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Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses |
Aburto NJ, Hanson S, Gutierrez H, Hooper L, Elliott P, Cappuccio FP |
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CRD summary The authors concluded that increased potassium intake reduced blood pressure in people with hypertension with no adverse effect on blood lipid concentrations, catecholamine concentrations or renal function in adults. Higher potassium intake was associated with a 24% lower risk of stroke. Although some results relied upon non-randomised studies which were prone to bias, the review conclusions seem reliable. Authors' objectives To evaluate the effects of increased potassium intake on cardiovascular risk factors and disease in adults and children. Searching A literature search was conducted to identify relevant existing systematic reviews. Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the WHO International Clinical Trials Registry Platform and LILACS were searched up to September 2011. Search terms were reported. There were no language restrictions. The reference lists of relevant studies were also searched. Study selection Eligible for inclusion were randomised, quasi-randomised and non-randomised controlled trials that compared increased versus lower potassium intake for at least four weeks; and prospective observational cohort studies that measured potassium intake and reported at least one outcome of interest after one year follow-up. Randomised controlled trials (RCTs) had to measure potassium intake by urinary potassium excretion from 24-hour urine collection, and study groups had to be balanced in their administration of concomitant interventions. The population of interest was healthy adults and children, specifically excluding HIV positive cases, hospital admissions and those with impaired urinary potassium excretion. The primary outcome of interest in adults and children was blood pressure; additionally in adults were all-cause mortality, cardiovascular disease, stroke,and coronary heart disease. Also of interest were adverse events relating to changes in blood lipids, catecholamine concentrations, renal function, and there reported events. Randomised controlled trials (RCTs), quasi-randomised trials, non-randomised trials and prospective cohort studies were all eligible for inclusion. RCTs had to compare increased versus lower potassium intake for at least four weeks. Trials had to measure potassium intake by urinary potassium excretion from 24-hour urine collection, and study groups had to be balanced in their administration of concomitant interventions. Prospective cohort studies had to measure potassium intake and report at least one outcome of interest after one year follow-up. The population of interest was healthy adults and children, specifically excluding HIV positive cases, hospital admissions and those with impaired urinary potassium excretion. The primary outcome of interest in adults and children was blood pressure; additionally in adults were all-cause mortality, cardiovascular disease, stroke and coronary heart disease. Also of interest were adverse events related to changes in blood lipids, catecholamine concentrations, renal function and their reported events. Studies were conducted worldwide (including the UK), and included male and female participants. Most interventions comprised potassium chloride supplements. The study duration of RCTs was between four weeks to 12 months. The age of included children ranged from five to 17 years. Two independent reviewers selected the studies for inclusion. Assessment of study quality The quality of RCTs, was assessed on the method of sequence generation, allocation concealment, blinding, selective reporting, loss to follow-up and completeness of reporting of outcome data. Cohort studies were assessed for potential confounding, methods of outcome data collection and comparability of study groups. Risk of bias was rated as low, unclear of high. Additionally, the quality of evidence was assessed using grading of recommendations assessment, development and evaluation (GRADE) criteria. It appeared that two reviewers were involved in the quality assessment. Data extraction Data were extracted to enable the presentation of risk ratios or mean differences, with 95% confidence intervals. Data extraction was carried out by two independent reviewers, and this was checked by a third reviewer. Disagreements were resolved by consensus. Study authors were contacted for missing data. Methods of synthesis Results were synthesised in a random-effects meta-analysis, using the inverse variance method. Statistical heterogeneity was quantified using Ι², where 75% was considered to represent important inconsistency. A range of subgroup analyses was conducted. Sensitivity analysis involved the removal of studies with high risk of bias. Funnel plots were used to assess the presence of small study bias. Results of the review Included in the meta-analyses were twenty-two RCTs (sample size range 12 to 353) and 11 cohort studies (sample size range 443 to 38,726) conducted in adults. There were four studies in children (two RCTs, one non-RCT and one cohort study). Studies in adults were considered not to be at high risk of bias. Studies in children were classed as high risk of bias. Blood pressure Increased potassium intake resulted in statistically significant reductions in systolic blood pressure (MD 3.49, 95% CI 1.82 to 5.15mm/Hg; 21 RCTs; 1,892 participants;Ι²=65%) and diastolic blood pressure (MD 1.96, 95% CI 0.86 to 3.06mm/Hg; 20 RCTs;1,783 participants; Ι²=55%). Subgroup analysis showed that reductions in blood pressure were statistically significant only in those with hypertension (systolic blood pressure MD 5.32, 95% CI 3.43 to 7.20mm/Hg; 16 studies; 902 participants; Ι² =21%); diastolic blood pressure MD 3.10, 95% CI 1.66 to 4.53mm/Hg; 16studies;828 participants; Ι²=24%). The largest reductions were found when potassium intake was 90 to 120mmol/day; although differences between groups were not statistically significant, and there was no apparent dose-response effect. Results from other subgroup analyses were reported in the paper. In children, non-statistically significant decreases were found for systolic and diastolic blood pressure (three RCTs) as a result of increased potassium intake; and one cohort study found that the highest third of potassium intake had a lower increase in blood pressure than the lowest third of potassium intake, when calculated over a seven year period. All-cause mortality and disease A statistically significant higher protection from stroke was achieved with higher potassium intake (RR 0.76, 95% CI 0.66 to 0.89; nine cohort studies; Ι²=59%). No statistical differences were found for cardiovascular disease (four studies) or coronary heart disease (three studies). The greatest protective effect was found when potassium intake was 90-120mmol/day, but differences between intake groups were not statistically significant. Adverse effects Where measured, there were no significant adverse effects resulting from potassium intake in adults. There were no evaluations of adverse effects in children. Sensitivity analysis did not materially alter the results for adults in terms of blood pressure, stroke risk and incident coronary heart disease. Funnel plots suggested some potential for small study bias in studies of adults. Authors' conclusions High quality evidence showed that increased potassium intake reduced blood pressure in people with hypertension and had no adverse effect on blood lipid concentrations, catecholamine concentrations or renal function in adults. Moderate quality evidence suggested that higher potassium intake was associated with a 24% lower risk of stroke. CRD commentary The review questions and inclusion criteria were clearly specified. Several relevant data sources were searched; attempts were made to minimise language bias, and publication bias was assessed. The review process included steps to minimise error and bias. Appropriate quality assessment tools were used, and the results of the assessment were incorporated into the discussion of findings. The chosen method of synthesis seemed appropriate; statistical heterogeneity was assessed, and relevant subgroup and sensitivity analyses were carried out. The authors drew attention to the potential limited generalisability of findings, in terms of extending populations groups with acute disease conditions. The authors' conclusion reflects the evidence presented, although it was unclear in some places why studies were left out of the meta-analyses. Despite the potential for bias from including non-randomised studies, this was a well-conducted review and the findings are likely to be reliable. Implications of the review for practice and research Practice: The authors stated that increased potassium intake was potentially beneficial to most people without impaired renal handling of potassium, in terms of the prevention and control of elevated blood pressure and stroke. Research: The authors stated that high quality randomised controlled trials were needed to evaluate the effect of potassium intake on blood pressure in children. Funding World Health Organisation; Kidney Evaluation Association Japan; Governments of Japan and Republic of Korea; National Institute of Health Research Biomedical Research Centre, Imperial College Healthcare NHS Trust. Bibliographic details Aburto NJ, Hanson S, Gutierrez H, Hooper L, Elliott P, Cappuccio FP. Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. BMJ 2013; 346:f1378 Indexing Status Subject indexing assigned by NLM MeSH Blood Pressure; Catecholamines /metabolism; Coronary Disease /metabolism /mortality /prevention & Female; Humans; Hypertension /metabolism /mortality /prevention & Lipid Metabolism; Male; Potassium, Dietary /administration & Randomized Controlled Trials as Topic; Risk Factors; Stroke /metabolism /mortality /prevention & control; control; control; dosage /pharmacology AccessionNumber 12013018173 Date bibliographic record published 09/04/2013 Date abstract record published 16/04/2013 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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