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Urinary Sodium and Potassium, and Risk of Ischemic and Hemorrhagic Stroke (INTERSTROKE): A Case-Control Study

Judge C 1 , O'Donnell MJ 1 , Hankey GJ 2 , Rangarajan S 3 , Chin SL 3 , Rao-Melacini P 3 Show all authors , Ferguson J 1 , Smyth A 1 , Xavier D 4 , Lisheng L 5 , Zhang H 6 , Lopez-Jaramillo P 7 , Damasceno A 8 , Langhorne P 9 , Rosengren A 10 , Dans AL 11 , Elsayed A 12 , Avezum A 13 , Mondo C 14 , Ryglewicz D 15 , Czlonkowska A 16 , Pogosova N 17 , Weimar C 18 , Diaz R 19 , Yusoff K 20 , Yusufali A 21 , Oguz A 22 , Wang X 6 , Lanas F 23 , Ogah OS 24 , Ogunniyi A 25 , Iversen HK 26 , Malaga G 27 , Rumboldt Z 28 , Oveisgharan S 29 , Al Hussain F 30 , Yusuf S 3

Affiliations 

  • 1 Department of Medicine, NUI Galway, Galway, Ireland
  • 2 School of Medicine and Pharmacology, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia
  • 3 Department of Medicine, Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
  • 4 Department of Medicine, St John's Medical College and Research Institute, Bangalore, India
  • 5 Department of Medicine, National Center of Cardiovascular Disease, Beijing, China
  • 6 Department of Medicine, Beijing Hypertension League Institute, Beijing, China
  • 7 Department of Medicine, Instituto de Investigaciones MASIRA, Universidad de Santander, Bucaramanga, Colombia
  • 8 Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique
  • 9 Department of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, Scotland, UK
  • 10 Department of Molecular and Clinical Medicine, University of Gothenburg and Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 11 College of Medicine, University of Philippines, Manila, Philippines
  • 12 Department of Surgery, Al Shaab Teaching Hospital, Khartoum, Sudan
  • 13 Department of Medicine, International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
  • 14 Department of Medicine, Kiruddu National Referral Hospital, Kampala, Uganda
  • 15 Military Institute of Aviation Medicine, Warsaw, Poland
  • 16 Department of Medicine, Military Institute of Aviation Medicine, Warsaw, Poland
  • 17 Department of Medicine, National Medical Research Center of Cardiology, Moscow, Russia
  • 18 Department of Neurology, University Hospital, Essen, Germany
  • 19 Department of Medicine, Estudios Clínicos Latino America (ECLA), Instituto Cardiovascular de Rosario (ICR), Rosario, Argentina
  • 20 Department of Medicine, Universiti Teknologi MARA, Selayang, Selangor and UCSI University, Kuala Lumpur, Malaysia
  • 21 Department of Medicine, Hatta Hospital, Dubai Health Authority/Dubai Medical College, Dubai, UAE
  • 22 Department of Internal Medicine, Istanbul Medeniyet University, Istanbul, Turkey
  • 23 Faculty of Medicine, Universidad de La Frontera, Temuco, Chile
  • 24 Department of Medicine, University College Hospital, Ibadan, Nigeria
  • 25 Department of Medicine, University College Hospital, Ibadan, Oyo State, Nigeria
  • 26 Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark
  • 27 School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru
  • 28 Department of Medicine, University of Split, Split, Croatia
  • 29 Department of Medicine, Rush Alzheimer Disease Research Center in Chicago, Chicago, Illinois, USA
  • 30 Department of Medicine, King Saud University, Riyadh, Saudi Arabia
Am J Hypertens, 2021 04 20;34(4):414-425.
PMID: 33197265 DOI: 10.1093/ajh/hpaa176

Abstract

BACKGROUND: Although low sodium intake (<2 g/day) and high potassium intake (>3.5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke.

METHODS: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes.

RESULTS: Compared with an estimated urinary sodium excretion of 2.8-3.5 g/day (reference), higher (>4.26 g/day) (odds ratio [OR] 1.81; 95% confidence interval [CI], 1.65-2.00) and lower (<2.8 g/day) sodium excretion (OR 1.39; 95% CI, 1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4.26 g/day) was significantly greater (P < 0.001) for intracerebral hemorrhage (ICH) (OR 2.38; 95% CI, 1.93-2.92) than for ischemic stroke (OR 1.67; 95% CI, 1.50-1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1.58 g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke.

CONCLUSIONS: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake-rather than low sodium intake-combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.

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

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