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.

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.

An evaluation of the relationship between specialist training in cardiology and implementation of evidence-based care of patients following acute myocardial infarction.

AIMS: Large clinical trials have provided evidence of prognostically beneficial treatment strategies for patients with acute myocardial infarction. However, the implementation of this evidence into routine clinical practice is suboptimal. We hypothesised that the speciality of the attending physician (cardiologist or not) would affect the use of evidence-based strategies. METHODS: Over a 3-month period (1st September to 30th November 1995), 3684 consecutive potential cases of acute myocardial infarction (AMI) in 20 adjacent hospitals in the Yorkshire Region were identified from coronary care registers, clinical coding and biochemistry records of cardiac enzyme assay requests. There were 2153 consecutive cases of AMI identified, of which 1643 patients were alive at discharge. We compared the admission use of aspirin and thrombolysis, and the use of aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and statins at discharge between cardiologists and other physicians. RESULTS: AMI patients under the care of cardiologists are more likely to receive aspirin and thrombolysis on the day of their event and to be prescribed aspirin, beta-blockers and statins on discharge. After correction for contraindications to their use, the above findings were broadly confirmed. DISCUSSION: Cardiologists are more likely than general physicians to use evidence-based treatment strategies recognised to improve AMI patient outcome. It is likely that this will translate into a reduction of mortality or other hard endpoints in patient outcomes.

Identifying acute myocardial infarction: effects on treatment and mortality, and implications for National Service Framework audit.

BACKGROUND: The National Service Framework (NSF) for Coronary Heart Disease requires annual clinical audit of the care of patients with myocardial infarction, with little guidance on how to achieve these standards and monitor practice. AIM: To assess which method of identification of acute myocardial infarction (AMI) cases is most suitable for NSF audit, and to determine the effect of the definition of AMI on the assessment of quality of care. DESIGN: Observational study. METHODS: Over a 3-month period, 2153 consecutive patients from 20 hospitals across the Yorkshire region, with confirmed AMI, were identified from coronary care registers, biochemistry records and hospital coding systems. The sensitivity and positive predictive value of AMI patient identification using clinical coding, biochemistry and coronary care registers were compared to a 'gold standard' (the combination of all three methods). RESULTS: Of 3685 possible cases of AMI singled out by one or more methods, 2153 patients were identified as having a final diagnosis of AMI. Hospital coding revealed 1668 (77.5%) cases, with a demographic profile similar to that of the total cohort. Secondary preventative measures required for inclusion in NSF were also of broadly similar distribution. The sensitivities and positive predictive values for patient identification were substantially less in the cohorts identified through biochemistry and coronary care unit register. Patients fulfilling WHO criteria (n=1391) had a 30-day mortality of 15.9%, vs. 24.2% for the total cohort. DISCUSSION: Hospital coding misses a substantial proportion (22.5%) of AMI cases, but without any apparent systematic bias, and thus provides a suitably representative and robust basis for NSF-related audit. Better still would be the routine use of multiple methods of case identification.

Poor prognosis of patients presenting with symptomatic myocardial infarction but without chest pain.

OBJECTIVE: To describe the clinical features, prognosis, and treatment of patients presenting with atypical forms of acute myocardial infarction. DESIGN: Consecutive cases of possible acute myocardial infarction were sought from coronary care registers, biochemistry records, and hospital management systems. Case notes were reviewed and predefined epidemiological and clinical variables were abstracted. SETTING: 20 adjacent hospitals in the former Yorkshire region. PATIENTS: 3684 consecutive cases of possible acute myocardial infarction admitted in a three month period were identified, of whom 2096 had a first episode of confirmed acute myocardial infarction. RESULTS: 20.2% of all patients admitted with an eventual diagnosis of acute myocardial infarction presented with symptoms other than chest pain. Compared with the group presenting with chest pain, these patients were older (76.6 v 69.1 years, p < 0.001), were more often women (54.6% v 35.3%, p < 0.001), and were more likely to have a history of heart failure (18.6% v 6.9%, p < 0.001). They had a higher 30 and 365 day mortality (49.2% and 61.0%, respectively) compared with patients presenting with chest pain (17.9% and 26.2%). In a Cox regression analysis the hazard ratio for presentation without chest pain was 1.60 (95% confidence interval 1.30 to 1.97) (p < 0.001) adjusted for age, heart rate, blood pressure, left ventricular impairment, and infarction with ST segment elevation as covariates. Importantly, they were also less likely to receive treatments with a proven ability to improve prognosis. CONCLUSIONS: Atypical presentation of myocardial infarction without chest pain is common and associated with increased mortality. This may result in part from a failure to use beneficial treatment strategies.

Use of cumulative mortality data in patients with acute myocardial infarction for early detection of variation in clinical practice: observational study.

OBJECTIVES: Use of cumulative mortality adjusted for case mix in patients with acute myocardial infarction for early detection of variation in clinical practice. DESIGN: Observational study. SETTING: 20 hospitals across the former Yorkshire region. PARTICIPANTS: All 2153 consecutive patients with confirmed acute myocardial infarction identified during three months. MAIN OUTCOME MEASURES: Variable life-adjusted displays showing cumulative differences between observed and expected mortality of patients; expected mortality calculated from risk model based on admission characteristics of age, heart rate, and systolic blood pressure. RESULTS: The performance of two individual hospitals over three months was examined as an example. One, the smallest district hospital in the region, had a series of 30 consecutive patients but had five more deaths than predicted. The variable life-adjusted display showed minimal variation from that predicted for the first 15 patients followed by a run of unexpectedly high mortality. The second example was the main tertiary referral centre for the region, which admitted 188 consecutive patients. The display showed a period of apparently poor performance followed by substantial improvement, where the plot rose steadily from a cumulative net lives saved of -4 to 7. These variations in patient outcome are unlikely to have been revealed during conventional audit practice. CONCLUSIONS: Variable life-adjusted display has been integrated into surgical care as a graphical display of risk-adjusted survival for individual surgeons or centres. In combination with a simple risk model, it may have a role in monitoring performance and outcome in patients with acute myocardial infarction.

A simple benchmark for evaluating quality of care of patients following acute myocardial infarction.

OBJECTIVE: To develop a simple risk model as a basis for evaluating care of patients admitted with acute myocardial infarction. METHODS: From coronary care registers, biochemistry records and hospital management systems, 2153 consecutive patients with confirmed acute myocardial infarction were identified. With 30 day all cause mortality as the end point, a multivariable logistic regression model of risk was constructed and validated in independent patient cohorts. The areas under receiver operating characteristic curves were calculated as an assessment of sensitivity and specificity. The model was reapplied to a number of commonly studied subgroups for further assessment of robustness. RESULTS: A three variable model was developed based on age, heart rate, and systolic blood pressure on admission. This produced an individual probability of death by 30 days (P(30)) where P(30) = 1/(1 + exp(-L(30))) and L(30) = -5.624 + (0.085 x age) + (0.014 x heart rate) - (0.022 x systolic blood pressure). The areas under the receiver operating characteristic curves for the reference and test cohorts were 0.79 (95% CI 0.76 to 0.82) and 0.76 (95% CI 0.72 to 0.79), respectively. To aid application of the model to routine clinical audit, a normogram relating observed mortality and sample size to the likelihood of a significant deviation from the expected 30 day mortality rate was constructed. CONCLUSIONS: This risk model is simple, reproducible, and permits quality of care of acute myocardial infarction patients to be reliably evaluated both within and between centres.

Clinical evaluation of low dose intradermally administered hepatitis B vaccine: a comparison of plasma-derived and recombinant yeast-derived vaccines.

A study of the safety and immunogenicity of plasma-derived and yeast-derived recombinant hepatitis B vaccines administered by the intradermal route is reported. Three groups of medical students were inoculated intradermally at 0, 1 and 6 months with 2 micrograms of vaccine. Group 1 (n = 24) were administered plasma-derived vaccine (Green Cross HB-vaccine), group 2 (n = 21) yeast-derived recombinant vaccine (Engerix B), and group 3 (n = 13) two doses of plasma-derived vaccine with a third dose of yeast-derived vaccine. One month after administration of the third dose of vaccine, seroconversion rates in each of the three groups were 83, 100 and 92%, respectively, with anti-HBs geometric mean titres (GMT) of 329 IU l-1, 1390 IU l-1 and 1061 IU l-1. Although differences in seroconversion rates were not statistically significant, the GMT in group 1 was significantly lower than that in group 2 (p less than 0.01) and group 3 (p less than 0.05). The results presented show that intradermal administration of plasma-derived or yeast-derived vaccine, or a combination of the two, can provoke an effective immunogenic response to hepatitis B virus at approximately 10% of the cost of intramuscular vaccination. In this study administration of yeast-derived vaccine yielded better results than plasma-derived vaccine when administered by the intradermal route.