Joint association of urinary sodium and potassium excretion with cardiovascular events and mortality: prospective cohort study
Authors: O’Donnell Martin , Mente Andrew , Rangarajan Sumathy , McQueen Matthew J , O’Leary Neil , Yin Lu , Liu Xiaoyun , Swaminathan Sumathi , Khatib Rasha , Rosengren Annika , Ferguson John , Smyth Andrew , Lopez-Jaramillo Patricio , Diaz Rafael , Avezum Alvaro , Lanas Fernando , Ismail Noorhassim , Yusoff Khalid , Dans Antonio , Iqbal Romaina , Szuba Andrzej , Mohammadifard Noushin , Oguz Atyekin , Yusufali Afzal Hussein , Alhabib Khalid F , Kruger Iolanthe M , Yusuf Rita , Chifamba Jephat , Yeates Karen , Dagenais Gilles , Wielgosz Andreas , Lear Scott A , Teo Koon , Yusuf Salim ,   the PURE Investigators
Published: March 2019

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.