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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.
11
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.
17
From the literature, it is also
evident that the overall prevalence of co-morbidities was higher
in hypokalaemic PA patients than in normokalaemic patients.
17
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,
18
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.
19
Furthermore, aldosterone has been associated
with endothelial dysfunction,
17
and nowalsowith a lack of arterial
compliance, independent of blood pressure.
19
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.
20
Cortisol can bind with the same high affinity as aldosterone
to the mineralocorticoid receptor
20
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.
20
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.
21
Our finding of a positive association between aldosterone
and cortisol (
p
= 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.
22
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,
6
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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