Lipid modification therapy (LMT) produces cardiovascular benefits principally through reductions in low density lipoprotein cholesterol (LDL-C). While recent evidence, using data from 454 participants in the Framingham Offspring Study (FOS), has suggested that increases in high density lipoprotein cholesterol (HDL-C) are also associated with a reduction in cardiovascular outcomes, independently of changes in LDL-C, replication of this finding is important. We therefore present further results using data from the EPIC Norfolk (UK) and Rotterdam (Netherlands) prospective cohort studies.
A total of 1,148 participants, 446 from the EPIC-Norfolk and 702 from the Rotterdam study were assessed for lipids before and after starting LMT. Subsequent risk of cardiovascular events, ascertained through linkage with mortality records and hospital databases, was investigated using Cox Proportional hazards regression. Random effects meta-analysis was used to combine results across studies.
Based on combined data from the EPIC-Norfolk and Rotterdam studies there was some evidence that change in HDL-C resulting from LMT was associated with reduced cardiovascular risk (hazard ratio per pooled SD (= 0. 34 mmol/l) increase = 0.74, 95% CI 0.56-0.99, adjusted for age, sex, and baseline HDL-C). However, this association was attenuated and was not (statistically) significant with further adjustments for non-HDL-C and for cigarette smoking history, prevalent diabetes, SBP, BMI, use of antihypertensive medication, previous MI, prevalent angina, previous stroke (0.92, 0.70-1.20).
Following adjustment for conventional non-lipid CVD risk factors, this study provides no evidence to support a significant benefit from increasing HDL-C independent of the effect of lowering non-HDL-C.
Lipids; Lipoproteins; HDL; Atherosclerosis; Myocardial infarction
The value of a family history for coronary heart disease (CHD) in addition to established cardiovascular risk factors in predicting an individual’s risk of CHD is unclear. In the EPIC-Norfolk cohort, we tested whether adding family history of premature CHD in first degree relatives improves risk prediction compared to the Framingham risk score (FRS) alone.
Methods and Results
This study comprised 10,288 men and 12,553 women aged 40 to 79 years participating in the EPIC-Norfolk cohort who where followed for an average of 10.9 ± 2.1 years (mean ± SD). We computed the Framingham risk score as well as a modified score taking into account family history of premature CHD. A family history of CHD was indeed associated with an increased risk of future CHD, independent of established risk factors (FRS-adjusted hazard ratio of 1.74 (95%CI 1.56-1.95) for family history of premature CHD). However, adding family history of CHD to the Framingham risk score resulted in a negative net reclassification of 2%. In the subgroup of individuals estimated to be at intermediate risk, family history of premature CHD resulted in an increase in net reclassification of 2%. The sensitivity increased with 0.4 % and the specificity decreased 0.8%.
Although family history of CHD was an independent risk factor of future CHD, its use did not improve classification of individuals into clinically relevant risk categories based on the FRS. Among study participants at intermediate risk of CHD, adding family history of premature CHD resulted in, at best, a modest improvement in reclassification of individuals into a more accurate risk category.
Recent studies have examined hemodynamic changes with stressors such as isometric handgrip and rapid atrial pacing in heart failure with preserved ejection fraction (HFpEF), but little is known regarding left ventricular (LV) pressure-volume responses during dynamic exercise.
Assess LV hemodynamic responses to dynamic exercise in patients with HFpEF.
Methods and Results
Twenty subjects with normal EF and exertional dyspnea underwent invasive hemodynamic assessment during dynamic exercise to evaluate for suspected HFpEF. LV end-diastolic pressure (LVEDP) was elevated at rest (>15mmHg, n=18) or with exercise (≥20mmHg, n=20) in all, consistent with HFpEF. Heart rate, blood pressure, arterial elastance and cardiac output increased with exercise (all p<0.001). Minimal and mean LV diastolic pressures increased by 43–56% with exercise (both p<0.0001), despite a trend toward reduction in LV end-diastolic volume (p=0.08). Diastolic filling time was abbreviated with increases in heart rate, and the proportion of diastole that elapsed prior to estimated complete relaxation increased (p<0.0001), suggesting inadequate relaxation reserve relative to the shortening of diastole. LV diastolic chamber elastance acutely increased 50% during exercise (p=0.0003). Exercise increases in LV filling pressures correlated with changes in diastolic relaxation rates, chamber stiffness and arterial afterload but were not related to alterations in preload volume, heart rate, or cardiac output.
In patients with newly-diagnosed HFpEF, LV filling pressures increase during dynamic exercise in association with inadequate enhancement of relaxation and acute increases in LV chamber stiffness. Therapies that enhance diastolic reserve function may improve symptoms of exertional intolerance in patients with hypertensive heart disease and early HFpEF.
Heart Failure; Diastolic Dysfunction; Haemodynamics; Exercise; Old Age
In myocardial infarction (MI), we studied whether documentation of ischemic symptoms is associated with quality of care and outcomes, and compared patient reports of ischaemic symptoms during interviews with chart documentation
Observational acute myocardial infarction study from 2003–2004 (Prospective Registry Evaluating Myocardial Infarction: Event and Recovery)
19 diverse US hospitals
2,094 consecutive MI patients (10,911 patients screened; 3,953 patients were eligible and enrolled) with both positive cardiac enzymes and other evidence of infarction (e.g., symptoms, electrocardiographic changes). Transferred patients and those with confounding noncardiac comorbidity were not included (n=1859).
Main outcome measures
Quality of care indicators and adjusted in-hospital survival
The records of 10% of all MI patients (217/2094) contained no documented ischaemic symptoms at presentation. Patients without documented symptoms were less likely (p<0.05) to: receive aspirin (89% vs. 96%) or beta-blockers (77% vs. 90%) within 24hr, reperfusion therapy for STEMI (7% vs. 58%) or to survive their hospitalization (adjusted OR=3.2, 95% CI 1.8–5.8). Survivors without documented symptoms were also less likely (p<0.05) to be discharged with aspirin (87% vs. 93%), beta-blockers (81% vs. 91%), ACE/ARB (67% vs. 80%), or smoking cessation counseling (46% vs. 66%). In the subset of 1,356 (65%) interviewed patients, most of those without documented ischaemic symptoms (75%) reported presenting symptoms consistent with ischaemia.
Failure to document patients’ presenting MI symptoms is associated with poorer quality of care from admission to discharge, and higher in-hospital mortality. Symptom recognition may represent an important opportunity to improve the quality of MI care.
The exact form of the association between systolic blood pressure (SBP) and heart failure (HF) risk in the elderly remains incompletely defined, especially in individuals not receiving antihypertensive medications. Our aim was to examine the association between SBP and HF risk in the elderly.
Competing-risks proportional hazards modeling of incident HF risk, utilizing 10-year follow-up data from two NIH-sponsored cohort studies; the Cardiovascular Health Study (inception: 1989-90 and 1992-93) and the Health ABC Study (inception: 1997-98).
4408 participants (age, 72.8 [4.9] years; 53.1% women, 81.7% white; 18.3% black) without prevalent HF and not receiving antihypertensive medications at baseline.
Main outcome measures
Incident HF, defined as first adjudicated hospitalisation for HF.
Over 10 years, 493 (11.1%) participants developed HF. Prehypertension (120-139 mmHg), stage 1 (140-159 mmHg), and stage 2 (≥160 mmHg) hypertension were associated with escalating HF risk; hazard ratios vs. optimal SBP (<120 mmHg) in competing-risks models controlling for clinical characteristics were 1.63 (95% CI, 1.23-2.16; P=0.001), 2.21 (95% CI, 1.65-2.96; P<0.001), and 2.60 (95% CI, 1.85-364; P<0.001), respectively. Overall 255 of 493 (51.7%) HF events occurred in participants with SBP <140 mm Hg at baseline. Increasing SBP was associated with higher HF risk in women than men; no race-SBP interaction was observed. In analyses with continuous SBP, HF risk had a continuous positive association with SBP to levels as low as 113 mmHg in men and 112 mmHg in women.
There is a continuous positive association between SBP and HF risk in the elderly for levels of SBP as low as <115 mmHg; over half of incident HF events occur in individuals with SBP <140 mmHg.
epidemiology; hypertension; heart failure; risk stratification
To evaluate the scale and clinical importance of loss to follow-up of past patients with serious congenital heart disease, using a common malformation as an example. To better understand the antecedents of loss to specialist follow-up and patients’ attitudes to returning.
Cohort study using NHS number functionality. Content and thematic analysis of telephone interviews of subset contacted after loss to follow-up.
Patients, intervention and setting
Longitudinal follow-up of complete consecutive list of all 1085 UK patients with repair of tetralogy of Fallot from single institution 1964–2009.
Main outcome measures
Survival, freedom from late pulmonary valve replacement, loss to specialist follow-up, shortfall in late surgical revisions related to loss to follow-up. Patients’ narrative about loss to follow-up.
216 (24%) of patients known to be currently alive appear not to be registered with specialist clinics; some are seen in general cardiology clinics. Their median age is 32 years and median duration of loss to follow-up is 22 years; most had been lost before Adult Congenital services had been consolidated in their present form. 48% of the late deaths to date have occurred in patients not under specialist follow-up. None of those lost to specialist follow-up has had secondary pulmonary valve replacement while 188 patients under specialist care have. Patients lost to specialist follow-up who were contacted by telephone had no knowledge of its availability.
Loss to specialist follow-up, typically originating many years ago, impacts patient management.
Individuals with electrocardiographically-determined left ventricular hypertrophy (ECG LVH) are at risk for multiple cardiovascular disease (CVD) outcomes simultaneously. We sought to characterize the competing incidences for subtypes of first CVD events or non-CVD death in those with and without ECG LVH.
We included participants in the Atherosclerosis Risk in Communities (ARIC) study. ECG LVH was defined according to Sokolow-Lyon criteria. We used competing Cox models to compare hazards for diverse outcomes within groups (e.g., among those with ECG LVH) and for a given event between groups (ECG LVH versus no ECG LVH).
After 15 years, men with ECG LVH at baseline (N = 383) had cumulative incidence of first CVD events and non-CVD deaths of 29.2% and 6.1%, respectively (hazard ratio 4.86; 95% CI, 3.04–7.77). In men without ECG LVH (N = 6576) the incidence of any first CVD event and non-CVD death was 18.9% and 6.9%, respectively (hazard ratio 2.67; 2.39–2.98). Similar associations were observed in women (N = 381 with and N = 8187 without ECG LVH). Coronary heart disease (CHD) was the most common first event in men with ECG LVH (15.0%) and heart failure (HF) was the most common first event in women with ECG LVH (10.5%). After adjustment for risk factors including systolic blood pressure, any CVD event remained the most likely first event.
Among middle-aged individuals with ECG LVH, the most likely first events are CHD in men and HF in women; these results may have implications for preventive approaches.
left ventricular hypertrophy; cardiovascular disease; coronary heart disease; stroke; heart failure
The prognostic impact of reduced glomerular filtration rate (GFR) in chronic heart failure (CHF) is increasingly recognised, but little is known about tubular damage in these patients.
To investigate the prevalence of tubular damage, and its association with GFR, and prognosis in patients with CHF.
Methods and results
In 90 patients with CHF, GFR and effective renal plasma flow (ERPF) were measured ([125I] iothalamate and [131I]hippuran clearances). The tubular markers neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1) as well as urinary albumin excretion were determined in 24 h urine collections. Mean GFR was 78±26 ml/min/1.73 m2. Urinary NGAL (175 (70—346) mg/g creatinine (gCr)), NAG (12 (6—17) U/gCr) and KIM-1 (277 (188—537) ng/gCr) levels were increased compared with 20 healthy controls (all p<0.001). Urinary NAG, but not NGAL or KIM-1 correlated with GFR (r=−0.34, p=0.001) and ERPF (r=−0.29, p=0.006). Both NAG (r=0.21, p=0.048) and KIM-1 (r=0.23, p=0.033) correlated with plasma N-terminal pro-brain natriuretic peptide levels. Both urinary KIM-1 (HR=1.15 (95% CI 1.02 to 1.30) per 100 ng/gCr increase, p=0.025) and NAG (HR=1.42 (95% CI 1.02 to 1.94) per 5 U/gCr increase, p=0.039), were associated with an increased risk of death or heart failure hospitalisations, independent of GFR.
Tubular damage, as indicated by increased urinary concentrations of NGAL, NAG and KIM-1 is common in patients with CHF and mildly reduced GFR. Both urinary KIM-1 and NAG showed prognostic information additional to GFR. These findings suggest an important role for tubular damage and tubular markers in cardiorenal interaction in heart failure.
Heart failure (HF) prevalence rises sharply among those aged 85 years and over. Previous population based echocardiographic studies of left ventricular (LV) dysfunction, the substrate for HF, have included only small numbers in this age group. We used domiciliary echocardiography to estimate the prevalence of LV systolic and diastolic dysfunction in 87–89 year olds and the proportion remaining undiagnosed.
Cross sectional analysis of data from Newcastle 85+ Study.
Primary care, North-East England.
376 men and women aged 87–89 years.
Domiciliary echocardiography was performed and LV systolic and diastolic function was graded. The presence of limiting dyspnoea was assessed by questionnaire. Previous diagnoses of HF were abstracted from general practice (GP) records.
32% of participants (119/376) had LV systolic dysfunction (ejection fraction (EF) ≤50%) and a further 20% (75/376) had moderate or severe LV diastolic dysfunction with preserved EF. Both echocardiographic assessment of LV function and dyspnoea status were available in 74% (278/376) of participants. Among these participants, limiting dyspnoea was present in approximately two thirds of those with significant (systolic or isolated moderate/severe diastolic) LV dysfunction. 84% (73/87) of participants with significant LV dysfunction and limiting dyspnoea did not have a pre-existing HF diagnosis in their GP records. Overall, 26% (73/278) of participants with both echocardiographic and dyspnoea data had undiagnosed, symptomatic, significant LV dysfunction.
Significant systolic and diastolic LV dysfunction is much commoner in community dwelling 87–89 year olds than previous studies have suggested. The majority are both symptomatic and undiagnosed.
Fontan; congenital heart disease; single ventricle; atrial tachycardia; arrhythmia surgery
Left atrial (LA) maximum volume (LAVmax) is an indicator of left ventricular (LV) diastolic function. However, LAVmax is also influenced by systolic events, whereas the LA minimum volume (LAVmin) is directly exposed to LV pressure. The authors hypothesised that LAVmin may be a better correlate of LV diastolic function than LAVmax.
357 participants from a community-based cohort study.
LA volumes and reservoir function, measured as total LA emptying volume (LAEV) and LA emptying fraction (LAEF), were assessed by real-time three-dimensional echocardiography. LV diastolic function was assessed by trans-mitral early (E) and late (A) Doppler velocities and mitral early diastolic velocity by tissue-Doppler (e′). LV systolic function was assessed by LV ejection fraction (LVEF) and global longitudinal strain (GLS) by speckle-tracking.
LAVmin significantly increased with worsening diastolic dysfunction (p<0.001), whereas the increase in LAVmax was less pronounced (p=0.07). LAEV and LAEF decreased with worsening diastolic dysfunction (both p<0.001). In linear regressions, LAVmin and LAVmax were significant predictors of E/e′, with higher parameter estimates for LAVmin. In multivariate models, LAVmin resulted strongly associated with E/e′ (β=0.45, p<0.001), whereas LAVmax was not (β=− 0.16, p=0.08). LA reservoir function was better associated with GLS than LVEF. In multivariate analyses, GLS was significantly associated with LAVmax (β=− 0.15, p=0.002), LAEV (β=−0.37, p<0.001) and LAEF (β=−0.28, p<0.001) but not with LAVmin.
LAVmin is a better correlate of LV diastolic function than LAVmax. The impact of LV longitudinal systolic function on LA reservoir function might explain the weaker relation between LAVmax and LV diastolic function.
The role of high sensitivity troponin T (hs-TnT) in the convalescence phase after an acute coronary syndrome (ACS) is unknown. The authors aim to assess the prognostic utility of a single hs-TnT level at 7-week post-ACS. Second, the authors evaluated whether any serial changes in hs-TnT between the index admission and 7 weeks post-ACS had any link with the prognosis. Third, the authors assessed whether the prognostic utility of hs-TnT is independent of various echocardiographic abnormalities.
The authors measured hs-TnT levels in 326 consecutive patients at 7 weeks after an ACS event. The composite end point of death from any cause or acute myocardial infarction was evaluated over a median duration of 30 months.
A high 7-week hs-TnT (>14 ng/l) predicted adverse clinical outcomes independent of conventional risk factors, left ventricular dysfunction and left ventricular hypertrophy on echocardiography (adjusted RR: 2.69 (95% CI 1.45 to 5.00)). Patients with persistent hs-TnT elevation at 7 weeks were also at an increased risk of cardiovascular events compared with those with an initial high hs-TnT which then normalised (unadjusted RR 3.39 (95% CI 2.02 to 5.68)).
The authors have demonstrated the prognostic utility of a single 7-week hs-TnT measurement in routine ACS patients and that it could be used to assist medium term risk stratification in this patient cohort. In addition, the authors also showed that hs-TnT predicted long-term adverse prognosis independent of various echo parameters. Future studies should evaluate whether tailoring specific treatment interventions to higher risk individuals as identified by an elevated hs-TnT during the convalescence phase of ACS would improve clinical outcomes.
High sensitivity troponin T; 7 weeks post-ACS; prognosis; echocardiographic abnormalities; coronary artery disease; atherosclerosis; risk stratification; EBM; clinical proof of concept studies; regional blood flow; coronary haemodynamics; chronic heart failure; aorta; great vessels and trauma; arrhythmias; sudden cardiac death; ventricular fibrillation; cardiac function
Recent studies have demonstrated that newly diagnosed glucose intolerance is common among patients with acute myocardial infarction (AMI). The purpose of this study was to assess the long-term clinical cardiovascular outcomes in participants with AMI with abnormal fasting glucose compared with normal fasting glucose and an abnormal oral glucose tolerance test (OGTT) compared with a normal OGTT.
A prospective study was performed in 275 consecutive patients with AMI, 85 of whom had pre-diagnosed diabetes mellitus (DM). Those without DM were divided into two groups based on the 75 g OGTT at the time of discharge. Abnormal glucose tolerance (AGT) was defined as 2 h glucose ≥140 mg/dl; 78 patients had normal glucose tolerance (NGT) and 112 had AGT. The same patients were also reclassified into the normal fasting glucose group (NFG; n=168) or the impaired fasting glucose group (IFG; n=22). The association between the glucometabolic status and long-term major adverse cardiovascular event rates was evaluated.
Kaplan–Meier survival curves showed that the AGT group had a worse prognosis than the NGT group and an equivalent prognosis to the DM group (p<0.0005). Cox proportional hazard model analysis showed that the HR of AGT to NGT for major adverse cardiovascular event rates was 2.65 (95% CI 1.37 to 5.15, p=0.004) while the HR of DM to NGT was 3.27 (1.68 to 6.38, p=0.0005). However, Cox HR of IFG to NFG for major adverse cardiovascular event rates was 1.83 (0.86 to 3.87), which was not significant.
In patients with AMI, an abnormal OGTT is a better risk factor for future adverse cardiovascular events than impaired fasting blood glucose.
Acute myocardial infarction; diabetes mellitus; postprandial hyperglycemia; cardiovascular events; prognosis; microvascular dysfunction; clinical cardiology; clinical coronary heart disease; diabetes; coronary hemodynamics; coronary artery disease; valvular disease; imaging and diagnostics; diabetic heart disease; peripheral vascular disease; diastolic dysfunction; endocarditis; surgery-valve; MRI; coronary artery disease; risk factors; EBM; heart failure
Cardiac surgery; cardiopulmonary bypass; artificial heart; surgery-coronary bypass; surgery-valve
Dissection; atrial fibrillation; cardiac surgery; valve surgery
Studies on the association between short-term exposure to ambient air pollution and heart rate variability (HRV) suggest that particulate matter (PM) exposure is associated with reductions in measures of HRV, but there is heterogeneity in the nature and magnitude of this association between studies. The authors performed a meta-analysis to determine how consistent this association is.
The authors searched the Pubmed citation database and Web of Knowledge to identify studies on HRV and PM.
Of the epidemiologic studies reviewed, 29 provided sufficient details to be considered. The meta-analysis included 18667 subjects recruited from the population in surveys, studies from patient groups, and from occupationally exposed groups.
Two investigators read all papers and computerised all relevant information.
The authors computed pooled estimates from a random-effects model. In the combined studies, an increase of 10 μg/m3 in PM2.5 was associated with significant reductions in the time-domain measurements, including low frequency (−1.66%, 95% CI −2.58% to −0.74%) and high frequency (−2.44%, 95% CI −3.76% to −1.12%) and in frequency-domain measurements, for SDNN (−0.12%, 95% CI −0.22% to −0.03%) and for rMSSD (−2.18%, 95% CI −3.33% to −1.03%). Funnel plots suggested that no publication bias was present and a sensitivity analysis confirmed the robustness of our combined estimates.
The meta-analysis supports an inverse relationship between HRV, a marker for a worse cardiovascular prognosis, and particulate air pollution.
Heart rate variability; air pollution; meta-analysis; cardiac function
Aim of FAST-MI 2010
To gather data on characteristics, management and outcomes of patients hospitalised for acute myocardial infarction (AMI) at the end of 2010 in France.
To provide cardiologists and health authorities national and regional data on AMI management every 5 years.
Metropolitan France. 213 academic (n=38), community (n=110), army hospitals (n=2), private clinics (n=63), representing 76% of centres treating AMI patients. Inclusion from 1 October 2010.
Consecutive patients included during 1 month, with a possible extension of recruitment up to one additional month (132 centres); 4169 patients included over the entire recruitment period, 3079 during the first 31 days; 249 additional patients declining participation (5.6%).
Consecutive adults with ST-elevation and non-ST-elevation AMI with symptom onset ≤48 h. Patients with AMI following cardiovascular procedures excluded.
Web-based collection of 385 items (demographic, medical, biologic, management data) recorded online from source files by external research technicians; case-record forms with automatic quality checks. Centralised biology in voluntary centres to collect DNA samples and serum. Long-term follow-up organised centrally with interrogation of municipal registry offices, patients' physicians, and direct contact with the patients.
Data management in Toulouse University. Statistical analyses: Université Paris Descartes, Université de Toulouse, Université Pierre et Marie Curie-Paris 06, Paris.
Endpoints and linkages to other data
In-hospital events; cardiovascular events, hospital admissions and mortality during follow-up. Linkage with Institute for National Statistics.
Access to data
Available for research to any participating clinician upon request to executive committee (email@example.com).
Registry; myocardial infarction; management; outcomes
To investigate the respective associations and clinical usefulness of the metabolic syndrome (MetS) and its individual components to predict the risk of first coronary heart disease (CHD) events in elderly.
The Three-City is a French prospective multisite community-based cohort.
Three large French cities: Bordeaux, Dijon and Montpellier.
7612 subjects aged 65 and over who were free of CHD at baseline.
Main outcome measures
The MetS was defined by the 2005 National Cholesterol Education Program Adult Treatment Panel III criteria.
During a median follow-up of 5.2 years, 275 first CHD events were adjudicated. The MetS was associated with increased risks of total (adjusted HR: 1.78; 95% CI 1.39 to 2.28), fatal (HR: 2.40; 95% CI 1.41 to 4.09) and non-fatal (HR: 1.64; 95% CI 1.24 to 2.17) CHD events. The association with total CHD was significant in women (HR: 2.56; 95% CI 1.75 to 3.75) but not in men (HR: 1.39; 95% CI 0.99 to 1.94; p for interaction=0.012). When in the same multivariable model, hyperglycemia and abdominal adiposity in women, hyperglycemia, lower HDL cholesterol and abdominal adiposity (inverse association) in men were the components significantly associated with CHD. The components of the MetS but not the MetS itself improved risk prediction beyond traditional risk factors (NRI= 9.35%, p<0;001).
The MetS is a risk marker for CHD in community-dwelling elderly subjects but may not be useful for CHD risk prediction purposes compared to its individual components.
Metabolic syndrome; coronary heart disease; elderly; risk stratification; psychology/psychiatry; epidemiology
Mutations involving cardiac ion channels result in abnormal action potential formation or propagation, leading to cardiac arrhythmias. Despite the large impact on society of sudden cardiac death resulting from such arrhythmias, understanding of the underlying cellular mechanism is poor and clinical risk stratification and treatment consequently limited. Basic research using molecular techniques, as well as animal models, has proved extremely useful in improving our knowledge of inherited arrhythmogenic syndromes. This offers the practitioner tools to accurately diagnose rare disorders and provides novel markers for risk assessment and a basis for new strategies of treatment.
Channelopathy; sudden cardiac death; Brugada; ventricular tachycardia; sudden adult death syndrome
To assess the cost-effectiveness of dabigatran etexilate, a new oral anticoagulant, versus warfarin and other alternatives for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation (AF).
A Markov model estimated the cost-effectiveness of dabigatran etexilate versus warfarin, aspirin or no therapy. Two patient cohorts with AF (starting age of <80 and ≥80 years) were considered separately, in line with the UK labelled indication. Modelled outcomes over a lifetime horizon included clinical events, quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratios (ICERs).
Patients treated with dabigatran etexilate experienced fewer ischaemic strokes (3.74 dabigatran etexilate vs 3.97 warfarin) and fewer combined intracranial haemorrhages and haemorrhagic strokes (0.43 dabigatran etexilate vs 0.99 warfarin) per 100 patient-years. Larger differences were observed comparing dabigatran etexilate with aspirin or no therapy. For patients initiating treatment at ages <80 and ≥80 years, the ICERs for dabigatran etexilate were £4831 and £7090/QALY gained versus warfarin with a probability of cost-effectiveness at £20 000/QALY gained of 98% and 63%, respectively. For the patient cohort starting treatment at ages <80 years, the ICER versus aspirin was £3457/QALY gained and dabigatran etexilate was dominant (ie, was less costly and more effective) compared with no therapy. These results were robust in sensitivity analyses.
This economic evaluation suggests that the use of dabigatran etexilate as a first-line treatment for the prevention of stroke and systemic embolism is likely to be cost-effective in eligible UK patients with AF.
Anticoagulation; Dabigatran etexilate; warfarin; stroke; cost-effectiveness; atrial fibrillation
To investigate the role of inflammation in the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy (HCM).
Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
Twenty-four patients with a single HCM-causing mutation D175N in the α-tropomyosin gene and 17 control subjects.
Main outcome measures
Endomyocardial biopsy samples taken from the patients with HCM were compared with matched myocardial autopsy specimens. Levels of high-sensitivity C-reactive protein (hsCRP) and proinflammatory cytokines were measured in patients and controls. Myocardial late gadolinium enhancement (LGE) in cardiac MRI (CMRI) was detected.
Endomyocardial samples in patients with HCM showed variable myocyte hypertrophy and size heterogeneity, myofibre disarray, fibrosis, inflammatory cell infiltration and nuclear factor kappa B (NF-κB) activation. Levels of hsCRP and interleukins (IL-1β, IL-1RA, IL-6, IL-10) were significantly higher in patients with HCM than in control subjects. In patients with HCM, there was a significant association between the degree of myocardial inflammatory cell infiltration, fibrosis in histopathological samples and myocardial LGE in CMRI. Levels of hsCRP were significantly associated with histopathological myocardial fibrosis. hsCRP, tumour necrosis factor α and IL-1RA levels had significant correlations with LGE in CMRI.
A variable myocardial and systemic inflammatory response was demonstrated in patients with HCM attributable to an identified sarcometric mutation. Inflammatory response was associated with myocardial fibrosis, suggesting that myocardial fibrosis in HCM is an active process modified by an inflammatory response.
Hypertrophic cardiomyopathy; inflammation; fibrosis; genetics; late gadolinium enhancement; coronary angioplasty; aortic stenosis; invasive cardiology; coronary artery disease; cardiomyopathy hypertrophic; tissue characters; HCM; MRI; myocardial function; myocardial perfusion; myocardial ischaemia; myocardial infarction; arrhythmias; endocrinology
Racial/ethnic differences in the incidence and severity of heart failure (HF) are not well understood, but may be related to pre-existing variations in myocardial function.
To examine racial/ethnic differences in regional myocardial function among asymptomatic individuals free of known cardiovascular disease.
Design, setting and patients
The Multi-Ethnic Study of Atherosclerosis is a prospective, observational study of individuals without baseline cardiovascular disease, representing four major racial/ethnic groups. A total of 1099 study participants underwent cardiac MRI with tissue tagging; for each study, peak systolic strain (Ecc) and strain rate (SRs) were determined in four left ventricular (LV) regions.
Main outcome measures
Multiple linear regression was used to analyse the relationship between race/ethnicity and regional strain (Ecc and SRs) while adjusting for cardiovascular risk factors.
Compared with other racial/ethnic groups, Chinese-Americans had the greatest magnitude of Ecc in a majority of LV regions (–19.60±3.78, p<0.05); Chinese-Americans also had the greatest absolute values for SRs in all regions, reflecting higher rate of systolic contraction (–2.01±0.76, p<0.05). Conversely, African-Americans had the lowest Ecc values (–17.50±4.00, p<0.05) in the majority of wall regions while Hispanics demonstrated the lowest rate of contractility in all wall regions (–1.44±0.50, p≤0.001) in comparison with the other racial/ethnic groups. These race-based differences remained significant in the majority of LV wall regions after adjusting for multiple variables, including hypertension and LV mass.
Important race-based differences in regional LV systolic function in a large cohort of asymptomatic individuals have been demonstrated. Further research is needed to investigate the possible mechanisms related to the race/ethnicity-based variations found in this study.