title: Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies.
abstract: 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Full funding sources listed at end of paper (see Acknowledgments).
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada; Department of Clinical Epidemiology and Biostatistics, Hamilton, ON, Canada. Electronic address: andrew.mente@phri.ca.
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authors.initials: A
authors.lastname: Mente
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada; Department of Medicine, Hamilton, ON, Canada; HRB-Clinical Research Facility, NUI Galway, Ireland.
authors.forename: Martin
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authors.lastname: O'Donnell
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada.
authors.forename: Sumathy
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authors.lastname: Rangarajan
authors.affiliation: Laval University Heart and Lungs Institute, Quebec City, QC, Canada.
authors.forename: Gilles
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authors.lastname: Dagenais
authors.affiliation: Faculty of Health Sciences, Simon Fraser University, BC, Canada; Division of Cardiology, Providence Health Care, BC, Canada.
authors.forename: Scott
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authors.lastname: Lear
authors.affiliation: Department of Laboratory Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Matthew
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authors.lastname: McQueen
authors.affiliation: Estudios Clínicos Latinoamérica, Rosario, Argentina.
authors.forename: Rafael
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authors.lastname: Diaz
authors.affiliation: Dante Pazzanese Institute of Cardiology, Sao Paulo, SP, Brazil.
authors.forename: Alvaro
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authors.affiliation: Fundacion Oftalmologica de Santander-FOSCAL, Medical School, Universidad de Santander Floridablanca-Santander, Colombia.
authors.forename: Patricio
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authors.lastname: Lopez-Jaramillo
authors.affiliation: Universidad de La Frontera, Temuco, Chile.
authors.forename: Fernando
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authors.lastname: Lanas
authors.affiliation: National Centre for Cardiovascular Diseases, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Wei
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authors.affiliation: Medical Research & Biometrics Center, National Center for Cardiovascular Diseases, FuWai Hospital, Beijing, China.
authors.forename: Yin
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authors.affiliation: Medical Research & Biometrics Center, National Center for Cardiovascular Diseases, FuWai Hospital, Beijing, China.
authors.forename: Sun
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authors.affiliation: Center for Disease Control & Prevention Nanchang County, Nanchang City, Jiangxi Province, China.
authors.forename: Lei
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authors.affiliation: Departments of Community Health Sciences and Medicine, Aga Khan University, Karachi, Pakistan.
authors.forename: Romaina
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authors.affiliation: Community Health & Epidemiology, St John's Research Institute, Bangalore, India.
authors.forename: Prem
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authors.affiliation: The School of Life Sciences and The Centre for Health, Population, and Development, Independent University, Bangladesh.
authors.forename: Rita
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authors.lastname: Yusuf
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia.
authors.forename: Khalid
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authors.lastname: Yusoff
authors.affiliation: Division of Angiology, Wroclaw Medical University, Wrocław, Poland; Department of Internal Medicine, 4th Military Hospital in Wroclaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szuba
authors.affiliation: Istanbul Medeniyet University, Faculty of Medicine, Department of Internal Medicine, Istanbul, Turkey.
authors.forename: Aytekin
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authors.lastname: Oguz
authors.affiliation: Sahlgrenska Academy University of Gothenburg, Gothenburg, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Rosengren
authors.affiliation: Hypertension Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Bahonar
authors.affiliation: Hatta Hospital, Dubai Health Authority, Dubai, UAE.
authors.forename: Afzalhussein
authors.initials: A
authors.lastname: Yusufali
authors.affiliation: MRC Unit for Hypertension and CVD/Hypertension in Africa Research Team, North-West University, Potchefstroom, North West Province, South Africa.
authors.forename: Aletta Elisabeth
authors.initials: AE
authors.lastname: Schutte
authors.affiliation: University of Zimbabwe, College of Health Sciences, Physiology Department, Harare, Zimbabwe.
authors.forename: Jephat
authors.initials: J
authors.lastname: Chifamba
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada; Department of Nephrology, University of Erlangen-Nurnberg and Munich General Hospitals, Munich, Germany.
authors.forename: Johannes F E
authors.initials: JF
authors.lastname: Mann
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada; Department of Clinical Epidemiology and Biostatistics, Hamilton, ON, Canada; Department of Medicine, Hamilton, ON, Canada.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada.
authors.forename: Koon
authors.initials: K
authors.lastname: Teo
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada; Department of Clinical Epidemiology and Biostatistics, Hamilton, ON, Canada; Department of Medicine, Hamilton, ON, Canada.
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000517:prevention & control; D004039:Diet, Sodium-Restricted; D005260:Female; D014943:Global Health; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000178:diet therapy* / Q000503:physiopathology / Q000652:urine; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012964:Sodium / Q000652:urine*; D012982:Sodium, Dietary / Q000008:administration & dosage*
chemical_list: D012982:Sodium, Dietary; D012964:Sodium