Acute coronary syndromes frequently arise from erosion of vulnerable plaques and subsequent thrombosis [
Previous studies have noted that histologic thumbprints of these vulnerable plaques were characterized by thin-capped atheroma with a lipid-rich core, few smooth muscle cells, numerous macrophages, adventitial inflammation, and positive remodeling [
The main challenge faced was that ACS often arises from lesions with only mild to moderate stenosis. Accordingly, disclosure of potentially vulnerable plaques may promote prevention of cardiovascular events [
Our objective was to study the coronary atherosclerotic lesion characteristics that predict the occurrence of non-ST segment elevation acute coronary syndromes compared to those with stable angina.
We did this cross-sectional study on 116 patients (50 patients with stable angina and 66 patients with non-ST segment elevation acute coronary syndromes) subjected to coronary catheterization between the periods from January 2017 to January 2018.
Stable angina is defined as a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arm. It is typically aggravated by exertion or emotional stress and relieved by nitroglycerin with no change in character for sixty days. Angina usually occurs in patients with CAD involving ≥1 large epicardial artery [
Chest pain in absence of persistent ST elevation with elevated cardiac biomarkers of necrosis is suggestive of NSTE-ACS [
Informed consents were obtained from all individual participants included in this study. The study had been approved by the institutional research ethical committee.
Patients with acute ST elevation myocardial infarction (STEMI), previous coronary artery bypass grafting (CABG), renal impairment, and thrombocytopenia were excluded.
Coronary angiography and interventions were done using Philips (CV20, 2011- Netherland) and Siemens (Axiom Artis DFC 35875) with 15 frames per second (fps) imaging speed.
Three hundred twelve coronary lesions were assessed by IVUS during diagnostic angiography, 216 lesions in 66 patients with NSTE-ACS (group I) versus 96 lesions in 50 patients with stable angina (group II).
We used iLab™ Ultrasound Imaging System (90539386-01A, 2009-Boston Scientific Inc., USA) to get IVUS runs, after administration of 200 mcg intracoronary nitroglycerin, using a 40 MHz 6F compatible catheter (Atlantis SR Pro).
Image acquisition was done through retrograde-automated transducer pullback at 0.5 mm/second. The pullback started from at least 10 mm distal to the studied lesions as the distal reference segment was defined as the site with the largest lumen distal to a stenosis but within the same segment [
Based on images depicted during pullback of the transducer, the lesion was defined as the image slice with the smallest lumen cross-sectional area [
The measurements were taken according to the American College of Cardiology guidelines, and reporting was done by two experienced IVUS readers [
Lumenal and external elastic membrane (EEM) cross-sectional areas (CSAs) were measured for each 1 mm of axial length, and then, plaque plus media (P&M) CSA was calculated by EEM CSA minus lumen CSA.
Plaque burden was calculated by P&M CSA divided by EEM CSA. The lesion was considered significant when percent area stenosis >70%.
The distal and proximal vessel reference segments were the most apparently normal segments within 10 mm distal and proximal to the coronary lesion.
The remodeling index (RI) was calculated by EEM CSA divided by the mean reference CSA [
The colored-coded iMap technique was used to get the characteristics of coronary plaques structure.
Precoded data were entered on the computer using “Microsoft Office Excel Software” program (2010) for Windows. Data were then transferred to the Statistical Package of Social Science Software program, version 21 (SPSS), to be statistically analyzed.
Data were summarized using mean, standard deviation, median, and interquartile range for quantitative variables and frequency and percentage for qualitative ones.
Comparison between groups was performed using the independent sample
Univariate regression analysis had been used to determine potential predictors of ACS.
Body mass index (BMI) was significantly higher in the stable angina (SA) group while the triglyceride level was higher in the NSTE-ACS group.
History of previous MI and PCI was significantly higher in the NSTE-ACS group (Table
Demographic and clinical data of stable angina and NSTE-ACS groups.
Patients characteristics | All ( |
NSTE-ACS group (I) ( |
SA group (II) ( |
|
---|---|---|---|---|
Age (years) | 52.2 ± 9.2 | 52.06 ± 9.15 | 52.05 ± 9.49 | 0.56 |
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Gender | ||||
Males | 90 (77.5%) | 48 (72.7%) | 42 (84%) | 0.18 |
Females | 26 (22.5%) | 18 (27.2%) | 8 (16%) | 0.11 |
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Risk factors | ||||
Hypertension | 76 (65.5%) | 44 (66.6%) | 32 (64%) | 0.45 |
Smoking | 74 (63.8%) | 42 (63.6%) | 32 (64%) | 0.56 |
Diabetes mellitus | 50 (43.1%) | 30 (45.5%) | 20 (40%) | 0.34 |
Dyslipidemia | 68 (58.6%) | 38 (57.6%) | 30 (60%) | 0.47 |
BMI | 26.2 ± 3.4 | 24.8 ± 3.3 | 27.9 ± 2.9 | 0.01 |
FH-IHD | 38 (32.7%) | 20 (30.3%) | 18 (36%) | 0.32 |
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Laboratory results | ||||
Total cholesterol (mg%) | 183.1 ± 33.03 | 173.33 ± 29.8 | 175.73 ± 27.3 | 0.73 |
LDL-C (mg%) | 132.7 ± 31.48 | 126.7 ± 36.4 | 118.86 ± 23.9 | 0.29 |
TGL (mg%) | 132.8 ± 66.9 | 149.6 ± 52.6 | 123.2 ± 32.9 | 0.045 |
Previous MI | 26 (22.4%) | 20 (30.3%) | 6 (12%) | 0.016 |
Previous PCI | 44 (37.9%) | 34 (51.5%) | 10 (20%) | 0.001 |
EF (%) | 59.03 ± 7.8 | 59.2 ± 9.1 | 58.9 ± 6.3 | 0.21 |
The study involved 312 coronary lesions, and the culprit lesions were 134 for which stenting was done. LM lesions were higher in the NSTE-ACS patients compared to SA patients. The Syntax score was significantly higher in the NSTE-ACS group compared to the SA group (Table
Angiographic data of stable angina and NSTE-ACS groups.
Angiographic criteria | All ( |
NSTE-ACS group (I) ( |
SA group (II) ( |
|
---|---|---|---|---|
Syntax score | 12.46 ± 7.6 | 18.7 ± 7.8 | 8.07 ± 2.5 | 0.001 |
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Affected vessel | ||||
LM | 21 (6.73%) | 18 (8.3%) | 3 (3.1%) | 0.04 |
LAD | 136 (43.6%) | 92 (42.6%) | 44 (45.8%) | |
CX | 74 (23.7%) | 49 (22.7%) | 25 (26.1%) | 0.15 |
RCA | 81 (25.9%) | 57 (26.4%) | 24 (25%) | |
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Site of lesion | ||||
Proximal | 158 (50.6%) | 113 (52.3%) | 45 (46.9%) | |
Mid | 106 (33.9%) | 69 (31.9%) | 37 (38.5%) | 0.24 |
Distal | 48 (15.4%) | 34 (15.7%) | 14 (14.6%) | |
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Stenting | 134 (42.9%) | 80 (37.04%) | 54 (56.3%) | 0.001 |
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Predilatation | 64 (20.5%) | 34 (15.7%) | 30 (31.3%) | 0.001 |
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Edge dissection | 2 (0.6%) | 2 (0.9%) | 0 | 0.62 |
Thrombus migration | 2 (0.6%) | 2 (0.9%) | 0 | 0.62 |
In-hospital mortality | 2 (0.6%) | 2 (0.9%) | 0 | 0.62 |
LM: left main artery; LAD: left anterior descending artery; CX: circumflex artery; RCA: right coronary artery.
Notably, the coronary lesions of NSTE-ACS patients had significantly less vessel area with negative remodeling index compared to those with the SA group. Also, the plaque burden and percent area stenosis were significantly smaller than those of the SA group (Table
Intravascular ultrasound criteria of SA and NSTE-ACS groups.
IVUS criteria | NSTE-ACS group | Stable angina group |
|
---|---|---|---|
Vessel area (EEM CSA) (mm2) | 9.86 ± 3.8 | 11.36 ± 2.9 | 0.001 |
Max. vessel diameter (mm) | 3.76 ± 0.71 | 4 ± 0.53 | 0.01 |
Min. vessel diameter (mm) | 3.23 ± 0.66 | 3.5 ± 0.51 | 0.01 |
Lesion MLA (mm2) | 4.69 ± 2.58 | 3.58 ± 1.23 | 0.001 |
Lesion max. diameter (mm) | 2.54 ± 0.62 | 2.26 ± 0.45 | 0.001 |
Lesion min. diameter (mm) | 2.05 ± 0.50 | 1.80 ± 0.38 | 0.001 |
Area stenosis (%) | 54.7 ± 14.9 | 68.6 ± 8.7 | 0.001 |
Plaque plus media (mm2) | 5.3 ± 2.54 | 7.7 ± 2.48 | 0.001 |
Plaque burden | 54.4 ± 14.7 | 67.8 ± 9.8 | 0.001 |
Lesion length (mm) | 17.53 ± 7.3 | 18.02 ± 9.6 | 0.68 |
Proximal reference area (mm2) | 11.19 ± 3.8 | 12.83 ± 3.35 | 0.05 |
Proximal max. RVD (mm) | 4.19 ± 0.47 | 4.24 ± 0.55 | 0.69 |
Proximal min. RVD (mm) | 3.79 ± 0.52 | 3.72 ± 0.62 | 0.58 |
Distal reference area (mm2) | 9.03 ± 3.5 | 8.79 ± 2.9 | 0.65 |
Distal max. RVD (mm) | 3.46 ± 0.54 | 3.63 ± 0.62 | 0.19 |
Distal min. RVD (mm) | 3.09 ± 0.56 | 3.30 ± 0.56 | 0.09 |
Mean reference area (mm2) | 9.94 ± 3.5 | 11.33 ± 3.08 | 0.01 |
Remodeling index | 0.95 ± 20 | 1.02 ± 0.14 | 0.008 |
EEM: external elastic membrane; CSA: cross-sectional area; MLA: minimal lumen area; RVD: reference vessel diameter.
Regarding lesion characteristics, NSTE-ACS group lesions had significantly more lipidic content, necrotic core, and calcifications with less fibrosis compared to the stable angina patients (Table
Intravascular ultrasound characteristics of coronary lesions.
Lesions structure | NSTE-ACS group | Stable angina group |
|
---|---|---|---|
Fibrosis (%) | 51.67 ± 7.07 | 70.37 ± 11.7 | 0.001 |
Lipidosis (%) | 21.8 ± 7.03 | 7.26 ± 3.47 | 0.001 |
Necrosis (%) | 18.08 ± 10.19 | 15.83 ± 4.9 | 0.02 |
Calcification (%) | 10.4 ± 5.2 | 4.19 ± 3.29 | 0.001 |
Coronary lesions component. (a) Stable angina patients. (b) ACS patients. Blue = fibrotic component. Green = lipidic component. Violet = calcium component. Red = necrotic component.
IVUS runs of LAD lesions. (a) Greyscale run of SA patient. (b) iMAP study of lesion in (a). (c) Greyscale run of NSTE-ACS patient. (d) iMAP study of lesion in (c). Green = fibrous component. Yellow = lipid component. Red = necrotic component. Blue = dense calcium.
Univariate regression analysis had been used to determine potential predictors of NSTE-ACS and had showed that the Syntax score and core composition especially calcification and lipid composition were significant predictors (Table
Predictors of NSTE-ACS.
|
Odds ratio | 95% CI for odds ratio | ||
---|---|---|---|---|
Lower | Upper | |||
Syntax score | 0.014 | 1.289 | 1.053 | 1.578 |
Calcific core percentage | 0.002 | 1.277 | 1.094 | 1.491 |
Necrotic core percentage | 0.053 | 1.089 | 0.999 | 1.187 |
Lipid core percentage | 0.001 | 1.320 | 1.167 | 1.494 |
Vessel CSA | 0.538 | 0.946 | 0.791 | 1.130 |
Plaque burden | 0.240 | 0.951 | 0.874 | 1.034 |
Predictors of NSTE-ACS.
Plaque destabilization is a biomechanical phenomenon depending on complex interactions between applied shear stresses, resulting in reactive oxygen species production and inflammation, blood laminar or turbulent flow characteristics, coronary lesion structural features, and biological processes that determine mechanical strength [
Plaque rupture refers to transmural fissuring of the atheroma fibrous cap and exposure of the underlying necrotic core with its proinflammatory and thrombogenic activities to circulating blood. It is the commonest form of plaque destabilization. The ruptured plaque usually has the features of a thin cap fibroatheroma [
Our study used IVUS to assess the atherosclerotic burden and the plaque vulnerability in culprit and nonculprit vessels during cardiac catheterization of patients with stable angina and NSTE-ACS. Both groups had similar risk factors of atherosclerosis except for hypertriglyceridaemia and BMI. NSTE-ACS patients had moderately stenosed coronary lesions with less plaque burden but negative remodeling index as compared to patients with stable angina.
Our results were similar to those of Ghaffari et al. [
Our study showed that NSTE-ACS patients had a higher ratio of lipidic content, dense deep calcium, and necrotic core components, while less fibrotic content compared to stable angina patients. This could explain the occurrence of ACS despite having moderately stenosed coronary lesions with less plaque burden. The lesion characteristics were similar to those in Nakamura et al.’s study [
The PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study [
Our study revealed that NSTE-ACS patients had lesions with significantly negative remodeling index as compared to patients with stable angina, which was consistent with the results of Koo et al. [
Our results revealed that SYNTAX score and core composition, especially calcification and lipid composition, were significant predictors for NSTE-ACS. This was different to a study by Zheng et al. [
The plaque vulnerability hypothesis was used to better describe the unpredictability of the future course of atherosclerosis. Vulnerable plaques have been defined as those plaques prone to becoming culprit plaques causing acute coronary events, regardless of stenosis, shape, or destabilization, without taking into account the effect of exogenous factors, such as shear stresses, blood laminar or turbulent flow characteristics, and vascular anatomy and function (e.g., bifurcation and tone, respectively) [
Finally, coronary lesions, even with less plaque burden, should not be underestimated because they could be vulnerable plaques and predispose to future cardiac events. IVUS helps to detect plaques morphology and vulnerability, but the PREDICTION study [
The clinical applicability of vulnerable plaques concept has led to advances in our understanding of pathogenesis and management of atherosclerosis. Patients with vulnerable nonculprit lesions require systemic approach rather than localized treatment. Intensifying medical treatment and life-style change may reduce the atherosclerosis burden and future cardiac events.
The current study was a single-center study with a small number of patients included.
The vulnerability rather than the stenotic severity is the most important factor that predispose to Non ST segment elevation acute coronary syndromes. The vulnerability is related to the lesion characteristics especially the lipidic core and calcification while lesion fibrosis favors lesion stability.
The data used to support the findings of this study have not been made available because of the hospital policy in respecting patients’ privacy.
No conflicts of interest and no funds had received for this study.