The blood pressure-salt sensitivity paradigm: pathophysiologically sound yet of no practical value

Nephrol Dial Transplant. 2016 Sep;31(9):1386-91. doi: 10.1093/ndt/gfw295. Epub 2016 Aug 11.

Abstract

Sodium plays an important pathophysiological role in blood pressure (BP) values and in the development of hypertension, and epidemiological studies such as the Intersalt Study have shown that the increase in BP occurring with age is determined by salt intake. Recently, a meta-analysis of 13 prospective studies has also shown the close relationship between excess sodium intake and higher risk of stroke and total cardiovascular events. However, the BP response to changing salt intake displayed a marked variability, as first suggested by Kawasaki et al. (The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Am J Med 1978; 64: 193-198) and later by Weinberger et al. (Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension 1986; 8: II127-II134), who recognized the heterogeneity of the BP response to salt and developed the concept of salt sensitivity. We have a large body of evidence in favour of a major role of metabolic and neuro-hormonal factors in determining BP salt sensitivity in association with the effect of genetic variation. There is evidence that salt sensitivity influences the development of organ damage, even independently-at least in part-of BP levels and the occurrence of hypertension. In addition, several observational studies indicate that salt sensitivity is clearly associated with a higher rate of cardiovascular events and mortality, independently of BP levels and hypertension. A cluster of factors with well-known atherogenic potential such as hyperinsulinaemia, dyslipidaemia and microalbuminuria-all known to be prevalent in salt-sensitive hypertension-might at least partially explain the increased cardiovascular risk observed in salt sensitive individuals. The gold standard for the evaluation of BP salt sensitivity is the BP response to a moderate reduction of salt intake for several weeks; nevertheless, these protocols often suffer of poor patient compliance to dietary instructions. To overcome this problem, short-term tests have been proposed that evaluate either large differences in salt intake for a few days or the response to intravenous administration of saline solution and short-acting diuretics. Recently, the use of ambulatory BP measurement has been proposed for the clinical assessment of BP salt sensitivity. Noteworthy, BP salt sensitivity, in whomever or however assessed, behaves as a continuous variable but salt sensitivity is used as a categorical parameter, with salt-sensitive individuals being defined as those with a difference in BP between low- and high-sodium intake >10%, and salt-resistant subjects those in whom BP does not increase or shows an increase <5% under sodium loading. The general conclusion that can and should be drawn from the above considerations is that the paradigm of salt sensitivity, despite its important pathophysiological meaning, is not helpful, so far, to the practising physician in clinical practice nor is it relevant or useful to the design and implementation of a population-based strategy of salt intake reduction; however, further studies are warranted for an accurate assessment of the salt-sensitivity phenotype in clinical practice. In the absence of a population strategy for salt intake reduction, the aim should be the generation of a 'low sodium environment' allowing for a dietary salt intake tailored on true human requirements and not on deleterious lifestyle habits.

Keywords: blood pressure; hypertension; salt; salt sensitivity; sodium.

MeSH terms

  • Blood Pressure / drug effects*
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / physiopathology*
  • Humans
  • Hypertension / etiology*
  • Hypertension / physiopathology*
  • Osmoregulation
  • Risk Factors
  • Sodium Chloride, Dietary / adverse effects*

Substances

  • Sodium Chloride, Dietary