CLINICAL STUDIES
Serum insulin-like growth factor-I level is independently associated with coronary artery disease progression in young male survivors of myocardial infarction: beneficial effects of bezafibrate treatment
Giacomo Ruotolo, MD, PhD*,
Peter Båvenholm, MD, PhD ,
Kerstin Brismar, MD, PhD ,
Suad Eféndic, MD, PhD,
Carl-G.öran Ericsson, MD, PhD ,
Ulf de Faire, MD, PhD,
Jan Nilsson, MD, PhD* and
Anders Hamsten, MD, PhD*
* Atherosclerosis Research Unit, King Gustaf V Research Institute, Stockholm, Sweden
Department of Emergency and Cardiovascular Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden
Department of Endocrinology and Diabetology, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden
Department of Medicine, Karolinska Institute, Danderyd Hospital, Stockholm, Sweden
Manuscript received March 29, 1999;
revised manuscript received September 20, 1999,
accepted November 3, 1999.
Reprint requests and correspondence: Dr. Anders Hamsten, King Gustaf V Research Institute, Karolinska Hospital, S-171 76, Stockholm, Sweden
HAMSTEN{at}instmed.ks.se
OBJECTIVES
We investigated whether the effect of bezafibrate on progression of coronary atherosclerosis in the BEzafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) was related to insulin-like growth factor (IGF)-I and glucose-insulin homeostasis.
BACKGROUND
BECAIT, the first double-blind, placebo-controlled, randomized, serial angiographic trial of a fibrate compound, demonstrated that progression of focal coronary atherosclerosis in young patients after infarction could be retarded by bezafibrate treatment.
METHODS
The treatment effects on serum concentrations of IGF-I and insulin-like growth factor binding protein (IGFBP)-1, as well as on basal and postload glucose and insulin levels, were examined, and on-trial determinations were related to the angiographic outcome measurements.
RESULTS
Bezafibrate treatment resulted in a significant reduction of serum IGF-I levels, both at two and five years, and on-trial serum IGF-I levels were directly related to changes in both minimal lumen diameter (r = 0.25, p < 0.05) and mean segment diameter (r = 0.29, p < 0.05). In contrast, none of the available indexes of insulin resistance (homeostasis model assessment estimate, basal and postload plasma insulin concentrations and serum IGFBP-1 levels) were related to the angiographic changes, nor were they significantly affected by bezafibrate treatment. Multiple stepwise regression analysis showed that the relation between on-trial serum IGF-I level and coronary artery disease (CAD) progression was independent of baseline angiographic score, age, body mass index, serum lipoprotein and plasma fibrinogen concentrations and measures of glucose–insulin homeostasis.
CONCLUSIONS
IGF-I could be implicated in the progression of premature CAD, and a reduction of serum IGF-I concentration could account partly for the effect of bezafibrate on progression of focal coronary atherosclerosis.
|
Abbreviations and Acronyms
| | BECAIT | = BEzafibrate Coronary Atherosclerosis Intervention Trial | | HDL | = high density lipoprotein | | HOMA | = homeostasis model assessment | | IGF | = insulin-like growth factor | | IGFBP | = insulin-like growth factor binding protein | | LDL | = low density lipoprotein | | Lp(a) | = lipoprotein (a) | | MLD | = minimal lumen diameter | | MSD | = mean segment diameter | | VLDL | = very low density lipoprotein |
|
This article has been cited by other articles:
|
|
|
|
 
R. M. Martin, D. Gunnell, E. Whitley, A. Nicolaides, M. Griffin, N. Georgiou, G. Davey Smith, S. Ebrahim, and J. M. P. Holly
Associations of Insulin-Like Growth Factor (IGF)-I, IGF-II, IGF Binding Protein (IGFBP)-2 and IGFBP-3 with Ultrasound Measures of Atherosclerosis and Plaque Stability in an Older Adult Population
J. Clin. Endocrinol. Metab.,
April 1, 2008;
93(4):
1331 - 1338.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Jorn Schneider, J. Klotsche, B. Saller, S. Bohler, C. Sievers, D. Pittrow, G. Ruf, W. Marz, W. Erwa, A. M Zeiher, et al.
Associations of age-dependent IGF-I SDS with cardiovascular diseases and risk conditions: cross-sectional study in 6773 primary care patients
Eur. J. Endocrinol.,
February 1, 2008;
158(2):
153 - 161.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Schneider, B. Saller, J. Klotsche, W. Marz, W. Erwa, H.-U. Wittchen, and G. K. Stalla
Opposite associations of age-dependent insulin-like growth factor-I standard deviation scores with nutritional state in normal weight and obese subjects.
Eur. J. Endocrinol.,
May 1, 2006;
154(5):
699 - 706.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Meyerhardt, J. A. Sloan, D. J. Sargent, R. M. Goldberg, M. Pollak, R. F. Morton, R. K. Ramanathan, S. K. Williamson, B. P. Findlay, and C. S. Fuchs
Associations between Plasma Insulin-Like Growth Factor Proteins and C-Peptide and Quality of Life in Patients with Metastatic Colorectal Cancer
Cancer Epidemiol. Biomarkers Prev.,
June 1, 2005;
14(6):
1402 - 1410.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-i. Kawachi, N. Takeda, A. Sasaki, Y. Kokubo, K. Takami, H. Sarui, M. Hayashi, N. Yamakita, and K. Yasuda
Circulating Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 Are Associated With Early Carotid Atherosclerosis
Arterioscler Thromb Vasc Biol,
March 1, 2005;
25(3):
617 - 621.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Colangelo, K. Liu, and S. M. Gapstur
Insulin-like Growth Factor-1, Insulin-like Growth Factor Binding Protein-3, and Cardiovascular Disease Risk Factors in Young Black Men and White Men: The CARDIA Male Hormone Study
Am. J. Epidemiol.,
October 15, 2004;
160(8):
750 - 757.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Kajantie, C. H. D. Fall, M. Seppala, R. Koistinen, L. Dunkel, H. Yliharsila, C. Osmond, S. Andersson, D. J. P. Barker, T. Forsen, et al.
Serum Insulin-like Growth Factor (IGF)-I and IGF-Binding Protein-1 in Elderly People: Relationships with Cardiovascular Risk Factors, Body Composition, Size at Birth, and Childhood Growth
J. Clin. Endocrinol. Metab.,
March 1, 2003;
88(3):
1059 - 1065.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Juul, T. Scheike, M. Davidsen, J. Gyllenborg, and T. Jorgensen
Low Serum Insulin-Like Growth Factor I Is Associated With Increased Risk of Ischemic Heart Disease: A Population-Based Case-Control Study
Circulation,
August 20, 2002;
106(8):
939 - 944.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. Heald, K.W. Siddals, W. Fraser, W. Taylor, K. Kaushal, J. Morris, R. J. Young, A. White, and J. M. Gibson
Low Circulating Levels of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) Are Closely Associated With the Presence of Macrovascular Disease and Hypertension in Type 2 Diabetes
Diabetes,
August 1, 2002;
51(8):
2629 - 2636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Vaessen, P. Heutink, J. A. Janssen, J. C. M. Witteman, L. Testers, A. Hofman, S. W. J. Lamberts, B. A. Oostra, H. A. P. Pols, and C. M. van Duijn
A Polymorphism in the Gene for IGF-I: Functional Properties and Risk for Type 2 Diabetes and Myocardial Infarction
Diabetes,
March 1, 2001;
50(3):
637 - 642.
[Abstract]
[Full Text]
|
|
|
|
