Cited by 886Sodium Intake and HealthBlood Pressure and Hypertension StudiesNutritional Studies and Diet

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Urinary Sodium and Potassium Excretion, Mortality, and Cardiovascular Events

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O'Donnell, Martin, Mente, Andrew, Rangarajan, Sumathy, McQueen, Matthew J., Wang, Xingyu, Liu, Lisheng, Yan, Hou, Lee, Shun Fu, Mony, Prem, Devanath, Anitha, Rosengren, Annika, Lopez-Jaramillo, Patricio, Diaz, Rafael, Avezum, Alvaro, Lanas, Fernando, Yusoff, Khalid, Iqbal, Romaina, Ilow, Rafal, Mohammadifard, Noushin, Gulec, Sadi, Yusufali, Afzal Hussein, Kruger, Lanthe, Yusuf, Rita, Chifamba, Jephat, Kabali, Conrad, Dagenais, Gilles, Lear, Scott A., Teo, Koon, Yusuf, Salim·2014·New England Journal of Medicine

DOI 10.1056/nejmoa1311889

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Abstract

BACKGROUND: The optimal range of sodium intake for cardiovascular health is controversial. METHODS: We obtained morning fasting urine samples from 101,945 persons in 17 countries and estimated 24-hour sodium and potassium excretion (used as a surrogate for intake). We examined the association between estimated urinary sodium and potassium excretion and the composite outcome of death and major cardiovascular events. RESULTS: The mean estimated sodium and potassium excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow-up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference range), a higher estimated sodium excretion (≥ 7.00 g per day) was associated with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence interval [CI], 1.02 to 1.30), as well as increased risks of death and major cardiovascular events considered separately. The association between a high estimated sodium excretion and the composite outcome was strongest among participants with hypertension (P=0.02 for interaction), with an increased risk at an estimated sodium excretion of 6.00 g or more per day. As compared with the reference range, an estimated sodium excretion that was below 3.00 g per day was also associated with an increased risk of the composite outcome (odds ratio, 1.27; 95% CI, 1.12 to 1.44). As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a reduced risk of the composite outcome. CONCLUSIONS: In this study in which sodium intake was estimated on the basis of measured urinary excretion, an estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a lower risk of death and cardiovascular events. (Funded by the Population Health Research Institute and others.).

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BackgroundSelf-citation
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Mirmiran, P., Bahadoran, Z., Nazeri, P., & Azizi, F. (2018) · Clinical and Experimental Hypertension · doi:10.1080/10641963.2018.1431261 · Cited by 28
“Data from the Prospective Urban Rural Epidemiology study, which investigated the levels of sodium (Na) and potassium (K) excretion and their association with blood pressure (BP), CVD outcomes and mortality indicate a positive association of Na intake with CVD risk and BP, and an inverse association of K with BP, CVD e…”
Background
Estimation of Salt Intake Assessed by 24-Hour Urinary Sodium Excretion among Somali Adults in Oslo, Norway
Chen, S., Dahl, C., Meyer, H. E., & Madar, A. A. (2018) · Nutrients · doi:10.3390/nu10070900 · Cited by 30
Mineralocorticoid receptor blockade suppresses dietary salt-induced ACEI/ARB-resistant albuminuria in non-diabetic hypertension: a sub-analysis of evaluate study
Nishimoto, M., Ohtsu, H., Marumo, T., Kawarazaki, W., Ayuzawa, N., Ueda, K., Hirohama, D., Kawakami-Mori, F., Shibata, S., Nagase, M., et al. (2019) · Hypertension Research · doi:10.1038/s41440-018-0201-7 · Cited by 28
ASN Kidney Health Guidance on Potassium and Phosphorus Food Additives
Biruete, A., Anderson, C. A. M., Bernier-Jean, A., Clase, C. M., Clegg, D. J., Crews, D. C., Denburg, M., Gallant, K. M. H., Gutiérrez, O. M., Ix, J. H., et al. (2025) · Journal of the American Society of Nephrology · doi:10.1681/asn.0000000873 · Cited by 31
Self-citation
Performance of 24-hour urinary creatinine excretion-estimating equations in relation to measured 24-hour urinary creatinine excretion in hospitalized hypertensive patients
Jędrusik, P., Symonides, B., & Gaciong, Z. A. (2019) · Scientific Reports · doi:10.1038/s41598-019-40416-w · Cited by 29
Is too much salt harmful? Yes
Agócs, R., Sugár, D., & Szabo, A. J. (2019) · Pediatric Nephrology · doi:10.1007/s00467-019-04387-4 · Cited by 25
Taste in Motion: The Effect of Projection Mapping of a Boiling Effect on Food Expectation, Food Perception, and Purchasing Behavior
Suzuki, Y., Narumi, T., Tanikawa, T., & Hirose, M. (2021) · Frontiers in Computer Science · doi:10.3389/fcomp.2021.662824 · Cited by 28
“Currently, excessive intake of salt is a serious problem (Mente et al., 2014; O’Donnell et al., 2014).”
Background
Associations of Adherence to the DASH Diet and the Mediterranean Diet With All-Cause Mortality in Subjects With Various Glucose Regulation States
Wang, J., Liu, W.-J., & Lee, C.-L. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.828792 · Cited by 27
Is Reducing Dietary Sodium Controversial? Is It the Conduct of Studies With Flawed Research Methods That Is Controversial? A Perspective From the World Hypertension League Executive Committee
Campbell, N. R. C., Lackland, D. T., Niebylski, M. L., & Nilsson, P. M. (2014) · Journal of Clinical Hypertension · doi:10.1111/jch.12437 · Cited by 26
“One study reported that sodium intake <3000 mg/d was associated with an increase in mortality and cardiovascular disease while confirming the health risks of dietary sodium >6000 mg/d.(1) The other study largely confirmed the association between sodium intake and increased blood pressure (BP) but, unlike rigorous rand…”
Background
Alcohol, Smoking, Physical Activity, Protein, and Lower Urinary Tract Symptoms: Prospective Longitudinal Cohort
Choo, M. S., Han, J. H., Shin, T. Y., Ko, K., Lee, W. K., Cho, S. T., Lee, S. K., & Lee, S. H. (2015) · International Neurourology Journal · doi:10.5213/inj.2015.19.3.197 · Cited by 26
“A highsodium diet was defined as a dietary sodium intake of ≥6 g per day [19].”
BackgroundSelf-citation
Association between 24h Urinary Sodium and Potassium Excretion and Estimated Glomerular Filtration Rate (eGFR) Decline or Death in Patients with Diabetes Mellitus and eGFR More than 30 ml/min/1.73m2
Nagata, T., Sobajima, H., Ohashi, N., Hirakawa, A., Katsuno, T., Yasuda, Y., Matsuo, S., Tsuboi, N., & Maruyama, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0152306 · Cited by 26
“Increased potassium intake has many beneficial effects on blood pressure (BP)[3,13] and risk of CVD[2,4].”
BackgroundInfluential
Deliciousness of food and a proper balance in fatty acid composition as means to improve human health and regulate food intake
Mouritsen, O. G. (2016) · Flavour · doi:10.1186/s13411-016-0048-2 · Cited by 26
“In the case of salt, epidemiological studies have indicated that the global increase in cardiovascular diseases and hypertension [3, 68] may be caused by increased intake of salt [24] although recent studies have shown that the situation is more complex [53].”
Background
Renal sodium handling and sodium sensitivity
Frame, A. A., & Wainford, R. D. (2017) · Kidney Research and Clinical Practice · doi:10.23876/j.krcp.2017.36.2.117 · Cited by 29
The association of estimated salt intake with blood pressure in a Viet Nam national survey
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Problems with the 2015 Dietary Guidelines for Americans. An Alternative.
DiNicolantonio, J. J., Harcombe, Z., & O’Keefe, J. H. (2016) · Europe PMC (PubMed Central) · Cited by 25
Urinary sodium excretion and risk of cardiovascular disease in the Chinese population: a prospective study
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Assessing whether a spot urine specimen can predict 24-h urinary sodium excretion accurately
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The association between serum sodium concentration, hypertension and primary cardiovascular events: a retrospective cohort study
Cole, N. I., Suckling, R., Swift, P. A., He, F. J., MacGregor, G. A., Hinton, W., van Vlymen, J. N., Hayward, N., Jones, S., & de Lusignan, S. (2018) · Journal of Human Hypertension · doi:10.1038/s41371-018-0115-5 · Cited by 25
Kir4.2 mediates proximal potassium effects on glutaminase activity and kidney injury
Terker, A. S., Zhang, Y., Arroyo, J. P., Cao, S., Wang, S., Fan, X., Denton, J. S., Zhang, M., & Harris, R. C. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111840 · Cited by 25
“2,3,5,19 If prevalent in humans, this mechanistic relationship has important implications for the clinical care of patients with CKD. Dietary K + restriction is a common component of the clinical approach to treating CKD.”
Effects of High Salt Intake on Blood Pressure and Cardiovascular Disease: The Role of COX Inhibitors
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Clinical outcomes and economic impact of the 2017 ACC/AHA guidelines on hypertension in China
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Self-citation
Assessment of Dietary Sodium and Potassium in Canadians Using 24-Hour Urinary Collection
Mente, A., Dagenais, G. R., Wielgosz, A. T., Lear, S. A., McQueen, M., Zeidler, J. G., Fu, L., DeJesus, J., Rangarajan, S., Bourlaud, A.-S., et al. (2015) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2015.06.020 · Cited by 27
Self-citation
Influence of Salt Intake on Association of Blood Uric Acid with Hypertension and Related Cardiovascular Risk
Hou, L., Zhang, M., Han, W., Tang, Y., Xue, F., Liang, S., Zhang, B., Wang, W., Asaiti, K., Wang, Y., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150451 · Cited by 24
“24 h urine collection was not used, but the second urine sample after waking here was thought as a satisfactory alternative to 24-h pooled urine in adults for extensive epidemiological surveys [15,31] and used in a large scale epidemiological field [32].”
Method
Dietary Sodium and Cardiovascular Disease
Smyth, A., O'Donnell, M. J., Mente, A., & Yusuf, S. (2015) · Current Hypertension Reports · doi:10.1007/s11906-015-0559-8 · Cited by 25
Self-citation
Estimating 24-Hour Urinary Sodium Excretion From Spot Urine Samples in Chronic Kidney Disease Patients
Hu, J., Wang, Y., Song, N., Zhang, X., Teng, J., Zou, J., & Ding, X. (2019) · Journal of Renal Nutrition · doi:10.1053/j.jrn.2019.02.002 · Cited by 26
Inwardly rectifying potassium channel 5.1: Structure, function, and possible roles in diseases
Zhang, J., Han, J., Li, L., Zhang, Q., Feng, Y., Jiang, Y., Deng, F., Zhang, Y., Wu, Q., Chen, B., et al. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.03.006 · Cited by 24
Estimating the health and economic effects of the voluntary sodium reduction targets in Brazil: microsimulation analysis
Nilson, E. A. F., Pearson‐Stuttard, J., Collins, B., Guzman-Castillo, M., Capewell, S., O’Flaherty, M., Jaime, P. C., & Kypridemos, C. (2021) · BMC Medicine · doi:10.1186/s12916-021-02099-x · Cited by 27
Low-normal serum potassium is associated with an increased risk of cardiovascular and all-cause death in community-based elderly
Lai, Y.-H., Leu, H., Yeh, W., Chang, H., & Pan, W. (2015) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2015.01.001 · Cited by 24
Facts, issues and controversies in salt reduction for the prevention of cardiovascular disease
Cappucci, F., & Capewell, S. (2015) · University of Warwick · doi:10.82444/warw.33693334 · Cited by 23
Urinary Sodium and Potassium Excretion and Dietary Sources of Sodium in Maputo, Mozambique
de Queiroz, A. R. F., Damasceno, A. A. M., Jessen, N., Novela, C., Moreira, P. A. M., Lunet, N., & Padrão, P. (2017) · Nutrients · doi:10.3390/nu9080830 · Cited by 23
“In addition to high sodium intake, a low intake of potassium, which is inversely related to blood pressure and to the risk of stroke [47], was also observed.”
Background
Interaction between Single Nucleotide Polymorphism and Urinary Sodium, Potassium, and Sodium-Potassium Ratio on the Risk of Hypertension in Korean Adults
Park, Y., Kwock, C. K., Kim, K., Kim, J., & Yang, Y. J. (2017) · Nutrients · doi:10.3390/nu9030235 · Cited by 23
Meat intake and incidence of cardiovascular disease in Japanese patients with type 2 diabetes: analysis of the Japan Diabetes Complications Study (JDCS)
Japan Diabetes Complications Study Group, Horikawa, C., Kamada, C., Tanaka, S., Tanaka, S., Araki, A., Ito, H., Matsunaga, S., Fujihara, K., Yoshimura, Y., et al. (2017) · European Journal of Nutrition · doi:10.1007/s00394-017-1592-y · Cited by 22
Interference With Endothelial PPAR (Peroxisome Proliferator–Activated Receptor)-γ Causes Accelerated Cerebral Vascular Dysfunction in Response to Endogenous Renin-Angiotensin System Activation
Nair, A. R., Agbor, L. N., Mukohda, M., Liu, X., Hu, C., Wu, J. F., & Sigmund, C. D. (2018) · Hypertension · doi:10.1161/hypertensionaha.118.11857 · Cited by 22
Activation of the kidney sodium chloride cotransporter by the β2-adrenergic receptor agonist salbutamol increases blood pressure
Poulsen, S. B., Cheng, L., Pentón, D., Kortenoeven, M. L. A., Matchkov, V. V., Loffing, J., Little, R., Murali, S. K., & Fenton, R. A. (2021) · Kidney International · doi:10.1016/j.kint.2021.04.021 · Cited by 24
Expansion of the National Salt Reduction Initiative
Choi, S. E., Brandeau, M. L., & Basu, S. (2015) · Medical Decision Making · doi:10.1177/0272989x15583846 · Cited by 23
“In all scenarios, we calculated how many people would potentially shift from above the level of sodium intake considered safe to below 3 g/d or 2 g/d, which are thresholds variously debated as being associated with elevated mortality.(18) We simulated the model 10,000 times using Monte Carlo sampling from the probabil…”
BackgroundMethod
Blood Pressure Control Should Focus on More Potassium: Controversies in Hypertension
Chan, R., Parikh, N., Ahmed, S., Ruzicka, M., & Hiremath, S. S. (2023) · Hypertension · doi:10.1161/hypertensionaha.123.20545 · Cited by 29
Effects of Potassium or Sodium Supplementation on Mineral Homeostasis: A Controlled Dietary Intervention Study
Humalda, J. K., Yeung, S. M. H., Geleijnse, J. M., Gijsbers, L., Riphagen, I. J., Hoorn, E. J., Rotmans, J. I., Vogt, L., Navis, G., Bakker, S. J. L., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa359 · Cited by 26
Estimated daily salt intake in relation to blood pressure and blood lipids: the role of obesity
Thuesen, B. H., Toft, U., Buhelt, L. P., Linneberg, A. R., Friedrich, N., Nauck, M., Wallaschofski, H., & Jørgensen, T. (2014) · European Journal of Preventive Cardiology · doi:10.1177/2047487314553201 · Cited by 23
“salt intake and CVD events is a J-shaped curve and in that study daily salt intakes below 7 g/day as well as above 15 g/day were associated with increased risk of CVD events.(15) The relatively constricted range of salt intake within the adult Danish population in this study is a major disadvantage when attempting to…”
Background
Agreement between 24-h dietary recalls and 24-h urine collections for estimating sodium intake in China, Japan, UK, USA
Wen, X., Zhou, L., Stamler, J., Chan, Q. M., Horn, L. V., Daviglus, M. L., Dyer, A. R., Elliott, P., Ueshima, H., Miura, K., et al. (2018) · Journal of Hypertension · doi:10.1097/hjh.0000000000001941 · Cited by 22
“The Prospective Urban Rural Epidemiology (PURE) Study enrolled and followed 156 424 persons from 17 countries and reported that both higher and lower levels of estimated Na excretion were associated with increased cardiovascular risk, resulting in a J-shaped association curve [23].”
Background
Sodium intake, health implications, and the role of population-level strategies
Aljuraiban, G. S., Jose, A. P., Gupta, P., Shridhar, K., & Prabhakaran, D. (2020) · Nutrition Reviews · doi:10.1093/nutrit/nuaa042 · Cited by 22
Relationship between dietary sodium and sugar intake: A cross‐sectional study of the National Health and Nutrition Examination Survey 2001‐2016
Gress, T., Mansoor, K., Rayyan, Y. M., Khthir, R. A., Tayyem, R., Tzamaloukas, A. H., Abraham, N. G., Shapiro, J. I., & Khitan, Z. J. (2020) · Journal of Clinical Hypertension · doi:10.1111/jch.13985 · Cited by 22
Daily Sodium and Potassium Excretion Can Be Estimated by Scheduled Spot Urine Collections
Doenyas‐Barak, K., Beberashvili, I., Bar‐Chaim, A., Averbukh, Z., Vogel, O. G., & Efrati, S. (2015) · The Nephron journals/Nephron journals · doi:10.1159/000430105 · Cited by 22

Authors: O'Donnell, M., Mente, A., Rangarajan, S., McQueen, M. J., Wang, X., Liu, L., Yan, H., Lee, S. F., Mony, P., Devanath, A., Rosengren, A., Lopez-Jaramillo, P., Diaz, R., Avezum, A., Lanas, F., Yusoff, K., Iqbal, R., Ilow, R., Mohammadifard, N., Gulec, S., Yusufali, A. H., Kruger, L., Yusuf, R., Chifamba, J., Kabali, C., Dagenais, G., Lear, S. A., Teo, K., & Yusuf, S.
Affiliations: Ollscoil na Gaillimhe – University of Galway (IE)
Population Health Research Institute (CA)
Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
St. John's Research Institute (IN)
University of Gothenburg (SE)
Universidad de La Frontera (CL)
UCSI University (MY)
Aga Khan University (PK)
Isfahan University of Medical Sciences (IR)
Independent University, Bangladesh (BD)
University of Zimbabwe (ZW)
Institut universitaire de cardiologie et de pneumologie de Québec (CA)
Providence Health Care (CA)
ORCID: O'Donnell, Martin
Mente, Andrew
Rangarajan, Sumathy
Wang, Xingyu
Liu, Lisheng
Lee, Shun Fu
Mony, Prem
Devanath, Anitha
Rosengren, Annika
Lanas, Fernando
Yusoff, Khalid
Iqbal, Romaina
Mohammadifard, Noushin
Yusuf, Rita
Chifamba, Jephat
Kabali, Conrad
Dagenais, Gilles
Lear, Scott A.
Teo, Koon
Yusuf, Salim
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2014-08-14
Volume: 371
Issue: 7
Pages: 612-623
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1311889
OpenAlex: W2106445408
Cited by: 886
References: 43
Citations by year: 2026: 29 · 2025: 37 · 2024: 55 · 2023: 60 · 2022: 73 · 2021: 84 · 2020: 82 · 2019: 68 · 2018: 81 · 2017: 76 · 2016: 100 · 2015: 98 · 2014: 41
FWCI: 95.89
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
Omeka S (Universidad de La Frontera) (submittedVersion, cc-by-nc-nd)
Boloka Institutional Repository (North-west University) (submittedVersion)
Funders: Canadian Institutes of Health Research
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords: sodium excretion, potassium excretion, sodium intake, potassium intake, mortality, cardiovascular events, hypertension
MeSH terms: Adult, Cardiovascular Diseases, Diet, Female, Follow-Up Studies, Humans, Male, Middle Aged, Mortality, Potassium, Sodium, Sodium, Dietary, Linear Models

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Urinary Sodium and Potassium Excretion, Mortality, and Cardiovascular Events

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