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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 6, November/December 2020
AFRICA
295
have lipolytic properties.
21
Further, atrial NPs exhibit possible
favourable effects on chronic inflammation.
22
Cross-sectional
studies have demonstrated that NP levels are reduced in subjects
with obesity, insulin resistance and type 2 diabetes,
8,23
conditions
that are more common in black Africans. Reduced NP response
is also associated with the activation of the renin–angiotensin
system in experimental studies,
24
an association that could
explain the inverse association of NPs and the MetS/insulin
resistance. Moreover, several studies have prospectively shown
that low levels of NPs are associated with insulin resistance and
diabetes.
6,7,9,25
NP levels were shown to be higher in women and increased
with age, therefore all our analyses were age and gender
adjusted.
26
Furthermore, a higher variability in NT-proBNP is
seen in African Americans than in Caucasians.
27
As for ethno-
stratified analyses, we found cross-sectional associations of low
NT-proBNP levels and higher BMI, HbA
1c
, insulin and TG levels
in Africans, whereas in Caucasians, low NT-proBNP levels were
associated with insulin resistance and higher insulin levels only.
These findings indicate that BNP may affect the propensity for
metabolic disturbances differently in Africans and Caucasians,
and may play a role in the cause of the higher rates of obesity,
insulin resistance, hypertension and diabetes as seen in black
Africans.
28,29
There is evidence that African Americans
13,14
but not
black Africans have lower NT-proBNP levels than Caucasians,
and low BNP levels are associated with higher LDL and TG
levels.
30
Although metabolic risk conditions are more common in
blacks, the prevalence of the MetS in black American children
and adults is likely underestimated due to the notion that
hypertriglyceridaemia, one of the characteristics of the MetS, is
observed less frequently in blacks than in whites.
31
Our findings on
associations of low NT-proBNP levels and hypertriglyceridaemia
in Africans but not Caucasians are therefore somewhat
contradictory. The differences might be explained in part by
higher intake of alcohol in the Africans in general.
32
It was shown that subjects with a combination of obesity,
diabetes and alcohol excess are prone to develop extremely
high TG values.
33
Both the Dallas Heart study and the ARIC
study demonstrated that NT-proBNP levels were lower in
African Americans than in Caucasians.
11,14
In our study, no
significant differences in NT-proBNP levels between Africans
and Caucasians were observed, although there was a trend for
Africans to have lower NT-proBNP levels (29.9 ng/l) compared
with Caucasians (34.1 ng/l). However, NT-proBNP concentration
is elevated in hypertension,
34
and a much larger proportion
of Africans was hypertensive (
n
= 116; 59.8%) compared to
Caucasians (
n
= 63; 31.0%), which might have influenced
(elevated) NT-proBNP levels in the African population.
Additionally, conditions other than cardiac structural
and functional changes influence NT-proBNP levels. Renal
dysfunction is known to elevate NT-proBNP levels due to renal
clearance of the prohormone.
35
Nonetheless, the proportion
of subjects with renal disease in both the Africans and
Caucasians was low (2.1 and 2.5%, respectively) and did not
differ significantly between the ethnicities. However, prevalence
of both cardiovascular and renal disease was assessed through
questionnaires, which might be negated by the reporting bias of
the participants. It remains to be explored whether the higher
diabetes rates in blacks might be, at least partially, explained by
genetically predisposed differences in NP levels.
6,7
Assessment of NT-proBNP is used in clinical routine to
identify subjects with heart failure. There is a need to evaluate,
and possibly implement, enforced prevention strategies for early
identification of subjects with the MetS and increased risk of
diabetes development. This type of preventative strategy that
could have a great impact on economic aspects of healthcare
might include screening for subjects in the lowest quartiles of
NT-proBNP. Together with other preventable risk factors, such
as a sedentary lifestyle, NT-proBNP deficiency might help to
identify individuals at highest risk of the MetS and diabetes
development, and focus on prevention efforts.
Study limitations
The data in the SABPA study were collected at a single regional
centre and the subjects were matched with regard to age, gender,
socio-economic status and ethnicity, which limits the applicability
to other populations. Also, as this was a cross-sectional study,
it shares the usual limitations of causality and control, as seen
for all cross-sectional studies. We had no data on prevalent heart
failure, which might have affected the outcome of the analyses.
Furthermore, NPs are unstable hormones that undergo
a rapid degradation in plasma. For this reason, immune-
assays that target the more stable N-terminal fragments of the
prohormones have been developed, and the N-terminal fragments
serve as surrogate markers of the biologically active peptides.
36
Nevertheless, one must bear in mind that the measurements of
the N-terminal fragments do not necessarily reflect actual levels
of the biologically active, mature BNP.
Our samples were stored at –80°C from the baseline
examination in 2008–2009 until analysis in 2015, which could be
a limitation to our study, considering storage might have affected
stability and degradation of NT-proBNP.
Conclusions
In a bi-ethnic cohort, NT-proBNP in the high-normal range was
associated with a lower prevalence of metabolic risk factors such
as high BMI, increased waist circumference, IGT, high insulin
levels and hypertriglyceridaemia, with strongest associations
for Africans in spite of similar NT-proBNP concentrations.
This indicates that BNP may affect the propensity for metabolic
disturbances differently in Africans and Caucasians.
The data that support the findings of this study are available from North-West
University, but restrictions apply to the availability of these data, which were
used under license for the current study, and so are not publicly available.
Data are however available from the authors upon reasonable request and
with the permission of North-West University.
This work was kindly supported by: North-West University; National
Research Foundation (NRF); Medical Research Council (MRC-SA);
Department of Education North-West Province; ROCHE diagnostics; South
Africa and Metabolic Syndrome Institute, France. Drs Magnusson and
Melander were supported by grants from the Swedish Medical Research
Council, the Swedish Heart and Lung Foundation, the Medical Faculty of
Lund University, Skane University Hospital, the Albert Pahlsson Research
Foundation, the Crafoord Foundation, the Ernhold Lundstroms Research
Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation,
the Southwest Skanes Diabetes Foundation, the King Gustaf V and Queen