Long-term excess mortality associated with diabetes following acute myocardial infarction: a population-based cohort study.

BACKGROUND: The long-term excess risk of death associated with diabetes following acute myocardial infarction is unknown. We determined the excess risk of death associated with diabetes among patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) after adjustment for comorbidity, risk factors and cardiovascular treatments. METHODS: Nationwide population-based cohort (STEMI n=281 259 and NSTEMI n=422 661) using data from the UK acute myocardial infarction registry, MINAP, between 1 January 2003 and 30 June 2013. Age, sex, calendar year and country-specific mortality rates for the populace of England and Wales (n=56.9 million) were matched to cases of STEMI and NSTEMI. Flexible parametric survival models were used to calculate excess mortality rate ratios (EMRR) after multivariable adjustment. This study is registered at ClinicalTrials.gov (NCT02591576). RESULTS: Over 1.94 million person-years follow-up including 120 568 (17.1%) patients with diabetes, there were 187 875 (26.7%) deaths. Overall, unadjusted (all cause) mortality was higher among patients with than without diabetes (35.8% vs 25.3%). After adjustment for age, sex and year of acute myocardial infarction, diabetes was associated with a 72% and 67% excess risk of death following STEMI (EMRR 1.72, 95% CI 1.66 to 1.79) and NSTEMI (1.67, 1.63 to 1.71). Diabetes remained significantly associated with substantial excess mortality despite cumulative adjustment for comorbidity (EMRR 1.52, 95% CI 1.46 to 1.58 vs 1.45, 1.42 to 1.49), risk factors (1.50, 1.44 to 1.57 vs 1.33, 1.30 to 1.36) and cardiovascular treatments (1.56, 1.49 to 1.63 vs 1.39, 1.36 to 1.43). CONCLUSIONS: At index acute myocardial infarction, diabetes was common and associated with significant long-term excess mortality, over and above the effects of comorbidities, risk factors and cardiovascular treatments.

Geographic variation in the treatment of non-ST-segment myocardial infarction in the English National Health Service: a cohort study.

OBJECTIVES: To investigate geographic variation in guideline-indicated treatments for non-ST-elevation myocardial infarction (NSTEMI) in the English National Health Service (NHS). DESIGN: Cohort study using registry data from the Myocardial Ischaemia National Audit Project. SETTING: All Clinical Commissioning Groups (CCGs) (n=211) in the English NHS. PARTICIPANTS: 357 228 patients with NSTEMI between 1 January 2003 and 30 June 2013. MAIN OUTCOME MEASURE: Proportion of eligible NSTEMI who received all eligible guideline-indicated treatments (optimal care) according to the date of guideline publication. RESULTS: The proportion of NSTEMI who received optimal care was low (48 257/357 228; 13.5%) and varied between CCGs (median 12.8%, IQR 0.7-18.1%). The greatest geographic variation was for aldosterone antagonists (16.7%, 0.0-40.0%) and least for use of an ECG (96.7%, 92.5-98.7%). The highest rates of care were for acute aspirin (median 92.8%, IQR 88.6-97.1%), and aspirin (90.1%, 85.1-93.3%) and statins (86.4%, 82.3-91.2%) at hospital discharge. The lowest rates were for smoking cessation advice (median 11.6%, IQR 8.7-16.6%), dietary advice (32.4%, 23.9-41.7%) and the prescription of P2Y12 inhibitors (39.7%, 32.4-46.9%). After adjustment for case mix, nearly all (99.6%) of the variation was due to between-hospital differences (median 64.7%, IQR 57.4-70.0%; between-hospital variance: 1.92, 95% CI 1.51 to 2.44; interclass correlation 0.996, 95% CI 0.976 to 0.999). CONCLUSIONS: Across the English NHS, the optimal use of guideline-indicated treatments for NSTEMI was low. Variation in the use of specific treatments for NSTEMI was mostly explained by between-hospital differences in care. Performance-based commissioning may increase the use of NSTEMI treatments and, therefore, reduce premature cardiovascular deaths. TRIAL REGISTRATION NUMBER: NCT02436187.

Importance of primary percutaneous coronary intervention for reducing mortality in ST-elevation myocardial infarction complicated by out of hospital cardiac arrest.

BACKGROUND: Current recommendations are for primary percutaneous coronary intervention (pPCI) in ST-elevation myocardial infarction (STEMI) complicated by out of hospital cardiac arrest (OHCA). However, information about longer-term outcomes is sparse, particularly among high-risk patients who do not regain consciousness promptly after resuscitation. METHODS AND RESULTS: Of 1836 consecutive patients admitted with STEMI for pPCI between April 2008-October 2011, 132 (7.2%) who had suffered OHCA with recovery of spontaneous circulation (ROSC) form the study population. 101 patients survived to hospital discharge (76.5%) with only one further death in the first year. Prognosis was worse for the 62 patients who were unconscious on arrival and required admission to the intensive therapy unit (ITU), only 54% of whom survived. Every additional minute in the time to ROSC increased the hazard of death by 1.7% while alertness upon ROSC and successful reperfusion in response to pPCI reduced the hazard of death by 90% and 65% respectively. Full neurological recovery was recorded in 85.1% of those who survived to be discharged but in only 30.6% of the 34 survivors who were admitted unconscious and received ITU treatment. Every additional minute in the time to ROSC increased the odds of neurological deficit by 7.0%. CONCLUSIONS: In patients with STEMI who are conscious after OHCA, high rates of survival can be achieved with pPCI, depending in part on the time it takes for ROSC. Prognosis is less good in the subgroup brought to hospital unconscious but even in this high risk group neurologically intact survival can be achieved in about one-third of cases, suggesting the benefit of immediate pPCI in STEMI patients successfully resuscitated after OHCA.

Case fatality rates for South Asian and Caucasian patients show no difference 2.5 years after percutaneous coronary intervention.

OBJECTIVE: To compare short and medium-term prognosis in South Asian and Caucasian patients undergoing percutaneous coronary intervention (PCI) to determine if there are ethnic differences in case death rates. DESIGN: Retrospective cohort study. SETTING: A cardiology referral centre in east London. PATIENTS: 9771 patients who underwent PCI from October 2003 to December 2007 of whom 7966 (81.5%) were Caucasian and 1805 (18.5%) were South Asian. MAIN OUTCOME MEASURES: In-hospital major adverse cardiac events (MACE; death, myocardial infarction, stroke and target vessel revascularisation), subsequent revascularisation rates (PCI and coronary artery bypass grafting; CABG) and all-cause mortality during a median follow-up of 2.5 years (range 1.5-3.6 years). RESULTS: South Asian patients were younger than Caucasian patients (59.69±0.27 vs 64.69±0.13 years, p<0.0001), and more burdened by cardiovascular risk factors, particularly type II diabetes mellitus (45.9%±1.2% vs 15.7%±0.4%, p<0.0001). The in-hospital rates of MACE were similar for South Asians and Caucasians (3.5% vs 2.8%, p=0.40). South Asians had higher rates of clinically driven PCI for restenosis and subsequent CABG, although Kaplan-Meier estimates of all-cause mortality showed no significant differences; this was regardless of whether PCI was performed post-acute coronary syndrome or as an elective procedure. The adjusted hazard of death for South Asians compared with Caucasians was 1.00 (95% CI 0.81 to 1.23). CONCLUSION: In this large PCI cohort, the in-hospital and longer-term mortality of South Asians appeared no worse than that of Caucasians. South Asians had higher rates of restenosis and CABG during follow-up. Data suggest that the excess coronary mortality for South Asians compared with Caucasians is not explained by differences in case-fatality rates.

Incidence and prognosis of angina pectoris in South Asians and Whites: 18 years of follow-up over seven phases in the Whitehall-II prospective cohort study.

BACKGROUND: Whether the higher coronary mortality in South Asians compared with White populations is due to a higher incidence of disease is not known. This study assessed cumulative incidence of chest pain in South Asians and Whites, and prognosis of chest pain. METHODS: Over seven phases of 18-year follow-up of the Whitehall-II study (9,775 civil servants: 9,195 White, 580 South Asian), chest pain was assessed using the Rose questionnaire. Coronary death/non-fatal myocardial infarction was examined comparing those with chest pain to those with no chest pain at baseline. RESULTS: South Asians had higher cumulative frequencies of typical angina by Phase 7 (17.0 versus 11.3%, P < 0.001) and exertional chest pain (15.4 versus 8.5%, P < 0.001) compared with Whites. Typical angina and exertional chest pain at baseline were associated with a worse prognosis compared with those with no chest pain in both groups (typical angina, South Asians: HR, 4.67 and 95% CI, 2.12-0.30; Whites: HR, 3.56 95% CI, 2.59-4.88). Baseline non-exertional chest pain did not confer a worse prognosis. Across all types of pain, prognosis was worse in South Asians. CONCLUSION: South Asians had higher cumulative incidence of angina than Whites. In both, typical angina and exertional chest pain were associated with worse prognosis compared with those with no chest pain.

Safety and efficacy of a rate control protocol for cardiac CT.

The clinical application of cardiac CT is increasing, but heart rate control is often required to prevent motion artefact. Here, we describe a protocol for heart rate control in patients undergoing outpatient CT coronary angiography (CTCA). Among 121 consecutive patients, 75 (61.9%) with a resting heart rate >60 beats per minute (bpm) required rate control medication. Our protocol called for oral metoprolol 100 mg to be given 60 min before scanning, with patients for whom beta-blockers were contraindicated receiving 240 mg oral verapamil. Additional 5 mg intravenous boluses (maximum for both drugs, 15 mg) were given if the heart rate remained >60 bpm prior to scanning. Of 71 patients treated with oral metoprolol, 59 (83%) achieved a rate 70 bpm at the time of scanning. No adverse events resulted from rate control medication. Image quality was closely related to heart rate. Severe motion artefact (Grade 3) occurred in only 0.9% of patients with a rate 70 bpm. In conclusion, the administration of oral metoprolol according to the described protocol is a safe and effective way of reducing heart rate and improving scan quality in the majority of patients undergoing CTCA.

How effective are rapid access chest pain clinics? Prognosis of incident angina and non-cardiac chest pain in 8762 consecutive patients.

OBJECTIVE: To determine whether rapid access chest pain clinics are clinically effective by comparison of coronary event rates in patients diagnosed with angina with rates in patients diagnosed with non-cardiac chest pain and the general population. DESIGN: Multicentre cohort study of consecutive patients with chest pain attending the rapid access chest pain clinics (RACPCs) of six hospitals in England. PARTICIPANTS: 8762 patients diagnosed with either non-cardiac chest pain (n = 6396) or incident angina without prior myocardial infarction (n = 2366) at first cardiological assessment, followed up for a median of 2.57 (interquartile range 1.96-4.15) years. MAIN OUTCOME MEASURES: Primary end point--death due to coronary heart disease (International Classification of Diseases (ICD)10 I20-I25) or acute coronary syndrome (non-fatal myocardial infarction (ICD10 I21-I23), hospital admission with unstable angina (I24.0, I24.8, I24.9)). Secondary end points--all-cause mortality (ICD I20), cardiovascular death (ICD10 I00-I99), or non-fatal myocardial infarction or non-fatal stroke (I60-I69). RESULTS: The cumulative probability of the primary end point in patients diagnosed with angina was 16.52% (95% confidence interval (CI) 14.88% to 18.32%) after 3 years compared with 2.73% (95% CI 2.29% to 3.25%) in patients with non-cardiac chest pain. Coronary standardised mortality ratios for men and women with angina aged <65 years were 3.52 (95% CI 1.98 to 5.07) and 4.39 (95% CI 1.14 to 7.64). Of the 599 patients who had the primary end point, 194 (32.4%) had been diagnosed with non-cardiac chest pain. These patients were younger, less likely to have typical symptoms, more likely to be south Asian and more likely to have a normal resting electrocardiogram than patients with angina who had the primary end point. CONCLUSION: RACPCs are successful in identifying patients with incident angina who are at high coronary risk, but there is a need to reduce misdiagnosis and improve outcomes in patients diagnosed with non-cardiac chest pain who accounted for nearly one third of cardiac events during follow-up.

Rapid-access chest pain clinics and the traditional cardiology out-patient clinic.

BACKGROUND: The National Service Framework for coronary heart disease recommends rapid-access chest pain clinics (RACPCs) for cardiological assessment of new-onset chest pain within 2 weeks of referral. AIM: To measure the extent to which an RACPC successfully substituted for an out-patient cardiology clinic (OPCC) at a general hospital, in assessing new-onset chest pain referrals. METHODS: Prospective measurement of attendance and waiting times for consecutive patients at the RACPC and OPCC, and multivariate analysis of factors associated with referral for angiography. RESULTS: From September 2002 to August 2004, 1382 patients with chest pain attended the RACPC, and 228 patients, the OPCC. All RACPC patients were seen within 24 h of referral, except those referred on Friday afternoons, or the day before national holidays. The mean +/- SD waiting time for OPCC appointments was 97 +/- 43 days. Of 208 OPCC patients, 30 (14%) fulfilled the RACPC referral criterion of recent onset chest pain (<4 weeks duration) vs. 926/1382 (67%) RACPC patients. Thus the RACPC substituted for the OPCC in 926/956 (97%) new chest pain referrals. Patients from the OPCC were 3.82 (95%CI 1.85-7.90) more likely to be referred for a coronary angiogram. compared to those attending the RACPC. DISCUSSION: The RACPC has provided efficient and effective substitution for the OPCC in the assessment of new chest pain referrals according to pre-defined referral criteria. Broadening the referral criterion of the RACPC to patients with chest pain of >4 weeks duration would result in more referrals.

Ivabradine -- the first selective sinus node I(f) channel inhibitor in the treatment of stable angina.

Heart rate, a major determinant of angina in coronary disease, is also an important predictor of cardiovascular mortality. Lowering heart rate is therefore one of the most important therapeutic approaches in the treatment of stable angina pectoris. To date, beta-blockers and some calcium-channel antagonists reduce heart rate, but their use may be limited by adverse reactions or contraindications. Heart rate is determined by spontaneous electrical pacemaker activity in the sinoatrial node controlled by the I(f) current. Ivabradine is the first specific heart rate-lowering agent that has completed clinical development for stable angina pectoris. It is selective for the I(f) current, lowering heart rate at concentrations that do not affect other cardiac ionic currents. Specific heart-rate lowering with ivabradine reduces myocardial oxygen demand, simultaneously improving oxygen supply. Ivabradine has no negative inotropic or lusitropic effects, preserving ventricular contractility, and does not change any major electrophysiological parameters unrelated to heart rate. Randomised clinical studies in patients with stable angina show that ivabradine effectively reduces heart rate, improves exercise capacity and reduces the number of angina attacks. It has superior anti-anginal and anti-ischaemic activity to placebo and is non-inferior to atenolol and amlodipine. Ivabradine therefore offers a valuable approach to lowering heart rate exclusively and provides an attractive alternative to conventional treatment for a wide range of patients with confirmed stable angina.

Declining case fatality rates for acute myocardial infarction in South Asian and white patients in the past 15 years.

OBJECTIVES: To determine whether case fatality rates in South Asian (Bangladeshi, Indian and Pakistani) patients with acute myocardial infarction have shown similar declines to those reported for white patients during the past 15 years. DESIGN: Cross-sectional, observational study. SETTING: Coronary care unit in east London. PATIENTS: 2640 patients-29% South Asian-admitted with acute myocardial infarction between January 1988 and December 2002. MAIN OUTCOME MEASURES: Differences over time in rates of in-hospital death, ventricular fibrillation and left ventricular failure. RESULTS: The proportion of South Asians increased from 22% in 1988-92 to 37% in 1998-2002. Indices of infarct severity were similar in South Asian and white patients, with declining frequencies of ST elevation infarction (88.2% to 77.5%, p < 0.0001), Q wave development (78.1% to 56.9%, p < 0.0001) and mean (interquartile range) peak serum creatine kinase concentrations (1250 (567-2078) to 1007 (538-1758) IU/l, p < 0.0001) between 1988-92 and 1998-2002. Rates of in-hospital death (13.0% to 9.4%, p < 0.01), ventricular fibrillation (9.2% to 6.0%, p < 0.001) and left ventricular failure (33.2% to 26.5%, p < 0.0001) all declined; these changes did not interact significantly with ethnicity. Odds ratios for the effect of time on risk of death increased from 0.81 (95% CI 0.70 to 0.93) to 1.02 (95% CI 0.87 to 1.21) after adjustment for ethnicity and indices of infarct severity (ST elevation, peak creatine kinase, Q wave development and treatment with a thrombolytic). CONCLUSIONS: In the past 15 years, death from acute myocardial infarction among South Asians has declined at a rate similar to that seen in white patients. This is largely caused by reductions in indices of infarct severity.

Women in cardiology: a UK perspective.

Women are particularly under-represented in cardiology in the UK, even though women outnumber men in admissions to medical school. Could this disparity be detrimental to the specialty in this country?

The effect of diabetes on heart rate and other determinants of myocardial oxygen demand in acute coronary syndromes.

AIMS: To compare major determinants of myocardial oxygen demand (heart rate, blood pressure and rate pressure product) in patients with and without diabetes admitted with acute coronary syndromes. METHODS: A cross-sectional study of the relation between diabetes and haemodynamic indices of myocardial oxygen demand in 2542 patients with acute coronary syndromes, of whom 1041 (41.0%) had acute myocardial infarction and 1501 (59.0%) unstable angina. RESULTS: Of the 2542 patients, 701 (27.6%) had diabetes. Major haemodynamic determinants of myocardial oxygen demand were higher in patients with than without diabetes: heart rate 80.0 +/- 20.4 vs. 75.2 +/- 19.2 beats/minute (P < 0.0001); systolic blood pressure 147.3 +/- 30.3 vs. 143.2 +/- 28.5 mmHg (P = 0.002); rate-pressure product 11533 +/- 4198 vs. 10541 +/- 3689 beats/minute x mmHg (P < 0.0001). Multiple regression analysis confirmed diabetes as a significant determinant of presenting heart rate [multiplicative coefficient (MC) 1.05; 95% confidence interval (CI) 1.03-1.07; P < 0.0001], rate pressure product (MC 1.09; CI 1.05-1.12; P < 0.0001) and systolic blood pressure, which was estimated to be 3.9 mmHg higher than in patients without diabetes (P=0.003). These effects of diabetes were independent of a range of baseline variables including acute left ventricular failure and mode of presentation (unstable angina or myocardial infarction). CONCLUSIONS: In acute coronary syndromes, heart rate and other determinants of myocardial oxygen demand are higher in patients with than without diabetes, providing a potential contributory mechanism of exaggerated regional ischaemia in this high-risk group.

C reactive protein for risk stratification in acute coronary syndromes? Verdict: unproven.

Although C reactive protein is intimately involved with the pathogenic mechanisms that drive acute coronary syndromes, there is no evidence that it is helpful for identifying patient groups who might benefit from particular treatment strategies

Management of stable angina.

Ischaemic heart disease may present as a wide variety of clinical entities including unstable or stable angina pectoris, acute myocardial infarction, and occasionally heart failure. Chronic stable angina is a common condition and results in a considerable burden for both the individual and society. The goals in management are (i) treatment of other conditions that may worsen angina; (ii) modification of risk factors and treatment with medications for coronary artery disease to improve outcome; and (iii) effective relief of anginal symptoms. There are limitations to the methods available to risk-stratify patients, and the optimal treatment strategy remains unclear. The benefits of lifestyle modification cannot be over-emphasised, and appropriate attention to modifiable risk factors is paramount. The mortality benefit of lipid lowering treatment and antiplatelet therapy is well proved. However the evidence base for anti-ischaemic therapy is less rigorous, being based mainly on extrapolations from studies of acute coronary syndromes. Angioplasty has been shown to be more effective in relief of symptoms than medical therapy alone, but provides no mortality benefit. Coronary artery bypass surgery, however, has been shown to reduce mortality in patients with severe proximal coronary disease when compared with medical management alone.

A single serum glucose measurement predicts adverse outcomes across the whole range of acute coronary syndromes.

OBJECTIVES: To analyse the relation between serum glucose concentration and hospital outcome across the whole spectrum of acute coronary syndromes. METHODS: This was a prospective cohort study of 2127 patients presenting with acute coronary syndromes. The patients were stratified into quartile groups (Q1 to Q4) defined by serum glucose concentrations of 5.8, 7.2, and 10.0 mmol/l. The relation between quartile group and major in-hospital complications was analysed. RESULTS: The proportion of patients with acute myocardial infarction increased incrementally across the quartile groups, from 21.4% in Q1 to 47.9% in Q4 (p < 0.0001). The trend for frequency of in-hospital major complications was similar, particularly left ventricular failure (LVF) (Q1 6.4%, Q4 25.2%, p < 0.0001) and cardiac death (Q1 0.7%, Q4 6.1%, p < 0.0001). The relations were linear, each glucose quartile increment being associated with an odds ratio of 1.46 (95% confidence interval (CI) 1.27 to 1.70) for LVF and 1.52 (95% CI 1.17 to 1.97) for cardiac death. Although complication rates were higher for a discharge diagnosis of acute myocardial infarction than for unstable angina, there was no evidence that the effects of serum glucose concentration were different for the two groups, there being no significant interaction with discharge diagnosis in the associations between glucose quartile and LVF (p = 0.69) or cardiac death (p = 0.17). Similarly there was no significant interaction with diabetic status in the associations between glucose quartile and LVF (p = 0.08) or cardiac death (p = 0.09). CONCLUSION: Admission glycaemia stratified patients with acute coronary syndromes according to their risk of in-hospital LVF and cardiac mortality. There was no detectable glycaemic threshold for these adverse effects. The prognostic correlates of admission glycaemia were unaffected by diabetic status and did not differ significantly between patients with acute myocardial infarction and those with unstable angina.

Bangladeshi patients present with non-classic features of acute myocardial infarction and are treated less aggressively in east London, UK.

OBJECTIVE: To analyse differences in the presentation and management of Bangladeshi and white patients with Q wave acute myocardial infarction (AMI). DESIGN: Prospective observational study. SETTING: East London teaching hospital. PARTICIPANTS: 263 white and 108 Bangladeshi patients admitted with Q wave AMI. MAIN OUTCOME MEASURE: Character of presenting symptoms, their interpretation by the patient, and the provision of emergency treatment. RESULTS: There were no significant differences between Bangladeshi and white patients in the time from pain onset to hospital arrival (arrival time 64.5 (117.5) minutes v 63.0 (140.3) minutes, p = 0.63), but once in hospital it took almost twice as long for Bangladeshi as for white patients to receive thrombolysis (median (interquartile range) door to needle time 42.5 (78.0) minutes v 26.0 (47.7) minutes, p = 0.012). Bangladeshis were significantly less likely than whites to complain of central chest pain (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.03 to 0.38; p = 0.0006) or to offer classic descriptions of the character of the pain (OR 0.25, 95% CI 0.09 to 0.74; p = 0.0118). These differences persisted after adjustment for age, sex, and risk factor profile differences including diabetes. Proportions of Bangladeshi and whites interpreting their symptoms as "heart attack" were similar (45.2% v 46.9%; p = 0.99). CONCLUSIONS: Bangladeshi patients with AMI often present with atypical symptoms, which may lead to slower triage in the casualty department and delay in essential treatment. This needs recognition by emergency staff if mortality rates in this high risk group are to be reduced.