Urinary Sodium Excretion Enhances the Effect of Alcohol on Blood Pressure

Data Availability Statement: Not applicable. Supplementary Materials: The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/healthcare10071296/s1, Table S1: UK Biobank data fields for blood pressure, physical and lifestyle variables used in the analysis, Table S2: Codes used to generate cardiovascular disease phenotypes in the analysis, Table S3: Genetic variants used to construct the genetic risk score for alcohol consumption, Table S4: Sex-specific effect of alcohol genetic risk on blood pressure and cardiovascular diseases, Table S5: Overview of association of urinary sodium with alcohol consumption and various outcomes. Copyright: © 2022 by the authors. Alcohol consumption is linked to urinary sodium excretion and both of these traits are linked to hypertension and cardiovascular diseases (CVDs). The interplay between alcohol consumption and sodium on hypertension, and cardiovascular diseases (CVDs) is not well-described. Here, we used genetically predicted alcohol consumption and explored the relationships between alcohol consumption, urinary sodium, hypertension, and CVDs. Methods: We performed a comparative analysis among 295,189 participants from the prospective cohort of the UK Biobank (baseline data collected between 2006 and 2010). We created a genetic risk score (GRS) using 105 published genetic variants in Europeans that were associated with alcohol consumption. We explored the relationships between GRS, alcohol consumption, urinary sodium, blood pressure traits, and incident CVD. We used linear and logistic regression and Cox proportional hazards (PH) models and Mendelian randomization in our analysis. Results: The median follow-up time for composite CVD and stroke were 6.1 years and 7.1 years respectively. Our analyses showed that high alcohol consumption is linked to low urinary sodium excretion. Our results showed that high alcohol GRS was associated with high blood pressure and higher risk of stroke and supported an interaction effect between alcohol GRS and urinary sodium on stage 2 hypertension (Pinteraction = 0.03) and CVD (Pinteraction = 0.03), i.e., in the presence of high urinary sodium excretion, the effect of alcohol GRS on blood pressure may be enhanced. Conclusions: Our results show that urinary sodium excretion may offset the risk posed by genetic risk of alcohol consumption. R.P. holds a fellowship supported by Rutherford Fund from Medical Research Council (MR/R0265051/1 and MR/R0265051/2). X.J. was supported by Rutherford Fund from Medical Research Council MR/R0265051/2. UKB genotyping was supported by the British Heart Foundation (grant SP/13/2/30111) for Large-scale comprehensive genotyping of UKB for cardiometabolic traits and diseases: UK CardioMetabolic Consortium.