High sodium intake may benefit women, not men, with high potassium diet
Sex-specific associations between potassium intake, blood pressure, and cardiovascular outcomes: the EPIC-Norfolk study
Introduction and methods
Several cohort studies have shown that a potassium replete diet is associated with lower blood pressure (BP) and lower CVD risk [1,2-5]. However, it is unknown whether these associations are sex specific and whether they depend on daily sodium consumption, given that women are more sodium sensitive [6-8].
Aim of the study
The goal was to analyze whether the association between daily potassium intake and either systolic BP (SBP) or CV events differs between men and women and whether these associations depend on daily sodium intake.
Data of 11,267 men and 13,696 women from the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk) study, a prospective population-based cohort study, were analyzed. Spot urine samples were used to estimate 24-hour excretion of sodium and potassium—which was considered to reflect daily intake—using the Kawasaki formula. Due to differences in potassium and sodium intake between men and women, sex-specific tertiles of potassium and sodium intake were defined.
Main outcomes were SBP at baseline and the composite outcome of hospitalization or death due to CVD during follow-up. Other outcomes of interest were diastolic BP, mean arterial pressure (MAP), the composite outcome of hospitalization or mortality from ischemic heart disease, and the composite of hospitalization or mortality from ischemic or hemorrhagic stroke.
Systolic blood pressure
- After adjustment for sex, age, and sodium intake, potassium intake was significantly associated with SBP (β=−0.8; P<0.001), and there was a significant interaction by sex (P<0.001).
- In men, there was no inverse association between potassium intake and SBP (β=−0.3; P=0.336) after adjustment for the same 3 confounders, nor an interaction by sodium intake (highest vs. lowest tertile) (P=0.481).
- In women, on the other hand, there was an inverse association between potassium intake and SBP (β=−1.3; P<0.001) and a highly significant interaction by sodium intake (highest vs. lowest tertile) (P<0.001).
- The inverse association between potassium intake and SBP in women was only seen for the highest tertile of sodium intake (β=−2.4; P<0.001).
- The associations of potassium intake with diastolic BP and with MAP also showed an interaction by sex.
- During a median follow-up time of 19.5 years, 6705 CV events occurred in men (59.5% of the male participants) and 6891 in women (50.3%).
- In a model adjusted for 9 confounders (including sex, BMI, and history of CVD), participants in the highest potassium intake tertile had a lower risk of CV events compared with those in the lowest tertile (hazard ratio (HR): 0.87; 95%CI: 0.82–0.93), and there was a significant interaction by sex (P=0.033).
- Using the same fully adjusted model, the association between potassium intake and risk of CV events for the highest versus the lowest potassium intake tertiles was stronger in women (HR: 0.89; 95%CI: 0.83-0.95) than in men (HR: 0.93; 95%CI: 0.87-1.00). However, there was no significant interaction by sodium intake (highest vs. lowest tertile) (P=0.611 for men and P=0.527 for women).
- There was a significant interaction by sex for the association between potassium intake (highest vs. lowest tertile) and ischemic heart disease events (P=0.016).
- The interaction between potassium intake (intermediate vs. lowest tertile) and sex was significant for ischemic stroke events (P=0.027) but not for hemorrhagic stroke events.
In this analysis of the EPIC-Norfolk cohort, the association between potassium intake and both SBP and CV events was sex specific. Moreover, the inverse relation between potassium intake and SBP was only present in women in the highest tertile of sodium intake. The association between potassium consumption and CV events was not influenced by sodium intake. The authors add that “[c]onsidering the natriuretic effects of potassium, these findings seem consistent with increased sodium sensitivity of BP in women.”