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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 2, March/April 2020
AFRICA
61
Patients without ACS had the most vasoreactivity compared to
the patients with ACS.
The mean PWV in the HIV+/ACS group was 4.1 m/s (SD
1.1), 4.6 m/s (SD 1.1) in the HIV-/ACS group and 3.9 m/s (SD
1.1) in the HIV+/no ACS group. These values were all low with
no significant differences between the three groups (
p
=
0.12)
(Table 1).
CIMT was measured in all three groups. The mean CIMT
of the two groups with ACS was not different. The CIMT in
the group without ACS (0.50;
±
0.08 mm) was marginally but
significantly lower than the CIMT of both the HIV+/ACS group
(0.66;
±
0.16 mm) and the HIV-/ACS group (0.70;
±
0.06 mm) (
p
=
0.0005 and
p
< 0.0001, respectively) (Table 1).
There were significant differences in the endothelial
biomarkers VCAM-1, ICAM-1, IL-6 and E-selectin in the three
groups (Table 2). The median VCAM-1 levels in HIV-positive
patients with and without ACS were significantly higher than
in the HIV-/ACS cohort (402 and 503 vs 287 ng/ml) (
p
=
0.033
and 0.024, respectively). Median ICAM-1 levels on the other
hand, were significantly higher in only the HIV-positive patients
without ACS compared to the other two cohorts (
p
=
0.0079 and
0.0010, respectively). The HIV+/no ACS group had significantly
lower median levels of IL-6 than both the HIV+/ACS and the
HIV-/ACS groups (
p
=
0.033 and 0.0050, respectively). The
median E-selectin levels in HIV+/ACS patients and HIV-/ACS
patients were significantly lower than that of the HIV+/no
ACS group (
p
=
0.0007 and 0.012, respectively). There was no
significant difference in median IL-1
β
, IL-1Ra, MCP-1, TNF-
α
,
P-selectin and PAI-1 levels between the groups.
Discussion
Studies suggest that an overall 1.5–2.0-fold increased risk of
acute myocardial infarction is conferred by HIV infection.
19,20
Common to most studies is that the mean age at presentation
of ACS in HIV-infected patients is a decade younger than the
general population, with a mean age of 50 years.
5,21,22
This is
similar to our cohort where the mean age was 51 years.
IHD in HIV-positive patients presenting with ACS have
different risk-factor profiles in developing and developed
regions. Traditional risk factors such as hypertension, diabetes
and dyslipidaemia are more common in developed regions. The
current study had fewer patients with hypertension, diabetes,
dyslipidaemia and family history of IHD in HIV-positive
patients with ACS.
In developing countries smoking appears to be the dominant
risk factor with prevalence rates of 24.4% in HIV-positive
males.
5,13,23
More than half of the HIV+/ACS patients in our
cohort were smokers with fewer other traditional risk factors.
Furthermore, there is evidence that smoking contributes to
endothelial dysfunction.
24
These findings make smoking cessation
an important modifiable risk factor for the prevention of IHD in
HIV-positive patients.
Mechanisms for the development of atherosclerosis in HIV
are multifactorial and include chronic inflammation and immune
activation. These in turnmay also lead to endothelial dysfunction,
further contributing to the pathogenesis of atherosclerosis.
13,19,25
Endothelial dysfunction is associated with increased levels of
reactive oxygen species and decreased nitric oxide levels and
hence decreased vascular reactivity.
6
HIV itself has been linked
to endothelial dysfunction.
13,26
This is supported by findings of a
significant improvement in FMD in patients in the first 24 weeks
after initiation of cART, suggesting that suppression of HIV
viraemia leads to improved endothelial function.
27
The HIV-1 envelope protein gp120 and the regulatory protein
Tat are associated with endothelial cell apoptosis and increased
cellular adhesion molecules (ICAM-1, E-selectin). Furthermore,
a prothrombotic state [increase of von Willebrand factor, PAI-1
and tissue plasminogen activator (t-PA)] have been implicated
in the pathogenesis of atherosclerosis in HIV-positive patients.
28
Telomere length and CDKN2A expression were both consistent
with increased biological ageing in HIV-infected individuals.
29
Anti-retroviral therapies may be linked to CAD, specifically
protease inhibitors, however the risk of CAD associated with
anti-retroviral therapy is small compared with the impressive
reductions in all-cause mortality with cART.
30
Table 2. Endothelial biomarkers
Median levels
(interquartile ranges)
HIV+/ACS
1
HIV-/ACS
2
HIV+/no ACS
3
p-
value for H0: no
between-group differences
p-
value for
post hoc
group
differences
VCAM-1 (ng/ml)
402 (292–609)
287 (257–412)
503 (292–822)
0.025
0.033
1,2
0.024
2,3
ICAM-1 (ng/ml)
172 (135–211)
167 (129–193)
225 (199–293)
0.0009
0.0079
1,3
0.0010
2,3
IL-6 (pg/ml)
5.9 (3.9–12.4)
10.7 (4.8–50)
3.8 (1.9–5.3)
0.0053
0.033
1,3
0.0050
2,3
E-selectin (ng/ml)
24.3 (19.1–30.6)
27.8 (21.5–42.2)
47.1 (31.8–65.8)
0.0005
0.0007
1,2
0.012
2,3
IL-1
β
(pg/ml)
0.36 (0.27–0.48)
0.32 (0.28–0.41)
0.38 (0.30–0.51)
0.29
IL-1Ra (pg/ml)
224 (173–266)
215 (120–258)
181 (125–258)
0.75
MCP-1 (pg/ml)
26.5 (15.0–41.2)
22.4 (18.0–33.3)
22.4 (16.5–27.4)
0.70
TNF-
α
(pg/ml)
2.5 (1.4–4.4)
2.0 (1.6–4.4)
2.5 (2.0–4.8)
0.60
P-selectin (ng/ml)
25.8 (20.3–32.9)
20.8 (19.3–24.6)
23.5 (19.6–29.7)
0.12
PAI-1 (ng/ml)
67.6 (36.7–149.8)
85.6 (34.7–138.4)
66.2 (35.6–91.7)
0.59
There were significant differences in the following endothelial biomarkers; VCAM-1, ICAM-1, IL-6 and E-selectin. The median VCAM-1 levels in HIV-positive patients
with and without ACS were significantly higher than in the HIV-/ACS cohort. However, median ICAM-1 levels were significantly higher in HIV-positive patients
without ACS than in the HIV+/ACS and HIV-/ACS cohorts. The HIV+/no ACS group had significantly lower median levels of IL-6 than both the HIV+/ACS and the
HIV-/ACS groups. The median E-selectin levels in the HIV+/ACS patients and HIV-/ACS patients were significantly lower than that of the HIV+/no ACS group. There
was no significant difference in median IL-1
β
, IL-1Ra, MCP-1, TNF-
α
, P-selectin and PAI-1 levels between the groups.
VCAM-1
=
vascular cellular adhesion molecule 1, ICAM-1
=
intercellular adhesion molecule 1, IL
=
interleukin, MCP-1
=
monocyte chemotactic protein 1, TNF-
α =
tumour necrosis factor alpha, PAI-1
=
plasminogen activator inhibitor 1.