Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies
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Background Several studies reported a U-shaped association between urinary sodium excretion and cardiovascular disease events and mortality. Whether these associations vary between those individuals with and without hypertension is uncertain. We aimed to explore whether the association between sodium intake and cardiovascular disease events and all-cause mortality is modified by hypertension status.Methods In this pooled analysis, we studied 133,118 individuals (63,559 with hypertension and 69,559 without hypertension), median age of 55 years (IQR 45-63), from 49 countries in four large prospective studies and estimated 24-h urinary sodium excretion (as group-level measure of intake). We related this to the composite outcome of death and major cardiovascular disease events over a median of 4.2 years (IQR 3.0-5.0) and blood pressure.Findings Increased sodium intake was associated with greater increases in systolic blood pressure in individuals with hypertension (2.08 mm Hg change per g sodium increase) compared with individuals without hypertension (1.22 mm Hg change per g; pinteraction<0.0001). In those individuals with hypertension (6835 events), sodium excretion of 7 g/day or more (7060 [11%] of population with hypertension: hazard ratio [HR] 1.23 [95% CI 1.11-1.37]; p<0.0001) and less than 3 g/day (7006 [11%] of population with hypertension: 1.34 [1.23-1.47]; p<0.0001) were both associated with increased risk compared with sodium excretion of 4-5 g/day (reference 25% of the population with hypertension). In those individuals without hypertension (3021 events), compared with 4-5 g/day (18,508 [27%] of the population without hypertension), higher sodium excretion was not associated with risk of the primary composite outcome (≥ 7 g/day in 6271 [9%] of the population without hypertension; HR 0.90 [95% CI 0.76-1.08]; p=0.2547), whereas an excretion of less than 3 g/day was associated with a significantly increased risk (7547 [11%] of the population without hypertension; HR 1.26 [95% CI 1.10-1.45]; p=0.0009).Interpretation Compared with moderate sodium intake, high sodium intake is associated with an increased risk of cardiovascular events and death in hypertensive populations (no association in normotensive population), while the association of low sodium intake with increased risk of cardiovascular events and death is observed in those with or without hypertension. These data suggest that lowering sodium intake is best targeted at populations with hypertension who consume high sodium diets.Funding Full funding sources listed at end of paper (see Acknowledgments).
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Available studies support that sodium restriction, even to low levels <65 to 100 mmol/d (1.5-3.0 g/d), yields significant linear reductions in BP among patients with high BP and resistant hypertension.
“For the time being, the available studies (albeit of short-term duration) support that sodium restriction, even to low levels <65 to 100 mmol/d (1.5–3.0 g/d), yields significant linear reductions in BP among patients with high BP153–155,349 and RH.58,161”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [349]
An estimated 1-g (43.5-mmol) reduction in daily sodium intake produces a 2.1- and 1.2-mm Hg decrease in SBP among hypertensive and normotensive patients, respectively.
“In a recent meta-analysis, an estimated 1-g (43.5-mmol) reduction in daily sodium intake produces a 2.1− and 1.2–mm Hg decrease in SBP among hypertensive and normotensive patients, respectively.349”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [349]
A reduced-sodium diet is well proven to decrease BP.
“A reduced-sodium diet is well proven to decrease BP.174,349”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [349]
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- Authors
- Mente, A., O'Donnell, M., Rangarajan, S., Dagenais, G., Lear, S., McQueen, M., Diaz, R., Avezum, A., Lopez-Jaramillo, P., Lanas, F., Li, W., Lu, Y., Yi, S., Rensheng, L., Iqbal, R., Mony, P., Yusuf, R., Yusoff, K., Szuba, A., Oguz, A., Rosengren, A., Bahonar, A., Yusufali, A., Schutte, A. E., Chifamba, J., Mann, J. F. E., Anand, S. S., Teo, K., & Yusuf, S.
- Affiliations
- Population Health Research Institute (CA)
- Ollscoil na Gaillimhe – University of Galway (IE)
- Institut universitaire de cardiologie et de pneumologie de Québec (CA)
- Providence Health Care (CA)
- McMaster University (CA)
- Universidad de La Frontera (CL)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Fu Wai Hospital (CN)
- Nanchang Center for Disease Control and Prevention (CN)
- Aga Khan University (PK)
- St. John's Research Institute (IN)
- Independent University, Bangladesh (BD)
- Universiti Teknologi MARA System (MY)
- Wroclaw Medical University (PL)
- University of Gothenburg (SE)
- Isfahan University of Medical Sciences (IR)
- Dubai Health Authority (AE)
- North-West University (ZA)
- University of Zimbabwe (ZW)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Corresponding author
- Mente, Andrew
- ORCID
- Mente, Andrew
- O'Donnell, Martin
- Rangarajan, Sumathy
- Dagenais, Gilles
- Lear, Scott
- Lanas, Fernando
- Li, Wei
- Iqbal, Romaina
- Mony, Prem
- Yusuf, Rita
- Yusoff, Khalid
- Szuba, Andrzej
- Rosengren, Annika
- Bahonar, Ahmad
- Yusufali, Afzalhussein
- Schutte, Aletta Elisabeth
- Chifamba, Jephat
- Mann, Johannes F E
- Anand, Sonia S
- Teo, Koon
- Yusuf, S
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 388
- Issue
- 10043
- Pages
- 465-475
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2404706218
- Cited by
- 483
- References
- 64
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 39 · 2023: 39 · 2022: 41 · 2021: 57 · 2020: 52 · 2019: 61 · 2018: 60 · 2017: 54 · 2016: 35 · 2012: 1
- FWCI
- 9.41
- Type
- journal article
- Language
- en
- Update notices
- erratum (2021-04-10)
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (acceptedVersion, cc-by-nc-nd)
- Arrow@dit (Dublin Institute of Technology) (acceptedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- eCommons - AKU (Aga Khan University) (submittedVersion, cc-by)
- Omeka S (Universidad de La Frontera) (submittedVersion, cc-by-nc-nd)
- ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by)
- Funders
- Heart and Stroke Foundation of Canada
- Hamilton Health Sciences Foundation
- 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, sodium intake, hypertension, cardiovascular events, all-cause mortality, systolic blood pressure, U-shaped relationship, low sodium intake, dietary sodium, blood pressure, pooled analysis, prospective cohort, cardiovascular risk modification, sodium reduction
- MeSH terms
- Adult, Aged, Aged, 80 and over, Blood Pressure, Cardiovascular Diseases, Diet, Sodium-Restricted, Female, Humans, Hypertension, Male, Middle Aged, Prospective Studies, Risk Factors, Sodium, Sodium, Dietary, Global Health, Risk Assessment
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