Health outcomes after myocardial infarction: A population study of 56 million people in England.

BACKGROUND: The occurrence of a range of health outcomes following myocardial infarction (MI) is unknown. Therefore, this study aimed to determine the long-term risk of major health outcomes following MI and generate sociodemographic stratified risk charts in order to inform care recommendations in the post-MI period and underpin shared decision making. METHODS AND FINDINGS: This nationwide cohort study includes all individuals aged ≥18 years admitted to one of 229 National Health Service (NHS) Trusts in England between 1 January 2008 and 31 January 2017 (final follow-up 27 March 2017). We analysed 11 non-fatal health outcomes (subsequent MI and first hospitalisation for heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes mellitus, dementia, depression, and cancer) and all-cause mortality. Of the 55,619,430 population of England, 34,116,257 individuals contributing to 145,912,852 hospitalisations were included (mean age 41.7 years (standard deviation [SD 26.1]); n = 14,747,198 (44.2%) male). There were 433,361 individuals with MI (mean age 67.4 years [SD 14.4)]; n = 283,742 (65.5%) male). Following MI, all-cause mortality was the most frequent event (adjusted cumulative incidence at 9 years 37.8% (95% confidence interval [CI] [37.6,37.9]), followed by heart failure (29.6%; 95% CI [29.4,29.7]), renal failure (27.2%; 95% CI [27.0,27.4]), atrial fibrillation (22.3%; 95% CI [22.2,22.5]), severe bleeding (19.0%; 95% CI [18.8,19.1]), diabetes (17.0%; 95% CI [16.9,17.1]), cancer (13.5%; 95% CI [13.3,13.6]), cerebrovascular disease (12.5%; 95% CI [12.4,12.7]), depression (8.9%; 95% CI [8.7,9.0]), dementia (7.8%; 95% CI [7.7,7.9]), subsequent MI (7.1%; 95% CI [7.0,7.2]), and peripheral arterial disease (6.5%; 95% CI [6.4,6.6]). Compared with a risk-set matched population of 2,001,310 individuals, first hospitalisation of all non-fatal health outcomes were increased after MI, except for dementia (adjusted hazard ratio [aHR] 1.01; 95% CI [0.99,1.02];p = 0.468) and cancer (aHR 0.56; 95% CI [0.56,0.57];p < 0.001). The study includes data from secondary care only-as such diagnoses made outside of secondary care may have been missed leading to the potential underestimation of the total burden of disease following MI. CONCLUSIONS: In this study, up to a third of patients with MI developed heart failure or renal failure, 7% had another MI, and 38% died within 9 years (compared with 35% deaths among matched individuals). The incidence of all health outcomes, except dementia and cancer, was higher than expected during the normal life course without MI following adjustment for age, sex, year, and socioeconomic deprivation. Efforts targeted to prevent or limit the accrual of chronic, multisystem disease states following MI are needed and should be guided by the demographic-specific risk charts derived in this study.

Determinants of multimorbidity in older adults in Iran: a cross-sectional study using latent class analysis on the Bushehr Elderly Health (BEH) program.

BACKGROUND AND OBJECTIVES: Multimorbidity, defined as the presence of two or more long-term health conditions in an individual, is one of the most significant challenges facing health systems worldwide. This study aimed to identify determinants of classes of multimorbidity among older adults in Iran. RESEARCH DESIGN AND METHODS: In a cross-sectional sample of older adults (aged ≥ 60 years) from the second stage of the Bushehr Elderly Health (BEH) program in southern Iran, latent class analysis (LCA) was used to identify patterns of multimorbidity. Multinomial logistic regression was conducted to investigate factors associated with each multimorbidity class, including age, gender, education, household income, physical activity, smoking status, and polypharmacy. RESULTS: In 2,426 study participants (mean age 69 years, 52% female), the overall prevalence of multimorbidity was 80.2%. Among those with multimorbidity, 3 latent classes were identified. These comprised: class 1, individuals with a low burden of multisystem disease (56.9%); class 2, individuals with predominantly cardiovascular-metabolic disorders (25.8%) and class 3, individuals with predominantly cognitive and metabolic disorders (17.1%). Compared with men, women were more likely to belong to class 2 (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.52-2.54) and class 3 (OR 4.52, 95% CI 3.22-6.35). Polypharmacy was associated with membership class 2 (OR 3.52, 95% CI: 2.65-4.68) and class 3 (OR 1.84, 95% CI 1.28-2.63). Smoking was associated with membership in class 3 (OR 1.44, 95% CI 1.01-2.08). Individuals with higher education levels (59%) and higher levels of physical activity (39%) were less likely to belong to class 3 (OR 0.41; 95% CI: 0.28-0.62) and to class 2 (OR 0.61; 95% CI: 0.38-0.97), respectively. Those at older age were less likely to belong to class 2 (OR 0.95). DISCUSSION AND IMPLICATIONS: A large proportion of older adults in Iran have multimorbidity. Female sex, polypharmacy, sedentary lifestyle, and poor education levels were associated with cardiovascular-metabolic multimorbidity and cognitive and metabolic multimorbidity. A greater understanding of the determinants of multimorbidity may lead to strategies to prevent its development.

Risk of cerebrovascular disease among 13 457 five-year survivors of childhood cancer: A population-based cohort study.

Survivors of childhood cancer treated with cranial irradiation are at risk of cerebrovascular disease (CVD), but the risks beyond age 50 are unknown. In all, 13457 survivors of childhood cancer included in the population-based British Childhood Cancer Survivor Study cohort were linked to Hospital Episode Statistics data for England. Risk of CVD related hospitalisation was quantified by standardised hospitalisation ratios (SHRs), absolute excess risks and cumulative incidence. Overall, 315 (2.3%) survivors had been hospitalised at least once for CVD with a 4-fold risk compared to that expected (95% confidence interval [CI]: 3.7-4.3). Survivors of a central nervous system (CNS) tumour and leukaemia treated with cranial irradiation were at greatest risk of CVD (SHR = 15.6, 95% CI: 14.0-17.4; SHR = 5.4; 95% CI: 4.5-6.5, respectively). Beyond age 60, on average, 3.1% of CNS tumour survivors treated with cranial irradiation were hospitalised annually for CVD (0.4% general population). Cumulative incidence of CVD increased from 16.0% at age 50 to 26.0% at age 65 (general population: 1.4-4.2%). In conclusion, among CNS tumour survivors treated with cranial irradiation, the risk of CVD continues to increase substantially beyond age 50 up to at least age 65. Such survivors should be: counselled regarding this risk; regularly monitored for hypertension, dyslipidaemia and diabetes; advised on life-style risk behaviours. Future research should include the recall for counselling and brain MRI to identify subgroups that could benefit from pharmacological or surgical intervention and establishment of a case-control study to comprehensively determine risk-factors for CVD.

Atrial fibrillation and oral anticoagulation in older people with frailty: a nationwide primary care electronic health records cohort study.

BACKGROUND: Atrial fibrillation (AF) is common in older people and is associated with increased stroke risk that may be reduced by oral anticoagulation (OAC). Frailty also increases with increasing age, yet the extent of OAC prescription in older people according to extent of frailty in people with AF is insufficiently described. METHODS: An electronic health records study of 536,955 patients aged ≥65 years from ResearchOne in England (384 General Practices), over 15.4 months, last follow-up 11th April 2017. OAC prescription for AF with CHA2DS2-Vasc ≥2, adjusted (demographic and treatments) risk of all-cause mortality, and subsequent cerebrovascular disease, bleeding and falls were estimated by electronic frailty index (eFI) category of fit, mild, moderate and severe frailty. RESULTS: AF prevalence and mean CHA2DS2-Vasc for those with AF increased with increasing eFI category (fit 2.9%, 2.2; mild 11.2%, 3.2; moderate 22.2%, 4.0; and severe 31.5%, 5.0). For AF with CHA2DS2-Vasc ≥2, OAC prescription was higher for mild (53.2%), moderate (55.6%) and severe (53.4%) eFI categories than fit (41.7%). In those with AF and eligible for OAC, frailty was associated with increased risk of death (HR for severe frailty compared with fit 4.09, 95% confidence interval 3.43-4.89), gastrointestinal bleeding (2.17, 1.45-3.25), falls (8.03, 4.60-14.03) and, among women, stroke (3.63, 1.10-12.02). CONCLUSION: Among older people in England, AF and stroke risk increased with increasing degree of frailty; however, OAC prescription approximated 50%. Given competing demands of mortality, morbidity and stroke prevention, greater attention to stratified stroke prevention is needed for this group of the population.

Association of treatments for acute myocardial infarction and survival for seven common comorbidity states: a nationwide cohort study.

BACKGROUND: Comorbidity is common and has a substantial negative impact on the prognosis of patients with acute myocardial infarction (AMI). Whilst receipt of guideline-indicated treatment for AMI is associated with improved prognosis, the extent to which comorbidities influence treatment provision its efficacy is unknown. Therefore, we investigated the association between treatment provision for AMI and survival for seven common comorbidities. METHODS: We used data of 693,388 AMI patients recorded in the Myocardial Ischaemia National Audit Project (MINAP), 2003-2013. We investigated the association between comorbidities and receipt of optimal care for AMI (receipt of all eligible guideline-indicated treatments), and the effect of receipt of optimal care for comorbid AMI patients on long-term survival using flexible parametric survival models. RESULTS: A total of 412,809 [59.5%] patients with AMI had at least one comorbidity, including hypertension (302,388 [48.7%]), diabetes (122,228 [19.4%]), chronic obstructive pulmonary disease (COPD, 89,221 [14.9%]), cerebrovascular disease (51,883 [8.6%]), chronic heart failure (33,813 [5.6%]), chronic renal failure (31,029 [5.0%]) and peripheral vascular disease (27,627 [4.6%]). Receipt of optimal care was associated with greatest survival benefit for patients without comorbidities (HR 0.53, 95% CI 0.51-0.56) followed by patients with hypertension (HR 0.60, 95% CI 0.58-0.62), diabetes (HR 0.83, 95% CI 0.80-0.87), peripheral vascular disease (HR 0.85, 95% CI 0.79-0.91), renal failure (HR 0.89, 95% CI 0.84-0.94) and COPD (HR 0.90, 95% CI 0.87-0.94). For patients with heart failure and cerebrovascular disease, optimal care for AMI was not associated with improved survival. CONCLUSIONS: Overall, guideline-indicated care was associated with improved long-term survival. However, this was not the case in AMI patients with concomitant heart failure or cerebrovascular disease. There is therefore a need for novel treatments to improve outcomes for AMI patients with pre-existing heart failure or cerebrovascular disease.

Clinical outcomes in patients with atrial fibrillation and frailty: insights from the ENGAGE AF-TIMI 48 trial.

BACKGROUND: Atrial fibrillation (AF) is common in older people with frailty and is associated with an increased risk of stroke and systemic embolism. Whilst oral anticoagulation is associated with a reduction in this risk, there is a lack of data on the safety and efficacy of direct oral anticoagulants (DOACs) in people with frailty. This study aims to report clinical outcomes of patients with AF in the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial by frailty status. METHODS: Post hoc analysis of 20,867 participants in the ENGAGE AF-TIMI 48 trial, representing 98.8% of those randomised. This double-blinded double-dummy trial compared two once-daily regimens of edoxaban (a DOAC) with warfarin. Participants were categorised as fit, living with pre-frailty, mild-moderate, or severe frailty according to a standardised index, based upon the cumulative deficit model. The primary efficacy endpoint was stroke or systemic embolism and the safety endpoint was major bleeding. RESULTS: A fifth (19.6%) of the study population had frailty (fit: n = 4459, pre-frailty: n = 12,326, mild-moderate frailty: n = 3722, severe frailty: n = 360). On average over the follow-up period, the risk of stroke or systemic embolism increased by 37% (adjusted HR 1.37, 95% CI 1.19-1.58) and major bleeding by 42% (adjusted HR 1.42, 1.27-1.59) for each 0.1 increase in the frailty index (four additional health deficits). Edoxaban was associated with similar efficacy to warfarin in every frailty category, and a lower risk of bleeding than warfarin in all but those living with severe frailty. CONCLUSIONS: Edoxaban was similarly efficacious to warfarin across the frailty spectrum and was associated with lower rates of bleeding except in those with severe frailty. Overall, with increasing frailty, there was an increase in stroke and bleeding risk. There is a need for high-quality, frailty-specific population randomised control trials to guide therapy in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00781391 . First registered on 28 October 2008.

Prescription of oral anticoagulants and antiplatelets for stroke prophylaxis in atrial fibrillation: nationwide time series ecological analysis.

AIMS: To investigate trends in the prescription of oral anticoagulants (OACs) and antiplatelet agents for atrial fibrillation (AF). METHODS AND RESULTS: Prescription data for 450 518 patients with AF from 3352 General Practices in England, was obtained from the GRASP-AF registry, 2009-2018. Annualized temporal trends for OAC and antiplatelet prescription were reported according to eligibility based on stroke risk (CHADS2 or CHA2DS2-VASc scores ≥1 or >2, respectively). From 2009 to 2018, the prevalence of AF increased from 1.6% [95% confidence interval (CI) 1.5-1.7%] to 2.4% (2.3-2.5%), and for those with AF the proportion prescribed OAC increased from 47.6% to 75.0% (P-trend < 0.001; relative risk 1.57, 95% CI 1.55-1.60) and for antiplatelet decreased from 37.4% to 9.2% (P-trend < 0.001). In early-years (2009-2013), eligible patients aged ≥80 years were less likely to be prescribed OAC than patients aged <80 years [odds ratio (OR) 0.55, 95% CI 0.51-0.59 for CHADS2≥1 in 2009] (all P-trends < 0.001). This 'OAC prescription gap' reduced over the study period (OR 0.93, 0.90-0.96 in 2018). Whilst the prescription of direct oral anticoagulant (DOAC) as a proportion of all OAC increased from 0.1% (95% CI 0.0-0.2%) in 2011 to 58.8% (58.4-59.2%) in 2018, it was inversely associated with patient age (P-trend < 0.001) and their risk of stroke. CONCLUSION: Between 2009 and 2018, in England, the use of OAC for stroke prophylaxis in AF increased, with DOAC accounting for over half of OAC uptake in 2018. Despite a reduction in the OAC-prescription gap, a new paradox exists relating to DOAC prescription for the elderly and those at higher risk of stroke.

New Horizons in the use of routine data for ageing research.

The past three decades have seen a steady increase in the availability of routinely collected health and social care data and the processing power to analyse it. These developments represent a major opportunity for ageing research, especially with the integration of different datasets across traditional boundaries of health and social care, for prognostic research and novel evaluations of interventions with representative populations of older people. However, there are considerable challenges in using routine data at the level of coding, data analysis and in the application of findings to everyday care. New Horizons in applying routine data to investigate novel questions in ageing research require a collaborative approach between clinicians, data scientists, biostatisticians, epidemiologists and trial methodologists. This requires building capacity for the next generation of research leaders in this important area. There is a need to develop consensus code lists and standardised, validated algorithms for common conditions and outcomes that are relevant for older people to maximise the potential of routine data research in this group. Lastly, we must help drive the application of routine data to improve the care of older people, through the development of novel methods for evaluation of interventions using routine data infrastructure. We believe that harnessing routine data can help address knowledge gaps for older people living with multiple conditions and frailty, and design interventions and pathways of care to address the complex health issues we face in caring for older people.

Association between time of hospitalization with acute myocardial infarction and in-hospital mortality.

AIMS: To study the association between time of hospitalization and in-hospital mortality for acute myocardial infarction (AMI). METHODS AND RESULTS: Patients admitted with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) across 243 hospitals in England and Wales between 1 January 2004 and 31 March 2013 were included. The outcome measure was in-hospital mortality. Adjusted odds ratios (ORs) for in-hospital mortality were estimated across six 4-hourly time periods over the 24-h clock using multilevel logistic regression, inverse-probability weighting propensity score, and instrumental variable analysis. Among 615 035 patients [median age 70.0 years, interquartile range 59.0-80.0 years; 406 519 (66.0%) men], there were 52 777 (8.8%) in-hospital deaths. At night, patients with NSTEMI were more frequently comorbid, and for STEMI had longer symptom-onset-to-reperfusion times. For STEMI, unadjusted in-hospital mortality was highest between 20:00 and 23:59 [4-h period range 8.4-9.9%; OR compared with 00:00-03:59 reference 1.13, 95% confidence interval (CI) 1.07-1.20], and for NSTEMI highest between 12:00 and 15:59 (8.0-8.8%; OR compared with 00:00-03:59 reference 1.07, 95% CI 1.03-1.12). However, these differences were only apparent in the earlier years of the study, and were attenuated by adjustment for demographics, comorbidities, and clinical presentation. Differences were not statistically significant after adjustment for acute clinical treatment provided. CONCLUSION: There is little evidence to support an association between time of hospitalization and in-hospital mortality for AMI; variation in in-hospital mortality may be explained by case mix and the use of treatments.

Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure.

PURPOSE: Low 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with adverse outcomes in selected populations with established chronic heart failure (CHF). However, it remains unclear whether 25[OH]D deficiency is associated with mortality and hospitalisation in unselected patients receiving contemporary medical and device therapy for CHF. METHODS: We prospectively examined the prevalence and correlates of 25[OH]D deficiency in 1802 ambulatory patients with CHF due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 45%) attending heart failure clinics in the north of England. RESULTS: 73% of patients were deficient in 25[OH]D (< 50 nmol/L). 25[OH]D deficiency was associated with male sex, diabetes, lower serum sodium, higher heart rate, and greater diuretic requirement. During a mean follow-up period of 4 years, each 2.72-fold increment in 25[OH]D concentration (for example from 32 to 87 nmol/L) is associated with 14% lower all-cause mortality (95% confidence interval (CI) 1, 26%; p = 0.04), after accounting for potential confounding factors. CONCLUSIONS: Low 25-hydroxyvitamin D deficiency is associated with increased mortality in patients with chronic heart failure due to left ventricular systolic dysfunction. Whether vitamin D supplementation will improve outcomes is, as yet, unproven.

Management of atrial fibrillation for older people with frailty: a systematic review and meta-analysis.

BACKGROUND: despite a large and growing population of older people with frailty and atrial fibrillation (AF), there is a lack of guidance on optimal AF management in this high-risk group. OBJECTIVE: to synthesise the existing evidence base on the association between frailty, AF and clinical outcomes. METHODS: a systematic review of studies examining the association between validated measures of frailty, AF and clinical outcomes, and meta-analysis of the association between frailty and oral anticoagulation (OAC) prescription. RESULTS: twenty studies (30,883 patients) were included, all observational. Fifteen were in hospital, four in the community, one in nursing care. Risk of bias was low-to-moderate. AF prevalence was 3%-38%. In people with AF, frailty was associated with increased stroke incidence, all-cause mortality, symptom severity and length of hospital stay.Meta-analysis of six studies showed frailty was associated with decreased OAC prescription at hospital admission (pooled adjusted OR 0.45 [95%CI 0.22-0.93], three studies), but not at discharge (pooled adjusted OR 0.40 [95%CI 0.13-1.23], three studies). A community-based study showed increased OAC prescription associated with frailty (OR 2.33 [95%CI 1.03-5.23]). CONCLUSION: frailty is common, and associated with adverse clinical outcomes in patients with AF. There is evidence of an association between frailty status and OAC prescription, with different direction of effect in community compared with hospital cohorts. Despite the majority of care for older people being provided in the community, there is a lack of evidence on the association between frailty, AF, anticoagulation and clinical outcomes to guide optimal care in this setting.

Is the association between blood pressure and mortality in older adults different with frailty? A systematic review and meta-analysis.

OBJECTIVE: to investigate whether the association between blood pressure and clinical outcomes is different in older adults with and without frailty, using observational studies. METHODS: MEDLINE, EMBASE and CINAHL were searched from 1st January 2000 to 13th June 2018. PROSPERO CRD42017081635. We included all observational studies reporting clinical outcomes in older adults with an average age over 65 years living in the community with and without treatment that measured blood pressure and frailty using validated methods. Two independent reviewers evaluated study quality and risk of bias using the ROBANS tool. We used generic inverse variance modelling to pool risks of all-cause mortality adjusted for age and sex. RESULTS: nine observational studies involving 21,906 older adults were included, comparing all-cause mortality over a mean of six years. Fixed effects meta-analysis of six studies demonstrated that in people with frailty, there was no mortality difference associated with systolic blood pressure <140 mm Hg compared to systolic blood pressure >140 mm Hg (HR 1.02, 95% CI 0.90 to 1.16). In the absence of frailty, systolic blood pressure <140 mm Hg was associated with lower risk of death compared to systolic blood pressure >140 mm Hg (HR 0.86, 95% CI 0.77 to 0.96). CONCLUSIONS: evidence from observational studies demonstrates no mortality difference for older people with frailty whose systolic blood pressure is <140 mm Hg, compared to those with a systolic blood pressure >140 mm Hg. Current evidence fails to capture the complexities of blood pressure measurement, and the association with non-fatal outcomes.

A 10 year study of hospitalized atrial fibrillation-related stroke in England and its association with uptake of oral anticoagulation.

Aims: To determine whether changing patterns of anticoagulant use in atrial fibrillation (AF) have impacted on stroke rates in England. Methods and results: English national databases, 2006-2016, were interrogated to assess stroke admissions and oral anticoagulant use. The number of patients with known AF increased linearly from 692 054 to 983 254 (prevalence 1.29% vs. 1.71%). Hospital episodes of AF-related stroke/100 000 AF patients increased from 80/week in 2006 to 98/week in 2011 and declined to 86/week in 2016 (2006-2011 difference 18.0, 95% confidence interval (CI) 17.9-18.1, 2011-2016 difference -12.0, 95% CI -12.1 to -11.9). Anticoagulant use amongst patients with CHA2DS2-VASc ≥2 increased from 48.0% to 78.6% and anti-platelet use declined from 42.9% to 16.1%; the greatest rate of change occurred in the second 5 year period (for anticoagulants 2006-2011 difference 4.8%, 95% CI 4.5-5.1%, 2011-2016 difference 25.8%, 95% CI 25.5-26.1%). After adjustment for AF prevalence, a 1% increase in anticoagulant use was associated with a 0.8% decrease in the weekly rate of AF-related stroke (incidence rate ratio 0.992, 95% CI 0.989-0.994). Had the use of anticoagulants remained at 2009 levels, 4068 (95% CI 4046-4089) more strokes would have been predicted in 2015/2016. Conclusion: Between 2006 and 2016, AF prevalence and anticoagulant use in England increased. From 2011, hospitalized AF-related stroke rates declined and were significantly associated with increased anticoagulant uptake.

Guideline-indicated treatments and diagnostics, GRACE risk score, and survival for non-ST elevation myocardial infarction.

Aims: To investigate whether improved survival from non-ST-elevation myocardial infarction (NSTEMI), according to GRACE risk score, was associated with guideline-indicated treatments and diagnostics, and persisted after hospital discharge. Methods and results: National cohort study (n = 389 507 patients, n = 232 hospitals, MINAP registry), 2003-2013. The primary outcome was adjusted all-cause survival estimated using flexible parametric survival modelling with time-varying covariates. Optimal care was defined as the receipt of all eligible treatments and was inversely related to risk status (defined by the GRACE risk score): 25.6% in low, 18.6% in intermediate, and 11.5% in high-risk NSTEMI. At 30 days, the use of optimal care was associated with improved survival among high [adjusted hazard ratio (aHR) -0.66 95% confidence interval (CI) 0.53-0.86, difference in absolute mortality rate (AMR) per 100 patients (AMR/100-0.19 95% CI -0.29 to -0.08)], and intermediate (aHR = 0.74, 95% CI 0.62-0.92; AMR/100 = -0.15, 95% CI -0.23 to -0.08) risk NSTEMI. At the end of follow-up (8.4 years, median 2.3 years), the significant association between the use of all eligible guideline-indicated treatments and improved survival remained only for high-risk NSTEMI (aHR = 0.66, 95% CI 0.50-0.96; AMR/100 = -0.03, 95% CI -0.06 to -0.01). For low-risk NSTEMI, there was no association between the use of optimal care and improved survival at 30 days (aHR = 0.92, 95% CI 0.69-1.38) and at 8.4 years (aHR = 0.71, 95% CI 0.39-3.74). Conclusion: Optimal use of guideline-indicated care for NSTEMI was associated with greater survival gains with increasing GRACE risk, but its use decreased with increasing GRACE risk.

Risk of Cerebrovascular Events in 178 962 Five-Year Survivors of Cancer Diagnosed at 15 to 39 Years of Age: The TYACSS (Teenage and Young Adult Cancer Survivor Study).

BACKGROUND: Survivors of teenage and young adult cancer are at risk of cerebrovascular events, but the magnitude of and extent to which this risk varies by cancer type, decade of diagnosis, age at diagnosis, and attained age remains uncertain. This is the largest-ever cohort study to evaluate the risks of hospitalization for a cerebrovascular event among long-term survivors of teenage and young adult cancer. METHODS: The population-based TYACSS (Teenage and Young Adult Cancer Survivor Study) (N=178,962) was linked to Hospital Episode Statistics data for England to investigate the risks of hospitalization for a cerebrovascular event among 5-year survivors of cancer diagnosed when 15 to 39 years of age. Observed numbers of first hospitalizations for cerebrovascular events were compared with that expected from the general population using standardized hospitalization ratios (SHRs) and absolute excess risks per 10 000 person-years. Cumulative incidence was calculated with death considered a competing risk. RESULTS: Overall, 2782 cancer survivors were hospitalized for a cerebrovascular event-40% higher than expected (SHR=1.4, 95% confidence interval, 1.3-1.4). Survivors of central nervous system (CNS) tumors (SHR=4.6, 95% confidence interval, 4.3-5.0), head and neck tumors (SHR=2.6, 95% confidence interval, 2.2-3.1), and leukemia (SHR=2.5, 95% confidence interval, 1.9-3.1) were at greatest risk. Males had significantly higher absolute excess risks than females (absolute excess risks =7 versus 3), especially among head and neck tumor survivors (absolute excess risks =30 versus 11). By 60 years of age, 9%, 6%, and 5% of CNS tumor, head and neck tumor, and leukemia survivors, respectively, had been hospitalized for a cerebrovascular event. Beyond 60 years of age, every year, 0.4% of CNS tumor survivors were hospitalized for a cerebral infarction (versus 0.1% expected), whereas at any age, every year, 0.2% of head and neck tumor survivors were hospitalized for a cerebral infarction (versus 0.06% expected). CONCLUSIONS: Survivors of a CNS tumor, head and neck tumor, and leukemia are particularly at risk of hospitalization for a cerebrovascular event. The excess risk of cerebral infarction among CNS tumor survivors increases with attained age. For head and neck tumor survivors, this excess risk remains high across all ages. These groups of survivors, particularly males, should be considered for surveillance of cerebrovascular risk factors and potential pharmacological interventions for cerebral infarction prevention.

Multimorbidity and survival for patients with acute myocardial infarction in England and Wales: Latent class analysis of a nationwide population-based cohort.

BACKGROUND: There is limited knowledge of the scale and impact of multimorbidity for patients who have had an acute myocardial infarction (AMI). Therefore, this study aimed to determine the extent to which multimorbidity is associated with long-term survival following AMI. METHODS AND FINDINGS: This national observational study included 693,388 patients (median age 70.7 years, 452,896 [65.5%] male) from the Myocardial Ischaemia National Audit Project (England and Wales) who were admitted with AMI between 1 January 2003 and 30 June 2013. There were 412,809 (59.5%) patients with multimorbidity at the time of admission with AMI, i.e., having at least 1 of the following long-term health conditions: diabetes, chronic obstructive pulmonary disease or asthma, heart failure, renal failure, cerebrovascular disease, peripheral vascular disease, or hypertension. Those with heart failure, renal failure, or cerebrovascular disease had the worst outcomes (39.5 [95% CI 39.0-40.0], 38.2 [27.7-26.8], and 26.6 [25.2-26.4] deaths per 100 person-years, respectively). Latent class analysis revealed 3 multimorbidity phenotype clusters: (1) a high multimorbidity class, with concomitant heart failure, peripheral vascular disease, and hypertension, (2) a medium multimorbidity class, with peripheral vascular disease and hypertension, and (3) a low multimorbidity class. Patients in class 1 were less likely to receive pharmacological therapies compared with class 2 and 3 patients (including aspirin, 83.8% versus 87.3% and 87.2%, respectively; ß-blockers, 74.0% versus 80.9% and 81.4%; and statins, 80.6% versus 85.9% and 85.2%). Flexible parametric survival modelling indicated that patients in class 1 and class 2 had a 2.4-fold (95% CI 2.3-2.5) and 1.5-fold (95% CI 1.4-1.5) increased risk of death and a loss in life expectancy of 2.89 and 1.52 years, respectively, compared with those in class 3 over the 8.4-year follow-up period. The study was limited to all-cause mortality due to the lack of available cause-specific mortality data. However, we isolated the disease-specific association with mortality by providing the loss in life expectancy following AMI according to multimorbidity phenotype cluster compared with the general age-, sex-, and year-matched population. CONCLUSIONS: Multimorbidity among patients with AMI was common, and conferred an accumulative increased risk of death. Three multimorbidity phenotype clusters that were significantly associated with loss in life expectancy were identified and should be a concomitant treatment target to improve cardiovascular outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03037255.

Temporal changes in treatments and outcomes after acute myocardial infarction among cancer survivors and patients without cancer, 1995 to 2013.

BACKGROUND: There is a paucity of information about treatment and mortality trends after acute myocardial infarction (AMI) for cancer survivors (CS). METHODS: In this population-based study, the authors compared temporal trends of treatments and outcomes (mortality, nonfatal cardiovascular outcomes), among CS and patients without cancer (the noncancer patient [NCP] group) with AMI in Ontario (Canada) using inverse probability treatment weight (IPTW)-adjusted modeling. RESULTS: Of 270,089 patients with AMI (22,907 CS, 247,182 NCP, 1995-2013; median follow-up, 10.1 and 11.0 years, respectively), the use of invasive coronary strategies and pharmacotherapies increased and mortality declined for CS and NCP (all Ptrend < .001). At 30 days after AMI, there was no difference between CS and NCP in the receipt of coronary angiography (incidence risk ratio [IRR], 0.98; 95% confidence interval [CI], 0.96-1.01; P = .23), percutaneous coronary intervention (IRR, 0.98; 95% CI, 0.94-1.02; P = .29), or bypass (IRR, 0.93; 95% CI, 0.85-1.02; P = .11). At 90 days after AMI, there was no difference in the receipt of ß-blockers, clopidogrel, or nitrates; but CS were less often prescribed angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and statins. CS had higher all-cause mortality at 30 days (adjusted hazard ratio [HR] 1.12; 95% CI, 1.07-1.17; P < .001), at 1 year (1.16; 95% CI, 1.12-1.20; P < .001), and long term (HR, 1.21; 95% CI, 1.17-1.25; P < .001) and had a greater risk of heart failure (HR, 1.08; 95% CI, 1.03-1.14; P = .001), but not myocardial re-infarction (HR, 0.98; 95% CI, 0.95-1.01; P = .22) or stroke (HR, 1.06; 95% CI, 0.97-1.16; P = .18). CONCLUSIONS: Among CS and NCP with AMI in Ontario, similar improvements in mortality and receipt of treatments were observed between 1995 and 2013. However, compared with NCP, CS had a higher risk of mortality and heart failure. Cancer 2018;124:1269-78. © 2017 American Cancer Society.

Performance of hospitals according to the ESC ACCA quality indicators and 30-day mortality for acute myocardial infarction: national cohort study using the United Kingdom Myocardial Ischaemia National Audit Project (MINAP) register.

Aims: To investigate the application of the European Society of Cardiology Acute Cardiovascular Care Association quality indicators (QI) for acute myocardial infarction for the study of hospital performance and 30-day mortality. Methods and results: National cohort study (n = 118,075 patients, n = 211 hospitals, MINAP registry), 2012-13. Overall, 16 of the 20 QIs could be calculated. Eleven QIs had a significant inverse association with GRACE risk adjusted 30-day mortality (all P < 0.005). The association with the greatest magnitude was high attainment of the composite opportunity-based QI (80-100%) vs. zero attainment (odds ratio 0.04, 95% confidence interval 0.04-0.05, P < 0.001), increasing attainment from low (0.42, 0.37- 0.49, P < 0.001) to intermediate (0.15, 0.13-0.16, P < 0.001) was significantly associated with a reduced risk of 30-day mortality. A 1% increase in attainment of this QI was associated with a 3% reduction in 30-day mortality (0.97, 0.97-0.97, P < 0.001). The QI with the widest hospital variation was 'fondaparinux received among NSTEMI' (interquartile range 84.7%) and least variation 'centre organisation' (0.0%), with seven QIs depicting minimal variation (<11%). GRACE risk score adjusted 30-day mortality varied by hospital (median 6.7%, interquartile range 5.4-7.9%). Conclusions: Eleven QIs were significantly inversely associated with 30-day mortality. Increasing patient attainment of the composite quality indicator was the most powerful predictor; a 1% increase in attainment represented a 3% decrease in 30-day standardised mortality. The ESC QIs for acute myocardial infarction are applicable in a large health system and have the potential to improve care and reduce unwarranted variation in death from acute myocardial infarction.

Association of Clinical Factors and Therapeutic Strategies With Improvements in Survival Following Non-ST-Elevation Myocardial Infarction, 2003-2013.

IMPORTANCE: International studies report a decline in mortality following non-ST-elevation myocardial infarction (NSTEMI). Whether this is due to lower baseline risk or increased utilization of guideline-indicated treatments is unknown. OBJECTIVE: To determine whether changes in characteristics of patients with NSTEMI are associated with improvements in outcomes. DESIGN, SETTING, AND PARTICIPANTS: Data on patients with NSTEMI in 247 hospitals in England and Wales were obtained from the Myocardial Ischaemia National Audit Project between January 1, 2003, and June 30, 2013 (final follow-up, December 31, 2013). EXPOSURES: Baseline demographics, clinical risk (GRACE risk score), and pharmacological and invasive coronary treatments. MAIN OUTCOMES AND MEASURES: Adjusted all-cause 180-day postdischarge mortality time trends estimated using flexible parametric survival modeling. RESULTS: Among 389 057 patients with NSTEMI (median age, 72.7 years [IQR, 61.7-81.2 years]; 63.1% men), there were 113 586 deaths (29.2%). From 2003-2004 to 2012-2013, proportions with intermediate to high GRACE risk decreased (87.2% vs 82.0%); proportions with lowest risk increased (4.2% vs 7.6%; P= .01 for trend). The prevalence of diabetes, hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, chronic renal failure, previous invasive coronary strategy, and current or ex-smoking status increased (all P < .001). Unadjusted all-cause mortality rates at 180 days decreased from 10.8% to 7.6% (unadjusted hazard ratio [HR], 0.968 [95% CI, 0.966-0.971]; difference in absolute mortality rate per 100 patients [AMR/100], -1.81 [95% CI, -1.95 to -1.67]). These findings were not substantially changed when adjusted additively by baseline GRACE risk score (HR, 0.975 [95% CI, 0.972-0.977]; AMR/100, -0.18 [95% CI, -0.21 to -0.16]), sex and socioeconomic status (HR, 0.975 [95% CI, 0.973-0.978]; difference in AMR/100, -0.24 [95% CI, -0.27 to -0.21]), comorbidities (HR, 0.973 [95% CI, 0.970-0.976]; difference in AMR/100, -0.44 [95% CI, -0.49 to -0.39]), and pharmacological therapies (HR, 0.972 [95% CI, 0.964-0.980]; difference in AMR/100, -0.53 [95% CI, -0.70 to -0.36]). However, the direction of association was reversed after further adjustment for use of an invasive coronary strategy (HR, 1.02 [95% CI, 1.01-1.03]; difference in AMR/100, 0.59 [95% CI, 0.33-0.86]), which was associated with a relative decrease in mortality of 46.1% (95% CI, 38.9%-52.0%). CONCLUSIONS AND RELEVANCE: Among patients hospitalized with NSTEMI in England and Wales, improvements in all-cause mortality were observed between 2003 and 2013. This was significantly associated with use of an invasive coronary strategy and not entirely related to a decline in baseline clinical risk or increased use of pharmacological therapies.

Disease trajectories following myocardial infarction: insights from process mining of 145 million hospitalisation episodes.

BACKGROUND: Knowledge of post-myocardial infarction (MI) disease risk to date is limited-yet the number of survivors of MI has increased dramatically in recent decades. We investigated temporally ordered sequences of all conditions following MI in nationwide electronic health record data through the application of process mining. METHODS: We conducted a national retrospective cohort study of all hospitalisations (145,670,448 episodes; 34,083,204 individuals) admitted to NHS hospitals in England (1st January 2008-31st January 2017, final follow-up 27th March 2017). Through process mining, we identified trajectories of all major disease diagnoses following MI and compared their relative risk (RR) and all-cause mortality hazard ratios (HR) to a risk-set matched non-MI control cohort using Cox proportional hazards and flexible parametric survival models. FINDINGS: Among a total of 375,669 MI patients (130,758 females; 34.8%) and 1,878,345 matched non-MI patients (653,790 females; 34.8%), we identified 28,799 unique disease trajectories. The accrual of multiple circulatory diagnoses was more common amongst MI patients (RR 4.32, 95% CI 3.96-4.72) and conferred an increased risk of death (HR 1.32, 1.13-1.53) compared with matched controls. Trajectories featuring neuro-psychiatric diagnoses (including anxiety and depression) following circulatory disorders were markedly more common and had increased mortality post MI (HR ranging from 1.11 to 1.73) compared with non-MI individuals. INTERPRETATION: These results provide an opportunity for early intervention targets for survivors of MI-such as increased focus on the psychological and behavioural pathways-to mitigate ongoing adverse disease trajectories, multimorbidity, and premature mortality. FUNDING: British Heart Foundation; Alan Turing Institute.