Advances in Genomics Research of Blood Pressure Responses to Dietary Sodium and Potassium Intakes

Abstract

More than half of US adults have hypertension by 40 years of age and a subsequent increase in atherosclerotic cardiovascular disease risk. Dietary sodium and potassium are intricately linked to the pathophysiology of hypertension. However, blood pressure responses to dietary sodium and potassium, phenomena known as salt and potassium sensitivity of blood pressure, respectively, are heterogenous and normally distributed in the general population. Like blood pressure, salt and potassium sensitivity are complex phenotypes, and previous research has shown that up to 75% of individuals experience a blood pressure change in response to such dietary minerals. Previous research has also implicated both high salt sensitivity and low salt sensitivity (or salt resistance) of blood pressure to an increased risk of hypertension and potentially atherosclerotic cardiovascular disease risk. Given the clinical challenges required to accurately measure the sodium and potassium response phenotypes, genomic characterization of these traits has become of interest for hypertension prevention initiatives on both the individual and population levels. Here, we review advances in human genomics research of blood pressure responses to dietary sodium and potassium by focusing on 3 main areas, including the phenotypic characterization of salt sensitivity and resistance, clinical challenges in diagnosing such phenotypes, and the genomic mechanisms that may help to explain salt and potassium sensitivity and resistance. Through this process, we hope to further underline the value of leveraging genomics and broader multiomics for characterizing the blood pressure response to sodium and potassium to improve precision in lifestyle approaches for primordial and primary atherosclerotic cardiovascular disease prevention.

Keywords: blood pressure; cardiovascular disease; diet; hypertension; sodium.

Figure 1.

Average change in blood pressure across sodium and potassium interventions. Figure adapted from He et al. “Gender Difference in Blood Pressure Responses to Dietary Sodium Intervention in the GenSalt Study”. Dashed line represents mean blood pressure response.

Figure 2.

A, Association of a salt sensitivity polygenic risk score with salt sensitivity. Figure adapted from Liu et al. “Genetic Predisposition and Salt Sensitivity in a Chinese Han Population: The EpiSS Study”. B, Combined effect of risk alleles on hypertension incidence in the GenSalt follow-up study. Figure adapted from He et al. “Genome-Wide Association Study Identifies 8 Novel Loci Associated with Blood Pressure Responses to Interventions in Chinese”. C, Blood pressure response to a low-sodium intervention per PRS quartile. D, Blood pressure response to a potassium intervention while maintaining a high-sodium diet per PRS quartile. Figures C and D adapted from Nierenberg et al. “Blood Pressure Genetic Risk Score Predicts Blood Pressure Responses to Dietary Sodium and Potassium.”