Layered plaques and coronary plaque vulnerability: an optical coherence tomography study

doi:10.21203/rs.3.rs-3116615/v1

Background

Layered plaques are a subclinical sign of plaque rupture or erosion, with plaque vulnerability and can be detected by optical coherence tomography (OCT). The study designed to evaluate the prevalence, angiographic, OCT characteristics of layered plaques in patients with acute coronary syndrome (ACS).

Methods and results

Consecutive ACS patients with 126 coronary culprit lesions underwent coronary angiography (CAG) and pre-intervention optical coherence tomography examination in this study. Patients were divided into layered plaque group (n = 57) and non-layered plaque group(n = 69) based on OCT plaque morphology. Layered plaque is heterogeneous signal-rich layered tissue of different optical signal intensity that close to the luminal surface, clearly demarcated from the underlying components on OCT. Patients with layered plaque were higher statin uptake rate compared to patients with non-layered plaque(P = 0.037). Uric acid (368.613 ± 91.840vs.327.901 ± 76.232µmol/L, P = 0.009) and Indirect bilirubin (IBil) (9.873 ± 5.252vs.8.130 ± 4.039, P = 0.037) level is higher in layered plaque group compare to patient with non-layered plaque. Longer lesion length in the layered plaque group compared with the non-layered plaque group (10(8,12) vs.8(5.5,10.0), P = 0.004). Higher lipid index (1400(631.5,2257) vs.1080(577.5,1455), P = 0.02)), Macrophage accumulation (49.1%vs.33.3%, P = 0.035) and TCFA (68.4%vs. 40.6%, P = 0.002) in the layered plaque group compared with the non-layered plaque group. Results of multivariate analyses showed that Uric acid was independent risk factors of layered plaque in our cohorts (P < 0.05).

Conclusions

This study demonstrate that layered plaques are associated with plaque vulnerability and progression of atherosclerosis at culprit lesions in patient with ACS.

Acute coronary syndrome

Layered plaque

Healed plaque

Optical coherence tomography

Acute coronary syndrome (ACS) is often caused by acute and severe thrombosis subsequent to plaque rupture or plaque erosion resulting in interrupted coronary blood flow[1].However, in the majority of coronary atherosclerotic plaque progression, the thrombotic lesion is silent and has no clinical presentation [2].At this point the body may undergoes a repeated process of plaque repair[3].However, repeated plaque repair processes can increase coronary lumen narrowing and plaque loading, which represents plaque progression[4].Optical coherence tomography (OCT) is an intracoronary imaging technique in which layered plaque as a plaque that is clearly demarcated from the underlying components, close to the luminal surface, and consists of non-homogeneous signals in different optical density layers [5, 6].Accordingly, layered plaques are a type of plaque in which previous plaque instability leads to repair, their presence often represents higher levels of inflammatory response and greater plaque vulnerability[7, 8].Previous studies have shown that layered plaques are a bridge between stable angina pectoris(SAP)and acute coronary syndromes, with a higher probability of subsequent major adverse cardiovascular events(MACE)[9, 10]. Identifying layered plaques can help in risk stratification for patients with high-risk plaque features[11]. In this study, we sought to explore the independent risk factors that predict layered plaque in patient with ACS based on OCT.

Study population

The statistics show that from a total of 165 patients with coronary heart disease (CHD) who underwent pre-intervention OCT examination between January 2020 and January 2023. For this analysis, 39 patients were excluded for in-stent thrombosis (n = 12), stable angina pectoris(n = 15),extreme age (n = 2), the lack of preintervention OCT examinations (n = 5), poor imaging quality mainly due to massive thrombus (n = 5).Of these,126 patients were met inclusion criteria and were eligible for the study, the study flowchart is as shown in Fig. 1, and the diagnosis of ACS includes ST-segment elevation myocardial infarction(STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and Unstable angina (UA).The diagnostic criteria for ACS are based on previous guidelines[12]. Demographic features, clinical data, ACS risk factors, blood biochemical indicators, CAG and OCT results were evaluated. This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University(K202306-05), all patients have signed an informed consent to participate.

Blood tests

All patients had peripheral blood drawn 8 hours prior to CAG in the fasting state. All quantitative tests, including white blood cell count, neutrophil count, lymphocyte count, platelet count, fibrinogen, D-dimer, triglycerides, total cholesterol, LDL, HDL, etc. are performed by our Laboratory Department using a Fully Automated Blood Cell Analyzer.

Coronary angiography analysis

Coronary angiography for all patients within 24 hours of admission, CAG and percutaneous coronary intervention (PCI) are mainly performed using the Judkins method with a radial approach. And the Angiographic analysis were performed by two 2 experienced cardiovascular physicians on baseline coronary angiograms acquired during the index. The location of lesion, type of lesion, diameter stenosis, and culprit lesion length were measured. The culprit lesion in ACS was defined as a combination of coronary angiographic findings, electrocardiographic changes, and/or abnormal left ventricular wall motion, with evidence of fractional flow reserve for ischaemia. The culprit lesion was defined as the degree of stenosis on coronary angiogram or the site of PCI.

OCT image acquisition and measurement

OCT was performed using the commercially available C7-XR OCT intravascular imaging system (C7-XRTM OCT Intravascular Imaging System, St. Jude Medical, St. Paul, MN, USA). Pullback speed was 20mm/s, and the total pullback distance of the system was 50 mm. All OCT images were analyzed by two independent investigators. During off-line review, the investigators was blinded to the patient data. Layered plaque as a layered plaque with heterogeneous signal-rich layered tissue of different optical signal intensity that close to the luminal surface, clearly demarcated from the underlying plaque[3, 5]. Layered plaques have the same characteristics as healed plaques on OCT, so the terms “layered plaques” and “healed plaques” can be used interchangeably. According to the present guide consensus for OCT [13],Lipid plaque was defined as a diffusely bordered signal-poor region with an overlying signal rich band, and lipid arc was measured every 1 mm. Fibrous plaque was defined as a plaque with homogeneous, high back-scattering signal. Calcifications were defined as signal-poor or heterogeneous areas delimited by sharp borders. Thin-cap fibroatheroma (TCFA) was defined as plaque with Lipid content ≥ two quadrants and the fibrous cap thickness ≤ 65 µm. Plaque rupture was identified as intimal tearing, disruption, or dissection of the fibrous cap. Plaque erosion was defined by the presence of attached thrombus overlying an intact and visualized plaque or luminal surface irregularity at the culprit lesion in the absence of thrombus. Vasa vasorum appear as signal-poor voids that are sharply delineated and can usually be followed in multiple contiguous frames. Cholesterol crystals appear in OCT images as thin, linear regions of high intensity. Macrophage accumulation was defined as the presence of signal-rich, distinct, or confluent punctate regions and generate a backward shadowing[13, 14]. Representative images of layered plaque and nonlayered plaque are shown in Fig. 2.

Statistical analysis

All statistical analysis was performed using business software (SPSS 24.0 IBM, New York, NY, USA). Normally distributed continuous data were expressed as means and standard deviations, and Student t test was used for comparison between groups; non-normally distributed continuous data were expressed as median M (P25, P75) and Mann-Whitney U test was used for comparison between groups; categorical data were expressed as frequencies and percentages (%), and were compared using χ² test or Fisher exact tests. To assess whether baseline characteristics and plaque characters had an impact on layered plaque, Significant variables in the univariable model were included in the multivariable logistic regression model. And multivariable logistic regression model was also used to adjust confounders and calculate odds ratios (OR) and 95% confidence intervals (CI). p value < 0.05 was considered statistically significant.

Baseline clinical characteristics

Finally, Among 126 patients,57 (45.2%) patients had layered plaque at the culprit lesions, and the baseline patient characteristics based on the presence or absence of layered plaques between the two groups are summarized in Table 1. Patients with layered plaque were higher statin uptake rate compared to those non-layered plaque (100%vs.89.9%, P=0.037). No significant differences in clinical presentation, CHD history or other baseline data were observed between the two groups.

Clinical biochemical indicators

Table2 shows the Clinical biochemical indicators of the two groups. It is observed that patients with layered plaque has higher level Uric acid (368.613±91.840vs.327.901±76.232μmol/L, P=0.009) and Indirect bilirubin (9.873±5.252vs.8.130±4.039, P=0.037) compare to patient with non-layered plaque. No other laboratory variables were significantly different between two groups.

Angiographic findings

CAG findings of the included ACS patients according to the layered plaque are presented in Table 3. Longer lesion length in the layered plaque group compared with the non-layered plaque group (10(8,12) vs.8(5.5,10.0), P=0.004). There was no significant difference in other CAG findings between those two groups.

Optical coherence tomography findings

The optical coherence tomography analysis results are shown in Table 4. The layered plaque group had a higher lipid index compared to the non-layered group (1400(631.5,2257) vs.1080(577.5,1455), P=0.02)). Macrophage accumulation in the layered plaque group was higher compared to the non-layered plaque group (49.1%vs.33.3%, P=0.035). The incidence of TCFA was higher in the layered plaque group than in the non-layered plaque group (68.4%vs. 40.6%, P=0.002). OCT characteristics of layered plaque and non-layered plaque at the culprit lesion in fig3. Moreover, no statistical difference was detected for OCT findings between those two groups.

Predictors for layered culprit plaque

Table 5 shows the results of multivariable analysis. The following variables were included in the multivariable model: Diabetes mellitus, BMI, Uric acid, IBil. In the multivariable model, Uric acid, Lesion length, TCFA were independent predictors for layered culprit plaque(all p＜0.05).

Prevalence of layered plaque in patients with ACS

The prevalence of a layered plaque at the culprit lesion was compared among different clinical presentations in fig4. The prevalence of layered culprit plaque was significantly higher in patients with unstable angina pectoris.

In the present study we demonstrated that layered plaques were associated with plaque vulnerability. Moreover, Uric acid was independently associated with coronary layered plaques. These findings suggest that Uric acid may be used as inexpensive markers for risk stratification in ACS patients.

With the development of intracoronary imaging techniques, the ability to identify vulnerable plaques has gradually improved, with the advantage of OCT being its higher resolution, as an in vivo diagnostic modality with excellent sensitivity and specificity for detecting plaque morphology and vessel wall microstructure.

The layered plaque consists mainly of proliferating smooth muscle cells forming loose type III collagen fibrils and proteoglycans, which then gradually transition to type I collagen fibrils and re-endothelialize. Histopathological layered plaques have a layered appearance on OCT views and are morphologically layered. The layered plaque reflects the repair process of previous plaque rupture and thrombus[15, 16], representing previous plaque instability. Plaque repair can cause further coronary lumen stenosis[17]. Layered plaques are generally observed in both SAP and ACS patients[18-20]. Previous studies have found that it is more common in patients with SAP. Because patients with stable angina have a greater weight of endogenous anti-thrombotic system, which is more resistant to thrombosis and prevents occlusive thrombus formation[21]. Our study found that layered plaques were mostly present in patients with unstable angina (71.9%vs. 21.8%，p＜0.001), which may be associated with more repair processes after plaque rupture or thrombosis. what is more, behind the formation of layered plaque is a greater vulnerability to plaque and inflammatory response, as more macrophage infiltration and TCFA presence is observed around the layered plaque, the presence of layered plaque is not a protective factor and may even be a possible acute thrombotic event in patients with ACS. From this it is clear that identify layered plaque is useful for optimizing the treatment of coronary artery disease and improve clinical outcomes for patients.

Clinical and angiography data in layered plaque

In an autopsy study, it was found that plaque ruptures were found in 61% of acute myocardial infarction who died suddenly of cardiac shock and were associated with layered plaque, silent plaque rupture is a form of wound healing that results in increased percent stenosis[22]. Mann and Davies reported that 73.2% of plaque types with luminal stenosis greater than 50% in ischaemic heart disease had layered plaques. Layered plaques also represent a higher degree of luminal stenosis and vulnerable plaque characteristics[23]. Our research also found longer lesion length in the layered plaque group compared with the non-layered plaque group. A retrospective observational study had discovered that higher lumen stenosis and lower stent expansion ratio and mean stent eccentricity index (SEI)when having layered plaque. Angiographically complex lesions (type B2/C) were more frequent in patients with layered culprit lesions[24]. In the present study, patients with stent implantation, there was a higher incidence of post-stenting failure and formation of in-stent atherosclerosis after stent expansion when possessing layered plaques[25]. Matsuo had also clarified layered plaques are positively correlated with lumen narrowing and plaque vulnerability[26]. An OCT and IVUS with iMap trial had shown that layered plaques were found in plaque rupture, suggesting that the risk of plaque rupture is higher when layered plaques are present. This shows that layered plaque can accelerate plaque progression[27]. Previous study finds hyperuricemia associated with plaque vulnerability, our research is consistent with this. Maybe associated with oxidative stress and endothelial damage caused by hyperuricemia.

OCT data in layered plaque

Russo discovered that patients with ACS had layered plaques ≥ 30% in the non-culprit lesions. And it was concluded that possession of layered plaques when composed of more macrophage infiltration, thinner fibrous cap, longer plaque length, longer lipid length and greater lipid index, further suggesting that having higher levels of inflammation when layered plaques are present [28]. In addition, our results showed that 28.1% AMI patient have layered plaques and layered plaques were associated with plaque vulnerability. In a 3-Vessel OCT Study, it was found that ACS caused by plaque erosion, followed by the formation of layered plaques, the combination of layered plaques at the site of plaque erosion had smaller minimal lumen area and greater degree of luminal stenosis. Both the culprit and non-culprit lesions, patients with layered plaque at the culprit site had higher incidence of lipid plaque, microchannels, cholesterol crystals, calcification than those without. Layered plaque is more likely to lead to adverse cardiovascular events later in the process[29]. A recent OCT study has demonstrated that layered plaques were detected in 74.5% of patients with ACS, and associated with thin-cap fibroatheromas[30]. Russo et al had reported that combined a layered plaque at the culprit vessel, greater plaque vulnerability, higher prevalence of calcifications, heavier lipid plaque and greater macrophage infiltration in possession of the layered plaque, suggesting that layered plaques are associated with vulnerable plaques again[19]. An OCT study investigating layered plaque in non-culprit lesions（NCLs）show that NCLs with layered plaque had more lipid-rich plaque, macrophage accumulations, microvessels and spotty calcification compared to NCLs without layered plaque[11].

Clinical outcomes with layered plaque

Araki reported that a new layer was detected in 25 of 41 plaques at follow-up in stable angina patient, and the presence of layered plaque is strongly associated with the occurrence of major adverse cardiovascular events after PCI, identified layered plaque as predictors of subsequent rapid lesion progression. but the exact mechanism is unclear[31]. In a large cohort study that included 726 non-culprit lesions which had undergone PCI, 21.9% of them were found to have layered plaques. Ischemia-driven revascularization (IDR) was found in up to 65 cases over a 2-year follow-up period. This leads to the conclusion that untreated layered plaque in PCI target vessel was present in 21.9% of patients and it was related to future non-culprit-related events[11]. the interaction of layered plaque with MACE still needs further study to clarify its specific mechanism.

Limitations

There are several limitations to this paper. First, this paper is a single-center retrospective study with a small sample size and average strength of argument, and larger clinical studies are needed to confirm the argument; second, only plaque characteristics of culprit vessels were included in this paper, and non-culprit vessels were not examined by OCT and therefore were not included in the study design and not all patients underwent 3-vessel OCT imaging.However, in clinical practice, OCT of 3 vessels is less commonly performed.Moreover it is sometimes difficult to distinguish layered plaques from other plaque components. However, in our study, there was greater interobserver agreement in the observation of layered plaques. Prognosis of patients not included, further research is needed on the correlation between layered plaques and long-term prognosis.

In patients with ACS, Uric acid was a predictor for layered plaques at culprit lesions. Layered plaques are prevalent and have more features of vulnerability and accelerated progression of atherosclerosis at culprit lesions.

Ethics approval and consent to participate

The study protocol was approved by the ethics committee of the First affiliated hospital of Xinjiang Medical University. All methods were performed in accordance with the relevant guidelines and regulations. Because of the retrospective design of the study, the need to obtain informed consent from eligible patients was waived by the ethics committee of the First affiliated hospital of Xinjiang Medical University.

Consent for publication

Not applicable.

Availability of data and materials

The data that support the findings of this study are available from the First Affiliated Hospital of Xinjiang Medical University but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the First Affiliated Hospital of Xinjiang Medical University. The permission to access and use the raw data was obtained from Zening Yu.

Competing interests

The authors declare that they have no competing interest.

Funding

This work was supported by a project grant from University Research Programme in Xinjiang Uygur Autonomous Region(XJEDU2021I015). This study was supported by research grants from the First Affiliated Hospital of Xinjiang Medical University to Dr. Yang Yining. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Authors' contributions

Conceived and designed the study: YY and YZ. Data collection and analyzed the data: YZ. Quality control the study and revision:CQ,LX,YY. Wrote the paper: YZ. The manuscript was approved by all above authors.

Acknowledgements

Not Applicable.

Partida, R.A., et al., Plaque erosion: a new in vivo diagnosis and a potential major shift in the management of patients with acute coronary syndromes. Eur Heart J, 2018. 39(22): p. 2070-2076.
Finn, A.V., et al., Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol, 2010. 30(7): p. 1282-92.
Vergallo, R. and F. Crea, Atherosclerotic Plaque Healing. N Engl J Med, 2020. 383(9): p. 846-857.
Fracassi, F., et al., Healed Culprit Plaques in Patients With Acute Coronary Syndromes. J Am Coll Cardiol, 2019. 73(18): p. 2253-2263.
Shimokado, A., et al., In vivo optical coherence tomography imaging and histopathology of healed coronary plaques. Atherosclerosis, 2018. 275: p. 35-42.
Ziada, K.M. and N. Misumida, In Vivo Identification of Healed Plaques in Culprit Lesions: Is What We're Seeing Really There? J Am Coll Cardiol, 2019. 73(18): p. 2264-2266.
Wang, C., et al., Characteristics and significance of healed plaques in patients with acute coronary syndrome and stable angina: an in vivo OCT and IVUS study. EuroIntervention, 2019. 15(9): p. e771-e778.
Yin, W.J., et al., Association between non-culprit healed plaque and plaque progression in acute coronary syndrome patients: an optical coherence tomography study. J Geriatr Cardiol, 2021. 18(8): p. 631-644.
Kurihara, O., et al., Clinical significance of healed plaque detected by optical coherence tomography: a 2-year follow-up study. J Thromb Thrombolysis, 2020. 50(4): p. 895-902.
Okamoto, H., et al., Prevalence and Clinical Significance of Layered Plaque in Patients With Stable Angina Pectoris　- Evaluation With Histopathology and Optical Coherence Tomography. Circ J, 2019. 83(12): p. 2452-2459.
Usui, E., et al., Prognostic impact of healed coronary plaque in non-culprit lesions assessed by optical coherence tomography. Atherosclerosis, 2020. 309: p. 1-7.
Mendis, S., et al., World Health Organization definition of myocardial infarction: 2008-09 revision. Int J Epidemiol, 2011. 40(1): p. 139-46.
Tearney, G.J., et al., Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol, 2012. 59(12): p. 1058-72.
Prati, F., et al., Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis. Eur Heart J, 2010. 31(4): p. 401-15.
Otsuka, F., et al., Pathology of coronary atherosclerosis and thrombosis. Cardiovasc Diagn Ther, 2016. 6(4): p. 396-408.
Yamamoto, M.H., et al., Serial 3-Vessel Optical Coherence Tomography and Intravascular Ultrasound Analysis of Changing Morphologies Associated With Lesion Progression in Patients With Stable Angina Pectoris. Circ Cardiovasc Imaging, 2017. 10(9).
Yahagi, K., et al., Pathophysiology of native coronary, vein graft, and in-stent atherosclerosis. Nat Rev Cardiol, 2016. 13(2): p. 79-98.
Kimura, S., et al., Optical coherence tomography and coronary angioscopy assessment of healed coronary plaque components. Int J Cardiovasc Imaging, 2021. 37(10): p. 2849-2859.
Russo, M., et al., Healed Plaques in Patients With Stable Angina Pectoris. Arterioscler Thromb Vasc Biol, 2020. 40(6): p. 1587-1597.
Yin, Y., et al., Optical Coherence Tomographic Features of Pancoronary Plaques in Patients With Acute Myocardial Infarction Caused by Layered Plaque Rupture Versus Layered Plaque Erosion. Am J Cardiol, 2022. 167: p. 35-42.
Araki, M., et al., Predictors for layered coronary plaques: an optical coherence tomography study. J Thromb Thrombolysis, 2020. 50(4): p. 886-894.
Burke, A.P., et al., Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation, 2001. 103(7): p. 934-40.
Mann, J. and M.J. Davies, Mechanisms of progression in native coronary artery disease: role of healed plaque disruption. Heart, 1999. 82(3): p. 265-8.
Kurihara, O., et al., Comparison of post-stent optical coherence tomography findings: Layered versus non-layered culprit lesions. Catheter Cardiovasc Interv, 2021. 97(7): p. 1320-1328.
Nakano, M., et al., Ex vivo assessment of vascular response to coronary stents by optical frequency domain imaging. JACC Cardiovasc Imaging, 2012. 5(1): p. 71-82.
Matsuo, Y., et al., Association of Hemodynamic Severity With Plaque Vulnerability and Complexity of Coronary Artery Stenosis: A Combined Optical Coherence Tomography and Fractional Flow Reserve Study. JACC Cardiovasc Imaging, 2019. 12(6): p. 1103-1105.
Hougaard, M., et al., Uncovered Culprit Plaque Ruptures in Patients With ST-Segment Elevation Myocardial Infarction Assessed by Optical Coherence Tomography and Intravascular Ultrasound With iMap. JACC Cardiovasc Imaging, 2018. 11(6): p. 859-867.
Russo, M., et al., Characteristics of non-culprit plaques in acute coronary syndrome patients with layered culprit plaque. Eur Heart J Cardiovasc Imaging, 2020. 21(12): p. 1421-1430.
Yin, Y., et al., Culprit and Non-Culprit Plaque Characteristics With vs. Without a Healed Phenotype in Patients With Acute Myocardial Infarction Caused by Plaque Erosion　- A 3-Vessel OCT Study. Circ J, 2022. 86(5): p. 846-854.
Dai, J., et al., Frequency, Predictors, Distribution, and Morphological Characteristics of Layered Culprit and Nonculprit Plaques of Patients With Acute Myocardial Infarction: In Vivo 3-Vessel Optical Coherence Tomography Study. Circ Cardiovasc Interv, 2020. 13(10): p. e009125.
Araki, M., et al., Predictors of Rapid Plaque Progression: An Optical Coherence Tomography Study. JACC Cardiovasc Imaging, 2021. 14(8): p. 1628-1638.

Table1 Baseline data

Variables	Layered plaque(n=57)	Non-layered plaque(n=69)	t/𝜒²	P value
Age, years	60.40±10.13	59.43±9.85	0.541	0.590
Male	48(84.2)	49(71.0)	3.068	0.08
Hypertension	38(66.7)	44(63.8)	0.115	0.734
Diabetes mellitus	14(24.6)	18(26.1)	0.038	0.845
Current smoking	27(47.4)	31(44.9)	0.075	0.784
Current drinking	21(36.8)	16(23.2)	2.805	0.094
Family history of CAD	12(21.1)	16(23.2)	0.009	0.925
BMI, kg/m²	26.37±2.93	26.45±3.68	0.134	0.893
Clinical presentation			2.727	0.099
AMI	16(28.1)	11(15.9)
UAP	41(71.9)	58(84.1)
Medications
Aspirin	57(100)	64(92.8)	2.610	0.163
Statins	57(100)	62(89.9)	4.342	0.037
β-Blockers	42(73.7)	51(73.9)	0.001	0.977
ACEI/ARB	33(57.9)	39(56.5)	0.24	0.877
CCB	27(47.4)	29(42.0)	0.360	0.548

Values are presented as n (%), or mean ± SD; CAD, Coronary artery disease; BMI, body mass index; UAP, unstable angina pectoris; AMI, acute myocardial infarction.

Table 2 Biochemical indices

Variables	Layered plaque(n=57)	Non-layered plaque(n=69)	t/𝜒²/ Z	P value
WBC count, ×10⁹L^-1	7.268±1.970	6.804±1.929	1.331	0.186
RBC count, ×10⁹L^-1	4.659±0.447	4.633±0.590	0.268	0.789
PLT count, ×10⁹L^-1	235.370±50.651	229.960±53.809	0.580	0.563
Neutrophil count, ×10⁹L^-1	4.571±1.980	4.325±1.694	0.753	0.453
Lymphocyte count, ×10⁹L^-1	1.931±0.616	1.910±0.620	0.193	0.847
HGB, g/L	139.350±13.474	140.960±15.956	0.603	0.548
Albumin, g/L	42.786±4.410	42.046±3.144	1.065	0.290
Fibrinogen, g/L	0.750(0.425,2.280)	0.820(0.460,2.370)	0.453	0.650
D-dimer, mg/L	88(54,151.5)	95(56,159)	0.620	0.535
Creatinine, μmol/L	76.726±23.524	82.191±29.525	0.405	0.686
Carbamide, mmol/L	6.011±1.539	5.753±2.844	0.613	0.541
Uric acid, μmol/L	368.613±91.840	327.901±76.232	2.672	0.009
eGFR	95.064±19.683	95.179±17.267	0.035	0.972
TBil, mmol/L	14.205±5.692	12.863±4.249	1.473	0.144
DBil, mmol/L	0.300(0.3,2.67)	0.300(0.3,3.45)	0.477	0.633
IBil, mmol/L	9.873±5.252	8.130±4.039	2.105	0.037
ALT, U/L	26.60(18.970,33.225)	25.50(19.600,33.340)	0.201	0.841
AST, U/L	26.09(18.950,40.110)	28.06(12.170,39.245)	0.179	0.858
TC, mmol/L	3.77±1.085	3.670±1.090	0.548	0.585
TG, mmol/L	1.81	1.47	0.735	0.462
LDL-C, mmol/L	2.219±0.876	2.203±0.905	0.099	0.921
HDL-C, mmol/L	1.009±0.214	0.920±0.288	1.917	0.058

Values are presented as n (%), or mean ± SD; WBC, white blood cell; RBC, red blood cell; PLT, Platelet; HGB, hemoglobin; TBil, total bilirubin; DBiL, direct bilirubin; IBiL, unconjugated bilirubin; ALT, alanine aminotransferase; AST, aspartate transaminase TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.

Table 3 Angiographic findings

Variables	Layered plaque(n=57)	Non-layered plaque(n=69)	t/𝜒²/ Z	P value
Target vessel			2.795	0.424
LAD	44(77.2)	50(72.5)
LCX	9(15.8)	10(14.5)
RCA	4(7.0)	9(13.0)
Number of vascular lesions			0.267	0.875
1	32(56.1)	36(52.2)
2	12(21.1)	17(24.6)
3	13(22.8)	16(23.2)
Location of target plaque			1.005	0.605
Proximal	39(68.4)	52(75.4)
Mid	15(26.3)	13(18.8)
Distal	3(5.3)	4(5.8)
Diameter stenosis, %	80(67.5,90.0)	80(60,90)	0.062	0.951
Lesion length，mm	10(8,12)	8(5.5,10.0)	2.882	0.004

Values are presented as n (%), or mean ± SD; LAD, Left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery.

Table 4 OCT findings

Variables	Layered plaque(n=57)	Non-layered plaque(n=69)	t/𝜒²/ Z	P value
FCT, μm	130(50,200)	120(60,200)	0.241	0.810
Lipid arc, degree	148(108.5,209.5)	135(88.5,179.00)	1.538	0.124
Lipid index	1400(631.5,2257)	1080(577.5,1455)	2.334	0.02
Macrophage accumulation			8.578	0.035
0	16(28.1)	36(52.2)
1	28(49.1)	23(33.3)
2	9(15.8)	10(14.5)
3	4(7.0)	1(1.5)
4	0(0)	0(0)
Cholesterol crystals	30(52.6)	27(39.1)	2.297	0.130
Vasa vasorum	27(47.4)	26(37.7)	1.202	0.273
Thrombus	8(14.0)	9(13.0)	0.026	0.871
Calcified nodule	10(17.5)	5(7.2)	3.156	0.076
Characteristic of plaque			2.553	0.466
Lipid	32(56.1)	46(66.7)
Calcified	9(15.8)	5(7.3)
Fibrotic	16(28.1)	19(27.5)
TCFA	39(68.4)	28(40.6)	9.717	0.002
plaque rupture	6(10.5)	4(5.80)	0.418	0.518
plaque erosion	2(3.5)	7(10.1)	1.193	0.275
MLA, mm²	1.77(1.30,2.50)	2.10(1.62,2.57)	1.694	0.09
NLA, mm²	7.78(6.32,8.89)	7.93(6.84,9.34)	0.647	0.518

Values are presented as n (%), or mean ± SD; OCT optical coherence tomography; FCT, fibrous cap thickness; TCFA, thin-cap fibroatheroma; MLA, minimal lumen area; NLA, normal lumen area

Table5 multivariate logistic regression for layered plaque

	Multivariate analysis
	OR (95% CI)	p value
Uric acid	1.006(1.001-1.011)	0.012
IBil	1.081(0.996-1.173)	0.063
Diabetes mellitus	2.601(0.404-2.173)	0.937
BMI	0.975(0.870-1.092)	0.658

OR, odds ratio; CI, confidence interval.

No competing interests reported.

Layered plaques and coronary plaque vulnerability: an optical coherence tomography study

Status:

Version 1

Abstract

Background

Methods and results

Conclusions

Figures

Introduction

Methods

Study population

Blood tests

Coronary angiography analysis

OCT image acquisition and measurement

Statistical analysis

Results

Discussion

Conclusion

Declarations

References

Tables

Additional Declarations

Status:

Version 1