Review ArticleSalt and essential hypertension: pathophysiology and implications for treatment
Introduction
Hypertension affects approximately 40% of the world population aged >25 years1 and has been estimated to cause 10.4 million deaths worldwide per year.2 Essential hypertension is defined as an elevated blood pressure where “secondary” causes of hypertension, such as renovascular disease or Cushing's disease, have been ruled out. This is not to say that essential hypertension does not have a root cause. In the following paragraphs, the role of elevated salt intake as a major causative factor behind this disease will be explored. Furthermore, how certain key factors (age, African descent, chronic kidney disease [CKD], and low potassium intake) contribute to its pathogenesis by interacting with dietary salt will be considered. Finally, we explore the implications for the pharmacologic treatment of this disease.
Section snippets
Salt Causes Hypertension
Humans currently consume much more salt than for which the species may be evolutionarily suited. It has been theorized that Paleolithic man consumed approximately 0.69 g of sodium per day.3 In comparison, the average present day human consumes approximately 4.9 g of sodium per day.4 This change in salt intake likely occurred <10,000 years ago with the advent of salt extraction technology,5 and it is unlikely that the human race has had enough time, on an evolutionary time scale, to have adapted
Hypertension Enhances Renal Salt Secretion
A kidney programmed for a low-salt diet but experiencing a high-salt diet may have difficulty excreting the excess salt. Indeed, a recent review of human salt loading trials showed a statistically significant increase in serum sodium concentration across both normotensive and hypertensive groups in the majority of the studies reviewed.13 The study of the longest duration was performed in 17 normotensive and 23 hypertensive subjects who were sequentially randomized to one of four levels of
Mechanisms of Blood Pressure Rise
How does the body sense excess salt and raise blood pressure? Early theories centered on increased plasma volume: sodium retention was thought to lead to increased serum sodium leading to increased thirst and plasma volume. This would then result in increased cardiac index and increased blood pressure. However, although cardiac index may initially rise in the setting of salt loading, this will usually return to normal while total peripheral resistance (TPR) will rise and remain elevated, at
Risk Factors for Salt-induced Hypertension
In the face of increased sodium intake, some individuals will maintain constant blood pressure, whereas others will demonstrate salt sensitivity and an increase in mean arterial pressure. This phenomenon may explain the wide variation in dietary salt to blood pressure response in observational and salt loading trials. In fact, one interventional salt loading study in healthy normotensive male volunteers found individual blood pressure increases ranging from 1.5% to 34%.26
Why this variation in
Implications for Treatment
If essential hypertension is a direct result of salt retention, as has been discussed in this article, any intervention that either decreases salt intake or increases salt excretion will lower blood pressure. An obvious first step in the management of the hypertensive patient should be lifestyle modification. If this fails, pharmacologic treatment can be considered.
Lifestyle modification includes dietary changes to restrict salt and increase potassium intake, such as the low-sodium DASH diet.42
Conclusions
It is important to be cognizant of evolutionary history. Essential hypertension may be the result of a human maladaptation to an increase in dietary salt intake and a decrease in dietary potassium intake that are recent on an evolutionary time scale. When renal sodium mechanisms are overwhelmed, the body responds by raising blood pressure to enhance urinary sodium excretion. However, this becomes maladaptive in the long run by increasing the risk of cardiovascular disease. Any physiological
Acknowledgments
The author would like to thank Dr Norman Campbell and Dr Sophia Chou for their help with reviewing the article.
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Conflicts of interest: We declare no conflicts of interest or sources of funding.