Clinical Modifiers of Salt Sensitivity: A Meta-Regression and Risk Translation Study.
Level 1 - systematic review of randomized trials
Systematic review and meta-regression of sodium intervention trials and observational studies
PubMed 42488947 · doi:10.1161/HYPERTENSIONAHA.126.27410
What was done
Authors searched PubMed, Embase, and Cochrane through April 2025 for sodium intervention trials and observational studies examining sodium-blood pressure responsiveness. Blood pressure responses were standardized per 50-mmol/d sodium difference, and random-effects meta-regression was used to identify clinical modifiers. A highly salt-sensitive phenotype was pre-defined as a systolic blood pressure (SBP) decrease >=3 mm Hg per 50-mmol/d reduction. The number needed to restrict (NNR) sodium intake by 100 mmol/d to prevent one cardiovascular event was calculated across clinical strata using risk translation modeling.
What was found
Across 160 included studies (255 estimates; n = 16,443), each 50-mmol/d higher urinary sodium excretion was associated with a 1.76 mm Hg higher SBP (95% CI, 1.54 to 1.98). Age and baseline SBP were the strongest modifiers, increasing SBP response by 0.41 mm Hg per 5 years of age and 0.23 mm Hg per 5 mm Hg baseline SBP. Salt-sensitive phenotype prevalence rose from 12.5% in participants aged <40 years to 56.5% in those >=60 years, and from 16.3% in those with baseline SBP <120 mm Hg to 54.1% in those with SBP >=130 mm Hg. Under a modeled 100-mmol/d sodium reduction, the NNR to prevent one cardiovascular event ranged from approximately 1,334 in younger, normotensive, lean individuals (age <60 years, SBP <130 mm Hg, BMI <25 kg/m²) to approximately 87 in older adults with hypertension and elevated BMI (age >=60 years, SBP >=130 mm Hg, BMI >=25 kg/m²), representing a 15-fold gradient.
Why it matters
This study shows that routine clinical markers (age, blood pressure, and BMI) identify individuals who experience substantially greater blood pressure reductions from sodium restriction, challenging uniform one-size-fits-all dietary guidance.
Limits
The meta-regression pooled both intervention trials and observational studies, and analysis was based on aggregate study-level rather than individual participant data. Cardiovascular event prevention numbers were derived from translation modeling rather than direct clinical trial endpoints.
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