Supplementary Material for: Challenges and Approach to Identifying Individuals with Salt Sensitivity of Blood Pressure

Background: Salt sensitivity of blood pressure (SSBP) is a trait observed in both humans and animals, characterized by an increase in blood pressure (BP) following salt loading or a drop in BP following salt depletion. Summary: This “intermediate” phenotype has been reported in a sizable portion of individuals regardless of their hypertensive status; hypertensives (27-51%), normotensives (18-47%). Further, in epidemiological studies, this phenotype is associated with increased adverse cardiovascular outcomes, risk factors, and reduced survival rates. Here in, we review the challenges in the assessment of SSBP, heterogeneity in the assessment method and protocols, and how these differences could affect the results. Further, we review how to identify individuals with SSBP in the clinic by using clinical and genetic data. No clinical approach has yet provided sufficient sensitivity and specificity to identify those with SSBP. Thus, SSBP is not routinely identified in the clinic. Current genetic data suggest that genotyping may support such an office approach. To date, studies in18 genes have provided sufficient evidence and reproducible data to identify potential mechanisms involved in subsets of subjects with hypertension and SSBP. Key message: Proof-of-concept clinical trials using genetic biomarkers to determine and treat individuals with SSBP are ongoing. Their results will provide critical evidence to support genetic-focused, mechanistically driven algorithms to identify and treat, specifically, individuals with SSBP—personalized medicine.