Clinical Modifiers of Salt Sensitivity: A Meta-Regression and Risk Translation Study

Hypertension guidelines generally recommend uniform sodium restriction although determinants of salt sensitivity, or sodium-blood pressure responsiveness, remain incompletely quantified. We estimated the population sodium-blood pressure dose-response, identified clinical modifiers, quantified high salt sensitivity prevalence, and derived the number needed to restrict sodium intake to prevent 1 cardiovascular event across clinical strata.

PubMed, Excerpta Medica Database, and Cochrane were searched from inception to April 2025 for sodium intervention trials and observational studies. Blood pressure response was standardized per 50-mmol/d sodium difference. Random-effects meta-regression evaluated clinical modifiers. A highly salt-sensitive phenotype was defined a priori as a systolic blood pressure (SBP) decrease ≥3 mm Hg per 50-mmol/d reduction.

We included 160 studies (255 estimates; n=16 443). Each 50-mmol/d higher urinary sodium excretion was associated with 1.76-mm Hg higher SBP (95% CI, 1.54-1.98). Age and baseline SBP were the strongest modifiers (0.41 mm Hg per 5 years; 0.23 mm Hg per 5 mm Hg). Salt-sensitive phenotype prevalence rose from 12.5% (age <40 years) to 56.5% (≥60 years) and from 16.3% (SBP <120 mm Hg) to 54.1% (≥130 mm Hg). Under a policy-relevant 100-mmol/d sodium reduction, number needed to restrict ranged from ≈1334 in younger, normotensive, lean individuals (age <60 years, SBP <130 mm Hg, and body mass index <25 kg/m²) to ≈87 in older adults with hypertension and elevated body mass index (age ≥60 years, SBP ≥130 mm Hg, and body mass index ≥25 kg/m²), a 15-fold gradient.

Salt sensitivity varied across age, SBP, and body mass index strata. These findings suggest that routinely measured clinical characteristics may help identify populations with greater expected blood pressure response to sodium reduction.