Abstract

Aims Serum C3 is a powerful indicator of the risk of myocardial infarction, which correlates with body mass index, serum lipids and blood pressure. This study was performed to ascertain whether such correlations may be explained by an association of C3 with fasting insulin, and to assess comparatively the relationships of C3 and traditional risk factors to previous myocardial infarction.

Methods and Results The fasting levels of C3, insulin, and the main risk factors were evaluated in 1090 unselected men aged 55-64 years, including 129 cases of previous ischaemic events (51 myocardial infarctions). In multivariate analysis C3 was associated with insulin (r=0·27,P <0·0001), cholesterol (r=0·18, P<0·0001), body mass index (r=0·13, P<0·0001), glucose (r=0·12, P=0·0001), systolic blood pressure (r=0·10, P<0·001), triglycerides (r=0·09, P<0·01) and HDL-cholesterol (r=−0·06, P<0·05). These variables explained 31% of the total C3 variance. Alcohol consumption and physical activity correlated inversely with C3, while no correlation was found with smoking and family history of myocardial infarction. C3 was associated with previous myocardial infarction and stroke, but not with angina pectoris and peripheral arterial disease. In logistic regression the variables associated with previous myocardial infarction were C3 (P=0·011), family history of myocardial infarction (P=0·018), ex-smoker status (P=0·020), age (P=0·025), glucose (P=0·028) and HDL-cholesterol (P=0·051, inverse relationship).

Conclusions The association of C3 with myocardial infarction persists retrospectively, and is more significant than any other association of traditional risk factors with previous myocardial infarction. Of the many variables associated with C3, fasting insulin is its main covariate, which suggests that C3 is a marker of a pro-atherogenic metabolic imbalance partly coinciding with insulin resistance.

f1
Correspondence: Antonio Muscari, MD, Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna–S. Orsola-Malpighi Hospital, Via Massarenti, 9-40138 Bologna, Italy.

References

1
Zimmer
B
, Hartung HP, Scharfenberger G, Bitter-Suermann P, Hadding U. Quantitative studies of the secretion of complement component C3 by resident, elicited and activated macrophages. Comparison with C2, C4 and Lysosomal enzyme release.
Eur J Immunol
 .
1982
;
12
:
426
–430
2
Libby
P
. Molecular bases of the acute coronary syndromes.
Circulation
 .
1995
;
91
:
2844
–2850
3
Alper
CA
, Johnson AM, Birtch AG, Moore FD. Human C′3: evidence for the liver as the primary site of synthesis.
Science
 .
1969
;
163
:
286
–288
4
Baumann
H
, Gauldie J. The acute phase response.
Immunol Today
 .
1994
;
15
:
74
–80
5
Muscari
A
, Bozzoli C, Puddu GM. Association of serum C3 levels with the risk of myocardial infarction.
Am J Med
 .
1995
;
98
:
357
–364
6
Muscari
A
, Massarelli G, Bastagli L. Relationship between serum C3 levels and traditional risk factors for myocardial infarction.
Acta Cardiologica
 .
1998
;
53
:
345
–354
7
Choy
LN
, Rosen BS, Spiegelman BM. Adipsin and an endogenous pathway of complement from adipose cells.
J Biol Chem
 .
1992
;
267
:
12736
–12741
8
Muscari
A
, Bozzoli C, Puddu GM. Correlations between serum lipids and complement components in adults without demonstrated atherosclerotic disease.
Atherosclerosis
 .
1990
;
81
:
111
–118
9
Ylitalo
K
, Porkka KVK, Meri S. Serum complement and familial combined hyperlipidemia.
Atherosclerosis
 .
1997
;
129
:
271
–277
10
Uza
G
, Cristea A, Cucuianu MP. Increased levels of the complement C3 protein in endogenous hypertriglyceridemia.
J Clin Lab Immunol
 .
1982
;
8
:
101
–105
11
Bozzoli
C
, Muscari A, Puddu GM. Associazione fra C3 sierico e ipertensione essenziale.
G Ital Cardiol
 .
1992
;
22
:
1361
–1366
12
Reaven
GM
. Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension. Parallels between human disease and rodent models.
Diabetes Care
 .
1991
;
14
:
195
–202
13
Juhan-Vague
I
, Thompson SG, Jespersen J. Involvement of the hemostatic system in the insulin resistance syndrome. A study of 1500 patients with angina pectoris.
Arterioscler Thromb
 .
1993
;
13
:
1865
–1873
14
Solymoss
BC
, Marcil M, Chaour M, Gilfix BM, Poitras AM, Campeau L. Fasting hyperinsulinism, insulin resistance syndrome, and coronary heart disease in men and women.
Am J Cardiol
 .
1995
;
76
:
1152
–1156
15
Després
JP
, Lamarche B, Mauriège P. Hyperinsulinemia as an independent risk factor for ischemic heart disease.
N Engl J Med
 .
1996
;
334
:
952
–957
16
Sternberg
JC
. A rate nephelometer for measuring specific proteins by immunoprecipitin reactions.
Clin Chem
 .
1977
;
23
:
1456
–1464
17
Allain
CC
, Poon LS, Chan CSG, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol.
Clin Chem
 .
1974
;
20
:
470
–475
18
Bucolo
G
, David H. Quantitative determination of serum triglycerides by the use of enzymes.
Clin Chem
 .
1973
;
19
:
476
–482
19
Bank
HL
. A quantitative enzyme-linked immunosorbent assay for rat insulin.
J Immunoassay
 .
1988
;
9
:
135
–158
20
Festa
A
, D'Agostino R Jr, Mykkanen L. Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a large population with different states of glucose tolerance: the Insulin Resistance Atherosclerosis Study (IRAS).
Arterioscler Thromb Vasc Biol
 .
1999
;
19
:
562
–568
21
Juhan-Vague
I
, Alessi MC, Joly P. Plasma plasminogen activator inhibitor-1 in angina pectoris. Influence of plasma insulin and acute-phase response.
Arteriosclerosis
 .
1989
;
9
:
362
–367
22
Hotamisligil
GS
, Budavari A, Murray D, Spiegelman BM. Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha.
J Clin Invest
 .
1994
;
94
:
1543
–1549
23
Yudkin
JS
, Stehouwer CDA, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction. A potential role for cytokines originating from adipose tissue?
Arterioscler Thromb Vasc Biol
 .
1999
;
19
:
972
–978
24
Campos
SP
, Baumann H. Insulin is a prominent modulator of the cytokine-stimulated expression of acute-phase plasma protein genes.
Mol Cell Biol
 .
1992
;
12
:
1789
–1797
25
Muscari
A
, Massarelli G, Bastagli L. Different relationship of C3, C-reactive protein and fibrinogen with arterial plaque echostructure (Abstr).
J Am Coll Cardiol
 .
1998
;
31
:
204
26
Baldo
A
, Sniderman AD, St-Luce S. The adipsin-acylation stimulating protein system and regulation of intracellular triglyceride synthesis.
J Clin Invest
 .
1993
;
92
:
1543
–1547
27
Germinario
R
, Sniderman AD, Manuel S, Lefebvre SP, Baldo A, Cianflone K. Coordinate regulation of triacyglycerol synthesis and glucose transport by acylation-stimulating protein.
Metabolism
 .
1993
;
42
:
574
–580
28
Goss
V
, Andus T, Tran-Thi TA, Bauer J, Decker K, Heinrich PC. Induction of acute phase proteins by dexamethasone in rat hepatocyte primary cultures.
Exp Cell Res
 .
1984
;
151
:
46
–54
29
Naitoh
Y
, Fukata J, Tominaga T. Interleukin-6 stimulates the secretion of adrenocorticotropic hormone in conscious, freely-moving rats.
Biochem Biophys Res Commun
 .
1988
;
155
:
1459
–1463
30
Szabo
G
, Mandrekar P, Girouard L, Catalano D. Regulation of human monocyte functions by acute ethanol treatment: decreased tumor necrosis factor-alpha, interleukin-1 beta, and elevated interleukin-10 and transforming growth factor-beta production.
Alcohol Clin Exp Res
 .
1996
;
20
:
900
–907
31
Smith
JK
, Chi DS, Krish G, Reynolds S, Cambron G. Effect of exercise on complement activity.
Ann Allergy
 .
1990
;
65
:
304
–310
32
Van der Poll
T
, Lowry SF. Epinephrine inhibits endotoxin-induced IL-1 beta production: roles of tumor necrosis factor-alpha and IL-10.
Am J Physiol
 .
1997
;
273
:
R1885
–1890
33
Burke
AP
, Farb A, Malcolm GT, Liang YH, Smialek J, Virmani R. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly.
N Engl J Med
 .
1997
;
336
:
1276
–1282
34
Mendall
MA
, Patel P, Ballam L, Strachan D, Northfield TC. C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study.
BMJ
 .
1996
;
312
:
1061
–1065
35
Scarabin
PY
, Aillaud MF, Amouyel P. Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction. The Prime Study.
Thromb Haemost
 .
1998
;
80
:
749
–756

Comments

0 Comments