CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 2, March/April 2010
104
AFRICA
smooth muscle cells in the 1970s and 1980s. A fusion of these
views led to the concept of the atheroma as a graveyard of acel-
lular lipid debris enrobed in a capsule of proliferated smooth
muscle cells.
8
Over the past decade, however, it has been appreci-
ated that inflammation plays a prominent role in atherosclerosis
and its complications.
Whereas most clinicians previously regarded atheroma as a
bland lesion, the current notion that inflammation and immune
response contribute to atherogenesis has garnered increased
interest.
9
A picture emerges of a chronic disease that, from
its origin to its ultimate complications, involves inflamma-
tory cells (T cells, monocytes, macrophages), inflammatory
proteins (cytokines, chemokines) and inflammatory responses
from vascular cells.
10
Both infection and inflammation induce
the systemic host response known as the acute-phase response
(APR) and produce many abnormalities that could increase
the risk of developing atherosclerosis, including alterations in
lipid and lipoprotein metabolism, which is often mediated by
cytokines, particularly TNF-
α
, IL-1 and IL-6.
11
Hence, atherosclerosis is increasingly being recognised as
a complex phenomenon involving the interaction of several
mechanisms: dyslipidaemia, inflammation, thrombosis and other
dysfunctional metabolic syndromes.
12
This study attempts to
evaluate the contribution of dyslipidaemia and inflammation in
the pathogenesis of myocardial infarction and to study a possible
interplay between these risk factors in the pathophysiology of
CAD.
Methods
The study population comprised 150 consecutive male first-
time acute myocardial infarction patients without past or family
history of coronary events, presenting to the medical emergency
of Lok Nayak Hospital, New Delhi. Acute myocardial infarc-
tion was diagnosed based on clinical, electrocardiographic and
biochemical criteria. Patients with a history suggestive of hepatic
or renal disease were excluded. Use of lipid-lowering drugs also
led to exclusion from the study group.
The patients were enrolled in the study group after giving
informed consent and filling in a structured questionnaire,
including details of classical risk factors such as family history
of CAD, hypertension and smoking. Any patient with a history
of diabetes, hypertension, past or family history of CAD were
excluded from the study.
The study evaluated the role of inflammation and dyslipidae-
mia in those patients without apparent risk. The role of smok-
ing could not be excluded from the study groups, as it is very
common in India. Body mass index (BMI) values were derived
from Quetelet’s formula (weight in kg/height in m
2
). Approval
was obtained from the ethical committee of the institution before
commencing the study.
Also enrolled were 150 non-diabetic, age-matched healthy
controls who satisfied the following criteria: normal glucose
tolerance test, absence of angina (Rose questionnaire), absence
of history of any vascular disease [acute myocardial infarction
(AMI), stroke or intermittent claudication] and normal 12-lead
resting electrocardiograms. A patient was diagnosed with AMI if
there was a clinical history of ischaemic-type chest pain lasting
for more than 20 minutes, substantiated by electrocardiographic
evidence of Q waves, ST elevation/depression, and a rise in
cardiac troponins/CK-MB.
13
Arterial hypertension was diagnosed in patients with resting
blood pressure values above 140/90 mmHg measured repeti-
tively (at least twice).
14
Diabetes was diagnosed based on the
criteria of the American Diabetes Association expert committee
on diagnosis and classification of diabetes mellitus, i.e., fasting
plasma glucose
≥
126 mg/dl, two hours post-load glucose
≥
200
mg/dl or two random plasma glucose values
≥
200 mg/dl.
15
A fasting blood sample was taken and serum was sepa-
rated and stored at –70°C until the assays were performed. Total
cholesterol and triglycerides were measured using commercially
available kits on the Olympus AU400 (Hamburg, Germany)
auto-analyzer. High-density lipoprotein (HDL) cholesterol was
determined, after precipitation of Apo-B-containing particles by
phosphotungstic acid-MgCl
2
. Low-density lipoprotein (LDL)
cholesterol was calculated for subjects with fasting serum trig-
lyceride levels
<
400 mg/dl, using Friedwald’s formula.
16
Apo-B and Apo-AI were assayed using commercial kits based
on an automated immunoturbidimetric method (Randox, UK).
C-reactive protein (CRP) was quantitated in the serum using
immunoturbidimetric assay kits from Randox, UK. TNF-
α
levels
were measured using commercial ELISA kits from Diaclone
Research, Belgium. Lp(a) levels were estimated using enzyme-
linked immunosorbent assay [Innotest Lp(a), Innogenetics,
Belgium]. This method uses mouse monoclonal anti-Lp(a) as
solid-phase antibody and sheep anti-Apo-B polyclonal antibody
labelled with horseradish peroxidase (HRP) as capturing anti-
body.
Statistical analysis
All the values are expressed as mean
±
SD. Continuous vari-
ables were compared with the Student’s
t
-test. As the parameters
followed a non-Gaussian distribution in the study population,
Spearman’s rank correlation was used to look for association
between different variables in the study group. Univariate logis-
tic regression analysis was performed to ascertain the role of the
different risk factors for CAD in our study. A
p
-value
<
0.05 was
considered significant. Statistical analyses were performed with
SPSS for windows version 12 (SPSS Inc).
Results
The clinical characteristics of the study group are shown in
Table 1. Significantly elevated levels of total cholesterol, tri-
glycerides, LDL cholesterol andApo-B were observed in patients
with AMI, compared with healthy control subjects (Table 2). The
patients with AMI also exhibited lower HDL cholesterol and
Apo-AI, compared with controls (Table 2). However, there was
no statistically significant difference between Apo-AI levels of
patients and controls.
Serum levels of inflammatory markers such as CRP and
TNF-
α
were measured in the study population and they exhibit-
ed a highly significant difference between the patients with AMI
and the controls. Spearman’s rank correlation showed a highly
significant positive correlation between TNF-
α
and lipoprotein
(a), while a similar correlation was observed between CRP
and lipoprotein (a) (Table 3). The positive correlation between
TNF-
α
(a pro-inflammatory cytokine) and lipoprotein (a) levels
indicates a probable interrelationship between dyslipidaemia and
