Introduction: Association between insulin resistance (IR) and prevalence of coronary artery calcification (CAC) has been inconsistent after adjustment for metabolic syndrome (MetS). In addition, relation of IR to progression of CAC has remained unclear. Recent basic science studies have reported that IR could promote atherosclerosis not only through the mechanisms that involve systemic factors such as dyslipidemia and hypertension, but also through the effect of perturbed insulin signaling at the cell level. Therefore we assessed the hypothesis that IR is associated with CAC prevalence or progression independently of MetS components in a general population.
Methods: We conducted a population-based study in a random sample of men aged 40-79 years living in Kusatsu City, Shiga, Japan, without prior coronary heart disease (Shiga Epidemiological Study of Subclinical Atherosclerosis; SESSA). IR was determined by homeostasis model assessment of IR index (HOMA-IR). We measured CAC at baseline and five years later with noncontrast computed tomography. CAC prevalence was defined as baseline CAC score > 0, and CAC progression as a change > 2.5 between the square root transformed values of baseline and follow-up CAC scores. Multivariate logistic regression was performed to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI) in total participants and in those without diabetes.
Results: Of 1022 total participants at baseline (mean age, 64 ± 10 years), CAC prevalence was found in 658 (64.4%), and of 804 participants at follow-up (mean follow-up duration, 4.9 ± 1.3 years), CAC progression in 371 (46.1%). Even after adjustment for MetS components in addition to other confounding factors, higher HOMA-IR was independently associated with CAC prevalence (OR, 1.35; 95% CI, 1.11-1.64; P = 0.003) and CAC progression (OR, 1.44; 95% CI, 1.18-1.74; P < 0.001). In participants without diabetes (N = 807 at baseline, N = 638 at follow-up), we observed similar positive associations of HOMA-IR with CAC prevalence (OR, 1.30; 95% CI 1.05-1.61; P = 0.016) and CAC progression (OR 1.31; 95% CI 1.03-1.67; P = 0.025). In contrast, fasting glucose and hemoglobin A1c were not related to CAC prevalence and progression.
Conclusion: In conclusion, higher IR was associated with CAC prevalence and progression independently of MetS components in general men and also in those without diabetes. Adding measuring of IR as routine clinical examination may provide additional predictive value beyond traditional risk assessment especially among population without diabetes.