Apolipoprotein B and the regression of lipidic plaque in statin-treated type 2 DM patients with coronary artery disease: the pre-specified sub-analysis from the OPTIMAL randomized controlled trial
Authors: Funabashi S , Kataoka Y , Kitahara S , Makino H , Nakao K , Takagi K , Otsuka F , Asaumi Y , Hosoda K , Yasuda S , Noguchi T 
Published: October 2024

Introduction

Type 2 diabetic mellitus (T2DM) patients more likely present vulnerable form of diseases. Despite lowering LDL-C level with a statin, their on-going cardiovascular risks still exist, which indicates the need to identify additional therapeutic targets in T2DM patients. Apolipoprotein B (ApoB) is a proatherogenic lipoprotein. Atherosclerosis is promoted via the influx of ApoB into vessel wall. The current ESC guideline recommends ApoB levels as a secondary therapeutic target under control of LDL-C levels with a statin. However, it remains to be fully determined about the association of ApoB levels with plaque vulnerability in statin-treated T2DM patients.

Purpose

To elucidate whether serial change in ApoB levels affects the degree of atheroma progression and lipidic plaque materials on NIRS/IVUS imaging.

Methods

The OPTIMAL randomized controlled trial compared the efficacy of continuous glucose monitoring guided versus HbA1c-guided glycemic control on coronary atherosclerosis in 94 statin-treated T2DM patients with CAD. Serial NIRS/IVUS imaging was conducted at baseline and week 48 to monitor non-culprit lesions. The current study included 71 patients with serial ApoB levels at both baseline and week 48. Clinical demographics and NIRS/IVUS-derived measures were compared in those with and without any reduction of ApoB levels.

Results

All of study subjects received a statin, and over 60% of them were treated with high-intensity statin. Under these lipid-lowering therapies, 60.6% of study subjects exhibited any reduction of ApoB levels, accompanied by a greater reduction of LDL-C levels. Patients with any reduction of ApoB levels were more likely to be older (67.4±10.0 vs. 71.7±7.3 years, p=0.03), whereas there were no significant differences in the proportion of established risk factors between the two groups. Baseline NIRS/IVUS-derived PAV (47.1±12.9 vs. 44.8±15.4%, p=0.54) and maxLCBI4mm [290.5 (205.5, 338.7) vs. 270.0 (97.0, 416.0), p=0.76] were comparable in patients with and without any reduction of ApoB. On serial NIRS/IVUS imaging analysis, the progression rate of atheroma volume did not differ between the two groups (-0.4±0.2 vs. -0.3±0.2mm3, p=0.77). However, patients with any reduction of ApoB more frequently presented a regression of maxLCBI4mm (27.6±0.1 vs. 61.5±0.1%, p=0.01). Multivariate analysis adjusting age, female and high-intensity statin use demonstrated change in ApoB as an independent factor associated with regression of maxLCBI4mm (OR=0.94, 95%CI=0.91-0.98, p=0.002).

Conclusion

In statin-treated T2DM patients with CAD, any reduction of ApoB levels was associated with a greater regression of NIRS-derived maxLCBI4mm. The current findings indicate a potential anti-atherosclerotic effect of lowering ApoB levels, which induces delipidation of diabetic coronary atheroma. ApoB may be an important therapeutic target to modulate lipidic plaque materials in T2DM patients receiving a statin.