CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 6, July 2012
332
AFRICA
smoking and diabetes mellitus was significantly higher in the
cases than the the controls. Subjects with none of the above risk
factors comprised 16% of the cases and 28% of the controls,
respectively.
The biochemical profile of the study population is given
in Table 2. Total cholesterol, triglyceride and LDL cholesterol
levels were higher in the patients compared to the controls (167.7
± 32.2 vs 150.1 ± 43. 9 mg/dl; 136.9 ± 61.7 vs 125.2 ± 49.6 mg/
dl; 112.7 ± 29.8 vs 100.5 ± 27.3 mg/dl, respectively). However
the differences were not statistically significant.
High-density lipoprotein (HDL) levels were significantly
lower in the cases than the controls (30.6 ± 6.8 vs 38.8 ± 7.6
mg/dl;
p
< 0.001). Lipoprotein (a) [lp(a)] levels demonstrated
a non-Gaussian distribution pattern with significantly higher
levels (34.8 ± 30.mg/dl) in the cases compared to 16.7 ± 13.5
mg/dl in the controls (
p
< 0.001). Significantly higher levels of
serum leptin, PAPP-A and hs-CRP were observed in the cases
compared to the controls (11.97 ± 8.5 vs 8.06 ± 5.8 ng/ml; 16.84
± 8.93 vs 10.4 ± 5.8 mIU/l and 5.46 ± 2.8 vs 2.93 ± 2.49 mg/l,
respectively).
In order to evaluate the performance of serum lp(a), leptin,
PAPP-A and hs-CRP levels as indicators of plaque rupture, the
receiver operating characteristics (ROC) curves were plotted.
Table 3 illustrates the findings elaborated by the ROC curves.
The area under the curve for hs-CRP was highest at 0.762,
followed closely by PAPP-A at 0.732. Cut-off points of these
parameters were determined from the curves, which could help
in prospective stratification of patients predisposed to unstable
atherosclerotic sequelae.
According to this, a cut off of 3.1 mg/l for hs-CRP has a
sensitivity of 77% and specificity of 73%. Similarly, a watershed
value of 11.75 mIU/l for PAPP-A exhibited 68% sensitivity
and 60% specificity. An attempt to increase the sensitivity was
accompanied by a corresponding reduction in specificity and
vice versa. Our study therefore proves the superiority of hs-CRP
as a marker of plaque rupture. However, PAPP-A also proved to
be a sensitive marker. Fig. 1 illustrates the ROC curves of the
different parameters in the study.
A positive correlation was observed between hs-CRP with
PAPP-A levels (
r
= 0.658,
p
< 0.01) and leptin (
r
= 0.612,
p
<
0.01). However, no such correlations were observed between
leptin, PAPP-A and lipid levels. This finding highlights the
interaction between hs-CRP and PAPP-A in initiating plaque
rupture. Multivariate regression analysis proved the superiority
of CRP over all the other parameters, with the order of
significance being CRP > CK-MB > HDL > total cholesterol/
HDL ratio > LDL/HDL ratio > fasting plasma glucose > lp(a)
> total cholesterol > LDL > insulin > triglycerides > PAPP-A >
leptin (Table 4).
Discussion
The burden of atherosclerotic disease is a major public health
problem in developed as well as developing countries and is
primarily attributed to physical inactivity, calorie-rich food
and a host of environmental and individualistic factors.
16
The
present study was undertaken to determine the efficacy of
the novel biomarkers, adipocytokines (leptin), inflammatory
mediator (hs-CRP) and a metalloproteinase (PAPP-A), for the
identification of unstable plaques.
In order to achieve the goal of our study, the patients presenting
to the hospital with acute coronary syndrome were classified as
cases or controls depending on the angiographic findings. Those
patients with normal coronary arteries comprised the control
group and those with documented lesions in their coronary
arteries were included in the patient group. The novelty of our
study lies in the comparison of four markers of cardiovascular
risk: dyslipidaemia [lp(a)], insulin reistance (leptin),
inflammation (hs-CRP) and matrix remodelling (PAPP-A), as
TABLE 2. BIOCHEMICAL PROFILE OFTHE STUDY POPULATION
Characteristics
Cases
Controls
p
-value
Total cholesterol (mg/dl)
167.7 ± 32.2 150.1 ± 43. 9 0.063
Triglycerides (mg/dl)
136.9 ± 61.7 125.2 ± 49.6
0.353
LDL-C (mg/dl)
112.7 ± 29.8 100.5 ± 27.3
0.067
HDL-C (mg/dl)
30.6 ± 6.8
38.8 ± 7.6 < 0.001
Lipoprotein (a) (mg/dl)
34.8 ± 30.1 16.7 ± 13.5 < 0.001
Leptin (ng/ml)
11.97 ± 8.5
8.06 ± 5.8
0.01
PAPP-A (mIU/l)
16.84 ± 8.93 10.4 ± 5.8 < 0.001
Hs-CRP (mg/l)
5.46 ± 2.8
2.93 ± 2.49 < 0.001
TABLE 3. RECEIVER OPERATING CHARACTERISTICS
OF THE PARAMETERS UNDER STUDY
Characteristics
AUC
p
-value
Cut offs chosen from
ROC curves
Lipoprotein (a)
0.778
0.001 15.9 mg/dl
Sensitivity 72%
Specificity 70%
Leptin
0.705
0.015 6.9 ng/ml
Sensitivity 66%
Specificity 60%
PAPP-A
0.901
0.002 11.75 mIU/l
Sensitivity 68%
Specificity 60%
Hs-CRP
0.849
< 0.001 3.1 mg/l
Sensitivity 77%
Specificity 73%
Fig. 1. ROC curves of the different parameters under study.
100
80
60
40
20
0
100
80
60
40
20
0
100
80
60
40
20
0
100
80
60
40
20
0
Sensitivity
Sensitivity
Sensitivity
Sensitivity
0 20 40 60 80 100
0 20 40 60 80 100
0 20 40 60 80 100
0 20 40 60 80 100
ROC (PAPPA)
ROC (LEPTIN)
ROC (CRP)
ROC (LPa)
100-Specificity
100-Specificity
100-Specificity
100-Specificity
