Identification of plaque ruptures using a novel discriminative model comprising biomarkers in patients with acute coronary syndrome

Abstract

Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), neutrophil gelatinase-associated lipocalin (NGAL), and matrix metalloproteinase-9 (MMP-9) are inflammatory biomarkers involved in plaque destabilization resulting in acute coronary syndrome (ACS). This study aimed to investigate the diagnostic value of a combination of biomarkers to discriminate plaque ruptures in the setting of ACS. Eighty-five ACS patients with optical coherence tomography (OCT) images of the culprit plaque were included and categorized into two groups: ACS with plaque rupture (Rupture group, n = 42) or without plaque rupture (Non-rupture group, n = 43) verified by OCT. A discriminative model of plaque rupture using several biomarkers was developed and validated. The Rupture group had higher white blood cell (WBC) counts and peak creatine kinase-myocardial band (CK-MB) levels (13.39 vs. 2.69 ng/mL, p = 0.0016). sLOX-1 (227.9 vs. 51.7 pg/mL, p < 0.0001) and MMP-9 (13.4 vs. 6.45 ng/mL, p = 0.0313) levels were significantly higher in the Rupture group, whereas NGAL showed a trend without statistical significance (59.03 vs. 53.80 ng/mL, p = 0.093). Receiver operating characteristic curves to differentiate Rupture group from Non-rupture group calculated the area under the curve for sLOX-1 (p < 0.001), MMP-9 (p = 0.0274), and NGAL (p = 0.0874) as 0.763, 0.645, and 0.609, respectively. A new combinatorial discriminative model including sLOX-1, MMP-9, WBC count, and the peak CK-MB level showed an area under the curve of 0.8431 (p < 0.001). With a cut-off point of 0.614, the sensitivity and specificity of plaque rupture were 62.2% and 97.6%, respectively. The new discriminative model using sLOX-1, MMP-9, WBC count, and peak CK-MB levels could better identify plaque rupture than each individual biomarker in ACS patients.

Association between apolipoprotein B/A1 ratio and coronary plaque vulnerability in patients with atherosclerotic cardiovascular disease: an intravascular optical coherence tomography study

“…Plaque rupture is responsible for nearly half of patients with ACS, while plaque erosion and calcified nodule account for 1/3 of patients and 2–7% of acute coronary events, respectively [ 16 , 17 ]. Other causes of ACS include spontaneous dissection, tight stenosis, and intramural hematoma [ 18 ].…”

“…The triglyceride glucose index combined with the morphological characteristics of plaque could be used to predict adverse events in patients with STEMI [ 41 ]. The combination of different biomarkers, such as soluble lectin-like oxidized LDL receptor-1, MMP-9, WBC count, and peak creatine kinase-MB, could also be used to identify plaque rupture compared with other individual biomarkers in patients with ACS [ 18 ].…”

Non-Invasive Modalities in the Assessment of Vulnerable Coronary Atherosclerotic Plaques

“…While it appears that the role of biomarkers in the assessment of VCAPs is limited to date ( Table 1 and Table 2 ), their combination into models might be of use. As shown in the study of Kook et al, such a model consisting of soluble lectin-like oxidized low-density lipoprotein receptor-1, MMP-9, white blood cell count, and the peak creatine kinase-myocardial band had decent AUROC (0.84), sensitivity (62.2%), and specificity (97.6%) for identification of plaque rupture in 85 patients with ACS, at a cutoff of 0.614 [ 35 ]. Furthermore, the addition of inflammatory biomarkers on top of imaging features of high-risk plaques may enhance the risk stratification for incident MACE [ 36 ].…”

Effect of combined lipid-lowering therapy on atherosclerotic plaque vulnerability in patients with acute coronary syndrome (Combi-LLT ACS): randomized trial protocol

“…За дестабилизацию бляшек отвечает не только изменение их липидного состава, но и инфильтрация иммуновоспалительными клетками и деградация внеклеточного матрикса сосудистой стенки, а также активная воспалительная реакция и неоваскуляризация бляшки [1,2]. Немаловажна роль в этом процессе маркеров матриксного ремоделирования (матриксная металлопротеиназа-9 (MMP-9), тканевый ингибитор металлопротеиназы 1 типа (TIMP-1)), миокардиального фиброза и воспаления сосудистой стенки (галектин 3 (GAL-3), высокочувствительный С-реактивный белок (всч-СРБ), нейтрофильно-лимфоцитарное отношение (NLR), липокалин, ассоциированный с нейтрофильной желатиназой (NGAL)) [3][4][5][6][7][8][9][10][11][12][13][14]. В последние годы активно развивается направление кардиоваскулярной визуализации -внутрисосудистый ультразвук, магнитный резонанс высокого разрешения, позитронно-эмиссионная томография-компьютерная томография, оптическая когерентная томография (ОКТ), которые позволяют получать представление об характеристиках уязвимых бляшек in vivo [15].…”