CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 3, April 2012
AFRICA
133
To evaluate
H pylori
infection as a possible risk factor, the rate
of developing outcomes was compared between seropositive and
seronegative patients. As shown in Table 2, of 204 seropositive
patients, in 48 (23.5
%
) subjects a cardiovascular event (as
defined earlier) occurred during the first month after enrollment,
compared to only 21 (9.1
%
) patients who developed short-term
outcomes among 229 seronegative participants (
p
<
0.000).
H
pylori
-infected patients were more than 2.5 times more likely to
develop short-term adverse outcomes, as defined in this study
(risk ratio: 2.58).
H pylori
seropositivity did not show any significant association
with long-term adverse outcomes during the one-year follow up
of patients; 97 (47.5
%
) patients among the 204
H pylori-
positive
participants developed long-term adverse outcomes, compared
to 97 (42.5
%
) of 229 subjects who were negative for
H pylori
antibodies (
p
>
0.05). Seropositive patients were only marginally
more likely to develop long-term adverse outcomes compared to
their seronegative counterparts (risk ratio: 1.12).
When short-term adverse outcomes were compared
individually between seropositive and seronegative participants,
the results showed a significantly higher incidence of UA, MI,
coronary angioplasty and SCD during the first month of follow
up among
H pylori
-infected patients (
p
<
0.01). However, eight
(3.4
%
) patients among the seronegative participants underwent
CABG surgery during the first month, compared to four
(1.9
%
) in the seropositive group (
p
<
0.01). Regarding long-
term adverse cardiovascular outcomes, none of the individual
events, including UA, MI, angioplasty, CABG and SCD differed
between seronegative and seropositive participants (
p
>
0.05).
To evaluate the effect of risk factors on incidence of adverse
cardiovascular events, a multivariate logistic regression model
was built using age, gender and classic risk factors, including
hypertension, DM, hyperlipidaemia, smoking and positive
family history for CAD, in addition to seropositivity for
H pylori
.
From all these risk factors, only
H pylori
infection proved to be
a significant and independent predictor of short-term adverse
cardiovascular outcomes (
R
=
3.05,
p
<
0.001). When this model
was used for long-term outcomes, only age was a significant
determinant of incidence of cardiovascular events (
R
=
1.04,
p
<
0.001).
Discussion
In this study, we prospectively evaluated the effects of
H pylori
seropositivity and classic cardiovascular risk factors on incidence
of future cardiovascular events among a cohort of 433 patients
presenting with ACS. The main new finding of this study was
to show a positive association between
H pylori
seropositivity
and incidence of short-term adverse cardiovascular events in
participants during the first month after presenting with ACS.
However, we failed to provide evidence for such an association
with long-term adverse outcomes during one year of follow
up. Furthermore, in this study we did not find any significant
relationship between
H pylori
seropositivity and any of the
studied risk factors.
Some viral and bacterial infections, such as
Chlamydia
pneumonia
, Hepatitis A virus, cytomegalovirus and
Herpes
simplex
virus have been implicated in affecting development
and course of coronary atherosclerotic diseases.
29
H pylori
is
similar to these pathogens as it is also an obligatory intracellular
pathogen and causes life-long persistent infection.
30
H pylori
also
establishes persistent antibodies targeted to it.
Several pathological mechanisms have been postulated to
explain the effect of
H pylori
infection on atherosclerosis. It has
been suggested to initiate an acute-phase response and to activate
TNF-
α
, IL-6 and fibrinogen, which are inflammatory cytokines
that can directly or indirectly propagate an inflammatory process
in arterial walls.
8,31
H pylori
has been also shown to cause platelet
aggregation, an important aspect of acute destabilisation of
atherosclerotic disease.
32
Another possible mechanism by which
H pylori
may cause endothelial damage is by causing aggravated
autoimmune hormonal responses because of antigenic mimicry,
13
such as immunological cross reactivity between bacterial and
human heat-shock proteins,
33
which can lead to coronary
calcification and early atherosclerosis.
34
In addition, direct
colonisation of the arterial wall by
H pylori
has been suggested,
21
and
H pylori
has been found in atheromas using the polymerase
chain reaction (PCR) technique.
35
We measured both
H pylori
IgG and IgA antibodies in the
participants. IgA and IgG seropositivity were measured in this
study, as it has been suggested that IgA seropositivity may reflect
more recent and active infection,
36
and its use may be appropriate
to evaluate the association between
H pylori
infection and
ischaemic heart disease.
37
In our study, we failed to show any significant association
between presence of the classic cardiac risk factors, including
hypertension, DM, hyperlipidaemia, smoking and positive family
history of CAD, and incidence of future adverse cardiovascular
outcomes. This was consistent with the results reported by Zhu
et al
., who also did not demonstrate a prognostic role for these
classic risk factors on future adverse cardiovascular events in
their study on 890 patients with CAD.
38
This may have been
partly due to extensive treatment of these risk factors among
patients diagnosed with CAD, which could have lessened their
observed prognostic effects in the study population. Therefore,
longer follow-up duration on larger sample populations may be
needed to document the prognostic effects of these factors.
It has previously been suggested that there may be a
relationship between the classic CAD risk factors and
H pylori
infection, which could explain the association between
H pylori
infection and CAD.
39,40
However, this study did not demonstrate
any significant association between
H pylori
seropositivity and
the presence of classic risk factors. Our results are in agreement
with those of Danesh
et al
., who did not find such an association
to be present in their meta-analysis of 18 different studies.
41
Interestingly, results from the present study exhibited a
positive association between
H pylori
infection and short-term
adverse cardiovascular outcomes. Patients who were seropositive
TABLE 2. INCIDENCE OF SHORT- AND LONG-
TERMADVERSE OUTCOMES BASED ON PATIENTS’
SEROPOSITIVITY FOR
H PYLORI
IGAAND/OR IGG.
DATA PRESENTEDAS NUMBER (PERCENT)
Total study
population
(n = 433)
n (
%
)
Patients with
short-term
outcomes*
n (
%
)
Patients with
long-term
outcomes
n (
%
)
H pylori
IgA and/or
IgG
+ 204 (47.1)
48 (23.5)
97 (47.5)
– 229 (52.9)
21 (9.1)
97 (42.4)
*For
χ
2
test,
p
< 0.000.
