Portal de Periódicos da CAPES

Can We End the Salt Wars With a Randomized Clinical Trial in a Controlled Environment?

2018; Lippincott Williams & Wilkins; Volume: 72; Issue: 1 Linguagem: Inglês

10.1161/hypertensionaha.118.11103

1524-4563

Daniel W. Jones, Friedrich C. Luft, Paul K. Whelton, Michael H. Alderman, John E. Hall, Eric D. Peterson, Robert M. Califf, David A. McCarron,

Hormonal Regulation and Hypertension

HomeHypertensionVol. 72, No. 1Can We End the Salt Wars With a Randomized Clinical Trial in a Controlled Environment? Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBCan We End the Salt Wars With a Randomized Clinical Trial in a Controlled Environment? Daniel W. Jones, Friedrich C. Luft, Paul K. Whelton, Michael H. Alderman, John E. Hall, Eric D. Peterson, Robert M. Califf and David A. McCarron Daniel W. JonesDaniel W. Jones From the Department of Medicine (D.W.J.) Department of Physiology (D.W.J.) , Friedrich C. LuftFriedrich C. Luft Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.C.L.) , Paul K. WheltonPaul K. Whelton Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA (P.K.W.) , Michael H. AldermanMichael H. Alderman Department of Medicine (M.H.A.) Department of Epidemiology and Public Health (M.H.A.), Albert Einstein College of Medicine, Bronx, NY , John E. HallJohn E. Hall Department of Physiology and Biophysics (J.E.H.), Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson , Eric D. PetersonEric D. Peterson Department of Medicine (E.D.P.) Duke Clinical Research Institute (E.D.P.), Duke University School of Medicine, Durham, NC , Robert M. CaliffRobert M. Califf Duke University, Durham, NC (R.M.C.) and David A. McCarronDavid A. McCarron Department of Nutrition, University of California, Davis (D.A.M.). Originally published7 May 2018https://doi.org/10.1161/HYPERTENSIONAHA.118.11103Hypertension. 2018;72:10–11is corrected byCorrection to: Can We End the Salt Wars With a Randomized Clinical Trial in a Controlled Environment?Correction to: Can We End the Salt Wars With a Randomized Clinical Trial in a Controlled Environment?Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: Previous Version of Record January 1, 2018: Previous Version 1 The 2013 Institute of Medicine (IOM; now the National Academy of Medicine) Report: Sodium intake in populations recommended that "clinical trials might focus on examining the effects of a range of sodium levels on risk of cardiovascular events, stroke, and mortality among patients in controlled environments."1 This recommendation was specific in 2 regards. It recommends a cardiovascular outcomes trial of dietary sodium reduction, and it recommends this be done in people in controlled environments. There are important reasons behind these specific recommendations.Despite the large body of data on the relationship between cardiovascular disease and dietary sodium from observational studies and the positive impact on blood pressure in randomized controlled clinical trials and current national guidelines recommending daily sodium intakes of ≤2300 mg/d, mean daily intake for Americans remains in the 3400 to 3500 mg/d range.2 Some scientists have questioned the justification for a reduced intake of dietary sodium.3 This disagreement within the scientific community has been reported in the lay press, leading both clinicians and some in the public to express uncertainty on the issue.4–6The IOM is not alone in calling for an outcomes clinical trial on dietary sodium. The World Heart Federation, the European Society of Hypertension, and the European Public Health Association joined together to call for a definitive clinical trial of sodium restriction.7 Indeed, for years, leading voices in this area of research have noted the absence of evidence from an outcomes-based clinical trial and advocated for execution of such a trial.The reason this trial has not been accomplished can be seen in the second specificity of the IOM recommendations: that the trial be performed in "patients in controlled environments." This statement recognizes the challenges of implementing a sodium reduction clinical outcomes trial. Such a trial would require a large number of participants in the intervention arm to maintain a reduced level of sodium intake for several years. Experience from behavioral intervention trials focused on blood pressure reduction demonstrates that in free-living people in the United States, maintaining even a modest reduction in sodium intake for >6 months is difficult for many adults.8–10 Adherence to 1800 to 2300 mg/d level of sodium has proven difficult in behavioral change clinical trials and clinical practice.The food environment for most Americans includes added sodium in processed and restaurant-prepared foods, making it difficult to sustain a reduced level of sodium intake. The only strategy for maintaining low sodium intake in free-living people for long periods is likely to be the consumption of prepared meals containing set amounts of sodium by study participants. This strategy of prepared meals is not likely to be financially feasible in a long-term study with a large number of free-living participants. Thus, the IOM Committee recommended that a dietary sodium reduction trial be performed in a controlled environment.8–10In May 2017, 6 of the authors of this article convened in Jackson, MS, to discuss the issue of dietary sodium and cardiovascular disease. The agenda called for discussion of existing evidence, evidence gaps and remaining questions, and possible next steps in research to clarify the questions. The group was carefully selected for balance on points of view regarding interpretation of existing evidence related to the role of sodium in cardiovascular disease. The group concluded that differences of opinion on existing data could only be resolved with a randomized clinical trial evaluating the impact of dietary sodium on hard clinical outcomes, including death, stroke, and myocardial infarction.Thoughts of the group on the rationale for an event-based clinical trial fell into 2 categories. Some members of the group thought that existing observational data on sodium and cardiovascular disease and clinical trial evidence on sodium and blood pressure were insufficient to support existing guidelines on sodium restriction. They expressed an opinion that a clinical trial with cardiovascular morbidity and mortality outcomes was necessary to resolve the issue. Others in the group submitted that existing data were sufficient to support current guidelines on sodium restriction to ≤2300 mg/d but thought that stronger evidence from an outcomes trial would convince more clinicians, patients, and policy makers to accomplish better implementation of these guidelines. There was consensus that a well-designed and executed randomized clinical trial was desirable, if feasible.Next, the group considered how a trial might be accomplished. There was agreement with the IOM Committee recommendation that a controlled environment would be essential for conduct of a successful events outcome trial in the United States. The ability to control the amount of sodium in prepared foods was considered an essential element in selecting a population and setting. Several populations living in a controlled environment were considered. In theory, study of active military personnel might provide a context where diet could be controlled. But this was ruled out because of the relatively young age of many active military personnel and concerns related to sodium restriction in individuals who might be losing large amounts of sodium through intense physical activity, especially those deployed in regions with hot climates. Residents of nursing homes would also offer an opportunity to control the sodium intake. Concerns with this option centered on the likelihood that a large number might have medical conditions requiring a prescribed sodium diet. Residents of retirement communities where group dining is available were also considered as a possibility. The concern with this group was the limited percentage of food intake that could be controlled.The group eventually arrived at a consensus that a clinical trial in a prison population (particularly federal prisons) might provide the best setting to conduct the trial. Positives for this approach included potential to control a large portion of dietary intake, a large population with multiple locations, possibility for use of a randomized cluster design, diversity of age and ethnicity, an existing research infrastructure, including an Institutional Review Board, and the existence of a large literature on the ethics of research in prisoners and the likelihood of benefitting future prisoners by demonstrating the level of dietary sodium that optimizes their health outcomes. Negatives considered included concern on the sensitivity of prison research, heterogeneous views of the ethics of prison research, and uncertainty as to whether enough prison sites could be enrolled.Several ethical issues must be addressed when considering a study in a prison population.11 One key principle is that any study to be performed must benefit the prisoners, not just the general population. In the case of dietary sodium, if one acknowledges that until an outcomes trial is performed there remains uncertainty about the ideal sodium intake for prisoners, it would seem imperative to ascertain the ideal intake for a group of people unable to make decisions on the sodium content of their food. Free-living individuals may make that choice for themselves, but prisoners depend on prison system leadership to assure an ideal sodium intake.Preliminary conversations with leadership of prison systems have been enlightening and helpful. A review of the idea by a prisoner rights ethics expert and initial engagement with potential funders have been encouraging. Similarly, we brought into our initial group 2 scientists with experience in complex randomized controlled trials and in federal policy (R.M.C. and E.D.P.). There are many issues to consider before moving forward in this direction. A first step is a formal proposal of a pilot study to assess current dietary sodium intake for some prison locations and to assess the feasibility of managing the level of sodium intake in these locations. Both the pilot phase and the long-term study will involve a representative group of prisoners in the concept and design of the study.The primary purpose of this communication is to notify the community of scientists interested in dietary sodium that we intend to explore the potential for conducting an event-based clinical trial that would help determine the value of a reduced dietary intake of sodium in preventing major cardiovascular events. We are cognizant of our need to seek advice and engagement from a wide range of professionals from the scientific community. That input will be welcomed. We think it is time to move beyond the call for a clinical trial to exploration of the feasibility of such a study. Our hope is that we will prove the feasibility of a full-scale trial. Results from such a study would inform decisions by policy makers, guideline groups, clinicians, patients, and the general public and will result in better health for all Americans and for people around the world.Sources of FundingThis study was supported by National Institutes of Health (NIH) grant 5MO1RR011248 (M.H. Alderman). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the NIH.DisclosuresD.A. McCarron reports serving as a consultant for the Grocery Manufacturers Association. D.A. McCarron reports serving on ConAgra Foods Scientific Advisory Board. D.A. McCarron reports serving on American Society Nutrition Board of Directors. D.A. McCarron reports receipt of funding from Academy of Nutrition and Dietetics (AND). The other authors report no conflicts of interest.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Daniel W. Jones, Mississippi Center for Obesity Research, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216. E-mail [email protected]References1. IOM (Institute of Medicine). Sodium Intake in Populations: Assessment of Evidence. Washington, DC: The National Academies Press. 2013.Google Scholar2. Cogswell ME, Zhang Z, Carriquiry AL, Gunn JP, Kuklina EV, Saydah SH, Yang Q, Moshfegh AJ. Sodium and potassium intakes among US adults: NHANES 2003–2008.Am J Clin Nutr. 2012; 96:647–57. doi: 10.3945/ajcn.112.034413.CrossrefMedlineGoogle Scholar3. Alderman MH. Dietary sodium: where science and policy diverge.Am J Hypertens. 2016; 29:424–427. doi: 10.1093/ajh/hpu256.CrossrefMedlineGoogle Scholar4. DiNicolantonio JJ, O'Keefe JH. The history of the salt wars.Am J Med. 2017; 130:1011–1014. doi: 10.1016/j.amjmed.2017.04.040.CrossrefMedlineGoogle Scholar5. Beard R. The Salt Wars.The New York Times – The Opinionator. https://opinionator.blogs.nytimes.com/2013/12/26/the-salt-wars/. Accessed December 26, 2013.Google Scholar6. Norm R, Campbell C, Lackland DT, Lisheng L, Zhang X, Nilsson PM, Niebylski ML, World hypertension executive. The World Hypertension League: where now and where to in salt reduction.Cardiovasc Diagn Ther. 2015; 5:238–242. doi: 10.3978/j.issn.2223-3652.2015.04.08.MedlineGoogle Scholar7. Mancia G, Oparil S, Whelton PK, McKee M, Dominiczak A, Luft FC, AlHabib K, Lanas F, Damasceno A, Prabhakaran D, La Torre G, Weber M, O'Donnell M, Smith SC, Narula J. The technical report on sodium intake and cardiovascular disease in low- and middle-income countries by the joint working group of the World Heart Federation, the European Society of Hypertension and the European Public Health Association.Eur Heart J. 2017; 38:712–719. doi: 10.1093/eurheartj/ehw549.MedlineGoogle Scholar8. The Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The trials of hypertension prevention, phase II.Arch Intern Med. 1997; 157:657–667. doi: 10.1001/archinte.1997.00440270105009CrossrefMedlineGoogle Scholar9. Whelton PK, Lawrence JA, Espeland MA, Applegate WB, Ettinger WH, Kostis JB, Kumanyika S, Lacy CR, Johnson KC, Folmar S, Cutler JA; for the TONE Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized control trial of nonpharmacologic interventions in the elderly (TONE).JAMA. 1998; 279:839–846. doi: 10.1001/jama.279.11.839.CrossrefMedlineGoogle Scholar10. Whelton PK, Kumanyika SK, Cook NR, Cutler JA, Borhani NO, Hennekens CH, Kuller LH, Langford H, Jones DW, Satterfield S, Lasser NL, Cohen JD; for the Trials of Hypertension Prevention Collaborative Research Group. Efficacy of non-pharmacologic intervention in adults with high normal blood pressure: results from phase I of the Trials of Hypertension Prevention (TOHP).Am J Clin Nutr. 1997; 65:652S–660S.CrossrefMedlineGoogle Scholar11. Gostin LO. Biomedical research involving prisoners: ethical values and legal regulation.JAMA. 2007; 297:737–740. doi: 10.1001/jama.297.7.737.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByJones D, Clark D, Morgan T and He F (2022) Potassium-Enriched Salt Substitution as a Population Strategy to Prevent Cardiovascular Disease, Hypertension, 79:10, (2199-2201), Online publication date: 1-Oct-2022. Rossitto G and Delles C (2021) Mechanisms of sodium‐mediated injury in cardiovascular disease: old play, new scripts, The FEBS Journal, 10.1111/febs.16155 Juraschek S, Millar C, Foley A, Shtivelman M, Cohen A, McNally V, Crevatis R, Post S, Mukamal K, Lipsitz L, Cluett J, Davis R and Sahni S (2021) The Effects of a Low Sodium Meal Plan on Blood Pressure in Older Adults: The SOTRUE Randomized Feasibility Trial, Nutrients, 10.3390/nu13030964, 13:3, (964) Burnier M (2020) Sodium intake and progression of chronic kidney disease—has the time finally come to do the impossible: a prospective randomized controlled trial?, Nephrology Dialysis Transplantation, 10.1093/ndt/gfaa120, 36:3, (381-384), Online publication date: 20-Feb-2021. Loughlin E, Judge C, Gorey S, Costello M, Murphy R, Waters R, Hughes D, Kenny R, O'Donnell M and Canavan M (2020) Increased Salt Intake for Orthostatic Intolerance Syndromes: A Systematic Review and Meta-Analysis, The American Journal of Medicine, 10.1016/j.amjmed.2020.05.028, 133:12, (1471-1478.e4), Online publication date: 1-Dec-2020. Foti K, Foraker R, Martyn-Nemeth P, Anderson C, Cook N, Lichtenstein A, de Ferranti S, Young D, Hivert M, Ross R, Deedwania P, Whitsel L and Appel L (2020) Evidence-Based Policy Making for Public Health Interventions in Cardiovascular Diseases: Formally Assessing the Feasibility of Clinical Trials, Circulation: Cardiovascular Quality and Outcomes, 13:11, Online publication date: 1-Nov-2020. Wilck N (2020) Der Einfluss der Mikrobiota auf den Blutdruck, Dialyse aktuell, 10.1055/a-1190-8056, 24:09, (360-366), Online publication date: 1-Nov-2020. O'Donnell M, Mente A, Alderman M, Brady A, Diaz R, Gupta R, López-Jaramillo P, Luft F, Lüscher T, Mancia G, Mann J, McCarron D, McKee M, Messerli F, Moore L, Narula J, Oparil S, Packer M, Prabhakaran D, Schutte A, Sliwa K, Staessen J, Yancy C and Yusuf S (2020) Salt and cardiovascular disease: insufficient evidence to recommend low sodium intake, European Heart Journal, 10.1093/eurheartj/ehaa586, 41:35, (3363-3373), Online publication date: 14-Sep-2020. Elliott P, Muller D, Schneider-Luftman D, Pazoki R, Evangelou E, Dehghan A, Neal B and Tzoulaki I (2020) Estimated 24-Hour Urinary Sodium Excretion and Incident Cardiovascular Disease and Mortality Among 398 628 Individuals in UK Biobank, Hypertension, 76:3, (683-691), Online publication date: 1-Sep-2020. Overwyk K, Quader Z, Maalouf J, Bates M, Webster J, George M, Merritt R and Cogswell M (2020) Dietary Sodium Intake and Health Indicators: A Systematic Review of Published Literature between January 2015 and December 2019, Advances in Nutrition, 10.1093/advances/nmaa049, 11:5, (1174-1200), Online publication date: 1-Sep-2020. Deschênes G (2020) Sodium—not harmful?, Pediatric Nephrology, 10.1007/s00467-019-04356-x, 35:9, (1771-1776), Online publication date: 1-Sep-2020. Cook N, He F, MacGregor G and Graudal N (2020) Sodium and health—concordance and controversy, BMJ, 10.1136/bmj.m2440, (m2440) Clark D, Colantonio L, Min Y, Hall M, Zhao H, Mentz R, Shimbo D, Ogedegbe G, Howard G, Levitan E, Jones D, Correa A and Muntner P (2019) Population-Attributable Risk for Cardiovascular Disease Associated With Hypertension in Black Adults, JAMA Cardiology, 10.1001/jamacardio.2019.3773, 4:12, (1194), Online publication date: 1-Dec-2019. Frame A, Farquhar W, Latulippe M, McDonough A, Wainford R and Wynne B (2019) Moving the Needle on Hypertension, Nutrition Today, 10.1097/NT.0000000000000375, 54:6, (248-256), Online publication date: 1-Nov-2019. Davy K and Davy B (2019) Advances in Nutrition Science and Integrative Physiology: Insights From Controlled Feeding Studies, Frontiers in Physiology, 10.3389/fphys.2019.01341, 10 Welsh C, Welsh P, Jhund P, Delles C, Celis-Morales C, Lewsey J, Gray S, Lyall D, Iliodromiti S, Gill J, Sattar N and Mark P (2019) Urinary Sodium Excretion, Blood Pressure, and Risk of Future Cardiovascular Disease and Mortality in Subjects Without Prior Cardiovascular Disease, Hypertension, 73:6, (1202-1209), Online publication date: 1-Jun-2019. López-Jaramillo P, Barbosa E, Molina D, Sanchez R, Diaz M, Camacho P, Lanas F, Pasquel M, Accini J, Ponte-Negretti C, Alcocer L, Cobos L, Wyss F, Sebba-Barroso W, Coca A and Zanchetti A (2019) Latin American Consensus on the management of hypertension in the patient with diabetes and the metabolic syndrome, Journal of Hypertension, 10.1097/HJH.0000000000002072, 37:6, (1126-1147), Online publication date: 1-Jun-2019. Robinson A, Edwards D and Farquhar W (2019) The Influence of Dietary Salt Beyond Blood Pressure, Current Hypertension Reports, 10.1007/s11906-019-0948-5, 21:6, Online publication date: 1-Jun-2019. Christopher P and Stein M (2019) Should a Prison Salt Trial Be Federally Funded?, Annals of Internal Medicine, 10.7326/M18-3382, 170:6, (409), Online publication date: 19-Mar-2019. Elijovich F and Laffer C (2019) Urinary sodium excretion measures and health outcomes, The Lancet, 10.1016/S0140-6736(19)30695-6, 393:10178, (1295), Online publication date: 1-Mar-2019. Petersen K, Rae S, Venos E, Malta D, Trieu K, Santos J, Thout S, Webster J, Campbell N and Arcand J (2018) Paucity of high-quality studies reporting on salt and health outcomes from the science of salt: A regularly updated systematic review of salt and health outcomes (April 2017 to March 2018), The Journal of Clinical Hypertension, 10.1111/jch.13450, 21:2, (307-323), Online publication date: 1-Feb-2019. Messerli F, Hofstetter L and Bangalore S (2018) Salt and heart disease: a second round of "bad science"?, The Lancet, 10.1016/S0140-6736(18)31724-0, 392:10146, (456-458), Online publication date: 1-Aug-2018. Related articlesCorrection to: Can We End the Salt Wars With a Randomized Clinical Trial in a Controlled Environment?Hypertension. 2018;72:e35-e35Correction to: Can We End the Salt Wars With a Randomized Clinical Trial in a Controlled Environment?Hypertension. 2019;73:e8-e8 July 2018Vol 72, Issue 1 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.118.11103PMID: 29735638 Originally publishedMay 7, 2018 PDF download Advertisement SubjectsClinical Studies