Controlled analysis of blood pressure sensitivity to sodium intake

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Abstract
The contribution of salt intake to the pathogenesis of hypertension holds longstanding interest. Recent studies employed the sensitivity of blood pressure (BP) to salt intake as an intermediate phenotype. The validity of this approach relative to the homogeneity of sodium-sensitive hypertension was investigated while simultaneously controlling multiple putative factors. Blood pressure responses to shifts in salt intake were measured in 274 individuals with essential hypertension in steady-state sodium balance on high (200 mEq) and low (10 mEq) sodium intakes. Univariate and multivariate analyses predicted systolic and diastolic sodium sensitivity based on interactions among demographic factors (age, gender, race, body mass index) and hypertensive type [low-renin (LR), modulator (M), non-modulator (NM)]. The influence of hypertension type on systolic salt sensitivity (SSS) depended on gender (P = 0.03). In females, highest SSS was in LR (21, 14, 13 mmHg for LR, M, NM, P = 0.02), while in males highest SSS was in NM (11, 10, 16 mmHg for LR, M, NM, P = 0.07). Age predicted SSS without interacting with other factors, producing a 2.4 mmHg increase per decade (P = 0.02). Hypertension type affected diastolic salt sensitivity (DSS) (P = 0.002) without interacting with other factors. M had less DSS (6 mmHg) than LR (9 mmHg) and NM (11 mmHg) (P< 0.01). For subjects in sodium balance, the distributions of SSS and DSS were unimodal and the mechanisms mediating SSS and DSS were different. Controlling for multiple demographic factors, at least two hypertensive types have largest BP responses to sodium intake, reducing the usefulness of blood pressure sensitivity to salt intake as an intermediate phenotype.