Abstract

Objective: To examine the association between intakes of sodium and potassium and the ratio of sodium to potassium and incident myocardial infarction and stroke. Design, Setting and Participants: Prospective cohort study of 180,156 Veterans aged 19 to 107 years with plausible dietary intake measured by food frequency questionnaire (FFQ) who were free of cardiovascular disease (CVD) and cancer at baseline in the VA Million Veteran Program (MVP). Main outcome measures: CVD defined as non-fatal myocardial infarction (MI) or acute ischemic stroke (AIS) ascertained using high-throughput phenotyping algorithms applied to electronic health records. Results: During up to 8 years of follow-up, we documented 4090 CVD cases (2499 MI and 1712 AIS). After adjustment for confounding factors, a higher sodium intake was associated with a higher risk of CVD, whereas potassium intake was inversely associated with the risk of CVD [hazard ratio (HR) comparing extreme quintiles, 95% confidence interval (CI): 1.09 (95% CI: 0.99–1.21, p trend = 0.01) for sodium and 0.87 (95% CI: 0.79–0.96, p trend = 0.005) for potassium]. In addition, the ratio of sodium to potassium (Na/K ratio) was positively associated with the risk of CVD (HR comparing extreme quintiles = 1.26, 95% CI: 1.14–1.39, p trend < 0.0001). The associations of Na/K ratio were consistent for two subtypes of CVD; one standard deviation increment in the ratio was associated with HRs (95% CI) of 1.12 (1.06–1.19) for MI and 1.11 (1.03–1.19) for AIS. In secondary analyses, the observed associations were consistent across race and status for diabetes, hypertension, and high cholesterol at baseline. Associations appeared to be more pronounced among participants with poor dietary quality. Conclusions: A high sodium intake and a low potassium intake were associated with a higher risk of CVD in this large population of US veterans.

Highlights

  • High sodium intake has been shown to be associated with a higher risk of hypertension and cardiovascular morbidity and mortality in an approximately linear dose-response manner [1–3]

  • We examined the associations of long-term intakes of sodium and potassium, measured by a semi-quantitative food frequency questionnaire, with incident myocardial infarction and stroke in a large cohort of US veterans with diverse socioeconomic and racial/ethnic backgrounds

  • Using combined information from the VA Corporate Data Warehouse (CDW) which is the VA electronic health records (EHR), Centers for Medicaid & Medicare Services database, and National Death Index database [12,13], we focused on cases of non-fatal myocardial infarction (MI) and acute ischemic stroke (AIS) [14–16]

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Summary

Introduction

High sodium intake has been shown to be associated with a higher risk of hypertension and cardiovascular morbidity and mortality in an approximately linear dose-response manner [1–3]. A recent meta-analysis of 261,732 participants with 10,150 cases of stroke reported that dietary sodium intake and sodium-to-potassium ratio were positively associated with risk of stroke without evidence of nonlinearity [4]. Based on this dose-response relationship, modeling-based studies estimated that 1.65 million cardiovascular deaths globally [1] and more than 50,000 myocardial infarctions and 30,000 strokes per year in the US were attributable to high sodium consumption, defined as intake level above 2.0 g per day [2].

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