57 / 76
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 6, November/December 2016
AFRICA
387
Cortisol:brain-derived neurotrophic factor ratio
associated with silent ischaemia in a black male cohort:
the SABPA study
Christiaan E Schutte, Leoné Malan, Jacobus D Scheepers, Woudri Oosthuizen, Marike Cockeran,
Nicolaas T Malan
Abstract
Aim:
Emotional distress has been associated with cardiovas-
cular disease (CVD) in Africans. Cortisol and brain-derived
neurotrophic factor (BDNF), as markers of emotional
distress, increase cardiometabolic risk. We therefore aimed to
investigate associations between cardiometabolic risk markers
and the cortisol-to-BDNF ratio (cortisol:BDNF).
Methods:
A cross-sectional study included a bi-ethnic gender
cohort (
n
=
406) aged 44.7
±
9.52 years. Ambulatory blood
pressure (ABPM), ECG, fasting serum cortisol and BDNF
levels and cardiometabolic risk markers were obtained.
Results:
Africans had increased incidence of hyperglycaemia
and 24-hour silent ischaemic events, and elevated 24-hour
blood pressure (BP) and cortisol:BDNF ratios compared
to Caucasians. Forward stepwise linear regression analysis
underscored a similar trend with associations between hyper-
glycaemia, 24-hour BP [Adj
R
2
0.21–0.29;
β
0.23 (0.1–0.4);
p
=
0.01], silent ischaemia [Adj
R
2
0.22;
β
0.40 (0.2–0.6);
p
<
0.01]
and cortisol:BDNF levels in Africans, mostly in the men.
Conclusion:
Attenuated cortisol levels in this group may
be indicative of emotional distress and if chronic, drive
the cortisol:BDNF ratio to desensitise BDNF. Desensitised
cortisol:BDNF may sustain cardiometabolic risk and induce
neurodegeneration in African men via silent ischaemia.
Compensatory increases in blood pressure to increase perfu-
sion and maintain homeostasis may increase coronary artery
disease risk.
Keywords:
cortisol, brain-derived neurotrophic factor (BDNF),
cardiometabolic disease
Submitted 20/3/15, accepted 29/5/16
Cardiovasc J Afr
2016;
27
: 387–391
www.cvja.co.zaDOI: 10.5830/CVJA-2016-065
Cardiovascular disease (CVD) is a major concern throughout
the world.
1
There are various factors that contribute to the
risk of CVD, such as alcohol abuse, obesity and urbanisation.
2
A significant contributing risk factor for CVD, stroke and
ischaemic heart disease is high blood pressure.
3
Indeed, the
South African National Health and Nutrition Examination
Survey (SANHANES) found that systolic hypertensive rates
ranged from 19.0 to 29.4% and diastolic hypertensive rates
ranged from 8.3 to 19.4%. The prevalence of hypertension and
psychological distress is escalating in South Africa, especially in
urban communities.
3-5
Prolonged exposure to a taxing emotionally stressful
environment, such as an urban lifestyle, disrupts homeostasis,
which can lead to chronic stress.
6,7
Amajor pathway for regulating
the stress response, the hypothalamic–pituitary–adrenal (HPA)
axis, secretes corticotropin-releasing factor (CRF). CRF induces
the release of adrenocorticotropic hormone (ACTH), where it
stimulates the synthesis and secretion of glucocorticoids, with
cortisol as the end product.
6
Furthermore it has been observed
that augmented HPA-axis responses towards challenges in
normotensive individuals enhance the risk of developing
hypertension.
8
Dysregulation of the HPA axis may also be a
result of unmitigated increases in cortisol where prolonged
elevations ultimately result in the down-regulation of CRF,
ACTH and subsequently cortisol.
9
Mineralocorticoid-based hypertension is associated with
an excess of extracellular fluid as a result of increased sodium
and water retention.
7
Resultant elevations in blood pressure
will emerge with increased total peripheral resistance responses,
which may burden the heart. This may contribute to silent
ischaemic events because of a decrease in coronary blood
supply.
3
Brain-derived neurotrophic factor (BDNF), a protein
complex and part of the neurotrophin family, is synthesised and
secreted by the central nervous system and plays a major role
in brain plasticity and survival of the developing neurons.
10
The
neurotrophic hypothesis of depression states that during times of
stress, BDNF is down-regulated, especially in the limbic areas,
influencing emotional responses.
7
It is suggested that the down-
regulation is caused by corticosterone.
11
The down-regulation may reduce neuroplasticity and
ultimately lead to neurodegeneration. As the reduction by itself
may not be enough to lead to destruction of hippocampal
neurons, it may lead to an increased vulnerability to neuronal
damage, especially during times of emotional distress.
11,12
This
suggests that attenuated levels of BDNF act in tandem with
lower levels of cortisol in individuals when psychological distress
is suspected.
BDNF circulates systemically and supports the notion
Hypertension in Africa Research Team (HART), North-West
University, Potchefstroom Campus, South Africa
Christiaan E Schutte, MSc
Leoné Malan, RN, PhD,
Leone.Malan@nwu.ac.zaJacobus D Scheepers, MSc
Woudri Oosthuizen, MSc
Nicolaas T Malan, DSc
Statistical Consultation Services, North-West University,
Potchefstroom Campus, South Africa
Marike Cockeran, MSc