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Low-Sodium Intake: A Risk Factor for Stroke?

      To the Editor:
      The recent findings by Kieneker et al
      • Kieneker L.M.
      • Eisenga M.F.
      • Gansevoort R.T.
      • et al.
      Association of low urinary sodium excretion with increased risk of stroke.
      represent the first convincing evidence that a low sodium intake might be linked to an increased cerebrovascular risk. The highly cited papers by a Canadian group
      • O'Donnell M.
      • Mente A.
      • Rangarajan S.
      • et al.
      PURE Investigators
      Urinary sodium and potassium excretion, mortality, and cardiovascular events.
      already claimed to show a sort of J-shaped association between sodium intake and cardiovascular events, but there are limitations to these studies, as has been discussed previously.
      • Campbell N.R.C.
      Dissidents and dietary sodium: concerns about the commentary by O'Donnell et al.
      Kieneker et al
      • Kieneker L.M.
      • Eisenga M.F.
      • Gansevoort R.T.
      • et al.
      Association of low urinary sodium excretion with increased risk of stroke.
      correctly studied the relationship between sodium intake and cerebrovascular events, evaluating multiple 24-hour urinary sodium excretions (UNaV) in a large (N>7000) cohort of Dutch patients. The authors observed an inverse association between sodium excretion and the risk of stroke, even after adjusting for confounders such as age, sex, diet, lifestyle, blood pressure, antihypertensive medications, plasma renin, aldosterone, and so on.
      The association of low sodium intake and increased risk of stroke is intriguing, and the authors discuss the possibility that an increase of lipids, renin-angiotensin-aldosterone system (RAAS) activity, or sympathetic discharge may be involved. The contribution of these factors is uncertain at present.
      • Campbell N.R.C.
      Dissidents and dietary sodium: concerns about the commentary by O'Donnell et al.
      Kieneker et al correctly noted the limits of the study
      • Kieneker L.M.
      • Eisenga M.F.
      • Gansevoort R.T.
      • et al.
      Association of low urinary sodium excretion with increased risk of stroke.
      : The mean sodium intake in this population is relatively low, reverse causality cannot be ruled out, and residual confounders are to be taken into account.
      In our opinion, there are other relevant considerations:
      • 1.
        The study population is at very low risk of stroke (number of observed events = 183 during a follow-up of more than 12 years), with a prevalence of 0.21% per year, in front of the actual stroke prevalence of 0.8% to 8.2 % per year (from 4x to 40x) in the general population across Europe.
        The burden of stroke in Europe.
        • Béjot Y.
        • Bailly H.
        • Durier J.
        • Giroud M.
        Epidemiology of stroke in Europe and trends for the 21st century.
      • 2.
        The group in the lowest quintile of UNaV has an average value of 83 mmol per 24 hours (really low; actually well below the current indications). In this group, the possible reverse causality should be investigated.
      • 3.
        The patients with the lowest UNaV show also the lowest potassium excretion, reflecting a low potassium intake. High potassium intake has protective cardiovascular effects. This is not taken into account in the discussion.
      • 4.
        In Figures A and B of their study,
        • Kieneker L.M.
        • Eisenga M.F.
        • Gansevoort R.T.
        • et al.
        Association of low urinary sodium excretion with increased risk of stroke.
        Kieneker et al report graphically the inverse (J-shaped?) relationship between UNaV and risk of stroke, after adjusting (A) for age and sex, and (B) additionally adjusting for height, weight, race, smoking status, and so on, but not for blood pressure and/or antihypertensive medication consumption, although these last adjustments may have clarified their findings.
      In our opinion, the paper by Kieneker et al
      • Kieneker L.M.
      • Eisenga M.F.
      • Gansevoort R.T.
      • et al.
      Association of low urinary sodium excretion with increased risk of stroke.
      is the first to have addressed correctly a possible inverse relation between sodium intake and risk of stroke; their conclusions are nevertheless clouded by a number of confounders.

      References

        • Kieneker L.M.
        • Eisenga M.F.
        • Gansevoort R.T.
        • et al.
        Association of low urinary sodium excretion with increased risk of stroke.
        Mayo Clin Proc. 2018; 93: 1803-1809
        • O'Donnell M.
        • Mente A.
        • Rangarajan S.
        • et al.
        • PURE Investigators
        Urinary sodium and potassium excretion, mortality, and cardiovascular events.
        N Engl J Med. 2014; 371 (Published correction appears in N Engl J Med. 2014;371(13):1267.): 612-623
        • Campbell N.R.C.
        Dissidents and dietary sodium: concerns about the commentary by O'Donnell et al.
        Int J Epidemiol. 2017; 46: 362-366
      1. The burden of stroke in Europe.
        (King's College of London, SAFE Secretariat. Stroke Association House)
        • Béjot Y.
        • Bailly H.
        • Durier J.
        • Giroud M.
        Epidemiology of stroke in Europe and trends for the 21st century.
        Presse Med. 2016; 45: e391-e398

      Linked Article

      • Association of Low Urinary Sodium Excretion With Increased Risk of Stroke
        Mayo Clinic ProceedingsVol. 93Issue 12
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          The positive relationship between sodium intake and blood pressure is well established. However, results of observational studies on dietary sodium intake and risk of stroke are inconsistent. Moreover, prospective studies with multiple 24-hour urine samples for accurate estimation of habitual sodium intake are scarce. We examined the association of urinary sodium excretion (UNaV) as an accurate estimate of intake with risk of stroke. We studied 7330 individuals free of cardiovascular events at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, a prospective, population-based cohort of Dutch men and women.
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      • In reply—Low-Sodium Intake: A Risk Factor for Stroke?
        Mayo Clinic ProceedingsVol. 94Issue 4
        • Preview
          We are grateful to Drs Musso and Dotto1 for the appraisal of our article on low urinary sodium excretion (UNaV) as an indicator of low sodium intake and increased risk of stroke.2 We agree that the mentioned earlier study by O’Donnell and colleagues,3 although representative of various populations by including more than 100,000 participants from 17 countries, has some limitations. In particular, the assessment of sodium intake via a single spot urine sample is a major limitation. Actual measurement of 24-hour UNaV in multiple urine collections (to account for day-to-day variability), as we did in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, has been shown to be a more accurate method for the assessment of usual sodium intake.
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