Challenges and Approach to Identifying Individuals with Salt Sensitivity of Blood Pressure

Abstract

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.

Striatin Gene Variants Are Associated With Salt Sensitivity of Blood Pressure by Mechanisms That Differ in Women and Men

“…We documented that as much as 60% of hypertensives and 47% of normotensives have SSBP depending on the population studied. 12 Women have more SSBP than men, those of African ancestry more than White participants, and older versus younger individuals. 8,9,17 While not all studies reported similar findings, usually, the effect of biological sex was consistent.…”

“…We assessed the role of STRN gene variants in women and men from the HyperPATH cohort. Details have been previously reported 5,8,[10][11][12][13] and are provided in Supplemental Material.…”

“…Maladaptive responses to a sodium load by one or more volume homeostatic pathways have been proposed to cause SSBP. 12 We investigated 2 of these: altered renal plasma flow (RPF) and dysfunction in the reninangiotensin-aldosterone system, particularly aldosterone. Evaluation of aldosterone levels indicated that G2 women had higher baseline aldosterone on liberal Na + than G0 with a β coefficient of 2.07 (P=0.014; Table 3).…”

Association between salt sensitivity of blood pressure and the risk of hypertension in a Chinese Tibetan population

“…So far, there is no agreement on the measurement of SSBP in the clinic. In general, two common methods have been used in clinical studies 35,40 . The first is to measure the response of BP to low and high dietary salt intake over 1−2 weeks, which is believed to be more clinically relevant and considered the gold standard.…”

“…In this study, the evaluation of salt sensitivity was performed by the modified Sullivan's acute oral saline load and diuresis shrinkage test (MSAOSL-DST), which has been previously used in a Chinese population for epidemiological investigations. [26][27][28] The details of MSAOSL-DST are as follows (Figure 1): each patient took an oral administration of 1000 mL of 0.9% saline solution within 30 min followed by 40…”