Meditation for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Interventions incorporating meditation to address stress, anxiety, and depression, and improve self-management, are becoming popular for many health conditions. Stress is a risk factor for cardiovascular disease (CVD) and clusters with other modifiable behavioural risk factors, such as smoking. Meditation may therefore be a useful CVD prevention strategy. OBJECTIVES: To determine the effectiveness of meditation, primarily mindfulness-based interventions (MBIs) and transcendental meditation (TM), for the primary and secondary prevention of CVD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases, and two trials registers on 14 November 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of 12 weeks or more in adults at high risk of CVD and those with established CVD. We explored four comparisons: MBIs versus active comparators (alternative interventions); MBIs versus non-active comparators (no intervention, wait list, usual care); TM versus active comparators; TM versus non-active comparators. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were CVD clinical events (e.g. cardiovascular mortality), blood pressure, measures of psychological distress and well-being, and adverse events. Secondary outcomes included other CVD risk factors (e.g. blood lipid levels), quality of life, and coping abilities. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included 81 RCTs (6971 participants), with most studies at unclear risk of bias. MBIs versus active comparators (29 RCTs, 2883 participants) Systolic (SBP) and diastolic (DBP) blood pressure were reported in six trials (388 participants) where heterogeneity was considerable (SBP: MD -6.08 mmHg, 95% CI -12.79 to 0.63, I2 = 88%; DBP: MD -5.18 mmHg, 95% CI -10.65 to 0.29, I2 = 91%; both outcomes based on low-certainty evidence). There was little or no effect of MBIs on anxiety (SMD -0.06 units, 95% CI -0.25 to 0.13; I2 = 0%; 9 trials, 438 participants; moderate-certainty evidence), or depression (SMD 0.08 units, 95% CI -0.08 to 0.24; I2 = 0%; 11 trials, 595 participants; moderate-certainty evidence). Perceived stress was reduced with MBIs (SMD -0.24 units, 95% CI -0.45 to -0.03; I2 = 0%; P = 0.03; 6 trials, 357 participants; moderate-certainty evidence). There was little to no effect on well-being (SMD -0.18 units, 95% CI -0.67 to 0.32; 1 trial, 63 participants; low-certainty evidence). There was little to no effect on smoking cessation (RR 1.45, 95% CI 0.78 to 2.68; I2 = 79%; 6 trials, 1087 participants; low-certainty evidence). None of the trials reported CVD clinical events or adverse events. MBIs versus non-active comparators (38 RCTs, 2905 participants) Clinical events were reported in one trial (110 participants), providing very low-certainty evidence (RR 0.94, 95% CI 0.37 to 2.42). SBP and DBP were reduced in nine trials (379 participants) but heterogeneity was substantial (SBP: MD -6.62 mmHg, 95% CI -13.15 to -0.1, I2 = 87%; DBP: MD -3.35 mmHg, 95% CI -5.86 to -0.85, I2 = 61%; both outcomes based on low-certainty evidence). There was low-certainty evidence of reductions in anxiety (SMD -0.78 units, 95% CI -1.09 to -0.41; I2 = 61%; 9 trials, 533 participants; low-certainty evidence), depression (SMD -0.66 units, 95% CI -0.91 to -0.41; I2 = 67%; 15 trials, 912 participants; low-certainty evidence) and perceived stress (SMD -0.59 units, 95% CI -0.89 to -0.29; I2 = 70%; 11 trials, 708 participants; low-certainty evidence) but heterogeneity was substantial. Well-being increased (SMD 0.5 units, 95% CI 0.09 to 0.91; I2 = 47%; 2 trials, 198 participants; moderate-certainty evidence). There was little to no effect on smoking cessation (RR 1.36, 95% CI 0.86 to 2.13; I2 = 0%; 2 trials, 453 participants; low-certainty evidence). One small study (18 participants) reported two adverse events in the MBI group, which were not regarded as serious by the study investigators (RR 5.0, 95% CI 0.27 to 91.52; low-certainty evidence). No subgroup effects were seen for SBP, DBP, anxiety, depression, or perceived stress by primary and secondary prevention. TM versus active comparators (8 RCTs, 830 participants) Clinical events were reported in one trial (201 participants) based on low-certainty evidence (RR 0.91, 95% CI 0.56 to 1.49). SBP was reduced (MD -2.33 mmHg, 95% CI -3.99 to -0.68; I2 = 2%; 8 trials, 774 participants; moderate-certainty evidence), with an uncertain effect on DBP (MD -1.15 mmHg, 95% CI -2.85 to 0.55; I2 = 53%; low-certainty evidence). There was little or no effect on anxiety (SMD 0.06 units, 95% CI -0.22 to 0.33; I2 = 0%; 3 trials, 200 participants; low-certainty evidence), depression (SMD -0.12 units, 95% CI -0.31 to 0.07; I2 = 0%; 5 trials, 421 participants; moderate-certainty evidence), or perceived stress (SMD 0.04 units, 95% CI -0.49 to 0.57; I2 = 70%; 3 trials, 194 participants; very low-certainty evidence). None of the trials reported adverse events or smoking rates. No subgroup effects were seen for SBP or DBP by primary and secondary prevention. TM versus non-active comparators (2 RCTs, 186 participants) Two trials (139 participants) reported blood pressure, where reductions were seen in SBP (MD -6.34 mmHg, 95% CI -9.86 to -2.81; I2 = 0%; low-certainty evidence) and DBP (MD -5.13 mmHg, 95% CI -9.07 to -1.19; I2 = 18%; very low-certainty evidence). One trial (112 participants) reported anxiety and depression and found reductions in both (anxiety SMD -0.71 units, 95% CI -1.09 to -0.32; depression SMD -0.48 units, 95% CI -0.86 to -0.11; low-certainty evidence). None of the trials reported CVD clinical events, adverse events, or smoking rates. AUTHORS' CONCLUSIONS: Despite the large number of studies included in the review, heterogeneity was substantial for many of the outcomes, which reduced the certainty of our findings. We attempted to address this by presenting four main comparisons of MBIs or TM versus active or inactive comparators, and by subgroup analyses according to primary or secondary prevention, where there were sufficient studies. The majority of studies were small and there was unclear risk of bias for most domains. Overall, we found very little information on the effects of meditation on CVD clinical endpoints, and limited information on blood pressure and psychological outcomes, for people at risk of or with established CVD. This is a very active area of research as shown by the large number of ongoing studies, with some having been completed at the time of writing this review. The status of all ongoing studies will be formally assessed and incorporated in further updates.

Exercise-based cardiac rehabilitation for adults with heart failure.

BACKGROUND: People with heart failure experience substantial disease burden that includes low exercise tolerance, poor health-related quality of life (HRQoL), increased risk of mortality and hospital admission, and high healthcare costs. The previous 2018 Cochrane review reported that exercise-based cardiac rehabilitation (ExCR) compared to no exercise control shows improvement in HRQoL and hospital admission amongst people with heart failure, as well as possible reduction in mortality over the longer term, and that these reductions appear to be consistent across patient and programme characteristics. Limitations noted by the authors of this previous Cochrane review include the following: (1) most trials were undertaken in patients with heart failure with reduced (< 45%) ejection fraction (HFrEF), and women, older people, and those with heart failure with preserved (≥ 45%) ejection fraction (HFpEF) were under-represented; and (2) most trials were undertaken in a hospital or centre-based setting. OBJECTIVES: To assess the effects of ExCR on mortality, hospital admission, and health-related quality of life of adults with heart failure. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and Web of Science without language restriction on 13 December 2021. We also checked the bibliographies of included studies, identified relevant systematic reviews, and two clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared ExCR interventions (either exercise only or exercise as part of a comprehensive cardiac rehabilitation) with a follow-up of six months or longer versus a no-exercise control (e.g. usual medical care). The study population comprised adults (≥ 18 years) with heart failure - either HFrEF or HFpEF. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, mortality due to heart failure, all-cause hospital admissions, heart failure-related hospital admissions, and HRQoL. Secondary outcomes were costs and cost-effectiveness. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 60 trials (8728 participants) with a median of six months' follow-up. For this latest update, we identified 16 new trials (2945 new participants), in addition to the previously identified 44 trials (5783 existing participants). Although the existing evidence base predominantly includes patients with HFrEF, with New York Heart Association (NYHA) classes II and III receiving centre-based ExCR programmes, a growing body of trials includes patients with HFpEF with ExCR undertaken in a home-based setting. All included trials employed a usual care comparator with a formal no-exercise intervention as well as a wide range of active comparators, such as education, psychological intervention, or medical management. The overall risk of bias in the included trials was low or unclear, and we mostly downgraded the certainty of evidence of outcomes upon GRADE assessment. There was no evidence of a difference in the short term (up to 12 months' follow-up) in the pooled risk of all-cause mortality when comparing ExCR versus usual care (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.71 to 1.21; absolute effects 5.0% versus 5.8%; 34 trials, 36 comparisons, 3941 participants; low-certainty evidence). Only a few trials reported information on whether participants died due to heart failure. Participation in ExCR versus usual care likely reduced the risk of all-cause hospital admissions (RR 0.69, 95% CI 0.56 to 0.86; absolute effects 15.9% versus 23.8%; 23 trials, 24 comparisons, 2283 participants; moderate-certainty evidence) and heart failure-related hospital admissions (RR 0.82, 95% CI 0.49 to 1.35; absolute effects 5.6% versus 6.4%; 10 trials; 10 comparisons, 911 participants; moderate-certainty evidence) in the short term. Participation in ExCR likely improved short-term HRQoL as measured by the Minnesota Living with Heart Failure (MLWHF) questionnaire (lower scores indicate better HRQoL and a difference of 5 points or more indicates clinical importance; mean difference (MD) -7.39 points, 95% CI -10.30 to -4.77; 21 trials, 22 comparisons, 2699 participants; moderate-certainty evidence). When pooling HRQoL data measured by any questionnaire/scale, we found that ExCR may improve HRQoL in the short term, but the evidence is very uncertain (33 trials, 37 comparisons, 4769 participants; standardised mean difference (SMD) -0.52, 95% CI -0.70 to -0.34; very-low certainty evidence). ExCR effects appeared to be consistent across different models of ExCR delivery: centre- versus home-based, exercise dose, exercise only versus comprehensive programmes, and aerobic training alone versus aerobic plus resistance programmes. AUTHORS' CONCLUSIONS: This updated Cochrane review provides additional randomised evidence (16 trials) to support the conclusions of the previous 2018 version of the review. Compared to no exercise control, whilst there was no evidence of a difference in all-cause mortality in people with heart failure, ExCR participation likely reduces the risk of all-cause hospital admissions and heart failure-related hospital admissions, and may result in important improvements in HRQoL. Importantly, this updated review provides additional evidence supporting the use of alternative modes of ExCR delivery, including home-based and digitally-supported programmes. Future ExCR trials need to focus on the recruitment of traditionally less represented heart failure patient groups including older patients, women, and those with HFpEF.

Exercise-based cardiac rehabilitation for coronary heart disease: a meta-analysis.

AIMS: Coronary heart disease is the most common reason for referral to exercise-based cardiac rehabilitation (CR) globally. However, the generalizability of previous meta-analyses of randomized controlled trials (RCTs) is questioned. Therefore, a contemporary updated meta-analysis was undertaken. METHODS AND RESULTS: Database and trial registry searches were conducted to September 2020, seeking RCTs of exercise-based interventions with ≥6-month follow-up, compared with no-exercise control for adults with myocardial infarction, angina pectoris, or following coronary artery bypass graft, or percutaneous coronary intervention. The outcomes of mortality, recurrent clinical events, and health-related quality of life (HRQoL) were pooled using random-effects meta-analysis, and cost-effectiveness data were narratively synthesized. Meta-regression was used to examine effect modification. Study quality was assessed using the Cochrane risk of bias tool. A total of 85 RCTs involving 23 430 participants with a median 12-month follow-up were included. Overall, exercise-based CR was associated with significant risk reductions in cardiovascular mortality [risk ratio (RR): 0.74, 95% confidence interval (CI): 0.64-0.86, number needed to treat (NNT): 37], hospitalizations (RR: 0.77, 95% CI: 0.67-0.89, NNT: 37), and myocardial infarction (RR: 0.82, 95% CI: 0.70-0.96, NNT: 100). There was some evidence of significantly improved HRQoL with CR participation, and CR is cost-effective. There was no significant impact on overall mortality (RR: 0.96, 95% CI: 0.89-1.04), coronary artery bypass graft (RR: 0.96, 95% CI: 0.80-1.15), or percutaneous coronary intervention (RR: 0.84, 95% CI: 0.69-1.02). No significant difference in effects was found across different patient groups, CR delivery models, doses, follow-up, or risk of bias. CONCLUSION: This review confirms that participation in exercise-based CR by patients with coronary heart disease receiving contemporary medical management reduces cardiovascular mortality, recurrent cardiac events, and hospitalizations and provides additional evidence supporting the improvement in HRQoL and the cost-effectiveness of CR.

Evaluating interventions to improve ethical decision making in clinical practice: a review of the literature and reflections on the challenges posed.

Since the 1980s, there has been an increasing acknowledgement of the importance of recognising the ethical dimension of clinical decision-making. Medical professional regulatory authorities in some countries now include ethical knowledge and practice in their required competencies for undergraduate and post graduate medical training. Educational interventions and clinical ethics support services have been developed to support and improve ethical decision making in clinical practice, but research evaluating the effectiveness of these interventions has been limited. We undertook a systematic review of the published literature on measures or models of evaluation used to assess the impact of interventions to improve ethical decision making in clinical care. We identified a range of measures to evaluate educational interventions, and one tool used to evaluate a clinical ethics support intervention. Most measures did not evaluate the key impact of interest, that is the quality of ethical decision making in real-world clinical practice. We describe the results of our review and reflect on the challenges of assessing ethical decision making in clinical practice that face both developers of educational and support interventions and the regulatory organisations that set and assess competency standards.

The effectiveness of group-based gardening interventions for improving wellbeing and reducing symptoms of mental ill-health in adults: a systematic review and meta-analysis.

BACKGROUND: There is increasing interest in the association between nature, health and wellbeing. Gardening is a popular way in which interaction with nature occurs and numerous gardening projects aim to facilitate wellbeing among participants. More research is needed to determine their effectiveness. AIM: To systematically evaluate the effectiveness of group-based gardening interventions for increasing wellbeing and reducing symptoms of mental ill-health in adults. METHODS: A systematic review of Randomised Controlled Trials was conducted following the protocol submitted to PROSPERO (CRD42020162187). Studies reporting quantitative validated health and wellbeing outcomes of the community residing, adult populations (18+) were eligible for inclusion. RESULTS: 24 studies met inclusion criteria: 20 completed and four ongoing trials. Meta-analyses suggest these interventions may increase wellbeing and may reduce symptoms of depression, however, there was uncertainty in the pooled effects due to heterogeneity and unclear risk of bias for many studies. There were mixed results for other outcomes. RESEARCH LIMITATIONS/IMPLICATIONS: Heterogeneity and small sample sizes limited the results. Poor reporting precluded meta-analysis for some studies. Initial findings for wellbeing and depression are promising and should be corroborated in further studies. The research area is active, and the results of the ongoing trials identified will add to the evidence base.

The impact of the COVID-19 pandemic on glycaemic control in people with diabetes: A systematic review and meta-analysis.

AIM: To identify, appraise and synthesize the available evidence on the impact of the coronavirus disease 2019 (COVID-19) pandemic and lockdown (LD) on glycaemic control in people with diabetes. MATERIALS AND METHODS: We searched multiple databases up to 2 February 2021 for studies reporting HbA1c, time in range (TIR), average or fasting glucose, severe hypoglycaemia and diabetic ketoacidosis. Data were pooled using random effects meta-analysis and are presented as mean difference (MD) with 95% confidence intervals (CI). This review was preregistered on PROSPERO (CRD42020179319). RESULTS: We include 59 studies; 44 (n = 15 464) were included in quantitative syntheses and 15 were narratively synthesized. Pooled data were grouped by diabetes type. Results from 28 studies (n = 5048 type 1 diabetes [T1D] and combined diabetes participants) showed that TIR increased during LD compared with before LD (MD 2.74%, 95% CI 1.80% to 3.69%). Data from 10 studies (n = 1294 T1D participants) showed that TIR increased after LD compared with before LD (MD 5.14%, 95% CI 3.12% to 7.16%). Pooled results from 12 studies (n = 4810 T1D and type 2 diabetes participants) resulted in average glucose decreasing after LD compared with before LD (MD -6.86 mg/dl, 95% CI -8.54 to -5.18). Results for other outcomes, including HbA1c, were not statistically significantly different. CONCLUSIONS: The COVID-19 pandemic was associated with small improvements across multiple outcomes of glycaemic control, although there was insufficient evidence to suggest that this led to changes in HbA1c. Most evidence came from people with access to diabetes technologies in high-income countries; more research is needed in less advantaged populations.

Vegan dietary pattern for the primary and secondary prevention of cardiovascular diseases.

BACKGROUND: Diet plays a major role in the aetiology of cardiovascular disease (CVD) and as a modifiable risk factor is the focus of many prevention strategies. Recently vegan diets have gained popularity and there is a need to synthesise existing clinical trial evidence for their potential in CVD prevention. OBJECTIVES: To determine the effectiveness of following a vegan dietary pattern for the primary and secondary prevention of CVD. SEARCH METHODS: We searched the following electronic databases on 4 February 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Web of Science Core Collection. We also searched ClinicalTrials.gov in January 2021. We applied no language restrictions. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) in healthy adults and adults at high risk of CVD (primary prevention) and those with established CVD (secondary prevention). A vegan dietary pattern excludes meat, fish, eggs, dairy and honey; the intervention could be dietary advice, provision of relevant foods, or both. The comparison group received either no intervention, minimal intervention, or another dietary intervention. Outcomes included clinical events and CVD risk factors. We included only studies with follow-up periods of 12 weeks or more, defined as the intervention period plus post-intervention follow-up. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and assessed risks of bias. We used GRADE to assess the certainty of the evidence. We conducted three main comparisons: 1. Vegan dietary intervention versus no intervention or minimal intervention for primary prevention; 2. Vegan dietary intervention versus another dietary intervention for primary prevention; 3. Vegan dietary intervention versus another dietary intervention for secondary prevention. MAIN RESULTS: Thirteen RCTs (38 papers, 7 trial registrations) and eight ongoing trials met our inclusion criteria. Most trials contributed to primary prevention: comparisons 1 (four trials, 466 participants randomised) and comparison 2 (eight trials, 409 participants randomised). We included only one secondary prevention trial for comparison 3 (63 participants randomised). None of the trials reported on clinical endpoints. Other primary outcomes included lipid levels and blood pressure. For comparison 1 there was moderate-certainty evidence from four trials with 449 participants that a vegan diet probably led to a small reduction in total cholesterol (mean difference (MD) -0.24 mmol/L, 95% confidence interval (CI) -0.36 to -0.12) and low-density lipoprotein (LDL) cholesterol (MD -0.22 mmol/L, 95% CI -0.32 to -0.11), a very small decrease in high-density lipoprotein (HDL) levels (MD -0.08 mmol/L, 95% CI -0.11 to -0.04) and a very small increase in triglyceride levels (MD 0.11 mmol/L, 95% CI 0.01 to 0.21). The very small changes in HDL and triglyceride levels are in the opposite direction to that expected. There was a lack of evidence for an effect with the vegan dietary intervention on systolic blood pressure (MD 0.94 mmHg, 95% CI -1.18 to 3.06; 3 trials, 374 participants) and diastolic blood pressure (MD -0.27 mmHg, 95% CI -1.67 to 1.12; 3 trials, 372 participants) (low-certainty evidence). For comparison 2 there was a lack of evidence for an effect of the vegan dietary intervention on total cholesterol levels (MD -0.04 mmol/L, 95% CI -0.28 to 0.20; 4 trials, 163 participants; low-certainty evidence). There was probably little or no effect of the vegan dietary intervention on LDL (MD -0.05 mmol/L, 95% CI -0.21 to 0.11; 4 trials, 244 participants) or HDL cholesterol levels (MD -0.01 mmol/L, 95% CI -0.08 to 0.05; 5 trials, 256 participants) or triglycerides (MD 0.21 mmol/L, 95% CI -0.07 to 0.49; 5 trials, 256 participants) compared to other dietary interventions (moderate-certainty evidence). We are very uncertain about any effect of the vegan dietary intervention on systolic blood pressure (MD 0.02 mmHg, 95% CI -3.59 to 3.62)  or diastolic blood pressure (MD 0.63 mmHg, 95% CI -1.54 to 2.80; 5 trials, 247 participants (very low-certainty evidence)). Only one trial (63 participants) contributed to comparison 3, where there was a lack of evidence for an effect of the vegan dietary intervention on lipid levels or blood pressure compared to other dietary interventions (low- or very low-certainty evidence). Four trials reported on adverse events, which were absent or minor. AUTHORS' CONCLUSIONS: Studies were generally small with few participants contributing to each comparison group. None of the included studies report on CVD clinical events. There is currently insufficient information to draw conclusions about the effects of vegan dietary interventions on CVD risk factors. The eight ongoing studies identified will add to the evidence base, with all eight reporting on primary prevention. There is a paucity of evidence for secondary prevention.

Exercise-based cardiac rehabilitation for coronary heart disease.

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.

Correction: Interventions for treating children and adolescents with overweight and obesity: an overview of Cochrane reviews.

This paper was originally published under a standard licence. This has now been amended to a CC BY licence in the PDF and HTML.

Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: The Seven Countries study in the 1960s showed that populations in the Mediterranean region experienced lower coronary heart disease (CHD) mortality probably as a result of different dietary patterns. Later observational studies have confirmed the benefits of adherence to a Mediterranean dietary pattern on cardiovascular disease (CVD) risk factors but clinical trial evidence is more limited. OBJECTIVES: To determine the effectiveness of a Mediterranean-style diet for the primary and secondary prevention of CVD. SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 9); MEDLINE (Ovid, 1946 to 25 September 2018); Embase (Ovid, 1980 to 2018 week 39); Web of Science Core Collection (Thomson Reuters, 1900 to 26 September 2018); DARE Issue 2 of 4, 2015 (Cochrane Library); HTA Issue 4 of 4, 2016 (Cochrane Library); NHS EED Issue 2 of 4, 2015 (Cochrane Library). We searched trial registers and applied no language restrictions. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) in healthy adults and adults at high risk of CVD (primary prevention) and those with established CVD (secondary prevention). Both of the following key components were required to reach our definition of a Mediterranean-style diet: high monounsaturated/saturated fat ratio (use of olive oil as main cooking ingredient and/or consumption of other traditional foods high in monounsaturated fats such as tree nuts) and a high intake of plant-based foods, including fruits, vegetables and legumes. Additional components included: low to moderate red wine consumption; high consumption of whole grains and cereals; low consumption of meat and meat products and increased consumption of fish; moderate consumption of milk and dairy products. The intervention could be dietary advice, provision of relevant foods, or both. The comparison group received either no intervention, minimal intervention, usual care or another dietary intervention. Outcomes included clinical events and CVD risk factors. We included only studies with follow-up periods of three months or more defined as the intervention period plus post intervention follow-up. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and assessed risk of bias. We conducted four main comparisons:1. Mediterranean dietary intervention versus no intervention or minimal intervention for primary prevention;2. Mediterranean dietary intervention versus another dietary intervention for primary prevention;3. Mediterranean dietary intervention versus usual care for secondary prevention;4. Mediterranean dietary intervention versus another dietary intervention for secondary prevention. MAIN RESULTS: In this substantive review update, 30 RCTs (49 papers) (12,461 participants randomised) and seven ongoing trials met our inclusion criteria. The majority of trials contributed to primary prevention: comparisons 1 (nine trials) and 2 (13 trials). Secondary prevention trials were included for comparison 3 (two trials) and comparison 4 (four trials plus an additional two trials that were excluded from the main analyses due to published concerns regarding the reliability of the data).Two trials reported on adverse events where these were absent or minor (low- to moderate-quality evidence). No trials reported on costs or health-related quality of life.Primary preventionThe included studies for comparison 1 did not report on clinical endpoints (CVD mortality, total mortality or non-fatal endpoints such as myocardial infarction or stroke). The PREDIMED trial (included in comparison 2) was retracted and re-analysed following concerns regarding randomisation at two of 11 sites. Low-quality evidence shows little or no effect of the PREDIMED (7747 randomised) intervention (advice to follow a Mediterranean diet plus supplemental extra-virgin olive oil or tree nuts) compared to a low-fat diet on CVD mortality (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.50 to 1.32) or total mortality (HR 1.0, 95% CI 0.81 to 1.24) over 4.8 years. There was, however, a reduction in the number of strokes with the PREDIMED intervention (HR 0.60, 95% CI 0.45 to 0.80), a decrease from 24/1000 to 14/1000 (95% CI 11 to 19), moderate-quality evidence). For CVD risk factors for comparison 1 there was low-quality evidence for a possible small reduction in total cholesterol (-0.16 mmol/L, 95% CI -0.32 to 0.00) and moderate-quality evidence for a reduction in systolic (-2.99 mmHg (95% CI -3.45 to -2.53) and diastolic blood pressure (-2.0 mmHg, 95% CI -2.29 to -1.71), with low or very low-quality evidence of little or no effect on LDL or HDL cholesterol or triglycerides. For comparison 2 there was moderate-quality evidence of a possible small reduction in LDL cholesterol (-0.15 mmol/L, 95% CI -0.27 to -0.02) and triglycerides (-0.09 mmol/L, 95% CI -0.16 to -0.01) with moderate or low-quality evidence of little or no effect on total or HDL cholesterol or blood pressure.Secondary preventionFor secondary prevention, the Lyon Diet Heart Study (comparison 3) examined the effect of advice to follow a Mediterranean diet and supplemental canola margarine compared to usual care in 605 CHD patients over 46 months and there was low-quality evidence of a reduction in adjusted estimates for CVD mortality (HR 0.35, 95% CI 0.15 to 0.82) and total mortality (HR 0.44, 95% CI 0.21 to 0.92) with the intervention. Only one small trial (101 participants) provided unadjusted estimates for composite clinical endpoints for comparison 4 (very low-quality evidence of uncertain effect). For comparison 3 there was low-quality evidence of little or no effect of a Mediterranean-style diet on lipid levels and very low-quality evidence for blood pressure. Similarly, for comparison 4 where only two trials contributed to the analyses there was low or very low-quality evidence of little or no effect of the intervention on lipid levels or blood pressure. AUTHORS' CONCLUSIONS: Despite the relatively large number of studies included in this review, there is still some uncertainty regarding the effects of a Mediterranean-style diet on clinical endpoints and CVD risk factors for both primary and secondary prevention. The quality of evidence for the modest benefits on CVD risk factors in primary prevention is low or moderate, with a small number of studies reporting minimal harms. There is a paucity of evidence for secondary prevention. The ongoing studies may provide more certainty in the future.

Exercise-based cardiac rehabilitation for adults with heart failure.

BACKGROUND: Chronic heart failure (HF) is a growing global health challenge. People with HF experience substantial burden that includes low exercise tolerance, poor health-related quality of life (HRQoL), increased risk of mortality and hospital admission, and high healthcare costs. The previous (2014) Cochrane systematic review reported that exercise-based cardiac rehabilitation (CR) compared to no exercise control shows improvement in HRQoL and hospital admission among people with HF, as well as possible reduction in mortality over the longer term, and that these reductions appear to be consistent across patient and programme characteristics. Limitations noted by the authors of this previous Cochrane Review include the following: (1) most trials were undertaken in patients with HF with reduced (< 45%) ejection fraction (HFrEF), and women, older people, and those with preserved (≥ 45%) ejection fraction HF (HFpEF) were under-represented; and (2) most trials were undertaken in the hospital/centre-based setting. OBJECTIVES: To determine the effects of exercise-based cardiac rehabilitation on mortality, hospital admission, and health-related quality of life of people with heart failure. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and three other databases on 29 January 2018. We also checked the bibliographies of systematic reviews and two trial registers. SELECTION CRITERIA: We included randomised controlled trials that compared exercise-based CR interventions with six months' or longer follow-up versus a no exercise control that could include usual medical care. The study population comprised adults (> 18 years) with evidence of HF - either HFrEF or HFpEF. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references and rejected those that were clearly ineligible for inclusion in the review. We obtained full papers of potentially relevant trials. Two review authors independently extracted data from the included trials, assessed their risk of bias, and performed GRADE analyses. MAIN RESULTS: We included 44 trials (5783 participants with HF) with a median of six months' follow-up. For this latest update, we identified 11 new trials (N = 1040), in addition to the previously identified 33 trials. Although the evidence base includes predominantly patients with HFrEF with New York Heart Association classes II and III receiving centre-based exercise-based CR programmes, a growing body of studies include patients with HFpEF and are undertaken in a home-based setting. All included studies included a no formal exercise training intervention comparator. However, a wide range of comparators were seen across studies that included active intervention (i.e. education, psychological intervention) or usual medical care alone. The overall risk of bias of included trials was low or unclear, and we downgraded results using the GRADE tool for all but one outcome.Cardiac rehabilitation may make little or no difference in all-cause mortality over the short term (≤ one year of follow-up) (27 trials, 28 comparisons (2596 participants): intervention 67/1302 (5.1%) vs control 75/1294 (5.8%); risk ratio (RR) 0.89, 95% confidence interval (CI) 0.66 to 1.21; low-quality GRADE evidence) but may improve all-cause mortality in the long term (> 12 months follow up) (6 trials/comparisons (2845 participants): intervention 244/1418 (17.2%) vs control 280/1427 (19.6%) events): RR 0.88, 95% CI 0.75 to 1.02; high-quality evidence). Researchers provided no data on deaths due to HF. CR probably reduces overall hospital admissions in the short term (up to one year of follow-up) (21 trials, 21 comparisons (2182 participants): (intervention 180/1093 (16.5%) vs control 258/1089 (23.7%); RR 0.70, 95% CI 0.60 to 0.83; moderate-quality evidence, number needed to treat: 14) and may reduce HF-specific hospitalisation (14 trials, 15 comparisons (1114 participants): (intervention 40/562 (7.1%) vs control 61/552 (11.1%) RR 0.59, 95% CI 0.42 to 0.84; low-quality evidence, number needed to treat: 25). After CR, a clinically important improvement in short-term disease-specific health-related quality of life may be evident (Minnesota Living With Heart Failure questionnaire - 17 trials, 18 comparisons (1995 participants): mean difference (MD) -7.11 points, 95% CI -10.49 to -3.73; low-quality evidence). Pooling across all studies, regardless of the HRQoL measure used, shows there may be clinically important improvement with exercise (26 trials, 29 comparisons (3833 participants); standardised mean difference (SMD) -0.60, 95% CI -0.82 to -0.39; I² = 87%; Chi² = 215.03; low-quality evidence). ExCR effects appeared to be consistent different models of ExCR delivery: centre vs. home-based, exercise dose, exercise only vs. comprehensive programmes, and aerobic training alone vs aerobic plus resistance programmes. AUTHORS' CONCLUSIONS: This updated Cochrane Review provides additional randomised evidence (11 trials) to support the conclusions of the previous version (2014) of this Cochane Review. Compared to no exercise control, CR appears to have no impact on mortality in the short term (< 12 months' follow-up). Low- to moderate-quality evidence shows that CR probably reduces the risk of all-cause hospital admissions and may reduce HF-specific hospital admissions in the short term (up to 12 months). CR may confer a clinically important improvement in health-related quality of life, although we remain uncertain about this because the evidence is of low quality. Future ExCR trials need to continue to consider the recruitment of traditionally less represented HF patient groups including older, female, and HFpEF patients, and alternative CR delivery settings including home- and using technology-based programmes.

Interventions for treating children and adolescents with overweight and obesity: an overview of Cochrane reviews.

Children and adolescents with overweight and obesity are a global health concern. This is an integrative overview of six Cochrane systematic reviews, providing an up-to-date synthesis of the evidence examining interventions for the treatment of children and adolescents with overweight or obesity. The data extraction and quality assessments for each review were conducted by one author and checked by a second. The six high quality reviews provide evidence on the effectiveness of behaviour changing interventions conducted in children <6 years (7 trials), 6-11 years (70 trials), adolescents 12-17 years (44 trials) and interventions that target only parents of children aged 5-11 years (20 trials); in addition to interventions examining surgery (1 trial) and drugs (21 trials). Most of the evidence was derived from high-income countries and published in the last two decades. Collectively, the evidence suggests that multi-component behaviour changing interventions may be beneficial in achieving small reductions in body weight status in children of all ages, with low adverse event occurrence were reported. More research is required to understand which specific intervention components are most effective and in whom, and how best to maintain intervention effects. Evidence from surgical and drug interventions was too limited to make inferences about use and safety, and adverse events were a serious consideration.

Omega-6 fats for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Omega-6 fats are polyunsaturated fats vital for many physiological functions, but their effect on cardiovascular disease (CVD) risk is debated. OBJECTIVES: To assess effects of increasing omega-6 fats (linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA)) on CVD and all-cause mortality. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to May 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing higher versus lower omega-6 fat intake in adults with or without CVD, assessing effects over at least 12 months. We included full texts, abstracts, trials registry entries and unpublished studies. Outcomes were all-cause mortality, CVD mortality, CVD events, risk factors (blood lipids, adiposity, blood pressure), and potential adverse events. We excluded trials where we could not separate omega-6 fat effects from those of other dietary, lifestyle or medication interventions. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias of included trials. We wrote to authors of included studies. Meta-analyses used random-effects analysis, while sensitivity analyses used fixed-effects and limited analyses to trials at low summary risk of bias. We assessed GRADE quality of evidence for 'Summary of findings' tables. MAIN RESULTS: We included 19 RCTs in 6461 participants who were followed for one to eight years. Seven trials assessed the effects of supplemental GLA and 12 of LA, none DGLA or AA; the omega-6 fats usually displaced dietary saturated or monounsaturated fats. We assessed three RCTs as being at low summary risk of bias.Primary outcomes: we found low-quality evidence that increased intake of omega-6 fats may make little or no difference to all-cause mortality (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.12, 740 deaths, 4506 randomised, 10 trials) or CVD events (RR 0.97, 95% CI 0.81 to 1.15, 1404 people experienced events of 4962 randomised, 7 trials). We are uncertain whether increasing omega-6 fats affects CVD mortality (RR 1.09, 95% CI 0.76 to 1.55, 472 deaths, 4019 randomised, 7 trials), coronary heart disease events (RR 0.88, 95% CI 0.66 to 1.17, 1059 people with events of 3997 randomised, 7 trials), major adverse cardiac and cerebrovascular events (RR 0.84, 95% CI 0.59 to 1.20, 817 events, 2879 participants, 2 trials) or stroke (RR 1.36, 95% CI 0.45 to 4.11, 54 events, 3730 participants, 4 trials), as we assessed the evidence as being of very low quality. We found no evidence of dose-response or duration effects for any primary outcome, but there was a suggestion of greater protection in participants with lower baseline omega-6 intake across outcomes.Additional key outcomes: we found increased intake of omega-6 fats may reduce myocardial infarction (MI) risk (RR 0.88, 95% CI 0.76 to 1.02, 609 events, 4606 participants, 7 trials, low-quality evidence). High-quality evidence suggests increasing omega-6 fats reduces total serum cholesterol a little in the long term (mean difference (MD) -0.33 mmol/L, 95% CI -0.50 to -0.16, I2 = 81%; heterogeneity partially explained by dose, 4280 participants, 10 trials). Increasing omega-6 fats probably has little or no effect on adiposity (body mass index (BMI) MD -0.20 kg/m2, 95% CI -0.56 to 0.16, 371 participants, 1 trial, moderate-quality evidence). It may make little or no difference to serum triglycerides (MD -0.01 mmol/L, 95% CI -0.23 to 0.21, 834 participants, 5 trials), HDL (MD -0.01 mmol/L, 95% CI -0.03 to 0.02, 1995 participants, 4 trials) or low-density lipoprotein (MD -0.04 mmol/L, 95% CI -0.21 to 0.14, 244 participants, 2 trials, low-quality evidence). AUTHORS' CONCLUSIONS: This is the most extensive systematic assessment of effects of omega-6 fats on cardiovascular health, mortality, lipids and adiposity to date, using previously unpublished data. We found no evidence that increasing omega-6 fats reduces cardiovascular outcomes other than MI, where 53 people may need to increase omega-6 fat intake to prevent 1 person from experiencing MI. Although benefits of omega-6 fats remain to be proven, increasing omega-6 fats may be of benefit in people at high risk of MI. Increased omega-6 fats reduce serum total cholesterol but not other blood fat fractions or adiposity.

Omega-6 fats for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Omega-6 fats are polyunsaturated fats vital for many physiological functions, but their effect on cardiovascular disease (CVD) risk is debated. OBJECTIVES: To assess effects of increasing omega-6 fats (linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA)) on CVD and all-cause mortality. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to May 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing higher versus lower omega-6 fat intake in adults with or without CVD, assessing effects over at least 12 months. We included full texts, abstracts, trials registry entries and unpublished studies. Outcomes were all-cause mortality, CVD mortality, CVD events, risk factors (blood lipids, adiposity, blood pressure), and potential adverse events. We excluded trials where we could not separate omega-6 fat effects from those of other dietary, lifestyle or medication interventions. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias of included trials. We wrote to authors of included studies. Meta-analyses used random-effects analysis, while sensitivity analyses used fixed-effects and limited analyses to trials at low summary risk of bias. We assessed GRADE quality of evidence for 'Summary of findings' tables. MAIN RESULTS: We included 19 RCTs in 6461 participants who were followed for one to eight years. Seven trials assessed the effects of supplemental GLA and 12 of LA, none DGLA or AA; the omega-6 fats usually displaced dietary saturated or monounsaturated fats. We assessed three RCTs as being at low summary risk of bias.Primary outcomes: we found low-quality evidence that increased intake of omega-6 fats may make little or no difference to all-cause mortality (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.12, 740 deaths, 4506 randomised, 10 trials) or CVD events (RR 0.97, 95% CI 0.81 to 1.15, 1404 people experienced events of 4962 randomised, 7 trials). We are uncertain whether increasing omega-6 fats affects CVD mortality (RR 1.09, 95% CI 0.76 to 1.55, 472 deaths, 4019 randomised, 7 trials), coronary heart disease events (RR 0.88, 95% CI 0.66 to 1.17, 1059 people with events of 3997 randomised, 7 trials), major adverse cardiac and cerebrovascular events (RR 0.84, 95% CI 0.59 to 1.20, 817 events, 2879 participants, 2 trials) or stroke (RR 1.36, 95% CI 0.45 to 4.11, 54 events, 3730 participants, 4 trials), as we assessed the evidence as being of very low quality. We found no evidence of dose-response or duration effects for any primary outcome, but there was a suggestion of greater protection in participants with lower baseline omega-6 intake across outcomes.Additional key outcomes: we found increased intake of omega-6 fats may reduce myocardial infarction (MI) risk (RR 0.88, 95% CI 0.76 to 1.02, 609 events, 4606 participants, 7 trials, low-quality evidence). High-quality evidence suggests increasing omega-6 fats reduces total serum cholesterol a little in the long term (mean difference (MD) -0.33 mmol/L, 95% CI -0.50 to -0.16, I2 = 81%; heterogeneity partially explained by dose, 4280 participants, 10 trials). Increasing omega-6 fats probably has little or no effect on adiposity (body mass index (BMI) MD -0.20 kg/m2, 95% CI -0.56 to 0.16, 371 participants, 1 trial, moderate-quality evidence). It may make little or no difference to serum triglycerides (MD -0.01 mmol/L, 95% CI -0.23 to 0.21, 834 participants, 5 trials), HDL (MD -0.01 mmol/L, 95% CI -0.03 to 0.02, 1995 participants, 4 trials) or low-density lipoprotein (MD -0.04 mmol/L, 95% CI -0.21 to 0.14, 244 participants, 2 trials, low-quality evidence). AUTHORS' CONCLUSIONS: This is the most extensive systematic assessment of effects of omega-6 fats on cardiovascular health, mortality, lipids and adiposity to date, using previously unpublished data. We found no evidence that increasing omega-6 fats reduces cardiovascular outcomes other than MI, where 53 people may need to increase omega-6 fat intake to prevent 1 person from experiencing MI. Although benefits of omega-6 fats remain to be proven, increasing omega-6 fats may be of benefit in people at high risk of MI. Increased omega-6 fats reduce serum total cholesterol but not other blood fat fractions or adiposity.

WITHDRAWN: Transcendental meditation for the primary prevention of cardiovascular disease.

BACKGROUND: A major determinant in cardiovascular disease (CVD) is stress. As transcendental meditation (TM) is thought to help in lowering negative stress indicators, it may be a beneficial strategy for the primary prevention of CVD. OBJECTIVES: To determine the effectiveness of TM for the primary prevention of CVD. SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 10); MEDLINE (Ovid) (1946 to week three November 2013); EMBASE Classic and EMBASE (Ovid) (1947 to week 48 2013); ISI Web of Science (1970 to 28 November 2013); and Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment Database and Health Economics Evaluations Database (November 2013). We also searched the Allied and complementary Medicine Database (AMED) (inception to January 2014) and IndMed (inception to January 2014). We handsearched trial registers and reference lists of reviews and articles and contacted experts in the field. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of at least three months' duration involving healthy adults or adults at high risk of CVD. Trials examined TM only and the comparison group was no intervention or minimal intervention. We excluded trials that involved multi-factorial interventions. Outcomes of interest were clinical CVD events (cardiovascular mortality, all-cause mortality and non-fatal events) and major CVD risk factors (e.g. blood pressure and blood lipids, occurrence of type 2 diabetes, quality of life, adverse events and costs). DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion, extracted data and assessed the risk of bias. MAIN RESULTS: We identified four trials (four papers) (430 participants) for inclusion in this review. We identified no ongoing studies. The included trials were small, short term (three months) and at risk of bias. In all studies, TM was practised for 15 to 20 minutes twice a day.None of the included studies reported all-cause mortality, cardiovascular mortality or non-fatal endpoints as trials were short term, but one study reported survival rate three years after the trial was completed. In view of the considerable statistical heterogeneity between the results of the studies for the only outcomes reported, systolic blood pressure (I2 = 72%) and diastolic blood pressure (I2 = 66%), we decided not to undertake a meta-analysis. None of the four trials reported blood lipids, occurrence of type 2 diabetes, adverse events, costs or quality of life. AUTHORS' CONCLUSIONS: Currently, there are few trials with limited outcomes examining the effectiveness of TM for the primary prevention of CVD. Due to the limited evidence to date, we could draw no conclusions as to the effectiveness of TM for the primary prevention of CVD. There was considerable heterogeneity between trials and the included studies were small, short term and at overall serious risk of bias. More and larger long-term, high-quality trials are needed.

Vitamin C supplementation for the primary prevention of cardiovascular disease.

BACKGROUND: Vitamin C is an essential micronutrient and powerful antioxidant. Observational studies have shown an inverse relationship between vitamin C intake and major cardiovascular events and cardiovascular disease (CVD) risk factors. Results from clinical trials are less consistent. OBJECTIVES: To determine the effectiveness of vitamin C supplementation as a single supplement for the primary prevention of CVD. SEARCH METHODS: We searched the following electronic databases on 11 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); Embase Classic and Embase (Ovid); Web of Science Core Collection (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database in the Cochrane Library. We searched trial registers on 13 April 2016 and reference lists of reviews for further studies. We applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials of vitamin C supplementation as a single nutrient supplement lasting at least three months and involving healthy adults or adults at moderate and high risk of CVD were included. The comparison group was no intervention or placebo. The outcomes of interest were CVD clinical events and CVD risk factors. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias. MAIN RESULTS: We included eight trials with 15,445 participants randomised. The largest trial with 14,641 participants provided data on our primary outcomes. Seven trials reported on CVD risk factors. Three of the eight trials were regarded at high risk of bias for either reporting or attrition bias, most of the 'Risk of bias' domains for the remaining trials were judged as unclear, with the exception of the largest trial where most domains were judged to be at low risk of bias.The composite endpoint, major CVD events was not different between the vitamin C and placebo group (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.89 to 1.10; 1 study; 14,641 participants; low-quality evidence) in the Physicians Health Study II over eight years of follow-up. Similar results were obtained for all-cause mortality HR 1.07, 95% CI 0.97 to 1.18; 1 study; 14,641 participants; very low-quality evidence, total myocardial infarction (MI) (fatal and non-fatal) HR 1.04 (95% CI 0.87 to 1.24); 1 study; 14,641 participants; low-quality evidence, total stroke (fatal and non-fatal) HR 0.89 (95% CI 0.74 to 1.07); 1 study; 14,641 participants; low-quality evidence, CVD mortality HR 1.02 (95% 0.85 to 1.22); 1 study; 14,641 participants; very low-quality evidence, self-reported coronary artery bypass grafting (CABG)/percutaneous transluminal coronary angioplasty (PTCA) HR 0.96 (95% CI 0.86 to 1.07); 1 study; 14,641 participants; low-quality evidence, self-reported angina HR 0.93 (95% CI 0.84 to 1.03); 1 study; 14,641 participants; low-quality evidence.The evidence for the majority of primary outcomes was downgraded (low quality) because of indirectness and imprecision. For all-cause mortality and CVD mortality, the evidence was very low because more factors affected the directness of the evidence and because of inconsistency.Four studies did not state sources of funding, two studies declared non-commercial funding and two studies declared both commercial and non-commercial funding. AUTHORS' CONCLUSIONS: Currently, there is no evidence to suggest that vitamin C supplementation reduces the risk of CVD in healthy participants and those at increased risk of CVD, but current evidence is limited to one trial of middle-aged and older male physicians from the USA. There is limited low- and very low-quality evidence currently on the effect of vitamin C supplementation and risk of CVD risk factors.

Whole grain cereals for the primary or secondary prevention of cardiovascular disease.

BACKGROUND: There is evidence from observational studies that whole grains can have a beneficial effect on risk for cardiovascular disease (CVD). Earlier versions of this review found mainly short-term intervention studies. There are now longer-term randomised controlled trials (RCTs) available. This is an update and expansion of the original review conducted in 2007. OBJECTIVES: The aim of this systematic review was to assess the effect of whole grain foods or diets on total mortality, cardiovascular events, and cardiovascular risk factors (blood lipids, blood pressure) in healthy people or people who have established cardiovascular disease or related risk factors, using all eligible RCTs. SEARCH METHODS: We searched CENTRAL (Issue 8, 2016) in the Cochrane Library, MEDLINE (1946 to 31 August 2016), Embase (1980 to week 35 2016), and CINAHL Plus (1937 to 31 August 2016) on 31 August 2016. We also searched ClinicalTrials.gov on 5 July 2017 and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) on 6 July 2017. We checked reference lists of relevant articles and applied no language restrictions. SELECTION CRITERIA: We selected RCTs assessing the effects of whole grain foods or diets containing whole grains compared to foods or diets with a similar composition, over a minimum of 12 weeks, on cardiovascular disease and related risk factors. Eligible for inclusion were healthy adults, those at increased risk of CVD, or those previously diagnosed with CVD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies. Data were extracted and quality-checked by one review author and checked by a second review author. A second review author checked the analyses. We assessed treatment effect using mean difference in a fixed-effect model and heterogeneity using the I2 statistic and the Chi2 test of heterogeneity. We assessed the overall quality of evidence using GRADE with GRADEpro software. MAIN RESULTS: We included nine RCTs randomising a total of 1414 participants (age range 24 to 70; mean age 45 to 59, where reported) to whole grain versus lower whole grain or refined grain control groups. We found no studies that reported the effect of whole grain diets on total cardiovascular mortality or cardiovascular events (total myocardial infarction, unstable angina, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, total stroke). All included studies reported the effect of whole grain diets on risk factors for cardiovascular disease including blood lipids and blood pressure. All studies were in primary prevention populations and had an unclear or high risk of bias, and no studies had an intervention duration greater than 16 weeks.Overall, we found no difference between whole grain and control groups for total cholesterol (mean difference 0.07, 95% confidence interval -0.07 to 0.21; 6 studies (7 comparisons); 722 participants; low-quality evidence).Using GRADE, we assessed the overall quality of the available evidence on cholesterol as low. Four studies were funded by independent national and government funding bodies, while the remaining studies reported funding or partial funding by organisations with commercial interests in cereals. AUTHORS' CONCLUSIONS: There is insufficient evidence from RCTs of an effect of whole grain diets on cardiovascular outcomes or on major CVD risk factors such as blood lipids and blood pressure. Trials were at unclear or high risk of bias with small sample sizes and relatively short-term interventions, and the overall quality of the evidence was low. There is a need for well-designed, adequately powered RCTs with longer durations assessing cardiovascular events as well as cardiovascular risk factors.

Low glycaemic index diets for the prevention of cardiovascular disease.

BACKGROUND: The glycaemic index (GI) is a physiological measure of the ability of a carbohydrate to affect blood glucose. Interest is growing in this area for the clinical management of people at risk of, or with, established cardiovascular disease. There is a need to review the current evidence from randomised controlled trials (RCTs) in this area. This is an update of the original review published in 2008. OBJECTIVES: To assess the effect of the dietary GI on total mortality, cardiovascular events, and cardiovascular risk factors (blood lipids, blood pressure) in healthy people or people who have established cardiovascular disease or related risk factors, using all eligible randomised controlled trials. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL in July 2016. We also checked reference lists of relevant articles. No language restrictions were applied. SELECTION CRITERIA: We selected RCTs that assessed the effects of low GI diets compared to diets with a similar composition but a higher GI on cardiovascular disease and related risk factors. Minimum trial duration was 12 weeks. Participants included were healthy adults or those at increased risk of cardiovascular disease, or previously diagnosed with cardiovascular disease. Studies in people with diabetes mellitus were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened and selected studies. Two review authors independently assessed risk of bias, evaluated the overall quality of the evidence using GRADE, and extracted data following the Cochrane Handbook for Systematic Reviews of Interventions. We contacted trial authors for additional information. Analyses were checked by a second reviewer. Continuous outcomes were synthesized using mean differences and adverse events were synthesized narratively. MAIN RESULTS: Twenty-one RCTs were included, with a total of 2538 participants randomised to low GI intervention (1288) or high GI (1250). All 21 included studies reported the effect of low GI diets on risk factors for cardiovascular disease, including blood lipids and blood pressure.Twenty RCTs (18 of which were newly included in this version of the review) included primary prevention populations (healthy individuals or those at high risk of CVD, with mean age range from 19 to 69 years) and one RCT was in those diagnosed with pre-existing CVD (a secondary prevention population, with mean age 26.9 years). Most of the studies did not have an intervention duration of longer than six months. Difference in GI intake between comparison groups varied widely from 0.6 to 42.None of the included studies reported the effect of low GI dietary intake on cardiovascular mortality and cardiovascular events such as fatal and nonfatal myocardial infarction, unstable angina, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, and stroke. The unclear risk of bias of most of the included studies makes overall interpretation of the data difficult. Only two of the included studies (38 participants) reported on adverse effects and did not observe any harms (low-quality evidence). AUTHORS' CONCLUSIONS: There is currently no evidence available regarding the effect of low GI diets on cardiovascular disease events. Moreover, there is currently no convincing evidence that low GI diets have a clear beneficial effect on blood lipids or blood pressure parameters.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide, yet ASCVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of ASCVD. OBJECTIVES: To determine the effect of fixed-dose combination therapy on all-cause mortality, fatal and non-fatal ASCVD events, and adverse events. We also sought to determine the effect of fixed-dose combination therapy on blood pressure, lipids, adherence, discontinuation rates, health-related quality of life, and costs. SEARCH METHODS: We updated our previous searches in September 2016 of CENTRAL, MEDLINE, Embase, ISI Web of Science, and DARE, HTA, and HEED. We also searched two clinical trials registers in September 2016. We used no language restrictions. SELECTION CRITERIA: We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure-lowering and one lipid-lowering component versus usual care, placebo, or an active drug comparator for any treatment duration in adults 18 years old or older, with no restrictions on presence or absence of pre-existing ASCVD. DATA COLLECTION AND ANALYSIS: Three review authors independently selected studies for inclusion and extracted the data for this update. We evaluated risk of bias using the Cochrane 'Risk of bias' assessment tool. We calculated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 < 50%) and random-effects models when heterogeneity was high (I2 ≥ 50%). We used the GRADE approach to evaluate the quality of evidence. MAIN RESULTS: In the initial review, we identified nine randomised controlled trials with a total of 7047 participants and four additional trials (n = 2012 participants; mean age range 62 to 63 years; 30% to 37% women) were included in this update. Eight of the 13 trials evaluated the effects of fixed-dose combination (FDC) therapy in populations without prevalent ASCVD, and the median follow-up ranged from six weeks to 23 months. More recent trials were generally larger with longer follow-up and lower risk of bias. The main risk of bias was related to lack of blinding of participants and personnel, which was inherent to the intervention. Compared with the comparator groups (placebo, usual care, or active drug comparator), the effects of the fixed-dose combination treatment on mortality (FDC = 1.0% versus control = 1.0%, RR 1.10, 95% CI 0.64 to 1.89,  I2 = 0%, 5 studies, N = 5300) and fatal and non-fatal ASCVD events (FDC = 4.7% versus control = 3.7%, RR 1.26, 95% CI 0.95 to 1.66, I2 = 0%, 6 studies, N = 4517) were uncertain (low-quality evidence). The low event rates for these outcomes and indirectness of evidence for comparing fixed-dose combination to usual care versus individual drugs suggest that these results should be viewed with caution. Adverse events were common in both the intervention (32%) and comparator (27%) groups, with participants randomised to fixed-dose combination therapy being 16% (RR 1.16, 95% CI 1.09 to 1.25, 11 studies, 6906 participants, moderate-quality evidence) more likely to report an adverse event . The mean differences in systolic blood pressure between the intervention and control arms was -6.34 mmHg (95% CI -9.03 to -3.64, 13 trials, 7638 participants, moderate-quality evidence). The mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.61 mmol/L (95% CI -0.88 to -0.35, 11 trials, 6565 participants, low-quality evidence) and -0.70 mmol/L (95% CI -0.98 to -0.41, 12 trials, 7153 participants, moderate-quality evidence), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 ≥ 80% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multidrug strategy by 44% (26% to 65%) compared with usual care (4 trials, 3835 participants, moderate-quality evidence). AUTHORS' CONCLUSIONS: The effects of fixed-dose combination therapy on all-cause mortality or ASCVD events are uncertain. A limited number of trials reported these outcomes, and the included trials were primarily designed to observe changes in ASCVD risk factor levels rather than clinical events, which may partially explain the observed differences in risk factors that were not translated into differences in clinical outcomes among the included trials. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, active comparator, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing, longer-term trials of fixed-dose combination therapy will help demonstrate whether short-term changes in risk factors might be maintained and lead to expected differences in clinical events based on these changes.

Psychological interventions for coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is the most common cause of death globally, although mortality rates are falling. Psychological symptoms are prevalent for people with CHD, and many psychological treatments are offered following cardiac events or procedures with the aim of improving health and outcomes. This is an update of a Cochrane systematic review previously published in 2011. OBJECTIVES: To assess the effectiveness of psychological interventions (alone or with cardiac rehabilitation) compared with usual care (including cardiac rehabilitation where available) for people with CHD on total mortality and cardiac mortality; cardiac morbidity; and participant-reported psychological outcomes of levels of depression, anxiety, and stress; and to explore potential study-level predictors of the effectiveness of psychological interventions in this population. SEARCH METHODS: We updated the previous Cochrane Review searches by searching the following databases on 27 April 2016: CENTRAL in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO). SELECTION CRITERIA: We included randomised controlled trials (RCTs) of psychological interventions compared to usual care, administered by trained staff, and delivered to adults with a specific diagnosis of CHD. We selected only studies estimating the independent effect of the psychological component, and with a minimum follow-up of six months. The study population comprised of adults after: a myocardial infarction (MI), a revascularisation procedure (coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI)), and adults with angina or angiographically defined coronary artery disease (CAD). RCTs had to report at least one of the following outcomes: mortality (total- or cardiac-related); cardiac morbidity (MI, revascularisation procedures); or participant-reported levels of depression, anxiety, or stress. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts of all references for eligibility. A lead review author extracted study data, which a second review author checked. We contacted study authors to obtain missing information. MAIN RESULTS: This review included 35 studies which randomised 10,703 people with CHD (14 trials and 2577 participants added to this update). The population included mainly men (median 77.0%) and people post-MI (mean 65.7%) or after undergoing a revascularisation procedure (mean 27.4%). The mean age of participants within trials ranged from 53 to 67 years. Overall trial reporting was poor, with around a half omitting descriptions of randomisation sequence generation, allocation concealment procedures, or the blinding of outcome assessments. The length of follow-up ranged from six months to 10.7 years (median 12 months). Most studies (23/35) evaluated multifactorial interventions, which included therapies with multiple therapeutic components. Ten studies examined psychological interventions targeted at people with a confirmed psychopathology at baseline and two trials recruited people with a psychopathology or another selecting criterion (or both). Of the remaining 23 trials, nine studies recruited unselected participants from cardiac populations reporting some level of psychopathology (3.8% to 53% with depressive symptoms, 32% to 53% with anxiety), 10 studies did not report these characteristics, and only three studies excluded people with psychopathology.Moderate quality evidence showed no risk reduction for total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.77 to 1.05; participants = 7776; studies = 23) or revascularisation procedures (RR 0.94, 95% CI 0.81 to 1.11) with psychological therapies compared to usual care. Low quality evidence found no risk reduction for non-fatal MI (RR 0.82, 95% CI 0.64 to 1.05), although there was a 21% reduction in cardiac mortality (RR 0.79, 95% CI 0.63 to 0.98). There was also low or very low quality evidence that psychological interventions improved participant-reported levels of depressive symptoms (standardised mean difference (SMD) -0.27, 95% CI -0.39 to -0.15; GRADE = low), anxiety (SMD -0.24, 95% CI -0.38 to -0.09; GRADE = low), and stress (SMD -0.56, 95% CI -0.88 to -0.24; GRADE = very low).There was substantial statistical heterogeneity for all psychological outcomes but not clinical outcomes, and there was evidence of small-study bias for one clinical outcome (cardiac mortality: Egger test P = 0.04) and one psychological outcome (anxiety: Egger test P = 0.012). Meta-regression exploring a limited number of intervention characteristics found no significant predictors of intervention effects for total mortality and cardiac mortality. For depression, psychological interventions combined with adjunct pharmacology (where deemed appropriate) for an underlying psychological disorder appeared to be more effective than interventions that did not (ß = -0.51, P = 0.003). For anxiety, interventions recruiting participants with an underlying psychological disorder appeared more effective than those delivered to unselected populations (ß = -0.28, P = 0.03). AUTHORS' CONCLUSIONS: This updated Cochrane Review found that for people with CHD, there was no evidence that psychological treatments had an effect on total mortality, the risk of revascularisation procedures, or on the rate of non-fatal MI, although the rate of cardiac mortality was reduced and psychological symptoms (depression, anxiety, or stress) were alleviated; however, the GRADE assessments suggest considerable uncertainty surrounding these effects. Considerable uncertainty also remains regarding the people who would benefit most from treatment (i.e. people with or without psychological disorders at baseline) and the specific components of successful interventions. Future large-scale trials testing the effectiveness of psychological therapies are required due to the uncertainty within the evidence. Future trials would benefit from testing the impact of specific (rather than multifactorial) psychological interventions for participants with CHD, and testing the targeting of interventions on different populations (i.e. people with CHD, with or without psychopathologies).