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Joint association of urinary sodium and potassium excretion with cardiovascular events and mortality: prospective cohort study

O'Donnell M 1 , Mente A 2 , Rangarajan S 2 , McQueen MJ 2 , O'Leary N 3 , Yin L 4 Show all authors , Liu X 4 , Swaminathan S 5 , Khatib R 6 , Rosengren A 7 , Ferguson J 3 , Smyth A 3 , Lopez-Jaramillo P 8 , Diaz R 9 , Avezum A 10 , Lanas F 11 , Ismail N 12 , Yusoff K 13 , Dans A 14 , Iqbal R 15 , Szuba A 16 , Mohammadifard N 17 , Oguz A 18 , Yusufali AH 19 , Alhabib KF 20 , Kruger IM 21 , Yusuf R 22 , Chifamba J 23 , Yeates K 24 , Dagenais G 25 , Wielgosz A 26 , Lear SA 27 , Teo K 2 , Yusuf S 2 , PURE Investigators

Affiliations 

  • 1 Population Health Research Institute, DBCVS Research Institute, McMaster University, 237 Barton St East, Hamilton, ON L8L 2X2, Canada odonnm@mcmaster.ca
  • 2 Population Health Research Institute, DBCVS Research Institute, McMaster University, 237 Barton St East, Hamilton, ON L8L 2X2, Canada
  • 3 HRB-Clinical Research Facility, Galway University Hospital, NUI Galway, Galway, Ireland
  • 4 Medical Research & Biometrics Centre, National Centre for Cardiovascular Diseases Cardiovascular, Fengcunxili, Mentougou District, Beijing, China
  • 5 Division of Nutrition, St John's Research Institute, Bangalore, Karnataka, India
  • 6 Departments of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  • 7 Sahlgrenska Academy, University of Gothenburg, and Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 8 Fundacion Oftalmologica de Santander (FOSCAL), Medical School, Universidad de Santander, Floridablanca-Santander, Colombia
  • 9 Estudios Clinicos Latinoamerica ECLA, Instituto Cardiovascular de Rosario, Rosario, Santa Fe, Argentina
  • 10 Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil
  • 11 Universidad de La Frontera, Temuco, Chile
  • 12 Department of Community Health. University Kebangsaan Malaysia Medical Centre, Malaysia
  • 13 Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur, Malaysia
  • 14 University of the Philippines-Manila, Ermita, Manila, Philippines
  • 15 Departments of Community Health Sciences and Medicine, Aga Khan University, Karachi, Pakistan
  • 16 Division of Angiology, Wroclaw Medical University, Wroclaw, Poland
  • 17 Isfahan Cardiovascular Research Centre, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
  • 18 Istanbul Medeniyet University, Faculty of Medicine, Department of Internal Medicine, Istanbul, Turkey
  • 19 Hatta Hospital, Dubai Medical University, Dubai Health Authority. Dubai, United Arab Emirates
  • 20 Department of Cardiac Sciences, King Fahad Cardiac Centre, College of Medicine, King Saud University. Riyadh, Saudi Arabia
  • 21 Faculty of Health Science, North-West University, Potchefstroom campus, Potchefstroom, South Africa
  • 22 School of Life Sciences and The Centre for Health, Population and Development. Independent University, Bangladesh, Dhaka, Bangladesh
  • 23 University of Zimbabwe, College of Health Sciences, Physiology Department, Harare, Zimbabwe
  • 24 Department of Medicine, Division of Nephrology, Queen's University, Kingston, Canada
  • 25 Laval University Heart and Lungs Institute, Quebec City, QC, Canada
  • 26 Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
  • 27 Faculty of Health Sciences, Simon Fraser University, and Division of Cardiology, Providence Health Care, BC, Canada
BMJ, 2019 03 13;364:l772.
PMID: 30867146 DOI: 10.1136/bmj.l772

Abstract

OBJECTIVE: To evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (<2.0 g sodium, >3.5 g potassium) in adults.

DESIGN: International prospective cohort study.

SETTING: 18 high, middle, and low income countries, sampled from urban and rural communities.

PARTICIPANTS: 103 570 people who provided morning fasting urine samples.

MAIN OUTCOME MEASURES: Association of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (<3 g/day), moderate (3-5 g/day), and high (>5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day).

RESULTS: Mean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of <2.0 g/day of sodium and >3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007).

CONCLUSIONS: These findings suggest that the simultaneous target of low sodium intake (<2 g/day) with high potassium intake (>3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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