Sex-specific associations between potassium intake, blood pressure, and cardiovascular outcomes: the EPIC-Norfolk study

Abstract

Aims: A potassium replete diet is associated with lower blood pressure (BP) and lower risk of cardiovascular disease (CVD). Whether these associations differ between men and women and whether they depend on daily sodium intake is unknown.

Methods and results: An analysis was performed in 11 267 men and 13 696 women from the EPIC-Norfolk cohort. Twenty-four hour excretion of sodium and potassium, reflecting intake, was estimated from sodium and potassium concentration in spot urine samples using the Kawasaki formula. Linear and Cox regression were used to explore the association between potassium intake, systolic BP (SBP), and CVD events (defined as hospitalization or death due to CVD). After adjustment for confounders, interaction by sex was found for the association between potassium intake and SBP (P < 0.001). In women, but not in men, the inverse slope between potassium intake and SBP was steeper in those within the highest tertile of sodium intake compared with those within the lowest tertile of sodium intake (P < 0.001 for interaction by sodium intake). Both in men and women, higher potassium intake was associated with a lower risk of CVD events, but the hazard ratio (HR) associated with higher potassium intake was lower in women than in men [highest vs. lowest potassium intake tertile: men: HR 0.93, 95% confidence interval (CI) 0.87-1.00; women: HR 0.89, 95% CI 0.83-0.95, P = 0.033 for interaction by sex].

Conclusion: The association between potassium intake, SBP, and CVD events is sex specific. The data suggest that women with a high sodium intake in particular benefit most from a higher potassium intake with regard to SBP.

Keywords: Blood pressure; Cardiovascular disease; Potassium intake; Sex differences; Sodium intake.

Structured Graphical Abstract

An analysis was performed in 11 267 men and 13 696 women from the EPIC-Norfolk cohort. Twenty-four hour excretion of sodium and potassium, reflecting intake, was estimated from sodium and potassium concentration in spot urine samples using the Kawasaki formula. Linear and Cox regression analyses showed that the association between potassium intake and both SBP and CVD risk is sex specific. Moreover, among women, the association between potassium intake and SBP was modified by sodium intake. EPIC-Norfolk, Norfolk cohort of the European Prospective Investigation into Cancer; CVD, cardiovascular disease; SBP, systolic blood pressure.

Figure 1

Interaction by sex for the association between potassium intake (g/day) and systolic blood pressure. Linear regression analysis for the association between potassium intake (g/day) and SBP with interaction by sex, adjusted for age, and sodium intake (tertiles). Interaction by sex was significant (P < 0.001). In men no association was observed between potassium intake (g/day) and SBP (P = 0.336), whereas in women this association was highly significant (P < 0.001). SBP, systolic blood pressure. The grey area represents the 95% confidence interval.

Figure 2

Association between potassium intake (g/day) and systolic blood pressure in men and women within every tertile of sodium intake. Sodium-stratified linear regression analyses for the association between potassium intake (g/day) and SBP in men and women, adjusted for age. Interaction by sodium intake (highest vs. lowest tertile) was significant in women (P < 0.001), but not in men (P = 0.481). In women within the highest tertile of sodium intake a strong inverse association between potassium intake and SBP was present (β = −2.4, P < 0.001). SBP, systolic blood pressure; CI, confidence interval.