Lowering the Triglyceride/High-Density Lipoprotein Cholesterol Ratio Is Associated With the Beneficial Impact of Pioglitazone on Progression of Coronary Atherosclerosis in Diabetic Patients: Insights From the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) Study

Abstract

The purpose of this study was to determine the factors associated with the favorable effect of pioglitazone on atheroma progression. Diabetes mellitus is associated with accelerated coronary atheroma progression. Pioglitazone slowed progression compared with glimepiride in this population. In all, 360 diabetic patients with coronary artery disease were treated with pioglitazone or glimepiride for 18 months in the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. Coronary atheroma progression was evaluated by serial intravascular ultrasound. The relationship between changes in biochemical parameters, percent atheroma volume, and total atheroma volume was investigated. Pioglitazone-treated patients demonstrated greater increases in high-density lipoprotein cholesterol (HDL-C) and reductions in glycated hemoglobin, triglycerides, and C-reactive protein. Significant correlations were observed between changes in percent atheroma volume and triglycerides (r = 0.15, p = 0.04), triglyceride/HDL-C ratio (r = 0.16, p = 0.03), and glycated hemoglobin (r = 0.16, p = 0.03) with pioglitazone, and changes in low-density lipoprotein cholesterol (r = -0.15, p = 0.05), apolipoprotein B (r = -0.16, p = 0.04), and apolipoprotein A-I (r = -0.20, p = 0.01) with glimepiride. Substantial atheroma regression, compared to progression, was associated with greater relative increases in HDL-C (14.2% vs. 7.8%, p = 0.04), relative decreases in triglycerides (-13.3% vs. -1.9%, p = 0.045), triglyceride/HDL-C ratio (-22.5 vs. -9.9%, p = 0.05), and decrease in glycated hemoglobin (-0.6% vs. -0.3%, p = 0.01). Multivariable analysis revealed that pioglitazone-induced effects on triglyceride/HDL-C were associated with changes in percent atheroma volume (p = 0.03) and total atheroma volume (p = 0.02). Favorable effects of pioglitazone on the triglyceride/HDL-C ratio correlated with delayed atheroma progression in diabetic patients. This finding highlights the potential importance of targeting atherogenic dyslipidemia in diabetic patients with coronary artery disease.