Relationship of Insulin Resistance to Prevalence and Progression of Coronary Artery Calcification Beyond Metabolic Syndrome Components: Shiga Epidemiological Study of Subclinical Atherosclerosis.
The association between insulin resistance (IR) and coronary artery calcification (CAC) has been uncertain after adjustment for metabolic syndrome components. We aimed to evaluate whether IR is associated with CAC prevalence or progression independently of metabolic syndrome components.



We conducted a population-based study in a random sample of Japanese men aged 40 to 79 years and determined IR using the homeostasis model assessment of insulin resistance (HOMA-IR). The associations of HOMA-IR and other diabetic parameters per 1-SD increase with CAC prevalence and progression were evaluated using multivariable logistic regression. Of 1006 total participants at baseline (mean age, 64±10 years), CAC prevalence was observed in 646 (64.2%), and of 789 participants at follow-up (mean duration, 4.9±1.3 years), CAC progression was observed in 365 (46.3%). After adjustment for covariates including metabolic syndrome components, higher HOMA-IR was independently associated with CAC prevalence (adjusted odds ratio 1.34, 95% confidence interval 1.10-1.63; P=0.003) and progression (odds ratio 1.32, 95% confidence interval 1.09-1.60; P=0.004). In participants without diabetes mellitus, positive associations were similarly observed (prevalence: odds ratio 1.29, 95% confidence interval 1.04-1.60; P=0.022; and progression: odds ratio 1.25, 95% confidence interval 1.01-1.55; P=0.042), whereas glucose and hemoglobin A1c were not associated with CAC prevalence and progression.



Higher IR was associated with CAC prevalence and progression independently of metabolic syndrome components in Japanese men and also in those without diabetes mellitus. Among diabetic measures, IR and fasting insulin, but not glucose and hemoglobin A1c, predicted CAC progression in men without diabetes mellitus.
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.). masahiro.yamazoe@gmail.com.
Masahiro
M
Yamazoe
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Takashi
T
Hisamatsu
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Katsuyuki
K
Miura
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Sayaka
S
Kadowaki
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Maryam
M
Zaid
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Aya
A
Kadota
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Sayuki
S
Torii
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Itsuko
I
Miyazawa
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Akira
A
Fujiyoshi
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Hisatomi
H
Arima
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Akira
A
Sekikawa
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Hiroshi
H
Maegawa
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Minoru
M
Horie
From the Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan (M.Y.); Center for Epidemiologic Research in Asia (M.Y., K.M., A.K., H.A., H.U.), Department of Public Health (M.Y., T.H., K.M., S.K., M.Z., A.K., S.T., A.F., H.A., H.U.), Department of Cardiovascular and Respiratory Medicine (T.H., S.T., M.H.), Division of Endocrinology and Metabolism, Department of Medicine (I.M., H.M.), Shiga University of Medical Science, Otsu, Japan; Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University, Izumo, Japan (T.H.); Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (H.A.); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (A.S.).
Hirotsugu
H
Ueshima
D000328:Adult; D000368:Aged; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D016009:Chi-Square Distribution; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology*; D018450:Disease Progression; D005215:Fasting / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D015999:Multivariate Analysis; D016017:Odds Ratio; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D061205:Vascular Calcification / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology*
D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human
atherosclerosis; coronary artery calcification; epidemiology; insulin resistance; metabolic syndrome