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

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.

Fig 1

Restricted cubic spline plot of association of estimated 24 hour urinary sodium excretion with composite of all cause mortality and major cardiovascular events, mortality, and major cardiovascular events (composite of cardiovascular death or myocardial infarction or stroke or heart failure). Plots adjusted for age (included as spline function), sex, education, current and former alcohol intake (units weekly), diabetes mellitus, body mass index, physical activity, history of cardiovascular events, use of cardiovascular drugs (blood pressure lowering, statins, or antidiabetics), history of tuberculosis, cancer, HIV, and current and former smoking. Dashed lines indicate 95% confidence intervals. Median intake is reference standard (4.9 g/day). Salt approximates 2.5×sodium g/day. Spline curve was truncated at 10 g/day in all plots

Fig 2

Restricted cubic spline plot of association of estimated 24 hour urinary potassium excretion with composite of all cause mortality and major cardiovascular events, mortality, and major cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and heart failure). Plots adjusted for age (included as spline function), sex, education, current and former alcohol intake (units weekly), diabetes mellitus, body mass index, physical activity, history of cardiovascular events, use of cardiovascular drugs (blood pressure lowering, statins, or antidiabetics), history of tuberculosis, cancer, HIV, and current and former smoking. Spline was truncated at 4 g/day in all plots

Fig 3

Heat map of risk for composite of cardiovascular events or death showing lowest risk in region of moderate sodium intake 3-5 g/day and higher potassium intake and highest risk in region of extremes of sodium excretion and low potassium excretion. The reference hazard for these hazard ratios was set at a value of sodium daily excretion/intake of 5.00 g and potassium daily excretion/intake of 2.25 g (median excretion of sodium and potassium), marked as X. The overlaid lines represent joint distribution quartiles; each region contains a quarter of the analysed participants. r=0.34

Fig 4

Association of urinary sodium excretion within tertiles of urinary potassium excretion. P for interaction is significant (P=0.007) for urinary potassium excretion×urinary sodium excretion above median intake, with lower magnitude of association with higher urinary potassium excretion. Plots adjusted for age (included as spline function), sex, education, current and former alcohol intake (units weekly), diabetes mellitus, body mass index, physical activity, history of cardiovascular events, use of cardiovascular drugs (blood pressure lowering, statins, or antidiabetics), history of tuberculosis, cancer, HIV, and current and former smoking

Fig 5

Association of urinary sodium excretion within tertiles of modified alternative healthy eating index (mAHEI) score. P for interactions not significant. Plots adjusted for age (included as spline function), sex, education, current and former alcohol intake (units weekly), diabetes mellitus, body mass index, physical activity, history of cardiovascular events, use of cardiovascular drugs (blood pressure lowering, statins, or antidiabetics), history of tuberculosis, cancer, HIV, and current and former smoking