Apolipoprotein CIII in statin-treated type 2 diabetic patients: Its implications for plaque progression and instability: The pre-specified analysis from the OPTIMAL randomized controlled trial.

AIMS: Apolipoprotein CIII (ApoCIII) has a variety of proatherogenic properties. Given that hyperglycemia induces ApoCIII transcription, this apolipoprotein may promote coronary atherosclerosis in type 2 diabetic patients. We aimed to elucidate whether ApoCIII affects plaque progression and instability in statin-treated type 2 diabetic patients.

METHODS AND

RESULTS

The OPTIMAL study was a prospective randomized controlled trial that employed serial NIRS/IVUS imaging to evaluate the efficacy of glycemic control on coronary atherosclerosis in 94 statin-treated type 2 diabetic patients (UMIN000036721). Of these, 78 patients with both ApoCIII levels and NIRS/IVUS images at baseline and week 48 were analyzed. Any increase in ApoCIII levels at week 48 was observed in 47.4 % of study participants. On-treatment LDL-C levels did not differ among participants with and without any increase in ApoCIII levels (1.76 ± 0.55 vs. 1.74 ± 0.55 mmol/L, p = 0.91). Serial changes in IVUS-derived atheroma volume were similar between two groups (-0.7 ± 2.2 vs. -2.4 ± 1.6 mm3, p = 0.51). However, greater progression in NIRS-derived maxLCBI4mm was observed in those with any increase in ApoCIII levels (91.2 ± 24.8 vs. -44.2 ± 23.5, p < 0.001). Even after adjusting for clinical characteristics, maxLCBI4mm in participants with any increase in ApoCIII levels still progressed (87.0 ± 24.9 vs. -44.2 ± 23.5, p < 0.001). Moreover, maxLCBI4mm less likely regressed in patients with any increase in ApoCIII levels (16.2 vs. 80.5 %, p < 0.001). Even in those achieving on-treatment LDL-C<1.4 mmol/L, maxLCBI4mm progressed in association with any increase in ApoCIII levels.

CONCLUSION

Circulating ApoCIII promoted the accumulation of lipidic plaque components in statin-treated type 2 diabetic patient, suggesting ApoCIII as a residual risk that requires therapeutic intervention.