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      Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses

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          Abstract

          Objective To conduct a systematic review of the literature and meta-analyses to fill the gaps in knowledge on potassium intake and health.

          Data sources Cochrane Central Register of Controlled Trials, Medline, Embase, WHO International Clinical Trials Registry Platform, Latin American and Caribbean Health Science Literature Database, and the reference lists of previous reviews.

          Study selection Randomised controlled trials and cohort studies reporting the effects of potassium intake on blood pressure, renal function, blood lipids, catecholamine concentrations, all cause mortality, cardiovascular disease, stroke, and coronary heart disease were included.

          Data extraction and synthesis Potential studies were independently screened in duplicate, and their characteristics and outcomes were extracted. When possible, meta-analysis was done to estimate the effects (mean difference or risk ratio with 95% confidence interval) of higher potassium intake by using the inverse variance method and a random effect model.

          Results 22 randomised controlled trials (including 1606 participants) reporting blood pressure, blood lipids, catecholamine concentrations, and renal function and 11 cohort studies (127 038 participants) reporting all cause mortality, cardiovascular disease, stroke, or coronary heart disease in adults were included in the meta-analyses. Increased potassium intake reduced systolic blood pressure by 3.49 (95% confidence interval 1.82 to 5.15) mm Hg and diastolic blood pressure by 1.96 (0.86 to 3.06) mm Hg in adults, an effect seen in people with hypertension but not in those without hypertension. Systolic blood pressure was reduced by 7.16 (1.91 to 12.41) mm Hg when the higher potassium intake was 90-120 mmol/day, without any dose response. Increased potassium intake had no significant adverse effect on renal function, blood lipids, or catecholamine concentrations in adults. An inverse statistically significant association was seen between potassium intake and risk of incident stroke (risk ratio 0.76, 0.66 to 0.89). Associations between potassium intake and incident cardiovascular disease (risk ratio 0.88, 0.70 to 1.11) or coronary heart disease (0.96, 0.78 to 1.19) were not statistically significant. In children, three controlled trials and one cohort study suggested that increased potassium intake reduced systolic blood pressure by a non-significant 0.28 (−0.49 to 1.05) mm Hg.

          Conclusions High quality evidence shows that increased potassium intake reduces blood pressure in people with hypertension and has 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 (moderate quality evidence). These results suggest that increased potassium intake is potentially beneficial to most people without impaired renal handling of potassium for the prevention and control of elevated blood pressure and stroke.

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          Most cited references48

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          Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group.

          The relations between 24 hour urinary electrolyte excretion and blood pressure were studied in 10,079 men and women aged 20-59 sampled from 52 centres around the world based on a highly standardised protocol with central training of observers, a central laboratory, and extensive quality control. Relations between electrolyte excretion and blood pressure were studied in individual subjects within each centre and the results of these regression analyses pooled for all 52 centres. Relations between population median electrolyte values and population blood pressure values were also analysed across the 52 centres. Sodium excretion ranged from 0.2 mmol/24 h (Yanomamo Indians, Brazil) to 242 mmol/24 h (north China). In individual subjects (within centres) it was significantly related to blood pressure. Four centres found very low sodium excretion, low blood pressure, and little or no upward slope of blood pressure with age. Across the other 48 centres sodium was significantly related to the slope of blood pressure with age but not to median blood pressure or prevalence of high blood pressure. Potassium excretion was negatively correlated with blood pressure in individual subjects after adjustment for confounding variables. Across centres there was no consistent association. The relation of sodium to potassium ratio to blood pressure followed a pattern similar to that of sodium. Body mass index and heavy alcohol intake had strong, significant independent relations with blood pressure in individual subjects.
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            Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice.

            Heterogeneity between study results can be a problem in any systematic review or meta-analysis of clinical trials. Identifying its presence, investigating its cause and correctly accounting for it in analyses all involve difficult decisions for the researcher. Our objectives were: to collate recommendations on the subject of dealing with heterogeneity in systematic reviews of clinical trials; to investigate current practice in addressing heterogeneity in Cochrane reviews; and to compare current practice with recommendations. We review guidelines for those undertaking systematic reviews and examine how heterogeneity is addressed in practice in a sample of systematic reviews, and their protocols, from the Cochrane Database of Systematic Reviews. Advice to reviewers is on the whole consistent and sensible. However, examination of a sample of Cochrane protocols and reviews demonstrates that the advice is difficult to follow given the small numbers of studies identified in many systematic reviews, the difficulty of pre-specifying important effect modifiers for subgroup analysis or meta-regression and the unresolved debate concerning fixed versus random effects meta-analyses. There was disagreement between protocols and reviews, often either regarding choice of important potential effect modifiers or due to the review identifying too few studies to perform planned analyses. Guidelines that address practical issues are required to reduce the risk of spurious findings from investigations of heterogeneity. This may involve discouraging statistical investigations such as subgroup analyses and meta-regression, rather than simply adopting a cautious approach to their interpretation, unless a large number of studies is available. The notion of a priori specification of potential effect modifiers for a retrospective review of studies is ill-defined, and the appropriateness of using a statistical test for heterogeneity to decide between analysis strategies is suspect.
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              Blood pressure response to changes in sodium and potassium intake: a metaregression analysis of randomised trials.

              The objective of the study was to assess the blood pressure response to changes in sodium and potassium intake and examine effect modification by age, gender, blood pressure, body weight and habitual sodium and potassium intake. Randomised trials of sodium reduction or potassium supplementation and blood pressure were identified through reference lists of systematic reviews and an additional MEDLINE search (January 1995-March 2001). A total of 40 sodium trials and 27 potassium trials in adults with a minimum duration of 2 weeks were selected for analysis. Data on changes in electrolyte intake and blood pressure during intervention were collected, as well as data on mean age, gender, body weight, initial electrolyte intake and initial blood pressure of the trial populations. Blood pressure effects of changes in electrolyte intake were assessed by weighted metaregression analysis, overall and in strata of trial population characteristics. Analyses were repeated with adjustment for potential confounders. Sodium reduction (median: -77 mmol/24 h) was associated with a change of -2.54 mmHg (95% CI: -3.16, -1.92) in systolic blood pressure and -1.96 mmHg (-2.41, -1.51) in diastolic blood pressure. Corresponding values for increased potassium intake (median: 44 mmol/24 h) were -2.42 mmHg (-3.75, -1.08) and -1.57 mmHg (-2.65, -0.50). Blood pressure response was larger in hypertensives than normotensives, both for sodium (systolic: -5.24 vs -1.26 mmHg, P < 0.001; diastolic: -3.69 vs -1.14 mmHg, P < 0.001) and potassium (systolic: -3.51 vs -0.97 mmHg, P=0.089; diastolic: -2.51 vs -0.34 mmHg, P=0.074). In conclusion, reduced intake of sodium and increased intake of potassium could make an important contribution to the prevention of hypertension, especially in populations with elevated blood pressure.
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                Author and article information

                Contributors
                Role: scientist
                Role: intern
                Role: independent consultant
                Role: senior lecturer in research synthesis and nutrition
                Role: professor
                Role: Cephalon professor of cardiovascular medicine & epidemiology
                Journal
                BMJ
                BMJ
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2013
                4 April 2013
                : 346
                : f1378
                Affiliations
                [1 ]Nutrition Policy and Scientific Advice Unit, Department of Nutrition for Health and Development, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland
                [2 ]200 Wheeler Avenue, Staten Island, NY 10314, USA
                [3 ]Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK
                [4 ]Department of Epidemiology and Biostatistics and MRC-HPA Centre for Environment and Health, Imperial College London, London, UK
                [5 ]World Health Organization Collaborating Centre for Nutrition, Warwick Medical School, Coventry CV2 2DX, UK
                Author notes
                Correspondence to: N J Aburto  nancy.aburto@ 123456wfp.org
                Article
                abun007498
                10.1136/bmj.f1378
                4816263
                23558164
                84957b6f-6fb5-42d7-b59b-96cfe8f24e4e
                © Aburto et al 2013

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

                History
                : 18 February 2013
                Categories
                Research

                Medicine
                Medicine

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