PMID- 37217967 OWN - NLM STAT- MEDLINE DCOM- 20230531 LR - 20230531 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 22 IP - 1 DP - 2023 May 22 TI - Evolocumab attenuate pericoronary adipose tissue density via reduction of lipoprotein(a) in type 2 diabetes mellitus: a serial follow-up CCTA study. PG - 121 LID - 10.1186/s12933-023-01857-w [doi] LID - 121 AB - BACKGROUND: Pericoronary adipose tissue (PCAT) density is a biomarker of vessel inflammation, which is supposed to be increased in patients with type 2 diabetes mellitus (T2DM). However, whether the coronary inflammation revealed by this novel index could be alleviated after evolocumab treatment in T2DM remains unknown. METHODS: From January 2020 to December 2022, consecutive T2DM patients with low-density lipoprotein cholesterol >/= 70 mg/dL on maximally tolerated statin and taking evolocumab were prospectively included. In addition, patients with T2DM who were taking statin alone were recruited as control group. The eligible patients underwent baseline and follow-up coronary CT angiography with an interval of 48-week. To render patients with evolocumab as comparable to those controls, a propensity-score matching design was used to select the matched pairs with a 1:1 ratio. Obstructive lesion was defined as the extent of coronary artery stenosis >/= 50%; the numbers inside the brackets were interquartile ranges. RESULTS: A total of 170 T2DM patients with stable chest pain were included [(mean age 64 +/- 10.6 [range 40-85] years; 131 men). Among those patients, 85 were in evolocumab group and 85 were in control group. During follow-up, low-density lipoprotein cholesterol (LDL-C) level (2.02 [1.26, 2.78] vs. 3.34 [2.53, 4.14], p < 0.001), and lipoprotein(a) (12.1 [5.6, 21.8] vs. 18.9 [13.2, 27.2], p = 0.002) were reduced after evolocumab treatment. The prevalence of obstructive lesions and high-risk plaque features were significantly decreased (p < 0.05 for all). Furthermore, the calcified plaque volume were significantly increased (188.3 [115.7, 361.0] vs. 129.3 [59.5, 238.3], p = 0.015), while the noncalcified plaque volume and necrotic volume were diminished (107.5 [40.6, 180.6] vs. 125.0 [65.3, 269.7], p = 0.038; 0 [0, 4.7] vs. 0 [0, 13.4], p < 0.001, respectively). In addition, PCAT density of right coronary artery was significantly attenuated in evolocumab group (- 85.0 [- 89.0, - 82.0] vs. - 79.0 [- 83.5, - 74.0], p < 0.001). The change in the calcified plaque volume inversely correlated with achieved LDL-C level (r = - 0.31, p < 0.001) and lipoprotein(a) level (r = - 0.33, p < 0.001). Both the changes of noncalcified plaque volume and necrotic volume were positively correlated with achieved LDL-C level and Lp(a) (p < 0.001 for all). However, the change of PCAT(RCA) density only positively correlated with achieved lipoprotein(a) level (r = 0.51, p < 0.001). Causal mediation analysis revealed Lp(a) level mediated 69.8% (p < 0.001) for the relationship between evolocumab and changes of PCAT(RCA). CONCLUSIONS: In patients with T2DM, evolocumab is an effective therapy to decrease noncalcified plaque volume necrotic volume, and increase calcified plaque volume. Furthermore, evolocumab could attenuate PCAT density, at least in part, via the reduction of lipoprotein(a). CI - (c) 2023. The Author(s). FAU - Yu, Meng-Meng AU - Yu MM AD - Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. FAU - Zhao, Xin AU - Zhao X AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. FAU - Chen, Yin-Yin AU - Chen YY AD - Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. FAU - Tao, Xin-Wei AU - Tao XW AD - Bayer Healthcare, No. 399, West Haiyang Road, Shanghai, 200126, China. FAU - Ge, Jun-Bo AU - Ge JB AD - Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. FAU - Jin, Hang AU - Jin H AD - Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. jin.hang@zs-hospital.sh.cn. FAU - Zeng, Meng-Su AU - Zeng MS AD - Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. mengsuzengfudan@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230522 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Cholesterol, LDL) RN - LKC0U3A8NJ (evolocumab) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipoprotein(a)) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Humans MH - Male MH - Middle Aged MH - Adipose Tissue MH - Cholesterol, LDL MH - Computed Tomography Angiography MH - Coronary Angiography MH - *Coronary Artery Disease MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy/pathology MH - Follow-Up Studies MH - *Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects MH - Inflammation MH - Lipoprotein(a) MH - *Plaque, Atherosclerotic/pathology MH - Female PMC - PMC10204214 OTO - NOTNLM OT - Coronary artery disease OT - Evolocumab OT - Lipoprotein(a) OT - Multidetector computed tomography OT - Pericoronary adipose tissue COIS- Xin-Wei Tao is a current medical science liaison in Bayer Healthcare. Other authors do not have any competing interests to declare. EDAT- 2023/05/23 01:06 MHDA- 2023/05/24 06:42 PMCR- 2023/05/22 CRDT- 2023/05/22 23:50 PHST- 2023/04/04 00:00 [received] PHST- 2023/05/12 00:00 [accepted] PHST- 2023/05/24 06:42 [medline] PHST- 2023/05/23 01:06 [pubmed] PHST- 2023/05/22 23:50 [entrez] PHST- 2023/05/22 00:00 [pmc-release] AID - 10.1186/s12933-023-01857-w [pii] AID - 1857 [pii] AID - 10.1186/s12933-023-01857-w [doi] PST - epublish SO - Cardiovasc Diabetol. 2023 May 22;22(1):121. doi: 10.1186/s12933-023-01857-w.