The Inverse Association between Potassium Intake and Cardiovascular Disease Risk: A Systematic Review and Meta-Analysis of Prospective Cohort Studies from 2008-2023

Background: Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide. Dietary interventions have emerged as potential strategies for risk reduction. Potassium, an essential mineral, has been implicated in various physiological processes relevant to cardiovascular health. Objective: This systematic review and meta-analysis aimed to evaluate the association between potassium intake and the risk of cardiovascular disease, including coronary heart disease (CHD), stroke, and overall CVD events, based on prospective cohort data. Methods: We conducted a systematic literature search for prospective cohort studies that reported relative risks (RRs) or hazard ratios (HRs) for CVD outcomes associated with potassium intake. Random-effects models were used to calculate pooled risk estimates and 95% confidence intervals (CIs). Methods In conducting this systematic review and meta-analysis, we sought to rigorously evaluate the association between dietary potassium intake and cardiovascular disease (CVD) risk. Our search spanned three major databases: PubMed, Embase, and the Cochrane Library, covering the period from January 2008 to December 2023. We aimed to identify prospective cohort studies that provided insights into how potassium intake affects CVD outcomes such as coronary heart disease, stroke, and overall CVD events. To ensure the robustness of our analysis, we established strict inclusion criteria. Studies were considered eligible if they assessed dietary potassium intake using validated methods and reported relative risks (RRs) or hazard ratios (HRs) for CVD outcomes. We excluded studies that did not meet these criteria, such as those with non-cohort designs, studies involving specific subpopulations with altered potassium metabolism, and those that did not report relevant risk estimates. The process of study selection, data extraction, and quality assessment was conducted independently by two reviewers. This dual-reviewer approach was designed to minimize bias and enhance the reliability of our findings. Any discrepancies between the reviewers were resolved through discussion or, if necessary, by consulting a third reviewer to reach a consensus. For the statistical analysis, we employed random-effects models to calculate pooled risk estimates, which allowed us to account for variability across the included studies. Additionally, we performed dose-response analyses to identify the optimal range of potassium intake associated with the greatest reduction in CVD risk. This nuanced analysis provided deeper insights into how varying levels of potassium intake could impact cardiovascular health. For the assessment of certainty were used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the certainty of evidence for each outcome. The GRADE approach evaluates evidence based on five domains: risk of bias, inconsistency, indirectness, imprecision, and publication bias. Each domain can lead to downgrading the certainty of evidence by one or two levels. The overall certainty of evidence was classified as high, moderate, low, or very low. Results A total of 18 prospective cohort studies, involving over 1.1 million participants and 112,000 CVD events, were included. Higher potassium intake was associated with a significantly lower risk of CVD events (pooled RR = 0.87, 95% CI: 0.81-0.93 for the highest vs. lowest intake category). Dose-response analysis revealed the greatest risk reduction at potassium intakes of approximately 3.5-4.0 g/day, with a 20% lower risk of CVD events (RR = 0.80, 95% CI: 0.73-0.88) compared to an intake of 1.5 g/day. Conclusion: This meta-analysis provides robust evidence that higher potassium intake, particularly in the range of 3.5-4.0 g/day, is associated with a reduced risk of cardiovascular disease, including coronary heart disease and stroke. The findings support the potential role of potassium-rich diets in CVD prevention.