#5776 HIGHER DIETARY NA/K RATIO IS ASSOCIATED WITH AN INCREASED RISK OF CARDIOVASCULAR OUTCOMES IN THE GENERAL POPULATION, BUT NOT IN CKD PATIENTS
Authors: Zwager Charlotte , Esseghir Malik , van Vliet Anne Myrthe , Daams Joost , Vogt Liffert , Engberink Rik Olde 
Published: June 2023

Abstract

Background and Aims
High sodium and low potassium intake have been recognized as cardiovascular risk factors. The combined effect of sodium and potassium intake, reflected by the dietary sodium-to-potassium ratio (Na/K ratio), may be an even better predictor of cardiovascular disease (CVD). The primary objective of this meta-analysis is to investigate the effect of the estimated dietary Na/K ratio on the composite outcome of cardiovascular events (CVE) and all-cause mortality. As the ideal sodium and potassium intake may be different for chronic kidney disease (CKD) patients, we will compare subjects with and without CKD.

Method
We performed a systematic search in MEDLINE and EMBASE databases from January 1946 to December 2022. We included randomized controlled trials and cohort studies with a mean follow-up duration of ≥1 year, which reported the association between the estimated dietary Na/K ratio and CVE and/or all-cause mortality. Two reviewers independently assessed the eligibility of identified studies, extracted data, and assessed the risk of bias according to the Cochrane Handbook Guidelines. We compared hazard ratios (HRs) among subgroups with increasing dietary Na/K ratio using the group with lowest estimated dietary Na/K ratio as a reference. We performed a random-effects meta-analysis using these HRs. A sensitivity analysis was performed using the leave-one-out approach. In a subgroup analysis, we compared CKD patients with the general population and adults with a history of CVD. We performed a meta-regression analysis to investigate the impact of the absolute increase in estimated dietary Na/K ratio (Δ Na/K) on the composite outcome, when adjusted for the mean estimated dietary Na/K ratio of the reference group and the follow-up duration of the studies.

Results
Of the 8,249 studies initially identified, 16 studies with 404,301 subjects were included in our main analysis. Mean age was 55.2 years, and 49% were male. For estimation of dietary Na/K ratio, 3 studies used spot urines, 3 studies used 24-hour urine collections, and 10 studies used food frequency questionnaires. Mean follow-up duration was 12 years. Higher estimated dietary Na/K ratio was associated with a significant higher risk for the composite endpoint of CVE and all-cause mortality (HR 1.16 [95% CI: 1.10-1.23], P&lt;0.00001, I2 = 41%) (Figure 1). We observed no significant changes in our results using the leave-one-out approach. In the subgroup analysis, we observed that increased estimated dietary Na/K ratio associated with significantly higher CVE and all-cause mortality risk in the general population (10 studies; 387,679 subjects; HR 1.17 [1.10-1.25], P&lt;0.00001, I2 = 48%), and in adults with a history of CVD (5 studies; 15,779 subjects; HR 1.18 [1.04-1.33], P = 0.008, I2 = 0%), but not in CKD patients (1 study; 843 subjects; mean eGFR 55 ± 29 mL/min/1.73m2; HR 0.68 [0.44-1.05], P = 0.08) (Figure 1). Six studies could be included in the meta-regression analysis. In the general population, we observed a significant positive association between Δ Na/K (P = 0.004) and the HR for the composite outcome of CVE and all-cause mortality, when adjusted for follow-up duration and the estimated dietary Na/K ratio of the reference group. For every unit increase in Δ Na/K ratio the HR increased by a factor 1.50 (Figure 2). No significant association was found in the CKD subgroup (p = 0.69).

Conclusion
Our data suggest that a higher estimated dietary Na/K ratio is associated with an increased risk for CVE and all-cause mortality in the general population and in patients with a history of CVD. These results could not be reproduced in limited data that was available for the CKD population.