The effect of dietary sodium modification on blood pressure in studies of subjects with systolic blood pressure less than 140mmHg: a systematic review protocol

Review question/objective The objective of this review is to establish the effect of modifying dietary sodium intake in normotensive subjects. More specifically, the objectives are to identify the effect of reducing or increasing sodium intake on blood pressure in normotensive subjects with systolic blood pressure (SBP) <140mmHg, and the effect of sodium reduction or supplementation on arterial function in subjects with baseline SBP <140mmHg. Background The pressure-natriuresis relationship that was first described by Guyton1 proposes a link between dietary sodium intake and renal sodium handling. Specifically, the hypothesis states that in a normal individual, consumption of a dietary sodium load will elicit a transient rise in blood pressure that stimulates the kidney to excrete sodium. The kidney will excrete excess sodium leading to restoration of normal blood pressure. This hypothesis explains how blood pressure is maintained over the longer term even though most individuals report day-to-day variation in sodium intake.1,2 Following this hypothesis, intervention studies in normotensive subjects may be expected to observe a small amount of variation in blood pressure with changes to dietary sodium intake, but this variation should be small enough to be considered clinically irrelevant. Intervention studies examining the effect of dietary sodium have reported a range of different responses from significant changes,3,4 to mild, to moderate effects on blood pressure to no effect at all.5,6 Normotensive studies that report blood pressure changes over the long-term have previously documented changes in systolic blood pressure (SBP) ranging from -1mmHg7 to increases of 8.2mmHg.4 Previous systematic reviews of blood pressure response to dietary sodium restriction have used Cochrane Collaboration methods.8-10 One such systematic review9 has been cited over 370 times, and has been used in the development of dietary guidelines.11 Two of these reviews attempted to conduct meta-analysis by dividing subjects into normotensive and hypertensive sub-groups.8,9 Both reviews failed to specify methods for determining whether studies recruited hypertensive or normotensive subjects and included some studies in the normotensive analyses with subjects who had baseline blood pressures above 140mmHg. Due to this, a wide range of baseline blood pressure readings and responses can be observed in normotensive analyses, which is inconsistent with Guyton's pressure natriuresis hypothesis. Therefore, the validity of the findings for blood pressure changes in healthy normotensive individuals in these analyses is limited in that the majority of the included studies recruited subjects with SBP above 140mmHg.4,12-16 Subjects with hypertension (SBP >140mmHg) have been shown to respond differently to dietary sodium and hence inclusion of these studies in previous normotensive analyses may have skewed the results.9 These analyses in “normotensive” populations could be improved if studies that recruited subjects with SBP >140mmHg were excluded. As well as examining blood pressure, a number of intervention studies have investigated the effects of dietary sodium intake on arterial function and found that these effects may be, at least partly, independent of blood pressure.17,18 As these effects may be key in extending our understanding of sodium intake and disease risk, they form part of the bigger picture for dietary sodium intake and chronic disease risk. It is therefore important to consider data on arterial function such as pulse wave analysis, pulse wave velocity, and flow mediated dilation in future meta-analyses of sodium restriction. There is enough evidence from normotensive studies conducted in subjects with SBP≤140mmHg to conduct a separate investigation of the effects on blood pressure and arterial function. This systematic review will consider the evidence for long-term dietary sodium restriction in subjects with SBP <140mmHg on arterial function.