Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:538-544
© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Insulin Resistance Syndrome Predicts the Risk of Coronary Heart Disease and Stroke in Healthy Middle-Aged Men
The 22-Year Follow-Up Results of the Helsinki Policemen Study
From the Department of Medicine (M.P., H.M., M.L., K.P.) and Computing Centre (P.H.), University of Kuopio, Kuopio, Finland.
Correspondence to Kalevi Pyörälä, MD, Department of Medicine, University of Kuopio, Puijonlaaksontie 2, PO Box 1627, 70211 Kuopio, Finland. E-mail kalevi.pyorala{at}uku.fi
Abstract—The interpretation of conventional multivariate analyses concerning the relation of insulin to the risk of atherosclerotic disease is complex because of correlations of insulin with other risk factors. Therefore, we applied factor analysis to study the clustering of risk factors in the baseline data of the Helsinki Policemen Study (970 healthy men aged 34 to 64 years) and investigated whether these clusterings predict coronary heart disease (CHD) and stroke risk. Areas under the glucose and insulin response curves (AUC glucose and AUC insulin) were used to reflect glucose and insulin levels during oral glucose tolerance tests. During the 22-year follow-up, 164 men had a CHD event, and 70 men had a stroke. Factor analysis of 10 risk factor variables produced 3 underlying factors: insulin resistance factor (comprising body mass index, subscapular skinfold, AUC insulin, AUC glucose, maximal O2 uptake, mean blood pressure, and triglycerides), lipid factor (cholesterol and triglycerides), and lifestyle factor (physical activity and smoking). In multivariate Cox models, the age-adjusted hazard ratio for insulin resistance factor during the 22-year follow-up was 1.28 (95% CI 1.10 to 1.50) with regard to CHD risk and 1.64 (95% CI 1.29 to 2.08) with regard to stroke risk. Lipid factor predicted the risk of CHD but not that of stroke, and lifestyle factor predicted a reduced CHD risk. Factor analysis including only 6 risk factor variables proposed to be central components of insulin resistance syndrome (body mass index, subscapular skinfold, AUC insulin, AUC glucose, mean blood pressure, and triglycerides) produced only a single insulin resistance factor that predicted the risk of CHD and stroke independently of other risk factors.
Key Words: coronary disease • epidemiology • insulin • insulin resistance syndrome • stroke
This article has been cited by other articles:
 |
|
 |
|
  T. Naya, N. Hosomi, H. Ohyama, S.-I. Ichihara, C. R. Ban, T. Takahashi, T. Taminato, A. Feng, M. Kohno, and J. A. Koziol Smoking, Fasting Serum Insulin, and Obesity Are the Predictors of Carotid Atherosclerosis in Relatively Young Subjects Angiology, January 1, 2008; 58(6): 677 - 684. [Abstract] [PDF]
|
|
|
|
 |
|
 M. T. Kearney, E. R. Duncan, M. Kahn, and S. B. Wheatcroft Insulin resistance and endothelial cell dysfunction: studies in mammalian models Exp Physiol, January 1, 2008; 93(1): 158 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Air and B. M. Kissela Diabetes, the Metabolic Syndrome, and Ischemic Stroke: Epidemiology and possible mechanisms Diabetes Care, December 1, 2007; 30(12): 3131 - 3140. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sierra-Johnson, A. Romero-Corral, V. K. Somers, F. Lopez-Jimenez, G. Walldius, A. Hamsten, M.-L. Hellenius, and R. M. Fisher ApoB/apoA-I ratio: an independent predictor of insulin resistance in US non-diabetic subjects Eur. Heart J., November 1, 2007; 28(21): 2637 - 2643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Fischoeder, H. Meyborg, D. Stibenz, E. Fleck, K. Graf, and P. Stawowy Insulin augments matrix metalloproteinase-9 expression in monocytes Cardiovasc Res, March 1, 2007; 73(4): 841 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Gami, B. J. Witt, D. E. Howard, P. J. Erwin, L. A. Gami, V. K. Somers, and V. M. Montori Metabolic Syndrome and Risk of Incident Cardiovascular Events and Death: A Systematic Review and Meta-Analysis of Longitudinal Studies J. Am. Coll. Cardiol., January 30, 2007; 49(4): 403 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Li, E. S Ford, L. C McGuire, and A. H Mokdad Association of metabolic syndrome and insulin resistance with congestive heart failure: findings from the Third National Health and Nutrition Examination Survey J. Epidemiol. Community Health, January 1, 2007; 61(1): 67 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Basili, G. Pacini, M. T. Guagnano, M. R. Manigrasso, F. Santilli, C. Pettinella, G. Ciabattoni, C. Patrono, and G. Davi Insulin Resistance as a Determinant of Platelet Activation in Obese Women J. Am. Coll. Cardiol., December 19, 2006; 48(12): 2531 - 2538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.D.H. Malnick and H. Knobler The medical complications of obesity QJM, September 1, 2006; 99(9): 565 - 579. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Blaha and T. A. Elasy Clinical Use of the Metabolic Syndrome: Why the Confusion? Clin. Diabetes, July 1, 2006; 24(3): 125 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. B. Mellen, W. T. Cefalu, and D. M. Herrington Diabetes, the Metabolic Syndrome, and Angiographic Progression of Coronary Arterial Disease in Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 189 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Wannamethee, A. G. Shaper, L. Lennon, and R. W. Morris Metabolic Syndrome vs Framingham Risk Score for Prediction of Coronary Heart Disease, Stroke, and Type 2 Diabetes Mellitus Arch Intern Med, December 12, 2005; 165(22): 2644 - 2650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Lawlor, G. Davey Smith, S. Ebrahim, C. Thompson, and N. Sattar Plasma Adiponectin Levels Are Associated with Insulin Resistance, But Do Not Predict Future Risk of Coronary Heart Disease in Women J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5677 - 5683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-M. Salmasi and M. Dancy The Glucose Tolerance Test, But Not HbA 1c, Remains the Gold Standard in Identifying Unrecognized Diabetes Mellitus and Impaired Glucose Tolerance in Hypertensive Subjects Angiology, September 1, 2005; 56(5): 571 - 579. [Abstract] [PDF]
|
|
|
|
|
|
R. Kahn, J. Buse, E. Ferrannini, and M. Stern The Metabolic Syndrome: Time for a Critical Appraisal: Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care, September 1, 2005; 28(9): 2289 - 2304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Levantesi, A. Macchia, R. Marfisi, M. G. Franzosi, A. P. Maggioni, G. L. Nicolosi, C. Schweiger, L. Tavazzi, G. Tognoni, F. Valagussa, et al. Metabolic Syndrome and Risk of Cardiovascular Events After Myocardial Infarction J. Am. Coll. Cardiol., July 19, 2005; 46(2): 277 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.A. Lteif, K. Han, and K.J. Mather Obesity, Insulin Resistance, and the Metabolic Syndrome: Determinants of Endothelial Dysfunction in Whites and Blacks Circulation, July 5, 2005; 112(1): 32 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Goodman, L. M. Dolan, J. A. Morrison, and S. R. Daniels Factor Analysis of Clustered Cardiovascular Risks in Adolescence: Obesity Is the Predominant Correlate of Risk Among Youth Circulation, April 19, 2005; 111(15): 1970 - 1977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Oh, F. B. Hu, J. E. Manson, M. J. Stampfer, and W. C. Willett Dietary Fat Intake and Risk of Coronary Heart Disease in Women: 20 Years of Follow-up of the Nurses' Health Study Am. J. Epidemiol., April 1, 2005; 161(7): 672 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Ferreira, J. W. R. Twisk, W. van Mechelen, H. C. G. Kemper, and C. D. A. Stehouwer Development of Fatness, Fitness, and Lifestyle From Adolescence to the Age of 36 Years: Determinants of the Metabolic Syndrome in Young Adults: The Amsterdam Growth and Health Longitudinal Study Arch Intern Med, January 10, 2005; 165(1): 42 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Prasad and A. A. Quyyumi Renin-Angiotensin System and Angiotensin Receptor Blockers in the Metabolic Syndrome Circulation, September 14, 2004; 110(11): 1507 - 1512. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. H. Huang, D. Gu, and T. Mazzone Oleic Acid Modulates the Post-translational Glycosylation of Macrophage ApoE to Increase Its Secretion J. Biol. Chem., July 9, 2004; 279(28): 29195 - 29201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J.G. Hanley, A. Festa, R. B. D'Agostino, L. E. Wagenknecht, P. J. Savage, R. P. Tracy, M. F. Saad, and S. M. Haffner Metabolic and Inflammation Variable Clusters and Prediction of Type 2 Diabetes: Factor Analysis Using Directly Measured Insulin Sensitivity Diabetes, July 1, 2004; 53(7): 1773 - 1781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Lawlor, S. Ebrahim, M. May, and G. Davey Smith (Mis)use of Factor Analysis in the Study of Insulin Resistance Syndrome Am. J. Epidemiol., June 1, 2004; 159(11): 1013 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schillaci, M. Pirro, G. Vaudo, F. Gemelli, S. Marchesi, C. Porcellati, and E. Mannarino Prognostic value of the metabolic syndrome in essential hypertension J. Am. Coll. Cardiol., May 19, 2004; 43(10): 1817 - 1822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.E. Schuitemaker, G.J. Dinant, G.A. Van Der Pol, A.F.M. Verhelst, and A. Appels Vital Exhaustion as a Risk Indicator for First Stroke Psychosomatics, April 1, 2004; 45(2): 114 - 118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Austin, K. L. Edwards, M. J. McNeely, W. L. Chandler, D. L. Leonetti, P. J. Talmud, S. E. Humphries, and W. Y. Fujimoto Heritability of Multivariate Factors of the Metabolic Syndrome in Nondiabetic Japanese Americans Diabetes, April 1, 2004; 53(4): 1166 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Bloomgarden Definitions of the Insulin Resistance Syndrome: The 1st World Congress on the Insulin Resistance Syndrome Diabetes Care, March 1, 2004; 27(3): 824 - 830. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Fonseca, C. Desouza, S. Asnani, and I. Jialal Nontraditional Risk Factors for Cardiovascular Disease in Diabetes Endocr. Rev., February 1, 2004; 25(1): 153 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Jaber, M. B. Brown, A. Hammad, Q. Zhu, and W. H. Herman The Prevalence of the Metabolic Syndrome Among Arab Americans Diabetes Care, January 1, 2004; 27(1): 234 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Tang, M. B. Miller, S. S. Rich, K. E. North, J. S. Pankow, I. B. Borecki, R. H. Myers, P. N. Hopkins, M. Leppert, and D. K. Arnett Linkage Analysis of a Composite Factor for the Multiple Metabolic Syndrome: The National Heart, Lung, and Blood Institute Family Heart Study Diabetes, November 1, 2003; 52(11): 2840 - 2847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W.F. Wilson and S. M. Grundy The Metabolic Syndrome: A Practical Guide to Origins and Treatment: Part II Circulation, September 30, 2003; 108(13): 1537 - 1540. [Full Text] [PDF]
|
|
|
|
|
|
J. B. Meigs, P. W.F. Wilson, D. M. Nathan, R. B. D'Agostino Sr., K. Williams, and S. M. Haffner Prevalence and Characteristics of the Metabolic Syndrome in the San Antonio Heart and Framingham Offspring Studies Diabetes, August 1, 2003; 52(8): 2160 - 2167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Knopp, B. Retzlaff, B. Fish, C. Walden, S. Wallick, M. Anderson, K. Aikawa, and S. E. Kahn Effects of Insulin Resistance and Obesity on Lipoproteins and Sensitivity to Egg Feeding Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): 1437 - 1443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. McCaffery, R. Niaura, J. F. Todaro, G. E. Swan, and D. Carmelli Depressive Symptoms and Metabolic Risk in Adult Male Twins Enrolled in the National Heart, Lung, and Blood Institute Twin Study Psychosom Med, May 1, 2003; 65(3): 490 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-J. Shen, J. F. Todaro, R. Niaura, J. M. McCaffery, J. Zhang, A. Spiro III, and K. D. Ward Are Metabolic Risk Factors One Unified Syndrome? Modeling the Structure of the Metabolic Syndrome X Am. J. Epidemiol., April 15, 2003; 157(8): 701 - 711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bonora, S. Kiechl, J. Willeit, F. Oberhollenzer, G. Egger, R. C. Bonadonna, and M. Muggeo Carotid Atherosclerosis and Coronary Heart Disease in the Metabolic Syndrome: Prospective data from the Bruneck Study Diabetes Care, April 1, 2003; 26(4): 1251 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ishizaka, Y. Ishizaka, E. Takahashi, T. Unuma, E.-i. Tooda, R. Nagai, M. Togo, K. Tsukamoto, H. Hashimoto, and M. Yamakado Association Between Insulin Resistance and Carotid Arteriosclerosis in Subjects With Normal Fasting Glucose and Normal Glucose Tolerance Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 295 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-M. Lakka, D. E. Laaksonen, T. A. Lakka, L. K. Niskanen, E. Kumpusalo, J. Tuomilehto, and J. T. Salonen The Metabolic Syndrome and Total and Cardiovascular Disease Mortality in Middle-aged Men JAMA, December 4, 2002; 288(21): 2709 - 2716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Golden, A. R. Folsom, J. Coresh, A. R. Sharrett, M. Szklo, and F. Brancati Risk Factor Groupings Related to Insulin Resistance and Their Synergistic Effects on Subclinical Atherosclerosis: The Atherosclerosis Risk in Communities Study Diabetes, October 1, 2002; 51(10): 3069 - 3076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Hanson, G. Imperatore, P. H. Bennett, and W. C. Knowler Components of the "Metabolic Syndrome" and Incidence of Type 2 Diabetes Diabetes, October 1, 2002; 51(10): 3120 - 3127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Laaksonen, H.-M. Lakka, J. T. Salonen, L. K. Niskanen, R. Rauramaa, and T. A. Lakka Low Levels of Leisure-Time Physical Activity and Cardiorespiratory Fitness Predict Development of the Metabolic Syndrome Diabetes Care, September 1, 2002; 25(9): 1612 - 1618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J.G. Hanley, A. J. Karter, A. Festa, R. D'Agostino Jr., L. E. Wagenknecht, P. Savage, R. P. Tracy, M. F. Saad, and S. Haffner Factor Analysis of Metabolic Syndrome Using Directly Measured Insulin Sensitivity: The Insulin Resistance Atherosclerosis Study Diabetes, August 1, 2002; 51(8): 2642 - 2647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J.G. Hanley, K. Williams, M. P. Stern, and S. M. Haffner Homeostasis Model Assessment of Insulin Resistance in Relation to the Incidence of Cardiovascular Disease: The San Antonio Heart Study Diabetes Care, July 1, 2002; 25(7): 1177 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. V. Chu, A. P. S. Kong, D. D. Kim, D. Armstrong, S. Baxi, R. Deutsch, M. Caulfield, S. R. Mudaliar, R. Reitz, R. R. Henry, et al. Differential Effects of Metformin and Troglitazone on Cardiovascular Risk Factors in Patients With Type 2 Diabetes Diabetes Care, March 1, 2002; 25(3): 542 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Srinivasan, L. Myers, and G. S. Berenson Predictability of Childhood Adiposity and Insulin for Developing Insulin Resistance Syndrome (Syndrome X) in Young Adulthood: The Bogalusa Heart Study Diabetes, January 1, 2002; 51(1): 204 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Rizos and D. P Mikhailidis Are high density lipoprotein (HDL) and triglyceride levels relevant in stroke prevention? Cardiovasc Res, November 1, 2001; 52(2): 199 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kain, A. J. Catto, J. Young, J. Bamford, J. Bavington, and P. J. Grant Insulin Resistance and Elevated Levels of Tissue Plasminogen Activator in First-Degree Relatives of South Asian Patients With Ischemic Cerebrovascular Disease Stroke, May 1, 2001; 32(5): 1069 - 1073. [Abstract] [Full Text]
|
|
|
|
|
|
I. F. Godsland, J. R. Rosankiewicz, A. J. Proudler, and D. G. Johnston Plasma Total Homocysteine Concentrations Are Unrelated to Insulin Sensitivity and Components of the Metabolic Syndrome in Healthy Men J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 719 - 723. [Abstract] [Full Text]
|
|
|
|
|
|
P. A. Sakkinen, P. Wahl, M. Cushman, M. R. Lewis, and R. P. Tracy Clustering of Procoagulation, Inflammation, and Fibrinolysis Variables with Metabolic Factors in Insulin Resistance Syndrome Am. J. Epidemiol., November 15, 2000; 152(10): 897 - 907. [Abstract] [Full Text] [PDF]
|
|