology of hypertension.
Methods
Current analysis was performed on 1,007 clinically diagnosed HTN patients (617 women and 390 men) aged 18-85 years. The hypertensives were recruited to the study by BP specialists at the North Estonia Medical Center, Centre of Cardiology, Tallinn or at the Cardiology Clinic, Tartu University Hospital, Estonia. Longitudinal BP data was extracted retrospectively from clinical records. Current and retrospective data of patient's medical history, medication intake and lifestyle habits were derived from self-administrated questionnaire and each variable was examined separately for men and women. Eleven biochemical parameters were measured from fasting serum samples of 756 patients.
Results
The distribution of recruited men and women was 39% and 61% respectively. Majority of Estonian HTN patients (85%) were overweight (BMI ≥ 25 kg/m2) and a total of 79% of patients had additional complications with cardiovascular system. In men, the hypertension started almost 5 years earlier than in women (40.5 ± 14.5 vs 46.1 ± 12.7 years), which led to earlier age of first myocardial infarction (MI) and overall higher incidence rate of MI among male patients (men 21.2%, women 8.9%, P < 0.0001). Heart arrhythmia, thyroid diseases, renal tubulo-intestinal diseases and hyperlipidemia were more prevalent in hypertensive women compared to men (P < 0.0001). An earlier age of HTN onset was significantly associated with smoking (P = 0.00007), obesity (BMI ≥ 30 kg/m2; P = 0.0003), increased stress (P = 0.0003) and alcohol consumption (P = 0.004).
Conclusion
Understanding the clinical profile of HTN patients contributes to CVD management. Estonian hypertension patients exhibited different disease and risk profiles of male and female patients. This well-characterized sample set provides a good resource for studying hypertension and other cardiovascular phenotypes.
doi:10.1186/1471-2261-11-55
PMCID: PMC3179926  PMID: 21880150

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