Abstract Body: Objective: Salt and potassium intake has been demonstrated to affect blood pressure. It is also shown that urinary sodium-to-potassium (Na/K) ratio strongly associates with high BP. Nonetheless, whether genetic and environmental factors modify this association remains unclear. In this study, we examined whether genetic and environmental factors associated with hypertension modify the linkage between urinary Na/K ratio and BP.

Methods: From the participants of the UK Biobank (UKB) study consisting of a general population aged 40-69 years living in the United Kingdom, we selected individuals who were not taking antihypertensives, who had complete data on systolic and diastolic BP (sBP and dBP), urinary Na/K ratio, polygenic risk score (PRS) for incident hypertension available in the UKB, lifestyle habits and laboratory data potentially affecting BP. The association between urinary Na/K and BP was assessed in a regression model, adjusted for potential covariates. Multiple regression models in which environmental factors and hypertension PRS were applied as interaction terms were also examined.

Results: A total of 303,993 individuals with a mean age of 55.4 ± 8.1 years, of whom 43.4% were male, were analyzed in this study. In univariate analysis, both urinary Na/K ratio and hypertension PRS were significantly and positively correlated with sBP and dBP (P < 0.001). In multiple regression models incorporating various clinical indices, urinary Na/K ratio was significantly and positively correlated with sBP and dBP, independently of other clinical factors (P < 0.001). This association remained significant after adjustment for hypertension PRS. In the interaction models, we found a significant positive interaction with age and negative interaction with BMI for both sBP and dBP (P < 0.001 for both). In addition, hypertension PRS showed a significant positive interaction with urinary Na/K ratio for dBP (P = 0.009), while the interaction was not significant for sBP (P = 0.152).

Discussion: Association of urinary Na/K ratio with BP are influenced by several clinical factors, such as BMI and age. In addition, the association is also affected by the genetic risk of developing hypertension as expressed by PRS. These insights may facilitate the personalized adaptation of lifestyle recommendations for individuals with hypertension.