Methodology of sodium sensitivity assessment. The example of age and sex.

Abstract

This article addresses the methodology of sodium sensitivity assessment There have been reports to suggest that a high sodium intake is a cause of elevated blood pressure and trials to indicate that a reduction in sodium intake may reduce blood pressure that is already high; the implications of these findings are discussed. Many studies on sodium sensitivity suffer from what could be called the "normal probability fallacy"; without appropriate control conditions, an intervention such as sodium restriction may incorrectly be assigned to a more pronounced response in a subgroup of the study population. As an example, findings are reviewed of age and sex as determinants of a response of blood pressure to variations in sodium intake. The limited data available suggest that subjects that are older and have higher blood pressure levels seem to benefit more from a reduction in sodium intake. In addition, elderly subjects at a high dietary sodium intake may have a higher risk of developing hypertension. Findings in both honexperimental and experimental studies tend to support this view. Findings on sex differences are less consistent A systematic approach to the assessment of factors and mechanisms responsible for sodium sensitivity in some subjects is needed to determine who might benefit most Until more data are available, there is little basis to discriminate sodium-sensitive from sodium-resistant hypertensive subjects. {Hypertension 1991;17[suppl I]:I-109-I-114) T he hypothesis that dietary sodium intake is related to blood pressure is not new. 1-2 Yet, even though many studies over the past decades have addressed this issue, controversy remains about the importance of salt in the etiology and treatment of primary hypertension.3 -4 One reason is that although some studies were able to demonstrate, for example, an effect of sodium restriction on blood pressure, the response is highly variable, with some subjects showing a fall in blood pressure and others apparently having a rise. This heterogeneity in blood pressure response to variations in sodium intake was noted as early as the first trial on salt intake and blood pressure 5 and has led some to suggest that among normotensive and hypertensive subjects there are specific subgroups that are sodium sensitive and others that are not. In accordance with this view, several characteristics have been proposed to discriminate sodium-sensitive from non-sodium-sensitive subjects. Moreover, a number of pathophysiological disturbances in sodium and volume homeostasis and other changes in circulatory

Blood pressure response to changes in sodium and potassium intake: a metaregression analysis of randomised trials

“…18 Our findings, however, which were adjusted for age, blood pressure level, and other potential confounders, provide no evidence for strong effect modification by gender. This study provides some support for the hypothesis of an increased blood pressure responsiveness to sodium at older age, 18 after adjustment for gender and blood pressure level. Potential effect modification of the potassium-blood pressure relation by age and body weight, which may not have reached statistical significance in our study because of limited power, warrants further investigation.…”

“…[13][14][15][16] Blood pressure response to sodium (and possibly also potassium) could be related to initial blood pressure level, age, gender, race, and genetic factors. 2,[17][18][19] Effect modifiers (eg, hypertension) could underly the selection of study populations in blood pressure trials. Therefore, blood pressure estimates from meta-analyses of randomised trials may not be applicable to the population as a whole.…”

The functional variant of the CLC-Kb channel T481S is not associated with blood pressure or hypertension in Swedes

“…Not only are age, sex and BMI well known to influence blood pressure, but also sodium handling in the kidney could be affected by sex [22], age [23], and BMI [24]. As the CLC-Kb is involved in the process of renal sodium transport, an interaction between the T481S genotype and either hormones such as oestrogens [22] or adipokines [24] or aging [23] could be of interest.…”

Plasma Ouabain-Like Factor During Acute and Chronic Changes in Sodium Balance in Essential Hypertension

“…Because community intervention projects and multicenter prospective trials of salt restriction have agreed on the conclusion that sustained compliance with high-salt diets is not easily achieved, 14,15 we studied hypertensive patients during both controlled sodium intake and moderate salt restriction for 2 weeks each period. On recruitment, BP was taken 3 times with a standard mercury sphygmomanometer at 2-minute intervals after patients were seated for Ն10 minutes.…”