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. 2021 Apr 20;34(4):414-425.
doi: 10.1093/ajh/hpaa176.

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

Conor Judge  1   2   3 , Martin J O'Donnell  1   2 , Graeme J Hankey  4 , Sumathy Rangarajan  2 , Siu Lim Chin  2 , Purnima Rao-Melacini  2 , John Ferguson  1 , Andrew Smyth  1 , Denis Xavier  5 , Liu Lisheng  6 , Hongye Zhang  7 , Patricio Lopez-Jaramillo  8 , Albertino Damasceno  9 , Peter Langhorne  10 , Annika Rosengren  11 , Antonio L Dans  12 , Ahmed Elsayed  13 , Alvaro Avezum  14 , Charles Mondo  15 , Danuta Ryglewicz  16 , Anna Czlonkowska  17 , Nana Pogosova  18 , Christian Weimar  19 , Rafael Diaz  20 , Khalid Yusoff  21 , Afzalhussein Yusufali  22 , Aytekin Oguz  23 , Xingyu Wang  7 , Fernando Lanas  24 , Okechukwu S Ogah  25 , Adesola Ogunniyi  26 , Helle K Iversen  27 , German Malaga  28 , Zvonko Rumboldt  29 , Shahram Oveisgharan  30 , Fawaz Al Hussain  31 , Salim Yusuf  2
Affiliations

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

Conor Judge et al. Am J Hypertens. .

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.

Keywords: blood pressure; hypertension; intracerebral hemorrhage; ischemic stroke; potassium; sodium; stroke.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Scatterplot of estimated urinary sodium and potassium excretion.
Figure 2.
Figure 2.
Mean systolic and diastolic blood pressure by sodium quartile (controls excluding baseline hypertension and prehospital diuretic use).
Figure 3.
Figure 3.
Association of estimated 24-hour sodium excretion (Tanaka) with risk of stroke and pathological stroke subtypes. Panel a shows a restricted cubic spline of the association between estimated 24-hour sodium excretion and risk of all stroke. Panel b shows a restricted cubic spline of the association between estimated 24-hour sodium excretion and risk of ischemic stroke. Panel c shows a restricted cubic spline of the association between estimated 24-hour sodium excretion and risk of intracerebral hemorrhage. All plots were adjusted for age, BMI, education level, alcohol intake, diabetes at baseline, atrial fibrillation/flutter at baseline, smoking, and physical activity level. The gray ribbons indicate 95% confidence interval. The green lines represent the median value for each population. The distribution of the exposure (sodium excretion) is plotted below each spline. Abbreviation: BMI, body mass index.
Figure 4.
Figure 4.
Association of estimated sodium excretion (Tanaka) and risk of ischemic stroke subtypes (TOAST classification). Panel a shows a restricted cubic spline of the association between estimated 24-hour sodium excretion and cardioembolic stroke (TOAST 1). Panel b shows a restricted cubic spline of the association between estimated 24-hour sodium excretion and large vessel stroke (TOAST 2). Panel c shows a restricted cubic spline of the association between estimated 24-hour sodium excretion and small vessel stroke (TOAST 3). Panel d shows a restricted cubic spline of the association between estimated 24-hour sodium excretion and stroke of undetermined cause (TOAST 4). All plots were adjusted for age, BMI, education level, alcohol intake, diabetes at baseline, atrial fibrillation/flutter at baseline, smoking, and physical activity level. The gray ribbons indicate 95% confidence interval. The distribution of the exposure (potassium excretion) is plotted below each spline. Abbreviation: BMI, body mass index.
Figure 5.
Figure 5.
Association of estimated 24-hour potassium excretion (Tanaka) with risk of stroke and pathological stroke subtypes. Panel a shows a restricted cubic spline of the association between estimated 24-hour potassium excretion and risk of all stroke. Panel b shows a restricted cubic spline of the association between estimated 24-hour potassium excretion and risk of ischemic stroke. Panel c shows a restricted cubic spline of the association between estimated 24-hour potassium excretion and risk of intracerebral hemorrhage. All plots were adjusted for age, BMI, education level, alcohol intake, diabetes at baseline, atrial fibrillation/flutter at baseline, smoking, and physical activity level. The gray ribbons indicate 95% confidence interval. The green lines represent the median value for each population. The distribution of the exposure (sodium excretion) is plotted below each spline. Abbreviation: BMI, body mass index.
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