Karen Rees

Bio: Karen Rees is an academic researcher from University of Warwick. The author has contributed to research in topics: Meta-analysis & Systematic review. The author has an hindex of 52, co-authored 120 publications receiving 15080 citations. Previous affiliations of Karen Rees include University of Bristol & Edinburgh Royal Infirmary.

Exercise-based cardiac rehabilitation for coronary heart disease

Abstract: Background Coronary heart disease (CHD) is the most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people living with CHD may need support to manage their symptoms and prognosis. Exercise‐based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane Review previously published in 2016. Objectives To assess the clinical effectiveness and cost‐effectiveness of exercise‐based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with 'no exercise' control, on mortality, morbidity and health‐related quality of life (HRQoL) in people with CHD. Search methods We updated searches from the previous Cochrane Review, by searching CENTRAL, MEDLINE, Embase, and two other databases in September 2020. We also searched two clinical trials registers in June 2021. Selection criteria We included randomised controlled trials (RCTs) of exercise‐based interventions with at least six months’ follow‐up, compared with 'no exercise' control. The study population comprised adult men and women who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or have angina pectoris, or coronary artery disease. Data collection and analysis We screened all identified references, extracted data and assessed risk of bias according to Cochrane methods. We stratified meta‐analysis by duration of follow‐up: short‐term (6 to 12 months); medium‐term (> 12 to 36 months); and long‐term ( > 3 years), and used meta‐regression to explore potential treatment effect modifiers. We used GRADE for primary outcomes at 6 to 12 months (the most common follow‐up time point). Main results This review included 85 trials which randomised 23,430 people with CHD. This latest update identified 22 new trials (7795 participants). The population included predominantly post‐MI and post‐revascularisation patients, with a mean age ranging from 47 to 77 years. In the last decade, the median percentage of women with CHD has increased from 11% to 17%, but females still account for a similarly small percentage of participants recruited overall ( < 15%). Twenty‐one of the included trials were performed in low‐ and middle‐income countries (LMICs). Overall trial reporting was poor, although there was evidence of an improvement in quality over the last decade. The median longest follow‐up time was 12 months (range 6 months to 19 years). At short‐term follow‐up (6 to 12 months), exercise‐based CR likely results in a slight reduction in all‐cause mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.73 to 1.04; 25 trials; moderate certainty evidence), a large reduction in MI (RR 0.72, 95% CI 0.55 to 0.93; 22 trials; number needed to treat for an additional beneficial outcome (NNTB) 75, 95% CI 47 to 298; high certainty evidence), and a large reduction in all‐cause hospitalisation (RR 0.58, 95% CI 0.43 to 0.77; 14 trials; NNTB 12, 95% CI 9 to 21; moderate certainty evidence). Exercise‐based CR likely results in little to no difference in risk of cardiovascular mortality (RR 0.88, 95% CI 0.68 to 1.14; 15 trials; moderate certainty evidence), CABG (RR 0.99, 95% CI 0.78 to 1.27; 20 trials; high certainty evidence), and PCI (RR 0.86, 95% CI 0.63 to 1.19; 13 trials; moderate certainty evidence) up to 12 months' follow‐up. We are uncertain about the effects of exercise‐based CR on cardiovascular hospitalisation, with a wide confidence interval including considerable benefit as well as harm (RR 0.80, 95% CI 0.41 to 1.59; low certainty evidence). There was evidence of substantial heterogeneity across trials for cardiovascular hospitalisations (I2 = 53%), and of small study bias for all‐cause hospitalisation, but not for all other outcomes. At medium‐term follow‐up, although there may be little to no difference in all‐cause mortality (RR 0.90, 95% CI 0.80 to 1.02; 15 trials), MI (RR 1.07, 95% CI 0.91 to 1.27; 12 trials), PCI (RR 0.96, 95% CI 0.69 to 1.35; 6 trials), CABG (RR 0.97, 95% CI 0.77 to 1.23; 9 trials), and all‐cause hospitalisation (RR 0.92, 95% CI 0.82 to 1.03; 9 trials), a large reduction in cardiovascular mortality was found (RR 0.77, 95% CI 0.63 to 0.93; 5 trials). Evidence is uncertain for difference in risk of cardiovascular hospitalisation (RR 0.92, 95% CI 0.76 to 1.12; 3 trials). At long‐term follow‐up, although there may be little to no difference in all‐cause mortality (RR 0.91, 95% CI 0.75 to 1.10), exercise‐based CR may result in a large reduction in cardiovascular mortality (RR 0.58, 95% CI 0.43 to 0.78; 8 trials) and MI (RR 0.67, 95% CI 0.50 to 0.90; 10 trials). Evidence is uncertain for CABG (RR 0.66, 95% CI 0.34 to 1.27; 4 trials), and PCI (RR 0.76, 95% CI 0.48 to 1.20; 3 trials). Meta‐regression showed benefits in outcomes were independent of CHD case mix, type of CR, exercise dose, follow‐up length, publication year, CR setting, study location, sample size or risk of bias. There was evidence that exercise‐based CR may slightly increase HRQoL across several subscales (SF‐36 mental component, physical functioning, physical performance, general health, vitality, social functioning and mental health scores) up to 12 months' follow‐up; however, these may not be clinically important differences. The eight trial‐based economic evaluation studies showed exercise‐based CR to be a potentially cost‐effective use of resources in terms of gain in quality‐adjusted life years (QALYs). Authors' conclusions This updated Cochrane Review supports the conclusions of the previous version, that exercise‐based CR provides important benefits to people with CHD, including reduced risk of MI, a likely small reduction in all‐cause mortality, and a large reduction in all‐cause hospitalisation, along with associated healthcare costs, and improved HRQoL up to 12 months' follow‐up. Over longer‐term follow‐up, benefits may include reductions in cardiovascular mortality and MI. In the last decade, trials were more likely to include females, and be undertaken in LMICs, increasing the generalisability of findings. Well‐designed, adequately‐reported RCTs of CR in people with CHD more representative of usual clinical practice are still needed. Trials should explicitly report clinical outcomes, including mortality and hospital admissions, and include validated HRQoL outcome measures, especially over longer‐term follow‐up, and assess costs and cost‐effectiveness.

Exercise-based cardiac rehabilitation for coronary heart disease (Review)

Abstract: BackgroundCoronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support to manage their symptoms and prognosis. Exercise-based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane systematic review previously published in 2011.ObjectivesTo assess the effectiveness and cost-effectiveness of exercise-based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with usual care on mortality, morbidity and HRQL in patients with CHD. To explore the potential study level predictors of the effectiveness of exercise-based CR in patients with CHD.Search methodsWe updated searches from the previous Cochrane review, by searching Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 6, 2014) from December 2009 to July 2014. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and Science Citation Index Expanded (December 2009 to July 2014).Selection criteriaWe included randomised controlled trials (RCTs) of exercise-based interventions with at least six months' follow-up, compared with a no exercise control. The study population comprised men and women of all ages who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or who have angina pectoris, or coronary artery disease. We included RCTs that reported at least one of the following outcomes: mortality, MI, revascularisations, hospitalisations, health-related quality of life (HRQL), or costs.Data collection and analysisTwo review authors independently screened all identified references for inclusion based on the above inclusion and exclusion criteria. One author extracted data from the included trials and assessed their risk of bias; a second review author checked data. We stratified meta-analysis by the duration of follow up of trials, i. e. short-term: 6 to 12 months, medium-term: 13 to 36 months, and long-term: > 3 years.Main resultsThis review included 63 trials which randomised 14,486 people with CHD. This latest update identified 16 new trials (3872 participants). The population included predominantly post-MI and post-revascularisation patients and the mean age of patients within the trials ranged from 47.5 to 71.0 years. Women accounted for fewer than 15% of the patients recruited. Overall trial reporting was poor, although there was evidence of an improvement in quality of reporting in more recent trials.As we found no significant difference in the impact of exercise-based CR on clinical outcomes across follow-up, we focused on reporting findings pooled across all trials at their longest follow-up (median 12 months). Exercise-based CR reduced cardiovascular mortality compared with no exercise control (27 trials; risk ratio (RR) 0.74, 95% CI 0.64 to 0.86). There was no reduction in total mortality with CR (47 trials, RR 0.96, 95% CI 0.88 to 1.04). The overall risk of hospital admissions was reduced with CR (15 trials; RR 0.82, 95% CI 0.70 to 0.96) but there was no significant impact on the risk of MI (36 trials; RR 0.90, 95% CI 0.79 to 1.04), CABG (29 trials; RR 0.96, 95% CI 0.80 to 1.16) or PCI (18 trials; RR 0.85, 95% CI 0.70 to 1.04).There was little evidence of statistical heterogeneity across trials for all event outcomes, and there was evidence of small study bias for MI and hospitalisation, but no other outcome. Predictors of clinical outcomes were examined across the longest follow-up of studies using univariate meta-regression. Results show that benefits in outcomes were independent of participants' CHD case mix (proportion of patients with MI), type of CR (exercise only vs comprehensive rehabilitation) dose of exercise, length of follow-up, trial publication date, setting (centre vs home-based), study location (continent), sample size or risk of bias.Given the heterogeneity in outcome measures and reporting methods, meta-analysis was not undertaken for HRQL. In five out of 20 trials reporting HRQL using validated measures, there was evidence of significant improvement in most or all of the sub-scales with exercise-based CR compared to control at follow-up. Four trial-based economic evaluation studies indicated exercise-based CR to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years.The quality of the evidence for outcomes reported in the review was rated using the GRADE method. The quality of the evidence varied widely by outcome and ranged from low to moderate.Authors' conclusionsThis updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based CR reduces the risk of cardiovascular mortality but not total mortality. We saw a significant reduction in the risk of hospitalisation with CR but not in the risk of MI or revascularisation. We identified further evidence supporting improved HRQL with exercise-based CR. More recent trials were more likely to be well reported and include older and female patients. However, the population studied in this review still consists predominantly of lower risk individuals following MI or revascularisation. Further well conducted RCTs are needed to assess the impact of exercise-based CR in higher risk CHD groups and also those presenting with stable angina. These trials should include validated HRQL outcome measures, explicitly report clinical event outcomes including mortality and hospital admissions, and assess costs and cost-effectiveness.

Exercise-based rehabilitation for coronary heart disease

Abstract: BACKGROUND: The burden of cardiovascular disease world-wide is one of great concern to patients and health care agencies alike. Cardiac rehabilitation aims to restore patients with heart disease to health through exercise only based rehabilitation or comprehensive cardiac rehabilitation. OBJECTIVES: To determine the effectiveness of exercise only or exercise as part of a comprehensive cardiac rehabilitation programme on the mortality, morbidity, health-related quality of life (HRQoL) and modifiable cardiac risk factors of patients with coronary heart disease. SEARCH STRATEGY: Electronic databases were searched for randomised controlled trials, using standardised trial filters, from the earliest date available to December 31st 1998. SELECTION CRITERIA: Men and women of all ages, in hospital or community settings, who have had myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, or who have angina pectoris or coronary artery disease defined by angiography. DATA COLLECTION AND ANALYSIS: Studies were selected independently by two reviewers, and data extracted independently. Authors were contacted where possible to obtain missing information. MAIN RESULTS: This systematic review has allowed analysis of an increased number of patients from approximately 4500 in earlier meta-analyses to 8440 (7683 contributing to the total mortality outcome). The pooled effect estimate for total mortality for the exercise only intervention shows a 27% reduction in all cause mortality (random effects model OR 0.73 (0.54, 0.98)). Comprehensive cardiac rehabilitation reduced all cause mortality, but to a lesser degree (OR 0.87 (0.71, 1.05)). Total cardiac mortality was reduced by 31% (random effects model OR 0.69 (0.51, 0.94)) and 26% (random effects model OR 0.74 (0.57, 0.96)) in the exercise only and comprehensive cardiac rehabilitation groups respectively. Neither intervention had any effect on the occurrence of non-fatal myocardial infarction. There was a significant net reduction in total cholesterol (pooled WMD random effects model -0.57 mmol/l (-0.83, -0.31)) and LDL (pooled WMD random effects model -0.51 mmol/l (-0.82, -0.19) in the comprehensive cardiac rehabilitation group. REVIEWER'S CONCLUSIONS: Exercise-based cardiac rehabilitation is effective in reducing cardiac deaths. It is not clear from this review whether exercise only or a comprehensive cardiac rehabilitation intervention is more beneficial. The population studied in this review is still predominantly male, middle aged and low risk. Identification of the ethnic origin of the participants was seldom reported. It is possible that patients who would have benefited most from the intervention were excluded from the trials on the grounds of age, sex or co-morbidity.

ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting With ST-Segment Elevation

Abstract: ACE : angiotensin-converting enzyme ACS : acute coronary syndrome ADP : adenosine diphosphate AF : atrial fibrillation AMI : acute myocardial infarction AV : atrioventricular AIDA-4 : Abciximab Intracoronary vs. intravenously Drug Application APACHE II : Acute Physiology Aand Chronic

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

Abstract: ACC/AHA : American College of Cardiology/American Heart Association ACCF/AHA : American College of Cardiology Foundation/American Heart Association ACE : angiotensin-converting enzyme ACEI : angiotensin-converting enzyme inhibitor ACS : acute coronary syndrome AF : atrial fibrillation

European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (Version 2012)

Abstract: ABI : ankle–brachial index ACCORD : Action to Control Cardiovascular Risk in Diabetes ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation AGREE : Appraisal of Guidelines Research and Evaluation AHA : American Heart Association apoA1 : apolipoprotein A1 apoB : apolipoprotein B CABG : coronary artery bypass graft surgery CARDS : Collaborative AtoRvastatin Diabetes Study CCNAP : Council on Cardiovascular Nursing and Allied Professions CHARISMA : Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation, Management, and Avoidance CHD : coronary heart disease CKD : chronic kidney disease COMMIT : Clopidogrel and Metoprolol in Myocardial Infarction Trial CRP : C-reactive protein CURE : Clopidogrel in Unstable Angina to Prevent Recurrent Events CVD : cardiovascular disease DALYs : disability-adjusted life years DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Trial ED : erectile dysfunction eGFR : estimated glomerular filtration rate EHN : European Heart Network EPIC : European Prospective Investigation into Cancer and Nutrition EUROASPIRE : European Action on Secondary and Primary Prevention through Intervention to Reduce Events GFR : glomerular filtration rate GOSPEL : Global Secondary Prevention Strategies to Limit Event Recurrence After MI GRADE : Grading of Recommendations Assessment, Development and Evaluation HbA1c : glycated haemoglobin HDL : high-density lipoprotein HF-ACTION : Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing HOT : Hypertension Optimal Treatment Study HPS : Heart Protection Study HR : hazard ratio hsCRP : high-sensitivity C-reactive protein HYVET : Hypertension in the Very Elderly Trial ICD : International Classification of Diseases IMT : intima-media thickness INVEST : International Verapamil SR/Trandolapril JTF : Joint Task Force LDL : low-density lipoprotein Lp(a) : lipoprotein(a) LpPLA2 : lipoprotein-associated phospholipase 2 LVH : left ventricular hypertrophy MATCH : Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke MDRD : Modification of Diet in Renal Disease MET : metabolic equivalent MONICA : Multinational MONItoring of trends and determinants in CArdiovascular disease NICE : National Institute of Health and Clinical Excellence NRT : nicotine replacement therapy NSTEMI : non-ST elevation myocardial infarction ONTARGET : Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial OSA : obstructive sleep apnoea PAD : peripheral artery disease PCI : percutaneous coronary intervention PROactive : Prospective Pioglitazone Clinical Trial in Macrovascular Events PWV : pulse wave velocity QOF : Quality and Outcomes Framework RCT : randomized clinical trial RR : relative risk SBP : systolic blood pressure SCORE : Systematic Coronary Risk Evaluation Project SEARCH : Study of the Effectiveness of Additional Reductions in Cholesterol and SHEP : Systolic Hypertension in the Elderly Program STEMI : ST-elevation myocardial infarction SU.FOL.OM3 : SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids Syst-Eur : Systolic Hypertension in Europe TNT : Treating to New Targets UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use VITATOPS : VITAmins TO Prevent Stroke VLDL : very low-density lipoprotein WHO : World Health Organization ### 1.1 Introduction Atherosclerotic cardiovascular disease (CVD) is a chronic disorder developing insidiously throughout life and usually progressing to an advanced stage by the time symptoms occur. It remains the major cause of premature death in Europe, even though CVD mortality has …