Abstract: FR-PO0508
Heterogeneity in Blood Pressure Response to Urinary Sodium and Potassium by Age and Hypertension Polygenic Risk
Session Information
- CKM: Clinical - Trials, Epidemiology, and Biomarkers
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 602 Cardiovascular-Kidney-Metabolic Health: Clinical
Authors
- Fujii, Wataru, Teikyo Daigaku, Itabashi, Tokyo, Japan
- Kochi, Yuta, Tokyo Kagaku Daigaku, Meguro, Tokyo, Japan
- Shibata, Shigeru, Teikyo Daigaku, Itabashi, Tokyo, Japan
Background
Whether dietary intervention can counteract the blood pressure (BP) effects of aging and genetic predisposition—two major non-modifiable cardiovascular risk factors—remains unclear. The urinary sodium-to-potassium (Na/K) ratio is a composite marker that may obscure distinct age-dependent BP profiles of its components, and whether genetic risk specifically modifies the sodium response has not been quantified in large cohorts.
Methods
We performed a cross-sectional analysis of 303,993 UK Biobank participants aged 40–69 years not taking antihypertensive medications. Three log-transformed, Z-standardized urinary electrolyte indices were examined: Na/K ratio, Na/Cr ratio (sodium excretion), and K/Cr ratio (potassium excretion). Multivariable linear regression was adjusted for sex, 10 genetic principal components, and established cardiometabolic covariates. Effect modification by age and a validated hypertension polygenic risk score (PRS) was tested using continuous interaction terms. For PRS analyses, Na/Cr ratio served as the primary exposure based on prior sodium-focused gene–environment evidence.
Results
Mean age was 55.4±8.1 years; 43.4% were male. The Na/K × age interaction was significant (β=0.28 for SBP, β=0.09 for DBP; both P<0.001). Decomposition revealed two distinct mechanisms underlying this age effect: (1) the Na/Cr ratio showed the strongest age modification, with the SBP-raising effect of sodium excretion 2.1-fold greater in the oldest vs youngest age quintile (Na/Cr × age β=0.64 for SBP, β=0.11 for DBP; both P<0.001); (2) the K/Cr ratio showed a qualitatively distinct pattern—the initially protective effect of potassium excretion attenuated with age, crossing zero for DBP (K/Cr × age β=0.51 for SBP, β=0.05 for DBP; P<0.001 and P=0.004). The Na/Cr × PRS interaction was significant for both SBP (β=0.13, P<0.001) and DBP (β=0.04, P=0.033); the composite Na/K × PRS interaction was non-significant for SBP (P=0.153).
Conclusion
The age-dependent amplification of the Na/K ratio effect on BP reflects two mechanistically distinct processes: increasing sodium sensitivity and decreasing potassium responsiveness with aging. Sodium restriction may yield greater BP benefits in older adults whereas potassium supplementation may be more effective in younger adults. High genetic risk amplifies the BP-raising effect of sodium excretion, supporting genotype-guided sodium reduction.