Impact of implementing Dutch versus European guideline risk factor targets in older patients with ischaemic heart disease.

BACKGROUND: In patients with ischaemic heart disease (IHD) aged > 70 years, Dutch and European guidelines recommend different treatment targets: low-density lipoprotein cholesterol (LDL-c) < 2.6 versus < 1.4 mmol/l and systolic blood pressure (SBP) < 140 versus < 130 mm Hg, respectively. How this impacts cardiovascular event-free life expectancy has not been investigated. The study objective was to compare estimated lifelong treatment benefits of implementing Dutch and European LDL­c and SBP targets. METHODS: Data from patients aged 71-80 years hospitalised for IHD in 2017-2019 were extracted from the PHARMO Database Network, which links primary and secondary healthcare settings, with follow-up until 31 December 2020. Potential benefit according to treatment strategy (in gain in event-free years) was estimated using the SMART-REACH model. RESULTS: Of the 3003 eligible patients, 1186 (39%) had missing LDL­c and/or SBP measurements. Of the 1817 included patients (36% women, median age at event: 74 years (interquartile range (IQR): 72-77), 84% achieved the Dutch targets for both LDL­c and SBP; for European targets, this was 23% and 61%, respectively. If Dutch targets were met for LDL­c and SBP (n = 1281), the additional effect of reaching European targets was a median gain of 0.6 event-free life years (IQR: 0.3-1.0). The greatest effect could be reached in patients not reaching Dutch targets (n = 501), with a median gain of 0.6 (IQR: 0.2-1.2) and 1.7 (IQR: 1.2-2.5) event-free years with Dutch versus European targets. CONCLUSION: In patients aged > 70 years with IHD, implementation of European targets resulted in a greater gain of event-free years compared with Dutch targets, especially in patients with poorer risk factor control. The considerable number of patients with missing risk factor documentation suggested additional opportunities for risk reduction.

A multilevel and multicenter assessment of health care system capacity to manage cardiovascular diseases in Africa: a baseline study of the Ghana Heart Initiative.

INTRODUCTION: Cardiovascular diseases (CVD) remain the leading cause of death worldwide, with over 70% of these deaths occurring in low- and middle-income regions such as Africa. However, most countries in Africa do not have the capacity to manage CVD. The Ghana Heart Initiative has been an ongoing national program since 2018, aimed at improving CVD care and thus reducing the death rates of these diseases in Ghana. This study therefore aimed at assessing the impact of this initiative by identifying, at baseline, the gaps in the management of CVDs within the health system to develop robust measures to bolster CVD management and care in Ghana. METHODS: This study employed a cross-sectional study design and was conducted from November 2019 to March 2020 in 44 health facilities in the Greater Accra region. The assessment covered CVD management, equipment availability, knowledge of health workers in CVD and others including the CVD management support system, availability of CVD management guidelines and CVD/NCD indicators in the District Health Information Management System (DHIMS2). RESULTS: The baseline data showed a total of 85,612 outpatient attendants over the period in the study facilities, 70% were women and 364(0.4%) were newly diagnosed with hypertension. A total of 83% of the newly diagnosed hypertensives were put on treatment, 56.3% (171) continued treatment during the study period and less than 10% (5%) had their blood pressure controlled at the end of the study (in March 2020). Other gaps identified included suboptimal health worker knowledge in CVD management (mean score of 69.0 ± 13.0, p < 0.05), lack of equipment for prompt CVD emergency diagnosis, poor management and monitoring of CVD care across all levels of health care, lack of standardized protocol on CVD management, and limited number of indicators on CVD in the National Database (i.e., DHIMS2) for CVD monitoring. CONCLUSION: This study shows that there are gaps in CVD care and therefore, there is a need to address such gaps to improve the capacity of the health system to effectively manage CVDs in Ghana.

Quality of athlete screening for high-risk cardiovascular conditions-A systematic review.

BACKGROUND: Sudden cardiac death (SCD) is the leading medical cause of death in athletes. To prevent SCD, screening for high-risk cardiovascular conditions (HRCC) is recommended. Screening strategies are based on a limited number of studies and expert consensus. However, evidence and efficacy of athlete HRCC screening is unclear. OBJECTIVE: To determine methodological quality and quality of evidence of athlete screening, and screening efficacy to detect HRCC in a systematic review. METHODS: We performed a systematic search of Medline, Embase, Scopus and Cochrane Library up to June 2021. We included articles containing original data of athlete cardiovascular screening, providing details of screening strategies, test results and HRCC detection. We assessed methodological quality of the included articles by QUADAS-2, quality of evidence of athlete HRCC screening by GRADE, and athlete HRCC screening efficacy by SWiM. RESULTS: Of 2720 citations, we included 33 articles (1991-2018), comprising 82 417 athletes (26.7% elite, 73.4% competitive, 21.7% women, 75.2% aged ≤35). Methodological quality was 'very low' (33 articles), caused by absence of data blinding and inappropriate statistical analysis. Quality of evidence was 'very low' (33 articles), due to observational designs and population heterogeneity. Screening efficacy could not be reliably established. The prevalence of HRCC was 0.43% with false positive rate (FPR) 13.0%. CONCLUSIONS: Methodological quality and quality of evidence on athlete screening are suboptimal. Efficacy could not be reliably established. The prevalence of screen detected HRCC was very low and FPR high. Given the limitations of the evidence, individual recommendations need to be prudent.

Effects of a transitional care programme on medication adherence in an older cardiac population: A randomized clinical trial.

AIMS: Medication non-adherence post-discharge is common among patients, especially those suffering from chronic medical conditions, and contributes to hospital admissions and mortality. This study aimed to evaluate the effect of the Cardiac Care Bridge (CCB) intervention on medication adherence post-discharge. METHODS: We performed a secondary analysis of the CCB randomized single-blind trial, a study in patients ≥70 years, at high risk of functional loss and admitted to cardiology departments in six hospitals. In this multi-component intervention study, community nurses performed medication reconciliation and observed medication-related problems (MRPs) during post-discharge home visits, and pharmacists provided recommendations to resolve MRPs. Adherence to high-risk medications was measured using the proportion of days covered (PDC), using pharmacy refill data. Furthermore, MRPs were assessed in the intervention group. RESULTS: For 198 (64.7%) of 306 CCB patients, data were available on adherence (mean age: 82 years; 58.9% of patients used a multidose drug dispensing [MDD] system). The mean PDC before admission was 92.3% in the intervention group (n = 99) and 88.5% in the control group (n = 99), decreasing to 85.2% and 84.1% post-discharge, respectively (unadjusted difference: -2.6% (95% CI -9.8 to 4.6, P = .473); adjusted difference -3.3 (95% CI -10.3 to 3.7, P = .353)). Post-hoc analysis indicated that a modest beneficial intervention effect may be restricted to MDD non-users (Pinteraction = .085). In total, 77.0% of the patients had at least one MRP post-discharge. CONCLUSIONS: Our findings indicate that a multi-component intervention, including several components targeting medication adherence in older cardiac patients discharged from hospital back home, did not benefit their medication adherence levels. A modest positive effect on adherence may potentially exist in those patients not using an MDD system. This finding needs replication.

Sarcopenia and its relation to protein intake across older ethnic populations in the Netherlands: the HELIUS study.

Objective: To examine the prevalence of sarcopenia and its association with protein intake in men and women in a multi-ethnic population.Design: We used cross-sectional data from the HELIUS (Healthy Life in an Urban Setting) study, which includes nearly 25,000 participants (aged 18-70 years) of Dutch, South-Asian Surinamese, African Surinamese, Turkish, Moroccan, and Ghanaian ethnic origin. For the current study, we included 5161 individuals aged 55 years and older. Sarcopenia was defined according to the EWGSOP2. In a subsample (N = 1371), protein intake was measured using ethnic-specific Food Frequency Questionnaires. Descriptive analyses were performed to study sarcopenia prevalence across ethnic groups in men and women, and logistic regression analyses were used to study associations between protein intake and sarcopenia.Results: Sarcopenia prevalence was found to be sex- and ethnic-specific, varying from 29.8% in Turkish to 61.3% in South-Asian Surinamese men and ranging from 2.4% in Turkish up to 30.5% in South-Asian Surinamese women. Higher protein intake was associated with a 4% lower odds of sarcopenia in the subsample (OR = 0.96, 95%-CI: 0.92-0.99) and across ethnic groups, being only significant in the South-Asian Surinamese group.Conclusion: Ethnic differences in the prevalence of sarcopenia and its association with protein intake suggest the need to target specific ethnic groups for prevention or treatment of sarcopenia.

Antihypertensives and Statin Therapy for Primary Stroke Prevention: A Secondary Analysis of the HOPE-3 Trial.

Background and Purpose: The HOPE-3 trial (Heart Outcomes Prevention Evaluation­3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups. Methods: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed. Results: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59­1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55­1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34­1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41­2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52­0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37­0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59­2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57­2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36­0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23­0.72]). Conclusions: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00468923.

Older patients' perspectives toward lifestyle-related secondary cardiovascular prevention after a hospital admission-a qualitative study.

BACKGROUND: lifestyle-related secondary prevention reduces cardiac events and is recommended irrespective of age. However, motivation may be influenced by age and disease progression. OBJECTIVE: to explore older cardiac patients' perspectives toward lifestyle-related secondary prevention after a hospital admission. METHODS: a generic qualitative design was used. Semi-structured interviews were performed with cardiac patients ≥ 70 years within 3 months after a hospital admission. The interview guide was based on the Attitudes, Social influence and self-Efficacy (ASE) model. All interviews were analysed using thematic analysis. RESULTS: eight themes emerged which were linked to the determinants of the ASE-model. The three themes (i) Perspectives are determined by general health and habits, (ii) feeling the threat as a motivator and (iii) balancing between health benefits and quality of life (QoL), were linked to attitude. Regarding social influence, the themes (iv) feeling both encouraged and hindered by family members, and (v) the healthcare professional says so, were identified. For the self-efficacy determinant, (vi) experiences from previous lifestyle changes, (vii) integrating advice in daily life and (viii) feeling limited by functional impairments, emerged as themes. CONCLUSION: most older cardiac patients made no lifestyle modifications after the last hospital admission and balanced possible benefits against their QoL. Functional impairments frequently limit implementation, in particular of physical activity. Patients' preferences and patient-centred outcomes focusing on QoL and functional independence may be the starting point when healthcare professionals discuss lifestyle modification in older patients. The involvement of family members may help patients to integrate lifestyle-related secondary prevention in daily life.

The nurse-coordinated cardiac care bridge transitional care programme: a randomised clinical trial.

BACKGROUND: after hospitalisation for cardiac disease, older patients are at high risk of readmission and death. OBJECTIVE: the cardiac care bridge (CCB) transitional care programme evaluated the impact of combining case management, disease management and home-based cardiac rehabilitation (CR) on hospital readmission and mortality. DESIGN: single-blind, randomised clinical trial. SETTING: the trial was conducted in six hospitals in the Netherlands between June 2017 and March 2020. Community-based nurses and physical therapists continued care post-discharge. SUBJECTS: cardiac patients ≥ 70 years were eligible if they were at high risk of functional loss or if they had had an unplanned hospital admission in the previous 6 months. METHODS: the intervention group received a comprehensive geriatric assessment-based integrated care plan, a face-to-face handover with the community nurse before discharge and follow-up home visits. The community nurse collaborated with a pharmacist and participants received home-based CR from a physical therapist. The primary composite outcome was first all-cause unplanned readmission or mortality at 6 months. RESULTS: in total, 306 participants were included. Mean age was 82.4 (standard deviation 6.3), 58% had heart failure and 92% were acutely hospitalised. 67% of the intervention key-elements were delivered. The composite outcome incidence was 54.2% (83/153) in the intervention group and 47.7% (73/153) in the control group (risk differences 6.5% [95% confidence intervals, CI -4.7 to 18%], risk ratios 1.14 [95% CI 0.91-1.42], P = 0.253). The study was discontinued prematurely due to implementation activities in usual care. CONCLUSION: in high-risk older cardiac patients, the CCB programme did not reduce hospital readmission or mortality within 6 months. TRIAL REGISTRATION: Netherlands Trial Register 6,316, https://www.trialregister.nl/trial/6169.

The performance of the Dutch Safety Management System frailty tool to predict the risk of readmission or mortality in older hospitalised cardiac patients.

BACKGROUND: Early identification of older cardiac patients at high risk of readmission or mortality facilitates targeted deployment of preventive interventions. In the Netherlands, the frailty tool of the Dutch Safety Management System (DSMS-tool) consists of (the risk of) delirium, falling, functional impairment, and malnutrition and is currently used in all older hospitalised patients. However, its predictive performance in older cardiac patients is unknown. AIM: To estimate the performance of the DSMS-tool alone and combined with other predictors in predicting hospital readmission or mortality within 6 months in acutely hospitalised older cardiac patients. METHODS: An individual patient data meta-analysis was performed on 529 acutely hospitalised cardiac patients ≥70 years from four prospective cohorts. Missing values for predictor and outcome variables were multiply imputed. We explored discrimination and calibration of: (1) the DSMS-tool alone; (2) the four components of the DSMS-tool and adding easily obtainable clinical predictors; (3) the four components of the DSMS-tool and more difficult to obtain predictors. Predictors in model 2 and 3 were selected using backward selection using a threshold of p = 0.157. We used shrunk c-statistics, calibration plots, regression slopes and Hosmer-Lemeshow p-values (PHL) to describe predictive performance in terms of discrimination and calibration. RESULTS: The population mean age was 82 years, 52% were males and 51% were admitted for heart failure. DSMS-tool was positive in 45% for delirium, 41% for falling, 37% for functional impairments and 29% for malnutrition. The incidence of hospital readmission or mortality gradually increased from 37 to 60% with increasing DSMS scores. Overall, the DSMS-tool discriminated limited (c-statistic 0.61, 95% 0.56-0.66). The final model included the DSMS-tool, diagnosis at admission and Charlson Comorbidity Index and had a c-statistic of 0.69 (95% 0.63-0.73; PHL was 0.658). DISCUSSION: The DSMS-tool alone has limited capacity to accurately estimate the risk of readmission or mortality in hospitalised older cardiac patients. Adding disease-specific risk factor information to the DSMS-tool resulted in a moderately performing model. To optimise the early identification of older hospitalised cardiac patients at high risk, the combination of geriatric and disease-specific predictors should be further explored.

Experiences of frail older cardiac patients with a nurse-coordinated transitional care intervention - a qualitative study.

BACKGROUND: Older cardiac patients are at high risk of readmission and mortality. Transitional care interventions (TCIs) might contribute to the prevention of adverse outcomes. The Cardiac Care Bridge program was a randomized nurse-coordinated TCI combining case management, disease management and home-based rehabilitation for hospitalized frail older cardiac patients. This qualitative study explored the experiences of patients' participating in this study, as part of a larger process evaluation as this might support interpretation of the neutral study outcomes. In addition, understanding these experiences could contribute to the design and application of future transitional care interventions for frail older cardiac patients. METHODS: A generic qualitative approach was used. Semi-structured interviews were performed with 16 patients ≥70 years who participated in the intervention group. Participants were selected by gender, diagnosis, living arrangement and hospital of inclusion. Data were analysed using thematic analysis. In addition, quantitative data about intervention delivery were analysed. RESULTS: Three themes emerged from the data: 1) appreciation of care continuity; 2) varying experiences with recovery and, 3) the influence of an existing care network. Participants felt supported by the transitional care intervention as they experienced post-discharge support and continuity of care. The perceived contribution of the program in participants' recovery varied. Some participants reported physical improvements while others felt impeded by comorbidities or frailty. The home visits by the community nurse were appreciated, although some participants did not recognize the added value. Participants with an existing healthcare provider network preferred to consult these providers instead of the providers who were involved in the transitional care intervention. CONCLUSION: Our results contribute to an explanation of the neutral study of a nurse-coordinated transitional care intervention. For future purpose, it is important to identify which patients might benefit most from TCIs. Furthermore, the intensity and content of TCIs could be more personalized by tailoring interventions to older cardiac patients' needs, considering their frailty, self-management skills and existing formal and informal caregiver networks.

The course of readmission in frail older cardiac patients.

AIM: The aim of this study is to explore patients' and (in)formal caregivers' perspectives on their role(s) and contributing factors in the course of unplanned hospital readmission of older cardiac patients in the Cardiac Care Bridge (CCB) program. DESIGN: This study is a qualitative multiple case study alongside the CCB randomized trial, based on grounded theory principles. METHODS: Five cases within the intervention group, with an unplanned hospital readmission within six months after randomization, were selected. In each case, semi-structured interviews were held with patients (n = 4), informal caregivers (n = 5), physical therapists (n = 4), and community nurses (n = 5) between April and June 2019. Patients' medical records were collected to reconstruct care processes before the readmission. Thematic analysis and the six-step analysis of Strauss & Corbin have been used. RESULTS: Three main themes emerged. Patients experienced acute episodes of physical deterioration before unplanned hospital readmission. The involvement of (in)formal caregivers in adequate observation of patients' health status is vital to prevent rehospitalization (theme 1). Patients and (in)formal caregivers' perception of care needs did not always match, which resulted in hampering care support (theme 2). CCB caregivers experienced difficulties in providing care in some cases, resulting in limited care provision in addition to the existing care services (theme 3). CONCLUSION: Early detection of deteriorating health status that leads to readmission was often lacking, due to the acuteness of the deterioration. Empowerment of patients and their informal caregivers in the recognition of early signs of deterioration and adequate collaboration between caregivers could support early detection. Patients' care needs and expectations should be prioritized to stimulate participation. IMPACT: (In)formal caregivers may be able to prevent unplanned hospital readmission of older cardiac patients by ensuring: (1) early detection of health deterioration, (2) empowerment of patient and informal caregivers, and (3) clear understanding of patients' care needs and expectations.

The Cardiac Care Bridge randomized trial in high-risk older cardiac patients: A mixed-methods process evaluation.

AIM: To evaluate healthcare professionals' performance and treatment fidelity in the Cardiac Care Bridge (CCB) nurse-coordinated transitional care intervention in older cardiac patients to understand and interpret the study results. DESIGN: A mixed-methods process evaluation based on the Medical Research Council Process Evaluation framework. METHODS: Quantitative data on intervention key elements were collected from 153 logbooks of all intervention patients. Qualitative data were collected using semi-structured interviews with 19 CCB professionals (cardiac nurses, community nurses and primary care physical therapists), from June 2017 until October 2018. Qualitative data-analysis is based on thematic analysis and integrated with quantitative key element outcomes. The analysis was blinded to trial outcomes. Fidelity was defined as the level of intervention adherence. RESULTS: The overall intervention fidelity was 67%, ranging from severely low fidelity in the consultation of in-hospital geriatric teams (17%) to maximum fidelity in the comprehensive geriatric assessment (100%). Main themes of influence in the intervention performance that emerged from the interviews are interdisciplinary collaboration, organizational preconditions, confidence in the programme, time management and patient characteristics. In addition to practical issues, the patient's frailty status and limited motivation were barriers to the intervention. CONCLUSION: Although involved healthcare professionals expressed their confidence in the intervention, the fidelity rate was suboptimal. This could have influenced the non-significant effect of the CCB intervention on the primary composite outcome of readmission and mortality 6 months after randomization. Feasibility of intervention key elements should be reconsidered in relation to experienced barriers and the population. IMPACT: In addition to insight in effectiveness, insight in intervention fidelity and performance is necessary to understand the mechanism of impact. This study demonstrates that the suboptimal fidelity was subject to a complex interplay of organizational, professionals' and patients' issues. The results support intervention redesign and inform future development of transitional care interventions in older cardiac patients.

Individual Treatment Effect Estimation of 2 Doses of Dabigatran on Stroke and Major Bleeding in Atrial Fibrillation.

BACKGROUND: We aimed to estimate absolute benefit and harm from treatment with dabigatran in individual patients with atrial fibrillation, and to select the optimal dose for each individual. METHODS: We derived and validated a prediction model for ischemic stroke/systemic embolism and major bleeding in patients with atrial fibrillation from the 3 treatment arms of the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy With Dabigatran Etexilate) (n=11 955 in derivation cohort, n=6158 in validation cohort). Readily available patient characteristics were included in Fine and Gray competing risk models (sex, age, smoking, antiplatelet drugs, previous vascular disease, diabetes mellitus, blood pressure, estimated glomerular filtration rate, and hemoglobin). Five-year risks for ischemic stroke/systemic embolism and major bleeding were estimated without anticoagulation therapy, and compared with high- and low-dose dabigatran. RESULTS: Model calibration was good, and discrimination was adequate with a c-statistic of 0.65 (95% CI, 0.62-0.70) for ischemic stroke/systemic embolism and 0.69 (95% CI, 0.66-0.71) for major bleeding. The 5-year absolute risk reduction for ischemic stroke/systemic embolism with dabigatran 150 mg twice daily ranged from <10% in 20% of patients to >25% in 14% of patients, and the 5-year absolute risk increase for major bleeding ranged from <5% in 53% of patients to 15% to 20% in 1% of patients. Comparing high-dose to low-dose dabigatran, the net benefit (absolute risk reduction minus absolute risk increase) was positive for 46% of patients. CONCLUSIONS: The absolute treatment benefits and harms of dabigatran in atrial fibrillation can be estimated based on readily available patient characteristics. Such treatment effect estimations can be used for shared decision making before starting dabigatran treatment and to determine the optimal dose. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00262600.

An initial exploration of subtraction electrocardiography to detect myocardial ischemia in the prehospital setting.

BACKGROUND: In the prehospital triage of patients presenting with symptoms suggestive of acute myocardial ischemia, reliable myocardial ischemia detection in the electrocardiogram (ECG) is pivotal. Due to large interindividual variability and overlap between ischemic and nonischemic ECG-patterns, incorporation of a previous elective (reference) ECG may improve accuracy. The aim of the current study was to explore the potential value of serial ECG analysis using subtraction electrocardiography. METHODS: SUBTRACT is a multicenter retrospective observational study, including patients who were prehospitally evaluated for acute myocardial ischemia. For each patient, an elective previously recorded reference ECG was subtracted from the ambulance ECG. Patients were classified as myocardial ischemia cases or controls, based on the in-hospital diagnosis. The diagnostic performance of subtraction electrocardiography was tested using logistic regression of 28 variables describing the differences between the reference and ambulance ECGs. The Uni-G ECG Analysis Program was used for state-of-the-art single-ECG interpretation of the ambulance ECG. RESULTS: In 1,229 patients, the mean area-under-the-curve of subtraction electrocardiography was 0.80 (95%CI: 0.77-0.82). The performance of our new method was comparable to single-ECG analysis using the Uni-G algorithm: sensitivities were 66% versus 67% (p-value > .05), respectively; specificities were 80% versus 81% (p-value > .05), respectively. CONCLUSIONS: In our initial exploration, the diagnostic performance of subtraction electrocardiography for the detection of acute myocardial ischemia proved equal to that of state-of-the-art automated single-ECG analysis by the Uni-G algorithm. Possibly, refinement of both algorithms, or even integration of the two, could surpass current electrocardiographic myocardial ischemia detection.

The contribution of obesity to the population burden of high metabolic cardiovascular risk among different ethnic groups. The HELIUS study.

BACKGROUND: The burden of cardiovascular risk is distributed unequally between ethnic groups. It is uncertain to what extent this is attributable to ethnic differences in general and abdominal obesity. Therefore, we studied the contribution of general and abdominal obesity to metabolic cardiovascular risk among different ethnic groups. METHODS: We used data of 21 411 participants of Dutch, South-Asian Surinamese, African-Surinamese, Ghanaian, Turkish or Moroccan origin in Healthy Life in an Urban Setting (Amsterdam, the Netherlands). Obesity was defined using body-mass-index (general) or waist-to-height-ratio (abdominal). High metabolic risk was defined as having at least two of the following: triglycerides ≥1.7 mmol/l, fasting glucose ≥5.6 mmol/l, blood pressure ≥130 mmHg systolic and/or ≥85 mmHg diastolic and high-density lipoprotein cholesterol <1.03 mmol/l (men) or <1.29 mmol/l (women). RESULTS: Among ethnic minority men, age-adjusted prevalence rates of high metabolic risk ranged from 32 to 59% vs. 33% among Dutch men. Contributions of general obesity to high metabolic risk ranged from 7.1 to 17.8%, vs. 10.1% among Dutch men, whereas contributions of abdominal obesity ranged from 52.1 to 92.3%, vs. 53.9% among Dutch men. Among ethnic minority women, age-adjusted prevalence rates of high metabolic risk ranged from 24 to 35% vs. 12% among Dutch women. Contributions of general obesity ranged from 14.6 to 41.8%, vs. 20% among Dutch women, whereas contributions of abdominal obesity ranged from 68.0 to 92.8%, vs. 72.1% among Dutch women. CONCLUSIONS: Obesity, especially abdominal obesity, contributes significantly to the prevalence of high metabolic cardiovascular risk. Results suggest that this contribution varies substantially between ethnic groups, which helps explain ethnic differences in cardiovascular risk.

Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease.

BACKGROUND: Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear. METHODS: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years. RESULTS: The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes). CONCLUSIONS: Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).

Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease.

BACKGROUND: Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease. METHODS: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years. RESULTS: The overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P=0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The results were also consistent in subgroups defined according to cardiovascular risk at baseline, lipid level, C-reactive protein level, blood pressure, and race or ethnic group. In the rosuvastatin group, there was no excess of diabetes or cancers, but there was an excess of cataract surgery (in 3.8% of the participants, vs. 3.1% in the placebo group; P=0.02) and muscle symptoms (in 5.8% of the participants, vs. 4.7% in the placebo group; P=0.005). CONCLUSIONS: Treatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; HOPE-3 ClinicalTrials.gov number, NCT00468923.).

Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease.

BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially. METHODS: In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years. RESULTS: The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups. CONCLUSIONS: The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).

Effects of Postacute Multidisciplinary Rehabilitation Including Exercise in Out-of-Hospital Settings in the Aged: Systematic Review and Meta-analysis.

OBJECTIVE: Many older individuals receive rehabilitation in an out-of-hospital setting (OOHS) after acute hospitalization; however, its effect on mobility and unplanned hospital readmission is unclear. Therefore, a systematic review and meta-analysis were conducted on this topic. DATA SOURCES: Medline OVID, Embase OVID, and CINAHL were searched from their inception until February 22, 2018. STUDY SELECTION: OOHS (ie, skilled nursing facilities, outpatient clinics, or community-based at home) randomized trials studying the effect of multidisciplinary rehabilitation were selected, including those assessing exercise in older patients (mean age ≥65y) after discharge from hospital after an acute illness. DATA EXTRACTION: Two reviewers independently selected the studies, performed independent data extraction, and assessed the risk of bias. Outcomes were pooled using fixed- or random-effect models as appropriate. The main outcomes were mobility at and unplanned hospital readmission within 3 months of discharge. DATA SYNTHESIS: A total of 15 studies (1255 patients) were included in the systematic review and 12 were included in the meta-analysis (7 assessing mobility using the 6-minute walk distance [6MWD] test and 7 assessing unplanned hospital readmission). Based on the 6MWD, patients receiving rehabilitation walked an average of 23 m more than controls (95% confidence interval [CI]=: -1.34 to 48.32; I2: 51%). Rehabilitation did not lower the 3-month risk of unplanned hospital readmission (risk ratio: 0.93; 95% CI: 0.73-1.19; I2: 34%). The risk of bias was present, mainly due to the nonblinded outcome assessment in 3 studies, and 7 studies scored this unclearly. CONCLUSION: OOHS-based multidisciplinary rehabilitation leads to improved mobility in older patients 3 months after they are discharged from hospital following an acute illness and is not associated with a lower risk of unplanned hospital readmission within 3 months of discharge. However, the wide 95% CIs indicate that the evidence is not robust.

The prognostic value of heart rate recovery in patients with coronary artery disease: A systematic review and meta-analysis.

BACKGROUND: Routine outpatient care of patients with coronary artery disease (CAD) lacks a simple measure of physical fitness and risk of mortality. Heart rate recovery (HRR) is noninvasive and easily obtainable in outpatient settings. Prior studies have suggested that delayed postexercise HRR in the first minutes is associated with mortality in several types of populations. However, a comprehensive overview of the prognostic value of delayed HRR for time to mortality specifically in CAD patients is not available. The purpose of the current meta-analysis is to evaluate the prognostic value of delayed HRR in CAD patients. METHODS: We conducted a systematic search in OVID MEDLINE and OVID EMBASE to identify studies reporting on HRR and risk of incident cardiovascular events or mortality in CAD patients. Hazard ratios for delayed versus nondelayed HRR were pooled using random-effects meta-analysis. RESULTS: Four studies were included, comprising 2,428 CAD patients. The study quality of the included studies was rated moderate (n = 2) to high (n = 2). Delayed HRR was defined by ≤12 to ≤21 beat/min in the recovery period. During follow-up (range 2.0-9.8 years), 151 patients died (6.2% [range 2.5%-19.5%]). Only data on mortality could be pooled. Heterogeneity was limited (I2 = 32%; P = .23); pooled unadjusted hazard ratio for mortality, based on 3 studies, was 5.8 (95% CI 3.2-10.4). CONCLUSIONS: In CAD patients, delayed HRR is significantly associated with all-cause mortality. As exercise testing is performed routinely in CAD patients, HRR can be considered in monitoring exercise; still, further research must investigate the addition of HRR in current risk scores.