Association of multimorbidity and changes in health-related quality of life following myocardial infarction: a UK multicentre longitudinal patient-reported outcomes study.

BACKGROUND: Multimorbidity is prevalent for people with myocardial infarction (MI), yet previous studies investigated single-health conditions in isolation. We identified patterns of multimorbidity in MI survivors and their associations with changes in HRQoL. METHODS: In this national longitudinal cohort study, we analysed data from 9566 admissions with MI from 77 National Health Service hospitals in England between 2011 and 2015. HRQoL was measured using EuroQol 5 dimension (EQ5D) instrument and visual analogue scale (EQVAS) at hospitalisation, 6, and 12 months following MI. Latent class analysis (LCA) of pre-existing long-term health conditions at baseline was used to identify clusters of multimorbidity and associations with changes in HRQoL quantified using mixed effects regression analysis. RESULTS: Of 9566 admissions with MI (mean age of 64.1 years [SD 11.9], 7154 [75%] men), over half (5119 [53.5%] had multimorbidities. LCA identified 3 multimorbidity clusters which were severe multimorbidity (591; 6.5%) with low HRQoL at baseline (EQVAS 59.39 and EQ5D 0.62) which did not improve significantly at 6 months (EQVAS 59.92, EQ5D 0.60); moderate multimorbidity (4301; 47.6%) with medium HRQoL at baseline (EQVAS 63.08, EQ5D 0.71) and who improved at 6 months (EQVAS 71.38, EQ5D 0.76); and mild multimorbidity (4147, 45.9%) at baseline (EQVAS 64.57, EQ5D 0.75) and improved at 6 months (EQVAS 76.39, EQ5D 0.82). Patients in the severe and moderate groups were more likely to be older, women, and presented with NSTEMI. Compared with the mild group, increased multimorbidity was associated with lower EQ-VAS scores (adjusted coefficient: -5.12 [95% CI -7.04 to -3.19] and -0.98 [-1.93 to -0.04] for severe and moderate multimorbidity, respectively. The severe class was more likely than the mild class to report problems in mobility, OR 9.62 (95% confidence interval: 6.44 to 14.36), self-care 7.87 (4.78 to 12.97), activities 2.41 (1.79 to 3.26), pain 2.04 (1.50 to 2.77), and anxiety/depression 1.97 (1.42 to 2.74). CONCLUSIONS: Among MI survivors, multimorbidity clustered into three distinct patterns and was inversely associated with HRQoL. The identified multimorbidity patterns and HRQoL domains that are mostly affected may help to identify patients at risk of poor HRQoL for which clinical interventions could be beneficial to improve the HRQoL of MI survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT01808027 and NCT01819103.

Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3: protocol for a longitudinal study.

INTRODUCTION: Patients with cardiovascular disease are living longer and are more frequently accessing healthcare resources. The Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3 national study is designed to improve understanding of the effect of quality of care on health-related outcomes for patients hospitalised with acute coronary syndrome (ACS). METHODS AND ANALYSIS: EMMACE-3 is a longitudinal study of 5556 patients hospitalised with an ACS in England. The study collects repeated measures of health-related quality of life, information about medications and patient adherence profiles, a survey of hospital facilities, and morbidity and mortality data from linkages to multiple electronic health records. Together with EMMACE-3X and EMMACE-4, EMMACE-3 will assimilate detailed information for about 13 000 patients across more than 60 hospitals in England. ETHICS AND DISSEMINATION: EMMACE-3 was given a favourable ethical opinion by Leeds (West) Research Ethics committee (REC reference: 10/H131374). On successful application, study data will be shared with academic collaborators. The findings from EMMACE-3 will be disseminated through peer-reviewed publications, at scientific conferences, the media, and through patient and public involvement. STUDY REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01808027. Information about the study is also available at EMMACE.org.

Mortality and missed opportunities along the pathway of care for ST-elevation myocardial infarction: a national cohort study.

AIMS: To examine the association between cumulative missed opportunities for care (CMOC) and mortality in patients with ST-elevation myocardial infarction (STEMI). METHODS: A cohort study of 112,286 STEMI patients discharged from hospital alive between January 2007 and December 2010, using data from the Myocardial Ischaemia National Audit Project (MINAP). A CMOC score was calculated for each patient and included: pre-hospital ECG, acute use of aspirin, timely reperfusion, prescription at hospital discharge of aspirin, thienopyridine inhibitor, ACE-inhibitor (or equivalent), HMG-CoA reductase inhibitor and ß-blocker, and referral for cardiac rehabilitation. Mixed-effects logistic regression models evaluated the effect of CMOC on risk-adjusted 30-day and 1-year mortality (RAMR). RESULTS: 44.5% of patients were ineligible for ≥1 care component. Of patients eligible for all nine components, 50.6% missed ≥1 opportunity. Pre-hospital ECG and timely reperfusion were most frequently missed, predicting further missed care at discharge (pre-hospital ECG incident rate ratio [95% CI]: 1.64 [1.58-1.70]; timely reperfusion 9.94 [9.51-10.40]). Patients ineligible for care had higher RAMR than those eligible for care (30-days: 1.7% vs. 1.1%; 1-year: 8.6% vs. 5.2%), whilst those with no missed care had lower mortality than patients with ≥4 CMOC (30-days: 0.5% vs. 5.4%, adjusted OR (aOR) per CMOC group 1.22, 95% CI: 1.05-1.42; 1-year: 3.2% vs. 22.8%, aOR 1.23, 1.13-1.34). CONCLUSIONS: Opportunities for care in STEMI are commonly missed and significantly associated with early and later mortality. Thus, outcomes after STEMI may be improved by greater attention to missed opportunities to eligible care.

The development of the NZ-based international upper limb surgery registry.

STUDY DESIGN: Implementation study. OBJECTIVES: To describe the development and potential value of the New Zealand (NZ) upper limb surgery registry and report the demographic and spinal cord injury characteristics of individuals with tetraplegia collated to date. SETTING: Multi Center-coordinated from Burwood Spinal Unit, NZ. METHODS: Following discussions with eight international units, clinical information and outcomes measures were agreed upon for use in this specific population. To implement this consensus, a web-based upper limb surgery registry was developed in NZ. Inclusion criteria included referral to a hand clinic for clinical assessment for suitability for tendon transfer surgery. Clinical data were collected regardless of acceptance of surgery thereby creating a self-selected control group. Twenty-eight years of retrospective NZ data was entered into the registry, as well as 3 years of prospective data collected in NZ. RESULTS: From 1982 to 2013, a total of 357 persons with tetraplegia were assessed as suitable for surgery. Of those, 223 individuals underwent surgery and 134 declined the intervention(s). The prospective group currently comprises 55 assessments with 23 surgery individuals and 32 who have declined surgery to date. CONCLUSION: Clinical information is now available within a web-based registry for all individuals reviewed in hand clinics from when upper limb surgery was first introduced. A broad range of outcomes of interest can easily be reported directly from the registry. The self-selected control group will allow comparative studies to be explicitly linked to the specific interventions of interest.

Trends in hospital treatments, including revascularisation, following acute myocardial infarction, 2003-2010: a multilevel and relative survival analysis for the National Institute for Cardiovascular Outcomes Research (NICOR).

OBJECTIVE: To investigate temporal changes in survival after acute myocardial infarction (AMI) by early invasive strategy. METHODS: Accelerated failure time and 6-month relative survival analyses stratified by thrombolysis or primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI) and coronary angiography for non-STEMI (NSTEMI) encompassing 583 466 patients across 247 hospitals in England and Wales over hospital admission periods 2003-2004, 2005-2006, 2007-2008 and 2009-2010. RESULTS: Survival improved significantly for STEMI patients who received reperfusion therapy (time ratio (TR) 1.47, 95% CI 1.22 to 2.78) and was stable for those who did not (TR 1.02, 95% CI 0.85 to 1.22). While there were significant improvements in survival for NSTEMI patients who underwent coronary angiography (TR 1.39, 95% CI 1.18 to 1.62), there was a significant decline for those who did not (TR 0.70, 95% CI 0.65 to 0.75). Patients without reperfusion therapy or coronary angiography had a greater number of comorbidities, but the use of secondary prevention medications was comparable with patients who received reperfusion therapy or coronary angiography. There was a significant hospital-level survival effect, with higher crude 6-month mortality in hospitals in the lowest coronary angiography and PPCI quartiles (angiography Q1: 16.4% vs Q4: 12.8%; PPCI Q1: 15.8% vs Q4: 12.4%). CONCLUSIONS: Survival rates after AMI have improved. Whereas survival estimates for STEMI patients who did not receive reperfusion therapy were stable, they worsened for NSTEMI patients not receiving coronary angiography.

An investigation of CYP2D6 genotype and response to metoprolol CR/XL during dose titration in patients with heart failure: a MERIT-HF substudy.

To explore the pharmacogenetic effects of the cytochrome P450 (CYP)2D6 genotype in patients with systolic heart failure treated using controlled/extended-release (CR/XL) metoprolol, this study assessed the CYP2D6 locus for the nonfunctional *4 allele (1846G>A; rs3892097) in the Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF; n = 605). Participants were characterized as extensive, intermediate, or poor metabolizers (EMs, IMs, or PMs, respectively), based on the presence of the CYP2D6*4 allele (EM: *1*1, 60.4%; IM: *1*4, 35.8%; and PM: *4*4, 3.8%). Plasma metoprolol concentrations were 2.1-/4.6-fold greater in the IM/PM groups as compared with the EM group (P < 0.0001). Metoprolol induced significantly lower heart rates and diastolic blood pressures during early titration, indicating a CYP2D6*4 allele dose-response effect (P < 0.05). These effects were not observed at maximal dose, suggesting a saturable effect. Genotype did not adversely affect surrogate treatment efficacy. CYP2D6 genotype modulates metoprolol pharmacokinetics/pharmacodynamics during early titration; however, the MERIT-HF-defined titration schedule remains recommended for all patients, regardless of genotype.

An evaluation of composite indicators of hospital acute myocardial infarction care: a study of 136,392 patients from the Myocardial Ischaemia National Audit Project.

BACKGROUND: Hospital acute myocardial infarction (AMI) care is increasingly evaluated using composite quality scores. We investigated the influence of three aggregation methods for an AMI indicator on mortality and hospital rank. METHODS AND RESULTS: We studied 136,392 patients discharged alive from 199 hospitals with AMI recorded in the Myocardial Ischaemia National Audit Project, between 01/01/2008 and 31/12/2009. A composite of prescription of aspirin, thienopyridine inhibitor, ß-blocker, angiotensin converting enzyme inhibitor, HMG CoA reductase enzyme inhibitor and enrolment in cardiac rehabilitation at discharge was aggregated as opportunity based (OBCS), weighted opportunity-based (WOBCS) and all-or-nothing (ANCS) scores. We quantified adjusted 30-day, 6-month and 1-year mortality rates and hospital performance rank. Median (IQR) scores were OBCS: 95.0% (3.5), WOBCS: 94.7% (0.8) and ANCS: 80.9% (11.8). The three methods affected the proportion of hospitals outside 99.8% credible limits of the national median (OBCS: 52.2%, WOBCS: 64.3% and ANCS: 37.7%) and hospital rank. Each 1% increase in composite score was significantly associated with a 1 to 3% and a 4% reduction in 6-month and 1-year mortality, respectively. However, the ANCS had fewer cases and no significant association with 30-day mortality. CONCLUSIONS: A hospital composite score, incorporating 6 aspects of AMI care, was significantly inversely associated with mortality. However, composite aggregation method influenced hospital rank, number of cases available for analysis and size of the association with all-cause mortality, with the ANCS performing least well. The use and choice of composite scores in hospital AMI quality improvement requires careful evaluation.

Age-dependent inequalities in improvements in mortality occur early after acute myocardial infarction in 478,242 patients in the Myocardial Ischaemia National Audit Project (MINAP) registry.

BACKGROUND: Mortality rates after acute myocardial infarction (AMI) have declined, but there is uncertainty regarding the extent of improvements in early mortality in the elderly. METHODS: Mixed-effects regression analysis of 30-day mortality using data from 478,242 patients with AMI at 215 hospitals in England and Wales stratified by STEMI/NSTEMI, sex, and age group. A hospital opportunity-based composite score (OBCS) for aspirin, ACE-inhibitor, statin, ß blocker, and referral for cardiac rehabilitation was used as measure of quality of hospital care. RESULTS: 30-day mortality rates (95% CI) fell from 10.7% (10.6 to 10.9%) in 2004/5 to 8.4% (8.3 to 8.6%) in 2008/9. The median (IQR) hospital OBCSs increased over time, 2004/5: 87.3 (7.2), 2006/7: 88.9 (6.3), 2008/9: 90.3 (6.1), P<0.001, and were similar between age groups (18 to <65 years, 65 to 79 years, and ≥ 80 years) for STEMI: 89.4 (6.5) vs. 89.4 (6.6), vs. 89.2 (6.5) and NSTEMI: 88.6 (7.3) vs. 88.8 (7.0) vs. 88.9 (7.0), respectively For males, all age groups except patients <65 years demonstrated a significant decrease in adjusted mortality. For females, only patients ≥ 80 years demonstrated a significant reduction in adjusted mortality. A 1% increase in hospital OBCS was associated with a 1% decrease in 30-day mortality (95% CI: 0.99 to 0.99, P<0.001). CONCLUSION: In England and Wales, for patients with AMI there are age and sex-dependent differences in improvements in 30-day mortality. Whereas young males with AMI have reached an acceptable performance plateau, all other groups are either improving or, more importantly, are yet to demonstrate this.

Statistical profiling of hospital performance using acute coronary syndrome mortality.

BACKGROUND: In order to improve the quality of care delivered to patients and to enable patient choice, public reports comparing hospital performances are routinely published. Robust systems of hospital 'report cards' on performance monitoring and evaluation are therefore crucial in medical decision-making processes. In particular, such systems should effectively account for and minimise systematic differences with regard to definitions and data quality, care and treatment quality, and 'case mix'. METHODS: Four methods for assessing hospital performance on mortality outcome measures were considered. The methods included combinations of Bayesian fixed- and random-effects models, and risk-adjusted mortality rate, and rank-based profiling techniques. The methods were empirically compared using 30-day mortality in patients admitted with acute coronary syndrome. Agreement was firstly assessed using median estimates between risk-adjusted mortality rates for a hospital and between ranks associated with a hospital's risk-adjusted mortality rates. Secondly, assessment of agreement was based on a classification of hospitals into low, normal or high performing using risk-adjusted mortality rates and ranks. RESULTS: There was poor agreement between the point estimates of risk-adjusted mortality rates, but better agreement between ranks. However, for categorised performance, the observed agreement between the methods' classification of the hospital performance ranged from 90 to 98%. In only two of the six possible pair-wise comparisons was agreement reasonable, as reflected by a Kappa statistic; it was 0.71 between the methods of identifying outliers with the fixed-effect model and 0.77 with the hierarchical model. In the remaining four pair-wise comparisons, the agreement was, at best, moderate. CONCLUSIONS: Even though the inconsistencies among the studied methods raise questions about which hospitals performed better or worse than others, it seems that the choice of the definition of outlying performance is less critical than that of the statistical approach. Therefore there is a need to find robust systems of 'regulation' or 'performance monitoring' that are meaningful to health service practitioners and providers.

The RATPAC (Randomised Assessment of Treatment using Panel Assay of Cardiac markers) trial: a randomised controlled trial of point-of-care cardiac markers in the emergency department.

OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of using a point-of-care cardiac marker panel in patients presenting to the emergency department (ED) with suspected but not proven acute myocardial infarction (AMI). DESIGN: Multicentre pragmatic open randomised controlled trial and economic evaluation. SETTING: Six acute hospital EDs in the UK. PARTICIPANTS: Adults presenting to hospital with chest pain due to suspected but not proven myocardial infarction, and no other potentially serious alternative pathology or comorbidity. INTERVENTIONS: Participants were allocated using an online randomisation system to receive either (1) diagnostic assessment using the point-of-care biochemical marker panel or (2) conventional diagnostic assessment without the panel. All tests and treatments other than the panel were provided at the discretion of the clinician. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients successfully discharged home after ED assessment, defined as patients who had (1) either left the hospital or were awaiting transport home with a discharge decision having been made at 4 hours after initial presentation and (2) suffered no major adverse event (as defined below) during the following 3 months. Secondary outcomes included length of initial hospital stay and total inpatient days over 3 months, and major adverse events (death, non-fatal AMI, life-threatening arrhythmia, emergency revascularisation or hospitalisation for myocardial ischaemia). Economic analysis estimated mean costs and quality-adjusted life-years (QALYs), and then estimated the probability of cost-effectiveness assuming willingness to pay of £20,000 per QALY gained. RESULTS: We randomised 1132 participants to point of care and 1131 to standard care, and analysed 1125 and 1118, respectively [mean age 54.5 years, 1307/2243 (58%) male and 269/2243 (12%) with known coronary heart disease (CHD)]. In the point-of-care group 358/1125 (32%) were successfully discharged compared with 146/1118 (13%) in the standard-care group [odds ratio (OR) adjusted for age, gender and history of CHD 3.81; 95% confidence interval (CI) 3.01 to 4.82, p < 0.001]. Mean length of the initial hospital stay was 29.6 hours versus 31.8 hours (mean difference = 2.1 hours; 95% CI -3.7 to 8.0 hours, p = 0.462), while median length of initial hospital stay was 8.8 hours versus 14.2 hours (p < 0.001). More patients in the point-of-care group had no inpatient days recorded during follow-up (54% vs 40%, p < 0.001), but mean inpatient days did not differ between the two groups (1.8 vs 1.7, p = 0.815). More patients in the point-of-care group were managed on coronary care [50/1125 (4%) vs 31/1118 (3%), p = 0.041]. There were 36 (3%) patients with major adverse events in the point-of-care group and 26 (2%) in the standard-care group (adjusted OR 1.31; 95% CI 0.78 to 2.20, p = 0.313). Mean costs per patient were £1217 with point-of-care versus £1006 with standard care (p = 0.056), while mean QALYs were 0.158 versus 0.161 (p = 0.250). The probability of standard care being dominant (i.e. cheaper and more effective) was 0.888. CONCLUSIONS: Point-of-care testing increases the proportion of patients successfully discharged home and reduces the median (but not mean) length of hospital stay. It is more expensive than standard care and unlikely to be considered cost-effective. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37823923. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 23. See the HTA programme website for further project information.

The influence of SLCO1B1 (OATP1B1) gene polymorphisms on response to statin therapy.

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are well established in the treatment of hypercholesterolaemia and the prevention of coronary artery disease. Despite this, there is wide inter-individual variability in response to statin therapy, in terms of both lipid-lowering and adverse drug reactions. The major site of statin action is within hepatocytes and recent interest has focussed on genetic variation in hepatic influx and efflux transporters for their potential to explain these differences. In this review we explore current literature regarding the pharmacokinetic and pharmacodynamic influence of the common c.388A>G and c.521T>C single-nucleotide polymorphisms (SNPs) within the solute carrier organic anion transporter 1B1 (SLCO1B1) gene, encoding the organic anion transporter polypeptide 1B1 (OATP1B1) influx transporter. We discuss their potential to predict the efficacy of statin therapy and the likelihood that patients will experience adverse effects.

Serum 99th centile values for two heart-type fatty acid binding protein assays.

BACKGROUND: We have previously demonstrated that heart-type fatty acid binding protein (H-FABP) is an independent prognostic marker for survival after acute coronary syndrome (ACS). This study aimed to define the 99th centile values for H-FABP as determined with two different assays, and to study the relationship with age, gender and renal function. METHODS: H-FABP was measured on redundant routine outpatient samples using the MARKIT-M (Dainippon) and the Evidence Investigator (Randox) assays. RESULTS: Two hundred and forty-two subjects with Siemens Ultra-TnI value <0.045 microg/L (99th centile) were studied. In all, 174 subjects had estimated glomerular filtration rate (eGFR) >60 mL/min. The 99th centile values for subjects with eGFR >60 mL/min for the Evidence Investigator H-FABP were 5.3 and 5.8 microg/L and for the MARKIT-M H-FABP were 8.3 and 9.1 microg/L in female and male subjects, respectively. There is an increase in H-FABP with age in subjects with normal renal function for both assays. Gender comparison showed no significant difference for either assay. Comparison of samples showed that subjects with eGFR <60 mL/min showed a median increase of 0.71 microg/L with Evidence Investigator assay and 1.09 microg/L with MARKIT-M assay compared with subjects with eGFR >60 mL/min. Calibration differences were confirmed by cross measurement of calibrators and recombinant H-FABP. CONCLUSIONS: We have defined the 99th centile values for H-FABP in a population of primary and secondary care outpatients that can be used to risk stratify patients with ACS. We have confirmed that H-FABP increases with renal dysfunction and age, but have not confirmed the gender difference previously reported.

Evaluation of risk scores for risk stratification of acute coronary syndromes in the Myocardial Infarction National Audit Project (MINAP) database.

OBJECTIVE: To compare the discriminative performance of the PURSUIT, GUSTO-1, GRACE, SRI and EMMACE risk models, assess their performance among risk supergroups and evaluate the EMMACE risk model over the wider spectrum of acute coronary syndrome (ACS). DESIGN: Observational study of a national registry. SETTING: All acute hospitals in England and Wales. PATIENTS: 100 686 cases of ACS between 2003 and 2005. MAIN OUTCOME MEASURES: Model performance (C-index) in predicting the likelihood of death over the time period for which they were designed. The C-index, or area under the receiver-operating curve, range 0-1, is a measure of the discriminative performance of a model. RESULTS: The C-indexes were: PURSUIT C-index 0.79 (95% confidence interval 0.78 to 0.80); GUSTO-1 0.80 (0.79 to 0.81); GRACE in-hospital 0.80 (0.80 to 0.81); GRACE 6-month 0.80 (0.79 to 0.80); SRI 0.79 (0.78 to 0.80); and EMMACE 0.78 (0.77 to 0.78). EMMACE maintained its ability to discriminate 30-day mortality throughout different ACS diagnoses. Recalibration of the model offered no notable improvement in performance over the original risk equation. For all models the discriminative performance was reduced in patients with diabetes, chronic renal failure or angina. CONCLUSION: The five ACS risk models maintained their discriminative performance in a large unselected English and Welsh ACS population, but performed less well in higher-risk supergroups. Simpler risk models had comparable performance to more complex risk models. The EMMACE risk score performed well across the wider spectrum of ACS diagnoses.

The heart rate hypothesis: ready to be tested.

There is increasing evidence that increased heart rate may be an independent risk factor for cardiovascular morbidity and mortality both in patients with ischaemic heart disease and in the general population. Elevated heart rate in coronary artery disease is a major determinant of oxygen consumption and appears to evoke most episodes of ischaemia. Increased resting heart rate may also contribute to the development of atherosclerosis, facilitate plaque destabilisation and initiate arrhythmias, leading to acute coronary events and sudden death. Reducing heart rate is a central aim in the treatment of stable angina pectoris; this therapeutic approach may have an essential role in lowering the incidence of cardiovascular morbidity and mortality in patients with pre-existing ischaemic heart disease. However, this heart rate hypothesis has not thus far been proven. Evidence suggests that the use of heart rate-lowering drugs may have a beneficial effect; however, most treatments for angina have additional negative inotropic effects on the heart. This hypothesis can now be tested following the recent development of selective heart rate drugs.

Predictors of in-hospital mortality for patients admitted with ST-elevation myocardial infarction: a real-world study using the Myocardial Infarction National Audit Project (MINAP) database.

OBJECTIVE: Although early thrombolysis reduces the risk of death in STEMI patients, mortality remains high. We evaluated factors predicting inpatient mortality for patients with STEMI in a "real-world" population. DESIGN: Analysis of the Myocardial Infarction National Audit Project (MINAP) database using multivariate logistic regression and area under the receiver operating curve analysis. SETTING: All acute hospitals in England and Wales. PATIENTS: 34 722 patients with STEMI from 1 January 2003 to 31 March 2005. RESULTS: Inpatient mortality was 10.6%. The highest odds ratios for inpatient survival were aspirin therapy given acutely and out-of-hospital thrombolysis, independently associated with a mortality risk reduction of over half. A 10-year increase in age doubled inpatient mortality risk, whereas cerebrovascular disease increased it by 1.7. The risk model comprised 14 predictors of mortality, C index = 0.82 (95% CI 0.82 to 0.83, p<0.001). A simple model comprising age, systolic blood pressure (SBP) and heart rate (HR) offered a C index of 0.80 (0.79 to 0.80, p<0.001). CONCLUSION: The strongest predictors of in-hospital survival for STEMI were aspirin therapy given acutely and out-of-hospital thrombolysis, Previous STEMI models have focused on age, SBP and HR We have confirmed the importance of these predictors in the discrimination of death after STEMI, but also demonstrated that other potentially modifiable variables impact upon the prediction of short-term mortality.

Effect of a common X-linked angiotensin II type 2-receptor gene polymorphism (-1332 G/A) on the occurrence of premature myocardial infarction and stenotic atherosclerosis requiring revascularization.

OBJECTIVES: To assess the association of the angiotensin II type 2 (AT2) receptor (-1332 G/A) gene polymorphism with premature coronary artery disease (CAD) and investigate for a further role in both myocardial infarction and predominantly stenotic atherosclerosis requiring revascularisation. METHODS AND RESULTS: We investigated 885 families, which consisted of at least one sibling affected with premature CAD and at least one unaffected sibling. Genotyping of subjects was performed using a restriction enzyme digestion of an initial 310 bp PCR fragment that included the AT2 (-1332 G/A) locus. The mean age of the 1143 individuals affected by premature CAD at the time of event was 50.6+/-9.1 years. The genetic data were analyzed for these families using the X-linked sibling transmission disequilibrium test (XS-TDT). We observed significant evidence for an association for the AT2 (-1332 G) locus and premature CAD (p-exact value=0.028). This was driven by a highly significant result in men (p-exact value=0.005). We performed further analyses to investigate for an association with myocardial infarction (Group 1) and stenotic atherosclerosis that was of sufficient severity as to require revascularization (Group 2). We found an increase in the frequency of the G/GG genotype in both Groups 1 and 2, being most marked in Group 2 (XS-TDT, p-exact value=0.0134); logistic regression (p=0.033, OR 1.38; 95% CI of 1.212-1.507). CONCLUSION: We have observed evidence of association between the X-linked AT2 (-1332 G/A) polymorphism and premature CAD with further evidence of a statistically significant association with stenotic atherosclerosis requiring revascularization.

The British Cardiac Society Working Group definition of myocardial infarction: implications for practice.

OBJECTIVE: To assess the impact on observed mortality of the British Cardiac Society (BCS) definition of myocardial infarction (MI) in 11 UK hospitals. DESIGN: Prospective observational registry. SETTING: 11 adjacent hospitals in the West Yorkshire region. PATIENTS: 2484 patients with the acute coronary syndrome (ACS) were identified during a six month period (28 April to 28 October 2003). Demographic, clinical, and treatment variables were collected on all patients. Deaths were monitored through the Office of National Statistics. Patients were categorised into three groups according to the BCS definition of MI: ACS with unstable angina (UA), ACS with myocyte necrosis, and ACS with clinical MI. RESULTS: 30 day mortality was 4.5%, 10.4%, and 12.9% (p < 0.001) in the ACS with UA, ACS with myocyte necrosis, and ACS with clinical MI groups, respectively. At six months the mortality for patients in the groups ACS with clinical MI and ACS with myocyte necrosis was similar (19.2% v 18.7%), being higher than for ACS with UA (8.6%). Same admission percutaneous coronary intervention was similar in groups with clinical MI and myocyte necrosis (11.1% v 10.7%, respectively) as was coronary artery bypass grafting (2.6% v 2.7%, respectively). However, these two groups differed significantly in the prescribing of secondary prevention (aspirin, 79% v 69%; statins, 80% v 68%; beta blockers, 66% v 53%; and angiotensin converting enzyme inhibitors, 65% v 53%; p < 0.001). CONCLUSIONS: At 30 days the new BCS categories for MI predict three distinct outcomes. However, within a contemporary UK population this was no longer apparent at six months, as mortality for patients with ACS with myocyte necrosis had risen to the same level as those for patients with ACS with clinical MI. One possible explanation for this is the apparent under use of drugs known to improve prognosis after traditionally defined MI.

External validation, extension and recalibration of Braunwald's simple risk index in a community-based cohort of patients with both STEMI and NSTEMI.

BACKGROUND: Using the simple risk index (SRI) that is based on age, heart rate and systolic blood pressure, we sought to evaluate the ability to predict outcome in AMI patients in a community-based population. METHODS AND RESULTS: We identified and evaluated 3684 consecutive patients with an admission diagnosis of possible AMI, who attended between 1st September and 30th November 1995. Two thousand one hundred fifty three patients had confirmed evidence of WHO definition AMI, of whom 1656 survived to hospital discharge. We evaluated the ability of the SRI to predict mortality over 30 days using the score generated by the equation (heart ratex[age/10]2)/systolic blood pressure. The SRI was a strong (c-statistic = 0.77 CI 0.74-0.79) predictor of 30-day mortality in both STEMI and all consecutive cases of WHO definition AMI. However, the model showed poor calibration when used on a community-based population with 30-day mortality being underestimated across all risk quintiles. Consequently we sought to recalibrate the quantitative aspects of the model for the total AMI population in the following way (Risk Index; 30-day mortality) (< or = 29.2; 9.2%), (29.3-37.8; 23.9%), (37.9-47.3; 34.6%), (47.4-61.5; 40.3%), (> or = 61.6; 65.5%). CONCLUSION: We have externally validated the SRI in an unselected cohort of consecutive WHO definition AMI patients. However, the original model consistently underestimated the likelihood of death at 30 days regardless of the calculated risk score. We have therefore suggested corrections to the risk estimates, to allow its application in an unselected community cohort.

Perindopril.

Perindopril is a third-generation ACE inhibitor that is characterised as a small, lipophilic molecule with a therapeutically active carboxyl side group. These and other features combine to make this a unique member of a very well-established class of drugs that have proven efficacy in a wide range of cardiovascular diseases. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) demonstrated benefit in the secondary prevention of patients with stroke, whereas the Perindopril and Remodelling in Elderly with Acute Myocardial Infarction (PREAMI) trial supports extended routine use after myocardial infarction. The most recent evidence from the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) show that perindopril is able to improve the prognosis of patients with a relatively low global cardiovascular risk, denoted either by the presence of stable coronary artery disease or of essential hypertension in conjunction with at least three other risk factors. The fact that major relative risk reductions have been reported for these two studies is matched by the significance of the findings to modern clinical practice. Both studies were conducted in the context of advance concomitant care that is typically better in clinical trials than in routine practice. In particular, the benefits observed were seen to be of a similar magnitude, and also independent of those resulting from statin therapy. Of particular interest is the likely complimentary action of these treatment strategies with regard to the stabilisation of atheromatous plaques. Perindopril is a well-established drug, the full value of which is only now becoming fully apparent.