CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 6, July 2012
334
AFRICA
of plaque rupture, myocardial infarction, revascularisation and
cardiovascular death in both troponin T-positive or -negative
patients.
51
Studiesinpatientswithstableanginahaveprovedthesuperiority
of PAPP-A over troponinT and hs-CRP levels.
52
Elevated PAPP-A
levels in asymptomatic hyperlipidaemic patients were associated
with increased echogenicity of carotid atherosclerotic plaques.
53
Experimental as well as epidemiological data substantiated the
role of PAPP-A in the detection of unstable CAD in patients
with normal troponin levels.
54,55
This could help in the prompt
identification and timely intervention in high-risk populations.
We also observed a statistically significant correlation
between PAPP-A and CRP levels in patients with ACS. It has
been reported that pro-inflammatory cytokines such as TNF-
α
stimulate PAPP-A synthesis by macrophages. The accumulation
of activated macrophages at the site of unstable plaques leads to
the release of PAPP-A by these cells.
56
The correlation between
these two mediators suggests the complex interplay between
various pathways that eventually converge to promote plaque
instability. Such an association between CRP and PAPP-A levels
was also reported by Heeschen
et al
.
51
and Jin-Lai
et al
.
57
A similar correlation was observed between CRP and leptin
levels. Obesity is associated with an inflammatory response
characterised by high levels of pro-inflammatory cytokines.
58
Receptors for leptin and cytokines are structurally related. Leptin
can also directly induce the production IL-6, which is the most
potent stimulator of CRP synthesis.
59
Hence a positive correlation
was observed between leptin and CRP levels. Obesity therefore
leads to a higher risk of CAD due to the synergism between
hyperleptinaemia and the on-going low-grade inflammatory
process.
Conclusions
Coronary artery disease is the root cause of mortalities due to
non-infectious aetiology. The initiation of florid plaque rupture
and the consequent complications lead to various life-threatening
sequelae of atherosclerotic disease. Hence, identification of
plaque vulnerability at the incipient stages may help in effective
and timely management.
Currently, detection of plaque status involves invasive
procedures such as coronary angiography and intravascular
ultrasound, which have their own shortcomings due to their
invasive nature and patient non-compliance, as well as financial
constraints. Therefore the identification of a simple blood test
that may aid in this endeavour is the need of the hour.
We observed hs-CRP and PAPP-A levels to be effective
indicators of plaque rupture. Interpretation of CRP data requires
consideration of confounding factors such as inflammation.
PAPP-A levels are not affected by infections or any underlying
inflammation. Therefore assessment of PAPP-A levels may be a
very attractive alternative for detecting unstable plaque activity
and hence useful in stratification and prognostication of subjects.
The ability of PAPP-A to detect plaque function even when
the other markers of myocardial injury such as troponins are
not elevated, is another justification for evaluation of PAPP-A
level as a novel marker of plaque vulnerability. The comparison
of PAPP-A and hs-CRP levels with the established biomarker
troponin T needs to be evaluated and the results substantiated by
studies carried out in large, population-based studies.
References
1.
Capewell S, McMurray J. Chest pains – please admit: is there an alter-
native? A rapid cardiological assessment service may prevent unneces-
sary admissions.
Br Med J
2000;
320
: 951.
2.
Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey
DE,
et al
. ACC/AHA 2007 Guidelines for the management of patients
with unstable angina/non–ST-elevation myocardial infarction. A report
of the American College of Cardiology/American Heart Association
Task Force on practice guidelines.
J Am Coll Cardiol
2007;
50
: 1–157.
3.
Mallika V, Goswami B, Rajappa M. Atherosclerosis-pathophysiology
and role of novel risk factors: a clinico-biochemical perspective.
Angiology
2007;
58
: 513–522.
4.
Wood D. Established and emerging cardiovascular risk factors.
Am
Heart J
2001;
141
: S49–57.
5.
Blake GJ, Ridker PM. C-reactive protein and other inflammatory risk
markers in acute coronary syndromes
. J Am Coll Cardiol
2003;
41
(4
Suppl S): 37S–42S.
6.
Knudson JD, Dick GM, Tune JD. Adipokines and coronary vasomotor
dysfunction.
Exp Biol Med
2007;
232
: 727–736.
7.
Friedman JM, Halaas JL. Leptin and the regulation of body weight in
mammals.
Nature
1998;
395
: 763–770.
8.
Dubey L, Zeng HS, Wang HJ, Liu RY. Potential role of adipocytokine
leptin in acute coronary syndrome.
Asian Cardiovasc Thorac Ann
2008;
16
: 124–128.
9.
Sainani GS, Karatela RA. Plasma leptin in insulin-resistant and insulin-
nonresistant coronary artery disease and its association with cardio-
metabolic risk factors among Asian Indians.
Metabol Syndrome Related
Disord
2009;
7
(4): 335–340.
10. Hoefle G, Saely CH, Risch L, Rein P, Koch L, Schmid F,
et al
. Leptin,
leptin soluble receptor and coronary atherosclerosis.
Eur J Clin Invest
2007;
37
: 629–636.
11. Thorn EM, Khan IA. Pregnancy-associated plasma protein-A: an
emerging cardiac biomarker.
Int J Cardiol
2007;
117
(3): 370–372.
12. Iversen KK, Dalsgaard M, Teisner AS, Schoos M, Teisner B, Nielsen
H,
et al
. Pregnancy-associated plasma protein – a, marker for outcome
in patients suspected for acute coronary syndrome.
Clin Biochem
2010;
43
: 851–857.
13. Bayes-Genis A, Conover CA, Overgaard MT, Bailey KR, Christiansen
M, Holmes DR jun,
et al
. Pregnancy- associated plasma protein A
as a marker of acute coronary syndromes.
N Engl J Med
2001;
345
:
1022–1029.
14. Aronson D, Goldberg A, Roguin A, Petcherski S, Rimer D, Gruberg L,
et al.
Effect of obesity on the relationship between plasma C-reactive
protein and coronary artery stenosis in patients with stable angina.
Atherosclerosis
2006;
185
(1): 137–142.
15. Zebrack, JS, Muhlestein JB, Horne BD, Anderson JL, Intermountain
Heart Collaboration Study Group. C-reactive protein and angiographic
coronary artery disease: independent and additive predictors of risk in
subjects with angina.
J Am Coll Cardiol
2002;
39
: 632–637.
16. Murray CJ, Lopez AD. Global mortality, disability and the contribu-
tion of risk factors: Global Burden of Disease Study.
Lancet
1997;
49
:
1498–1504.
17. Karaduman M, Oktenli C, Musabak U, Sengul A, Yesilova Z, Cingoz
F,
et al.
Leptin, soluble interleukin-6 receptor, C-reactive protein and
soluble vascular cell adhesion molecule-1 levels in human coronary
atherosclerotic plaque.
Clin Exp Immunol
2006;
143
(3): 452–457.
18. Wallace AM, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A,
et al
. on behalf of the WOSCOPS Executive Committee Plasma leptin
and the risk of cardiovascular disease in the west of Scotland coronary
prevention study (WOSCOPS).
Circulation
2001;
104
: 3052–3056.
19. Soderberg S, Ahren B, Jansson JH, Johnson O, Hallmans G, Asplund K,
et al
. Leptin is associated with increased risk of myocardial infarction.
J Intern Med
1999;
246
: 409–418.
20. Qasim A, Mehta NN, Tadesse MG, Wolfe ML, Rhodes T, Girman C,
et
al
. Adipokines, Insulin Resistance and Coronary Artery Calcification.
J Am Coll Cardiol
2008;
52
(3): 231–236.
21. Ren J. Leptin and hyperleptinemia – from friend to foe for cardiovascu-
lar function.
J Endocrinol
2004;
181
: 1–10.
