CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 2, March 2012
76
AFRICA
non-enzymatic formation of advanced glycation end products
(AGEs).
20
The DAG–PKC pathway affects cardiovascular and
renal structure and function in many ways, e.g. the regulation of
endothelial permeability, vascular tone, cell growth, angiogen-
esis, and cytokine and leucocyte activation.
20
Moreover, insulin
resistance/hyperinsulinaemia-induced activation of the sympa-
thetic nervous and renin–angiotensin–aldosterone systems could
contribute to cardiovascular and renal damage through oxidative
stress and inflammation.
21-23
Alteration in kidney function predominated in patients with
a longer duration of diabetes, enhancing the effect of both
chronic hyperglycaemia and the ageing process.
3,24
The latter is
associated with changes in vascular structure and function due to
clustering of multiple risk factors, including insulin resistance/
hyperinsulinaemia, oxidative stress and inflammation.
25
Arterial
stiffness, an independent predictor of morbidity and mortality,
has been reported to increase with age and is associated with
high systolic and pulse pressure.
3,24,26
Moreover, the decrease in
the number of nephrons, which occurs with ageing, may result
in hyperfiltration, hypertrophy and elevation in glomerular capil-
lary pressure.
27
The high prevalence of LVH in CKD patients found in our
study agrees with that of other studies.
28-31
LVH in CKD is
thought to result partly from uraemia-associated risk factors
such as anaemia, calcium-phosphate products and hyperhomo-
cysteinaemia.
4
Moreover, renal dysfunction activates the renin–
angiotensine–aldosterone system, with subsequent formation of
angiotensin II, known to be essential for the development and
progression of LVH.
32
The risk of CVD and death increases with
the decline in glomerular filtration rate (GFR) and the major
increase in risk occurs at a GFR
<
60 ml/min per 1.73 m
2
.
4
LVH has been reported to predispose to ischaemic heart
disease, arrhythmias and congestive heart failure.
33
Our results
indicate that patients with severe CKD had higher propor-
tions of abnormal LV geometry, with concentric remodelling
and concentric hypertrophy as the most frequent pattern. Both
eccentric and concentric hypertrophy may occur in individu-
als with CKD.
4
Eccentric hypertrophy is thought to result from
volume overload, leading to cardiomyocyte drop out. Concentric
hypertrophy is typically the result of hypertension and increased
afterload and is exacerbated by anaemia, hyperparathyroidism
and high angiotensin II concentrations. Eccentric and concentric
hypertrophy have different impacts on the prognosis.
4
Concentric
hypertrophy confers the worst prognosis, followed by eccentric
hypertrophy and concentric remodelling.
33
Moderate CKD and a high proportion of hypertension could
explain the pre-eminence of concentric hypertrophy observed in
the present study. In Nigerian hypertensive patients, Aje
et al
.
reported greater systolic, diastolic, pulse and mean blood pres-
sure among patients with concentric hypertrophy in comparison
with those with normal geometric patterns.
34
In our study, hyperuricaemia emerged as the only predictor
of LVH in CKD patients. The mechanisms that could account
for increased uric acid levels in CKD include overproduction
to counteract oxidative stress and endothelial dysfunction, the
severity of diabetes and/or hypertension, impaired renal uric
acid clearance, and insulin resistance/hyperinsulinaemia-induced
proximal renal tubular reabsorption of sodium and urate.
35,36
The
association between hyperuricaemia and LVH could rely upon
an association of uric acid with other risk factors, either isolated
or combined in the metabolic syndrome.
32
The coexistence of
hyperuricaemia and LVH has been recognised as an independent
and powerful predictor of CVD.
36-38
The interpretation of the results of our study is confounded
by some limitations. The cross-sectional design of the work
precludes any causal relationship between CKD and associated
risk factors. Moreover, the sample size did not allow sufficient
power to detect additional associations. One wonders to what
extent the conclusions of this clinic-based study could be extrap-
olated to the general population, given the bias in the referral of
patients. The findings of our study bear, however, some clinical
implications for CKD identification, treatment protocol and esti-
mated prognosis in hypertensive patients.
Conclusion
This study has shown that LVH is common among type 2 diabe-
tes patients with CKD. Concentric LVH was the geometric LV
pattern most frequently encountered and its frequency increased
with the decline in renal function. Hyperuricaemia emerged as
the unique independent predictor of the risk of LVH.
The authors thank Prof JJ Muyembe, head of the National Institute of
Biomedical Research/Ministry of Health, for the facilities obtained for
the measurements of cholesterol and its sub-fractions. Particular thanks
go to Prof E Kintoki, Division of Cardiology and Dr M Lelo, Division of
Radiology and Imaging, Department of Internal Medicine, University of
Kinshasa Hospital for their contribution to the evaluation of left ventricular
mass and geometry.
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