Olusoga Sofola, University of Lagos, Nigeria
Salt they say adds spice to life, as well as to culinary tastes – hence the propensity to indulge in excessive salt consumption! However, high salt intake has been shown to be associated with high blood pressure (BP), as reported in the large world-wide INTERSALT study (Stamler, 1997). Hitherto, blood pressure values had been assumed to be similar across races, until studies began to emerge reporting that BP values were higher in black African-Americans compared to their Caucasian counterparts. Since then, the WHO has recognised and pegged salt intake to less than 5g (about one teaspoon) per day, while also acknowledging that high salt intake may result in higher BP increases in blacks than in Caucasians.
This seemingly innocuous observation ultimately led to the development of a controversial theory, which attributed the hereditary, salt-sensitive, higher blood pressure values observed in African Americans to the exertions of slavery on their ancestors. Today, shifting perspectives and new evidence from studies on the native African populations have begun to cast a cloud of doubt over the validity of this school of thought.
Salt dependency, blood pressure and global perspectives
In 2013 the incidences of hypertension in the United States were estimated to be 44% and 32% in blacks and whites, respectively (Go et al., 2013). The explanations for this disparity in the prevalence of hypertension for blacks had been hinged on the possible mutation or modification of a “salt gene” in blacks following trans-shipment across the Atlantic during the slave trade era in the 16th to 19th centuries (Wilson and Grim, 1991). It was postulated that their sojourn in the hot environment of the ships’ holds and subsequent forced labour in the searing heat of the agricultural fields of the southern states would have resulted in an increase in salt loss, primarily from diarrhoea and sweating and compounded by a low dietary intake of salt. These situations, it was argued, provided selection pressures for adaptations that enhanced sodium retention by the kidneys which may have been beneficial in this environment but would also result in elevated BP. This sodium conservation mechanism was then argued to pass down through generations following transmission of these supposedly “beneficial” genetic adaptations. However, in the more recent times, it has been reported that native blacks in their environment in Africa also have a high prevalence of hypertension (Amira et al., 2014; Gomez-Olive et al., 2017), and it has become necessary to revisit the “slave journey-hereditary sodium retention” theory to challenge it and if necessary, expunge it entirely (Lujan and DiCarlo, 2018).
Salt-sensitive status and β-ENaC polymorphism
Various methods have been developed to investigate and quantify an individual’s tendency toward an increase in sodium retention. Traditionally the “Salt Sensitivity” testing technique has been most widely utilised. This test measures the rise in BP after a salt load with an elevation in BP above 5 mmHg considered salt-sensitive and anything less classified as salt-resistant. A study by Morris et al. (1999) indicated salt sensitivity rates of 73% and 36% in black Americans and Caucasians, respectively. Interestingly, native Nigerians were found to have salt sensitivity rates of approximately 56% in hypertensives versus 34% in normotensives, suggesting that hypertensive subjects tended to be more sensitive to salt ingestion (Elias et al., 2014). This is particularly concerning when taken together with the finding that hypertensive Nigerian subjects have significantly higher sodium intakes than normotensive subjects, as measured by salt taste threshold testing and 24 hour urinary sodium excretion revealed (Azinge et al., 2011).
Among the plausible explanations for the similarly high prevalence of hypertension in African Americans and native Africans are the genetic factors which affect the renal handling of sodium. Hence, a focus of research on the polymorphisms in the genes encoding the subunits of the heterotrimeric epithelial sodium channel (ENaC) that controls the final adjustments in renal sodium excretion. This is especially true of the T549M polymorphism in the beta subunit of ENaC (β-ENaC) which occurs in about 8% of blacks but is rarely present in Caucasians (Swift and MacGregor, 2004). Baker et al. (1998) also reported similar prevalence of the T594M polymorphism in hypertensive blacks living in the London area of the UK, but of particular note was the observation that these patients were more responsive to anti-hypertensive treatment with amiloride, a diuretic drug that promotes urinary salt and water loss through ENaC blockade. In our own work with native Nigerian subjects (Elias et al., 2019), we found a 5% incidence of the β-ENaC T594M variant and discovered the presences of an additional five previously undescribed β-ENaC polymorphisms in the population. This brought the total prevalence of sequenced β-ENaC polymorphisms in our cohort to 13%, with hypertensive subjects being more than twice as likely to be a carrier of a β-ENaC variant than normotensive subjects.
Based on these observations, it is almost obvious that gene polymorphism in blacks, in addition to higher salt sensitivity may contribute to the greater incidence of high blood pressure in black Africans, as it is the case with African-Americans.
Low plasma renin, aldosterone and suggested treatment modality in black hypertensives
We also know that hypertension in blacks is also often characterised by low levels of plasma renin activity, which is paradoxical considering high levels of renin are often associated with elevated BPs. Based on these observations, decision-making protocols for choosing appropriate anti-hypertensive strategies may need to be examined further. In particular it may be prudent to re-evaluate and redefine the first-line use of renin-angiotensin-aldosterone system (RAAS) pathway inhibitors such as angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in treatment, in addition to the use of amlodipine, the calcium channel antagonist. A recent review looking in more detail at the therapeutic strategies involving RAAS has suggested that decisions be based on the phenotyping results of renin and/or aldosterone status, whereby amiloride can be used for low renin–low aldosterone subjects while aldosterone antagonists such as spironolactone be used for cases of primary aldosteronism (Spence and Rayner, 2018). In particular, the observation of a high percentage of gain-of-function β-ENaC gene mutations in Africans lends credence to the use of amiloride as an effective treatment as it directly counteracts the effects of the ENaC mutation (Baker et al., 1998). It is our suggestion that amiloride or in combination with another thiazide diuretic will be useful in treating hypertensive blacks, especially those carrying the highly prevalent T594M β-ENaC mutation (Elias et al., 2019).
Salt ingestion plays a crucial role in the elevation of blood pressure, especially in blacks. While this is entirely unrelated to the detrimental impact of slavery on humans as previously asserted, this may be caused by genetic polymorphisms that affect the renal handling of sodium ions, that are observed with similar prevalence in both native Africans and African Americans.
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