Salt Sensitivity, Pulse Pressure, and Death in Normal and Hypertensive Humans

TLDR

Salt sensitivity, age, and blood pressure are linked to cardiovascular events in hypertensive people, yet its impact on mortality in normotensive individuals had not been shown. We followed 430 normotensive and 278 hypertensive adults for up to 27 years, assessing salt sensitivity and recording outcomes in 596 participants (123 deaths). Age, baseline blood pressure, sodium sensitivity, and male sex independently predicted death; normotensive salt‑sensitive subjects over 25 had mortality comparable to hypertensive patients, while salt‑resistant normotensives survived longer, demonstrating that salt sensitivity predicts mortality independent of blood pressure.

Abstract

Although factors such as age, blood pressure, and its responsiveness to changes in sodium balance and extracellular fluid volume status (salt sensitivity) are associated with an increased risk of end-organ disease and cardiovascular events in hypertensive subjects, no such relationship with mortality has been demonstrated for salt sensitivity in normotensive subjects. We conducted long-term follow-up of 430 normal and 278 hypertensive subjects in whom assessment of salt sensitivity of blood pressure was performed as long as 27 years ago. We ascertained the status of 596 subjects (85% of the total population), 123 (21%) of whom had died. The following initial measurements were significantly (P <0.002) associated with subjects who had died compared with subjects known to be alive: age at study, pulse pressure, systolic, diastolic, and mean arterial pressures, hypertension, salt sensitivity, baseline renin levels, and body mass index (but not body weight). A stepwise logistic regression found the following independent predictors of death (odds ratio, 95% CI): age at initial study (1.08, 1.06 to 1.10), baseline blood pressure (1.03, 1.01 to 1.04), sodium sensitivity (1.73, 1.02 to 2.94), and male gender (1.91, 1.15 to 3.17). When survival curves were examined, normotensive salt-sensitive subjects aged >25 years when initially studied were found to have a cumulative mortality similar to that of hypertensive subjects, whereas salt-resistant normotensive subjects had increased survival ( P <0.001). These observations provide unique evidence of a relationship between salt sensitivity and mortality that is independent of elevated blood pressure.