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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 4, July/August 2019
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AFRICA
of non-calcific coronary artery plaques on CCTA, compared
with HIV-negative controls.
16
HIV-infected women also showed a
significantly higher percentage of non-calcified plaque on CCTA
compared to HIV-negative women.
18
Using dual-source CCTA, features of non-calcified plaque have
also been found in early atherosclerosis of healthy HIV-negative
populations with a family history of early onset of coronary artery
disease.
19
Therefore, the plaque morphology of atherosclerosis in
HIV-positive populations, as found in our study, was very similar
to that found in early atherosclerosis in HIV-negative populations.
Our findings suggest that the difference in atherosclerotic plaque
characteristics of HIV-positive compared to HIV-negative
populations is that the atherosclerosis was more extensive in
HIV-positive patients and with less calcification. The reasons
for these differences are unclear but are probably related to the
link between HIV infection and atherosclerosis, independent of
traditional cardiovascular risk factors.
Data from the Strategies for Management of Antiretroviral
Therapy (SMART) study suggest that immune, inflammatory
and viral factors contribute to higher prevalence of coronary
artery disease in HIV-positive patients.
20
Undetectable viral
loads do not equate to amelioration of ongoing inflammation
and while inflammation and immune activation are diminished
with cART, they are not abolished. HIV infection, even in the
presence of cART, not only initiates endothelial dysfunction
and immune cell activation but activates a number of cellular
pathways.
21
As HIV predominantly infects T cells and macrophages,
there is induction of oxidative and endoplasmic reticulum stress,
dysregulation of autophagy and inflammasome formation, all
of which may contribute to HIV-associated atherosclerosis.
21
In addition, HIV-positive patients presenting with ACS have
been found to have a ‘thrombo-inflammatory’ state caused
by heightened platelet function, hypercoagulability and
inflammation.
22
Mechanisms that promote thrombosis such as
increased levels of soluble p-selectin, CD-40L and microparticles
have been demonstrated in HIV-positive patients with ACS.
22
This inflammatory and thrombotic milieu may well be involved
in the pathogenesis of the ‘athero-thrombotic plaque’, as was
found in 40% of our patients.
Disease severity may also contribute to atherosclerosis. An
association between reduced CD4 cell count and non-calcified
coronary artery plaque as well as the presence of coronary
stenosis greater than 50% in HIV-positive compared to
HIV-negative patients have been reported.
16,23
The average CD4
count in our cohort was low (301 cells/mm
3
), despite 50% being
on cART at the time of presentation with ACS.
Higher rates of ACS in the general population have been
reported in a number of studies to be associated with fibrous and
fibro-fatty plaque, compared to mixed or calcified plaques.
14,16,23
Non-calcified plaques, as found in our cohort, represent an
earlier stage of atherosclerosis and are more prone to rupture,
leading to ACS.
24
Furthermore, HIV-positive patients have
a larger burden of coronary atherosclerosis, particularly
non-calcified plaque, compared to HIV-negative patients with
similar cardiovascular risk factors.
14
Therefore the presence of
more extensive non-calcific fibrous and fibro-fatty plaque and
its vulnerability to rupture could explain the higher prevalence
and earlier onset of ACS in HIV-positive compared with
HIV-negative patients.
IHD in HIV-positive patients most commonly manifests
with an acute episode of ACS. Studies to date suggest distinct
demographic characteristics of ACS presentation in HIV-positive
patients.
25-28
The mean age at presentation of ACS in HIV-positive
patients is a decade younger (mean age 50 years) than the general
population, with patients more likely to be male, current smokers
and to have lower high-density lipoprotein cholesterol levels.
This is similar to our cohort where the mean age was 51.1
±
8.1
years, the majority being male (65%) and more than half (55%)
current smokers.
It is also recognised that ACS in HIV-positive patients
presents with different risk-factor profiles in developing
compared to developed regions.
25
Traditional risk factors such as
hypertension, diabetes and dyslipidaemia are more common in
developed regions, whereas in the developing regions, smoking
is the predominant risk factor.
25,29
Similarly, in our study few
patients had hypertension, diabetes, dyslipidaemia or a family
history of IHD but there was a high prevalence of smoking
(55%).
The most common modes of presentation of ACS in our
cohort were STEMI, a low TIMI score (TIMI 2) and single-
vessel disease angiographically. These findings are consistent
with other studies in HIV-positive patients.
26-28
In some regions,
HIV-positive patients with ACS may present without classic
atheromatous plaques but with a large burden of thrombus in
the infarct-related artery.
25
In our cohort, a high thrombotic
burden was present in 40% of ACS patients. Of interest is that
the profile of ACS in developed countries is changing. In a
recent study from six United States centres, half (50.4%) of all
HIV-positive patients presenting with an ACS had type 2 MI,
which occurs in the setting of supply-and-demand mismatch.
30
In many studies, including the current study, only half of
HIV-positive patients presenting with ACS were on cART.
However, the expectation is that in future, many more patients
will be on cART based on the findings of the SMART study,
which found that patients who deferred or interrupted cART
had a 70% increased hazard of cardiovascular disease events.
20
The widespread adoption of cART will hopefully translate not
only to better long-term outcomes but also lead to substantially
fewer cardiac events.
Limitations
This was a single-centre study with a small sample size. There
was no case–control group of HIV-negative patients who had
IVUS and VH imaging. There were clinical limitations, for
example, repeat coronary angiography was not performed on all
patients to determine in-stent restenosis. However, the focus of
this study was not on long-term outcomes but coronary artery
plaque characteristics at ACS presentation.
Conclusion
HIV-positive patients presented at a young age, with STEMI
being the most common mode of presentation. In these patients,
atherosclerosis, as determined by VH-IVUS, was extensive.
The left anterior coronary artery had the largest burden of
disease and this disease burden was predominantly located
in the proximal coronary arteries. Imaging using VH-IVUS
demonstrated that atherosclerosis in young HIV-positive patients