This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (48)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal

The Kuopio Ischaemic Heart Disease Risk Factor Study

Hanna-Maaria Lakka, MD; Timo A. Lakka, MD, PhD; Jaakko Tuomilehto, MD, PhD; Juhani Sivenius, MD, PhD; Jukka T. Salonen, MD, PhD

Arch Intern Med. 2000;160:1160-1168.

Background  The role of hyperinsulinemia as a cardiovascular risk factor is controversial. We studied whether hyperinsulinemia is independently associated with increased cardiovascular morbidity and mortality.

Methods  Fasting serum insulin level and other cardiovascular risk factors were determined in 1521 men in eastern Finland aged 42 to 60 years with neither cardiovascular disease nor diabetes at baseline. Forty-five cardiovascular deaths, 110 acute coronary events, 48 strokes, and 163 any cardiovascular events occurred during an average follow-up of 9.5 years. A total of 163 cardiovascular events (45 cardiovascular deaths, 110 acute coronary events, and 48 strokes) occurred during an average follow-up of 9.5 years.

Results  In Cox regression analysis adjusting for age and examination years, fasting serum insulin level as a continuous variable was directly associated with the risk of cardiovascular death (P=.006), acute coronary events (P=.04), and stroke (P=.02). Men with insulin levels of 52 to 66 pmol/L, 67 to 89 pmol/L, and 90 pmol/L or more (3 highest quartiles) had 1.4-fold (95% confidence interval, 0.5-3.7), 1.4-fold (95% confidence interval, 0.5-3.7), and 2.5-fold (95% confidence interval, 1.0-5.9; P=.05) cardiovascular mortality, respectively, compared with men with insulin levels of less than 52 pmol/L (lowest quartile) (P=.04 for linear trend). Adjustment for serum lipid levels, blood pressure, and obesity reduced the excess cardiovascular mortality in the highest insulin quartile by 7%, 33%, and 67%, respectively. There were no statistically significant differences in the incidence of acute coronary events and stroke between the insulin quartiles.

Conclusions  Hyperinsulinemia had a modest association with increased cardiovascular mortality in middle-aged men. This relationship was largely explained by obesity, hypertension, and dyslipidemia. Hyperinsulinemia had even weaker associations with the risk of acute coronary event and stroke.

From the Research Institute of Public Health, University of Kuopio (Drs H.-M. Lakka, T. A. Lakka, and Salonen), and Departments of Medicine (Dr T. A. Lakka) and Neurology and Neuroscience (Dr Sivenius), Kuopio University Hospital, Kuopio, Finland; and Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland (Dr Tuomilehto).

RELATED ARTICLE

Archives of Internal Medicine Reader's Choice: Continuing Medical Education
Arch Intern Med. 2000;160(8):1206-1207.
FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Relationship of Glycemic Control, Exogenous Insulin, and C-Peptide Levels to Ischemic Heart Disease Mortality Over a 16-Year Period in People With Older-Onset Diabetes: The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR)
Hirai et al.
Diabetes Care 2008;31:493-497.
ABSTRACT | FULL TEXT  

Diabetes, the Metabolic Syndrome, and Ischemic Stroke: Epidemiology and possible mechanisms
Air and Kissela
Diabetes Care 2007;30:3131-3140.
FULL TEXT  

Circulating concentrations of insulin markers and coronary heart disease: a quantitative review of 19 Western prospective studies
Sarwar et al.
Eur Heart J 2007;28:2491-2497.
ABSTRACT | FULL TEXT  

Treadmill Aerobic Training Improves Glucose Tolerance and Indices of Insulin Sensitivity in Disabled Stroke Survivors: A Preliminary Report
Ivey et al.
Stroke 2007;38:2752-2758.
ABSTRACT | FULL TEXT  

Effect of Eucaloric High- and Low-Sucrose Diets With Identical Macronutrient Profile on Insulin Resistance and Vascular Risk: A Randomized Controlled Trial
Black et al.
Diabetes 2006;55:3566-3572.
ABSTRACT | FULL TEXT  

Exogenous Insulin Use and Hypertension in Adult Patients With Type 2 Diabetes Mellitus.
Tseng
Arch Intern Med 2006;166:1184-1189.
ABSTRACT | FULL TEXT  

Metabolic Syndrome and the Risk of Stroke in Middle-Aged Men
Kurl et al.
Stroke 2006;37:806-811.
ABSTRACT | FULL TEXT  

Basal Insulin Therapy in Type 2 Diabetes
Bethel and Feinglos
J Am Board Fam Med 2005;18:199-204.
ABSTRACT | FULL TEXT  

Proinsulin Concentration Is an Independent Predictor of All-Cause and Cardiovascular Mortality: An 11-year follow-up of the Hoorn Study
Alssema et al.
Diabetes Care 2005;28:860-865.
ABSTRACT | FULL TEXT  

Biochemical risk markers: a novel area for better prediction of renal risk?
Stuveling et al.
Nephrol Dial Transplant 2005;20:497-508.
FULL TEXT  

Sex Hormone-Binding Globulin and Insulin-Like Growth Factor-Binding Protein-1 as Indicators of Metabolic Syndrome, Cardiovascular Risk, and Mortality in Elderly Men
Kalme et al.
J. Clin. Endocrinol. Metab. 2005;90:1550-1556.
ABSTRACT | FULL TEXT  

Depression and early retirement: prospective population based study in middle aged men
Karpansalo et al.
J. Epidemiol. Community Health 2005;59:70-74.
ABSTRACT | FULL TEXT  

Metabolic Syndrome and the Risk of Prostate Cancer in Finnish Men: A Population-Based Study
Laukkanen et al.
Cancer Epidemiol. Biomarkers Prev. 2004;13:1646-1650.
ABSTRACT | FULL TEXT  

Uric Acid Level as a Risk Factor for Cardiovascular and All-Cause Mortality in Middle-aged Men: A Prospective Cohort Study
Niskanen et al.
Arch Intern Med 2004;164:1546-1551.
ABSTRACT | FULL TEXT  

Pioglitazone Reduces Atherogenic Index of Plasma in Patients with Type 2 Diabetes
Tan et al.
Clin. Chem. 2004;50:1184-1188.
ABSTRACT | FULL TEXT  

Association of the Mitochondrial DNA 16189 T to C Variant with Lacunar Cerebral Infarction: Evidence from a Hospital-Based Case-Control Study
LIOU et al.
Ann. N. Y. Acad. Sci. 2004;1011:317-324.
ABSTRACT | FULL TEXT  

Cardiorespiratory fitness and risk of disability pension: a prospective population based study in Finnish men
Karpansalo et al.
Occup. Environ. Med. 2003;60:765-769.
ABSTRACT | FULL TEXT  

Carbohydrates, dietary glycaemic load and glycaemic index, and risk of acute myocardial infarction
Tavani et al.
Heart 2003;89:722-726.
ABSTRACT | FULL TEXT  

Diabetes, Plasma Insulin, and Cardiovascular Disease: Subgroup Analysis From the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT)
Rubins et al.
Arch Intern Med 2002;162:2597-2604.
ABSTRACT | FULL TEXT  

The Metabolic Syndrome and Total and Cardiovascular Disease Mortality in Middle-aged Men
Lakka et al.
JAMA 2002;288:2709-2716.
ABSTRACT | FULL TEXT  

Insulin resistance and risk for stroke
Kernan et al.
Neurology 2002;59:809-815.
ABSTRACT | FULL TEXT  

Low Levels of Leisure-Time Physical Activity and Cardiorespiratory Fitness Predict Development of the Metabolic Syndrome
Laaksonen et al.
Diabetes Care 2002;25:1612-1618.
ABSTRACT | FULL TEXT  

Abdominal obesity is associated with increased risk of acute coronary events in men
Lakka et al.
Eur Heart J 2002;23:706-713.
ABSTRACT | FULL TEXT  

Low Dietary Folate Intake Is Associated With an Excess Incidence of Acute Coronary Events : The Kuopio Ischemic Heart Disease Risk Factor Study
Voutilainen et al.
Circulation 2001;103:2674-2680.
ABSTRACT | FULL TEXT  

Insulin Resistance and Elevated Levels of Tissue Plasminogen Activator in First-Degree Relatives of South Asian Patients With Ischemic Cerebrovascular Disease
Kain et al.
Stroke 2001;32:1069-1073.
ABSTRACT | FULL TEXT  

Fish Oil-Derived Fatty Acids, Docosahexaenoic Acid and Docosapentaenoic Acid, and the Risk of Acute Coronary Events : The Kuopio Ischaemic Heart Disease Risk Factor Study
Rissanen et al.
Circulation 2000;102:2677-2679.
ABSTRACT | FULL TEXT  

Hyperinsulinemia and the Risk for Stroke
JWatch Neurology 2000;2000:6-6.
FULL TEXT