Cardiovascular Journal of Africa: Vol 31 No 3 (May/June 2020)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 3, May/June 2020

134

AFRICA

enzyme (ACE) inhibitor therapy and may therefore be a valuable

alternative to currently employed screening assays.

In the

current study, due to the small sample size and participants

utilising different hypertensive medication, we could not explore

the AA2 ratio in full for the diagnosis of PA.

The PA-like phenotype in hypertensive black men was

further characterised by a decrease in serum K

levels and was

associated with higher aldosterone levels, which may aggravate

cardiovascular complications.

From the literature, it is also

evident that the overall prevalence of co-morbidities was higher

in hypokalaemic PA patients than in normokalaemic patients.

In more than 22 000 Pakistani patients, the risk of sudden

cardiac attack or sudden cardiac death and all-cause mortality

was associated with hyperkalaemia,

however no significant

relationship existed between hypokalaemia and outcome.

The association between left ventricular hypertrophy (Cornell

product) and aldosterone rather supports cardiac co-morbidities,

as excess aldosterone levels might be a risk factor for arrhythmic

disorders occurring either via left ventricular hypertrophy or

cardiac fibrosis.

Furthermore, aldosterone has been associated

with endothelial dysfunction,

and nowalsowith a lack of arterial

compliance, independent of blood pressure.

Lower K

levels

and a lack of compliance concurrently with high aldosterone

levels and associated ACR (a marker of kidney and endothelial

dysfunction) may be detrimental to the cardiovascular health of

hypertensive black men.

Blood pressure control was driven by the TPR and

renin–angiotensin system (see Table 2) in the hypertensive

low-aldosterone group. Aldosterone is a mineralocorticoid

hormone, having 30–50% of its total plasma concentration in

free form. Cortisol on the other hand is a glucocorticoid hormone

and has 100-fold higher free levels in circulation than aldosterone,

with high intrinsic mineralocorticoid activity, although its action

is blunted by local conversion to cortisone at the kidney level.

Cortisol can bind with the same high affinity as aldosterone

to the mineralocorticoid receptor

and it may modulate the

mineralocorticoid receptor-binding effects of aldosterone.

From the literature, it is evident that the long-term increase

in both cortisol and aldosterone reflect changes in risk factors

for cardiovascular disease, such as increases in dietary fat, high

salt intake, low levels of physical activity and high stress levels,

which may lead to the phenotype of aldosterone-associated

hypertension.

Stress can indeed alter the aldosterone phenotype,

as chronic depression was associated with a desensitised renin

system and volume-loading hypertension in a black cohort over

three years.

Our finding of a positive association between aldosterone

and cortisol (

= 0.058) in the hypertensive high-aldosterone

group further enhances previous findings where hypothalamic–

pituitary–adrenal axis dysregulation and compensatory double

product (systolic blood pressure × heart rate) increased and

acted as a possible defence mechanism to alleviate perfusion

deficits, which potentiated ischaemic heart disease risk.

The

interaction of endogenous levels of aldosterone and cortisol

may therefore disrupt blood pressure control and result in an

increased proportion of hypertension.

Low-renin hypertension is more common in blacks and is

characterised by increased Na

retention and suppressed renin

and aldosterone levels,

3,21,23

and may be psychosocial in origin.

21, 23

Salt and water retention are greater in blacks, not only because

there is an increased likelihood of PA, but also because of genetic

variants that affect the function of the renal tubular epithelial

sodium channel (ENaC). There are a number of genetic causes

of both these phenotypes.

24,25

PA is an overlooked but frequent cause of secondary

hypertension and because only a few hypertensive patients are

screened worldwide for PA,

mineralocorticoid blockade is also

unlikely to be used as treatment for hypertension. It is also worth

mentioning that low levels of both aldosterone and angiotensin

II would identify patients with a Liddle syndrome phenotype,

who would respond best to amiloride.

26,27

Our data highlight the fact that hypertensive black patients

with low K

levels should be screened for PA in order to

treat them adequately so as to bring the high prevalence of

hypertension in sub-Saharan Africa under control. Because PA

is also a common occurrence in resistant hypertension, screening

for it may further improve hypertension treatment and control

in South Africa.

A strength of this sub-study is that use was made of state-

of-the-art analysis of the RAAS parameters. A weakness is that

follow-up data were not used to determine causality.

Conclusion

The AA2 ratio, which should be explored further to replace the

aldosterone-to-renin ratio for the diagnosis of PA, was used to

identify the PA-like phenotype in black men. Excess aldosterone

was associated with endothelial dysfunction and left ventricular

hypertrophy, independent of blood pressure.

We thank the participants in this sub-study, as well as the staff who participat-

ed in collecting the data. Dr M Poglitsch has stocks in Attoquant Diagnostics

GmbH. The research was funded by the Metabolic Syndrome Institute,

France; South African Medical Research Council; National Research

Foundation; North-West University; North-West Department of Education

and ROCHE Diagnostics, South Africa. The funding organisations played

no role in designing or conducting the study, collecting, managing, analysing

and interpreting the data, preparing, reviewing or approving the manuscript.

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