Supplementary Material for: Estimated dietary Na+/K+ -ratio and cardiovascular disease: a systematic review and meta-analysis.

Introduction
High sodium and low potassium intake are associated with cardiovascular disease. This meta-analysis investigates the combined effect of dietary sodium and potassium intake (Na/K-ratio), on cardiovascular outcome.

Methods
We systematically searched MEDLINE and EMBASE databases (1946 – 2024) for randomized controlled trials and cohort studies reporting the association between estimated dietary Na/K-ratio and cardiovascular events or mortality in adults. Two authors independently screened articles, extracted data, and assessed risk of bias (ROBINS-E tool). We pooled results using random-effects models and compared outcomes across the general population, patients with chronic kidney disease, and those with a history of cardiovascular disease. The study was registered in PROSPERO (ID: CRD42024450279).

Results
Twenty-four studies were included. Participants were 59±11 years old, 49±22% were men and the estimated dietary Na/K-ratio was 2.0±0.6 mmol/mmol. The risk of bias was low in 9% of the studies, high in 39% of the studies and 52% of the studies were appraised as some concerns. Higher estimated dietary Na/K-ratio was associated with a higher risk for cardiovascular events and mortality (HR 1.10 [95% CI: 1.06-1.16]), which was apparent in the general population and subjects with a history of cardiovascular disease. In patients with chronic kidney disease, only limited data was available.

Conclusion
Higher estimated dietary Na/K-ratio is associated with an increased incidence of cardiovascular events and mortality in the general population and patients with a cardiovascular disease history.