BACKGROUND:Coronary atherosclerosis is a pan-coronary process. However, some studies investigated only one coronary artery and extrapolated the findings to the pan-vascular process. AIMS:We utilized a three-vessel optical coherence tomography (OCT) database to investigate whether plaque features in the left anterior descending coronary artery (LAD) mirror vulnerability in the remaining coronary vessels. METHODS:We analyzed 131 patients who underwent OCT imaging of the LAD, left circumflex (LCx), and right coronary artery (RCA). Vulnerable features, including thin-cap fibroatheroma (TCFA), lipid-rich plaque, macrophages, microvessels, and cholesterol crystals, were evaluated in each vessel. Vulnerable features in the LAD and non-LAD vessels were correlated at patient and plaque levels. RESULTS:At the patient level, vulnerable features in the LAD correlated with those in non-LAD vessels (TCFA p < 0.001; lipid-rich plaque p < 0.001; macrophages p = 0.010; microvessels p = 0.012; cholesterol crystals p = 0.045). However, an LAD-only strategy would have missed 30%-75% of patients with vulnerable features in non-LAD vessels; the adjusted miss rates were 58.7% for TCFA, 28.2% for lipid-rich plaque, 44.3% for macrophages, 36.9% for microvessels, and 75.7% for cholesterol crystals. At the plaque level, a similar number of high-risk plaques in non-LAD arteries would have been overlooked by the LAD-only approach, with the adjusted miss rates ranging from 74.3% for cholesterol crystals to 26.7% for lipid-rich plaque. CONCLUSIONS:Vulnerable plaque features in the LAD were associated with their presence in the other coronary arteries. However, a single-vessel LAD assessment would have missed a substantial proportion of patients with vulnerable features in the LCx or RCA.

Background Cardiovascular risk factors (RFs) are commonly used in clinical practice to predict future adverse cardiovascular outcomes, including acute coronary syndromes (ACS). A recent study reported an association between RFs and plaque vulnerability in patients with ACS. Objectives This study aimed to investigate the association between RFs (modifiable and non-modifiable) and pan-coronary plaque burden, plaque phenotype, and features of vulnerability. Methods In patients undergoing 3-vessel optical coherence tomography imaging, modifiable (dyslipidemia, hypertension, diabetes mellitus, obesity, smoking) and non-modifiable (age, sex, family history) RFs were recorded. Plaque number, plaque phenotype, and vulnerable features were analyzed. Results A total of 534 plaques from 131 patients (36.6% ACS) were analyzed. As the number of RFs increased, the number of plaques (P trend = 0.001) as well as plaques with a vulnerable phenotype (thin-cap fibroatheromas [TCFAs], P trend = 0.001) increased. An increasing number of RFs was also associated with a higher number of vulnerable features (P trend < 0.001), including more thin fibrous caps (P trend = 0.001), lipid-rich plaques (LRPs), macrophages, microvessels, and cholesterol crystals (all P trend ≤ 0.001). In multivariable analyses, only modifiable RF burden was associated with increased pan-coronary vulnerability (incidence rate ratio [IRR]: 1.36; 95% CI: 1.18-1.57; P < 0.001), including a higher prevalence of TCFAs (IRR: 1.48; 95% CI: 1.20-1.83; P < 0.001), LRPs (IRR: 1.35; 95% CI: 1.15-1.59; P < 0.001), and cholesterol crystals (IRR: 1.50; 95% CI: 1.21-1.87; P < 0.001). Conclusions As the number of cardiovascular RFs increased, the number of plaques, plaques with a high-risk phenotype, and vulnerable features also increased. Only increasing modifiable RF burden was associated with greater pan-coronary vulnerability, including more TCFAs and LRPs. Clinical Trial Registration: ClinicalTrials.gov NCT01110538

AIMS:Cardiovascular risk factors predict adverse clinical outcomes, including acute coronary syndromes (ACS). A recent study showed a close correlation between the number of modifiable risk factors and plaque vulnerability. However, the relationship between non-modifiable risk factors (NMRFs) and plaque characteristics has been unexplored. This study aimed to correlate the number of NMRFs with coronary plaque characteristics defined by optical coherence tomography (OCT). METHODS AND RESULTS:Patients with ACS were divided into four groups based on the number of NMRFs (age ≥70 years, male sex, and family history of coronary artery disease). Lesion characteristics in both culprit and non-culprit plaques were analysed. A total of 2345 plaques (1663 culprit and 682 non-culprit plaques) were analysed. In culprit plaques, the prevalence of both OCT-defined vulnerable features and plaque rupture did not increase as the number of NMRFs increased (P-trend > 0.05 for each vulnerable feature and P-trend for plaque rupture: 0.856). In non-culprit plaques, no association between the number of NMRFs and vulnerable features was observed. However, the number of NMRF was directly correlated with calcified plaque (OR 2.60, 95% CI 2.01-3.37, P < 0.001) and inversely correlated with erosion (OR 0.72, 95% CI 0.61-0.84, P < 0.001). CONCLUSION:In patients with ACS, the burden of NMRFs was not correlated with OCT-defined plaque vulnerability or the prevalence of plaque rupture, both at culprit and non-culprit lesions. Conversely, a higher number of NMRF was linked to a greater probability of calcified plaque and a lower probability of plaque erosion. CLINICAL TRIAL REGISTRATION:Clinicaltrials.gov NCT01110538, NCT03479723, NCT04523194. https://www.umin.ac.jp/ctr/, UMIN000047254.

BACKGROUND:Invasive intracoronary imaging represents the gold standard for identifying vulnerable coronary plaques, but it is not suitable for widespread clinical use. Coronary computed tomography angiography (CTA) may offer a noninvasive alternative. OBJECTIVES:This study aims to integrate coronary CTA-derived plaque morphology, pericoronary inflammation, and plaque burden into a unified morphology-inflammation-burden (MIB) score and to evaluate its association with plaque vulnerability and clinical outcomes. METHODS:Patients undergoing coronary CTA followed by optical coherence tomography (OCT) and intravascular ultrasound (IVUS) were followed for a median of 31 months. High-risk plaque, pericoronary adipose tissue attenuation, and total plaque burden (TPB) were quantified and compared with invasive imaging. A vulnerable lesion was defined as ≥2 vulnerability features on OCT. RESULTS:A total of 438 patients (median age 67 years) and 1,038 plaques were included; 45.4% presented with non-ST-segment elevation acute coronary syndrome. High-risk plaque, elevated pericoronary adipose tissue attenuation, and high TPB were independently associated with OCT-defined vulnerability (P < 0.05 for all). TPB correlated with IVUS percent atheroma volume (Pearson's r = 0.69; P < 0.001). The MIB score demonstrated a stepwise increase in vulnerability, exceeding a predicted risk of 90% in the highest category. Vulnerable patients, defined by the presence of ≥1 untreated lesion with a high MIB score, had a significantly higher rate of cardiac death, acute coronary syndrome, or revascularization (15.3% vs 4.4%; P < 0.001). CONCLUSIONS:A coronary CTA-derived MIB score correlates with plaque vulnerability by intracoronary imaging and identifies patients at increased risk for adverse events. These findings support the value of coronary CTA for noninvasive risk stratification in clinical practice. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194).

The mechanisms of luminal narrowing after percutaneous coronary intervention (PCI) with directional coronary atherectomy (DCA) and drug-coated balloon (DCB) remains unclear. This study aimed to investigate the pattern and mechanisms of luminal narrowing after DCA/DCB using optical coherence tomography (OCT). Patients who underwent DCA/DCB for de novo lesions and serial OCT imaging at 3, 6, and 18 months were evaluated to determine the pattern of luminal narrowing. Among 40 patients who had follow-up (F/U) OCT at 3 months post-PCI, 33 and 23 patients had F/U at 6 and 18 months, respectively. Thirty-six of the 40 (90.0%) cases exhibited a layered pattern at the 3-month F/U, 31 of 33 (93.9%) at the 6-month F/U, and 22 of 23 (95.7%) at the 18-month F/U. Layer progression was identified in 21 of 33 (63.6%) and 4 of 23 (17.4%) at the 6- and 18-month F/Us, respectively. The patients with layer progression tended to have a higher prevalence of diabetes (16.7% vs 52.4%, p = 0.067), a lower rate of dual-antithrombotic therapy (DATT) use (58.3% vs 19.0%, p = 0.052) between the 3- and 6-month F/Us, and a significantly higher rate of no or low-intensity statin use (0.0% vs 41.7%, p = 0.037) between the 6- and 18-month F/Us. In Conclusion, layer progression and luminal narrowing occurred mainly during the first 6 months after DCA/DCB. Patients with luminal narrowing tended to have a higher prevalence of diabetes, standard DATT duration, and no or low-intensity statin use.

OBJECTIVES:Plaque disruption and subsequent healing are important contributors to coronary plaque progression; however, the biological mechanisms underlying this process remain incompletely understood. Optical coherence tomography (OCT) enables the identification of previously disrupted plaques, referred to as layered plaques. Proteomic analysis can characterize the molecular signature of layered plaques, providing insights into the biology of plaque disruption and healing. Furthermore, layered plaques indicate a more advanced stage of atherosclerotic disease, and their noninvasive identification could enhance patient risk stratification. This study aimed to identify plasma proteins associated with layered plaques at the culprit lesion in patients with stable angina pectoris (SAP). METHODS:Patients undergoing coronary angiography and OCT for SAP, with periprocedural blood sample collection, were enrolled. A proteomic analysis was subsequently performed, assessing 1470 proteins using the Olink explore 1536 reagent kit. RESULTS:Among 51 patients, OCT identified 31 (60.8%) patients with layered plaques at the culprit lesion. Patients with layered plaques exhibited 2.23- and 2.11-fold higher concentrations of interleukin-17A (IL17A) and matrix metalloproteinase-1 (MMP1), respectively ( P = 0.013 and P < 0.001), compared to those without layered plaques. Multivariable regression models demonstrated that IL17A and MMP1 were associated with layered plaques independent of known predictors (diameter stenosis > 70%, B2/C American College of Cardiology/American Heart Association lesion, and multivessel disease). Adding both proteins to the known predictors significantly improved the area under the curve (AUC) for layered plaque detection (AUC 0.831 vs. 0.581; P = 0.007). CONCLUSION:In patients with SAP, IL17A, and MMP1 were independently associated with layered plaques identified by OCT.

Background The association between high-risk plaque (HRP) on coronary computed tomography angiography (CTA) and the level of perivascular inflammation has not been fully investigated. Methods Patients who underwent both CTA and optical coherence tomography (OCT) were included. The level of perivascular inflammation was assessed by pericoronary adipose tissue (PCAT) attenuation at two levels: lesion-specific and the proximal segment of the culprit vessel. HRP features included positive remodeling (PR), low-attenuation plaque (LAP), napkin-ring sign (NRS), and spotty calcification (SC). Results OCT features of plaque vulnerability were evaluated in culprit vessels. A total of 1360 lesions (413 culprit lesions and 947 non-culprit lesions) from 413 patients were evaluated. Lesion-specific PCAT attenuation was higher in lesions with any HRP feature except SC (present vs. absent: PR -71.3 +/- 10.1 vs. -74.1 +/- 11.7, P < 0.001; LAP -71.7 +/- 9.9 vs. -73.0 +/- 11.4, P = 0.025; NRS -70.3 +/- 9.6 vs. -72.9 +/- 11.1, P = 0.001; and SC -71.9 +/- 9.9 vs. -73.0 +/- 11.5, P = 0.082). After adjusting for confounders, only PR was associated with higher lesion-specific PCAT attenuation. The number of lesions with PR significantly correlated with higher levels of perivascular inflammation measured by culprit vessel PCAT attenuation. The number of lesions with PR was associated with higher lipid index and macrophage grade at culprit vessels. Conclusions Among 4 HRP features, only PR was significantly associated with higher lesion-specific PCAT attenuation. The number of plaques with PR correlated with the level of perivascular inflammation and vulnerability. Trial Registration clinicaltrials.gov Identifier: NCT04523194.

Background Cardiovascular risk factors are strongly associated with adverse clinical outcomes, including acute coronary syndrome (ACS). Although individual risk factors have been related to specific plaque phenotypes, the relationship between the cumulative number of risk factors and plaque vulnerability has not been systematically explored. Objectives The purpose of this study was to investigate the association between the number of cardiovascular risk factors and plaque vulnerability defined by optical coherence tomography. Methods Patients with ACS were divided into 5 groups based on their number of traditional risk factors (diabetes, hypertension, hyperlipidemia, smoking) or into 2 groups (0-1 vs ≥2 risk factors). Features of vulnerability in both culprit and nonculprit lesions were analyzed. Results Of 2,187 plaques analyzed, 1,581 were culprit and 606 nonculprit plaques. In culprit plaques, the prevalence of lipid-rich plaques (P trend = 0.027), thin-cap fibroatheromas (P trend = 0.006), macrophages (P trend <0.001), microvessels (P trend <0.001), and cholesterol crystals (P trend = 0.032) increased as the number of risk factors increased. The presence of ≥2 risk factors was independently associated with all vulnerable features except lipid-rich plaques. Plaque rupture showed an increasing prevalence as the number of risk factors increased (P trend = 0.015), whereas plaque erosion showed a decreasing trend (P trend <0.001). In nonculprit plaques, only macrophages, cholesterol crystals, and the cumulative number of vulnerable features in each plaque exhibited a significant positive association with the number of risk factors. Conclusions In patients with ACS, an increasing number of cardiovascular risk factors were strongly associated with greater plaque vulnerability, especially for culprit lesions. These findings may explain the relationship between traditional risk factors and adverse clinical outcomes.

BACKGROUND: It is not known whether there is a sex difference in the association between perivascular inflammation and plaque vulnerability. The aim of this study was to investigate the sex-specific association between perivascular inflammation and plaque vulnerability. METHODS: Patients who underwent coronary computed tomography angiography and optical coherence tomography were enrolled. All images were analyzed at a core laboratory. The level of perivascular inflammation was assessed by pericoronary adipose tissue attenuation on computed tomography angiography and the level of plaque vulnerability by optical coherence tomography. Patients were classified into 3 groups according to tertile levels of culprit vessel pericoronary adipose tissue attenuation (low inflammation, ≤−73.1 Hounsfield units; moderate inflammation, −73.0 to −67.0 Hounsfield units; or high inflammation, ≥−66.9 Hounsfield units). RESULTS: A total of 968 lesions in 409 patients were included: 184 lesions in 82 women (2.2 plaques per patient) and 784 lesions in 327 men (2.4 plaques per patient). Women were older (median age, 71 versus 65 years; P <0.001) and had less severe coronary artery disease with a lower plaque burden than men. In women, it was found that perivascular inflammation was significantly associated with plaque vulnerability, with a higher prevalence of thin-cap fibroatheroma and greater macrophage grades in the high inflammation group compared with the low inflammation group (low versus moderate versus high inflammation in women: 18.5% versus 31.8% versus 46.9%, P =0.002 for low versus high inflammation; 3 versus 4 versus 12, P <0.001 for low versus high inflammation, respectively). However, no significant differences were observed among the 3 groups in men. CONCLUSIONS: Perivascular inflammation was associated with a higher prevalence of thin-cap fibroatheroma and more significant macrophage accumulation in women but not in men. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04523194.

Biomarkers are widely used for the diagnosis and monitoring of cardiovascular disease. However, markers for coronary high-risk plaques have not been identified. The aim of this study was to identify proteins specific to coronary high-risk plaques. Fifty-one patients (71.2 ± 11.1 years, male: 66.7 https://www.umin.ac.jp/ctr/ , UMIN000041692

Layered plaque, a signature of previous plaque destabilization and healing, is a known predictor for rapid plaque progression; however, the mechanism of which is unknown. The aim of the current study was to compare the level of vascular inflammation and plaque vulnerability in layered plaques to investigate possible mechanisms of rapid plaque progression. This is a retrospective, observational, single-center cohort study. Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) for stable angina pectoris (SAP) were selected. Plaques were defined as any tissue (noncalcified, calcified, or mixed) within or adjacent to the lumen. Perivascular inflammation was measured by pericoronary adipose tissue (PCAT) attenuation at the plaque levels on CTA. Features of plaque vulnerability were assessed by OCT. Layered plaques were defined as plaques presenting one or more layers of different optical densities and a clear demarcation from underlying components on OCT. A total of 475 plaques from 195 patients who presented with SAP were included. Layered plaques (n = 241), compared with non-layered plaques (n = 234), had a higher level of vascular inflammation (-71.47 ± 10.74 HU vs. -73.69 ± 10.91 HU, P = 0.026) as well as a higher prevalence of the OCT features of plaque vulnerability, including lipid-rich plaque (83.8 https://classic.clinicaltrials.gov/ct2/show/NCT04523194 . Level of vascular inflammation and plaque vulnerability in patients with versus without layered plaque phenotype. In patients with stable angina pectoris, layered plaques had a higher level of pericoronary adipose tissue attenuation indicating a higher level of perivascular inflammation and a higher prevalence of optical coherence tomography features of plaque vulnerability

Background Protruding aortic plaque is known to be associated with an increased risk for future cardiac and cerebrovascular events. However, the relationship between protruding aortic plaque and coronary plaque characteristics has not been systematically investigated. Methods and Results A total of 615 patients who underwent computed tomography angiography, and preintervention optical coherence tomography imaging were included. Coronary plaque characteristics were compared to evaluate coronary plaque vulnerability in patients with protruding aortic plaque on computed tomography angiography. 615 patients, the 186 (30.2%) patients with protruding aortic plaque were older and had more comorbidities such as hypertension, chronic kidney disease, and a prior myocardial infarction than those without. They also had a higher prevalence of coronary plaques with vulnerable features such as thin‐cap fibroatheroma (85 [45.7%] versus 120 [28.0%], P<0.001), lipid‐rich plaque (165 [88.7%] versus 346 [80.7%], P=0.014), macrophages (147 [79.0%] versus 294 [68.5%], P=0.008), layered plaque (117 [62.9%] versus 213 [49.7%], P=0.002), and plaque rupture (96 [51.6%] versus 111 [25.9%], P<0.001). Patients with protruding aortic plaque experienced more major adverse cardiac and cerebrovascular events, including all‐cause mortality, nonfatal acute coronary syndromes, and stroke (27 [14.7%] versus 21 [4.9%], P<0.001; 8 [4.3%] versus 1 [0.2%], P<0.001; 5 [2.7%] versus 3 [0.7%], P=0.030; and 5 [2.7%] versus 2 [0.5%], P=0.013, respectively). Conclusions The current study demonstrates that patients with protruding aortic plaque have more features of coronary plaque vulnerability and are at increased risk of future adverse events.

Background It was recently reported that thin‐cap fibroatheroma (TCFA) detected by optical coherence tomography was an independent predictor of future cardiac events in patients with diabetes. However, the clinical usefulness of this finding is limited by the invasive nature of optical coherence tomography. Computed tomography angiography (CTA) characteristics of TCFA have not been systematically studied. The aim of this study was to investigate CTA characteristics of TCFA in patients with diabetes. Methods and Results Patients with diabetes who underwent preintervention CTA and optical coherence tomography were included. Qualitative and quantitative analyses were performed for plaques on CTA. TCFA was assessed by optical coherence tomography. Among 366 plaques in 145 patients with diabetes, 111 plaques had TCFA. The prevalence of positive remodeling (74.8% versus 50.6%, P<0.001), low attenuation plaque (63.1% versus 33.7%, P<0.001), napkin‐ring sign (32.4% versus 11.0%, P<0.001), and spotty calcification (55.0% versus 34.9%, P<0.001) was significantly higher in TCFA than in non‐TCFA. Low‐density noncalcified plaque volume (25.4 versus 15.7 mm3, P<0.001) and remodeling index (1.30 versus 1.20, P=0.002) were higher in TCFA than in non‐TCFA. The presence of napkin‐ring sign, spotty calcification, high low‐density noncalcified plaque volume, and high remodeling index were independent predictors of TCFA. When all 4 predictors were present, the probability of TCFA increased to 82.4%. Conclusions The combined qualitative and quantitative plaque analysis of CTA may be helpful in identifying TCFA in patients with diabetes. Registration Information URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.

Background The left internal mammary artery (LIMA) is protected from developing atherosclerosis. Perivascular inflammation, which is closely associated with atherosclerosis, can be measured by perivascular adipose tissue attenuation on computed tomography angiography. Whether the absence of atherosclerosis in LIMA is related to the lower level of perivascular inflammation is unknown. This study was performed to compare the level of perivascular inflammation between LIMA in situ and native coronary arteries in patients with coronary artery disease. Methods and Results A total of 573 patients who underwent both computed tomography angiography and optical coherence tomography imaging were included. The level of perivascular adipose tissue attenuation between LIMA in situ and coronary arteries was compared. Perivascular adipose tissue attenuation around LIMA in situ was significantly lower around the 3 coronary arteries (−82.9 [−87.3 to −78.0] versus −70.8 [−75.9 to −65.9]; P <0.001), irrespective of the level of pericoronary inflammation or the number of vulnerable features on optical coherence tomography. When patients were divided into high and low pericoronary inflammation groups, those in the high inflammation group had more target vessel failure (hazard ratio, 2.97 [95% CI, 1.16–7.59]; P =0.017). Conclusions The current study demonstrated that perivascular adipose tissue attenuation was significantly lower around LIMA in situ than around native coronary arteries. The lower level of perivascular inflammation may be related to the low prevalence of atherosclerosis in LIMA. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT04523194.

BACKGROUND:Coronary artery calcification is an integral part of atherosclerosis. It has been suggested that early coronary artery calcification is associated with active inflammation, and advanced calcification forms as inflammation subsides. Inflammation is also an important factor in plaque vulnerability. However, the relationship between coronary artery calcium burden, vascular inflammation, and plaque vulnerability has not been fully investigated. OBJECTIVES:This study aimed to correlate calcified plaque burden (CPB) at the culprit lesion with vascular inflammation and plaque vulnerability. METHODS:Patients with coronary artery disease who had both computed tomography angiography and optical coherence tomography were included. The authors divided the patients into 4 groups: 1 group without calcification at the culprit lesion; and 3 groups based on the CPB tertiles. CPB was calculated as calcified plaque volume divided by vessel volume in the culprit lesion. The authors compared pericoronary adipose tissue (PCAT) attenuation for vascular inflammation and optical coherence tomography-derived vulnerable features among the 4 groups. RESULTS:Among 578 patients, the highest CPB tertile showed significantly lower PCAT attenuation of culprit vessel compared with the other groups. The prevalence of features of plaque vulnerability (including lipid-rich plaque, macrophage, and microvessel) was also lowest in the highest CPB tertile. In the patients with calcification, higher age, statin use, and lower PCAT attenuation were independently associated with CPB. CONCLUSIONS:Greater calcium burden is associated with a lower level of vascular inflammation and plaque vulnerability. A greater calcium burden may represent advanced stable plaque without significant inflammatory activity. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194).

Abstract Background Although the incidence of acute myocardial infarction has been declining over the past decade, the etiology of this trend is unknown. One possible explanation could be changes in coronary plaque phenotype. Purpose The aim of this study was to investigate the changes in plaque characteristics over the last 10 years. Methods Patients who presented with acute coronary syndrome and underwent preintervention optical coherence tomography (OCT) imaging from 2008 to 2018 were included. Patients were divided into 4 periods: (P1) 2008-2010, (P2) 2011-2013, (P3) 2014-2015, and (P4) 2016-2018. Plaque characteristics at culprit lesion in each period were compared. Results Among 1144 patients, 594 (51.9%) presented with ST-segment–elevation myocardial infarction (STEMI). The prevalence of thin-cap fibroatheroma decreased from P1 to P4 in both STEMI group (57.4% to 24.6%, P<0.001) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) group (40.4% to 17.0%, P<0.001) (Figure). Conclusions The prevalence of OCT features of plaque vulnerability has decreased over the past 10 years. A decrease in plaque vulnerability may explain the favorable trend in cardiovascular events.Prevalence of thin-cap fibroatheroma

BACKGROUND:Coronary artery calcium score (CACS) is widely used for risk stratification. However, in patients with established coronary artery disease, its clinical implication and relationship with plaque vulnerability are unclear. We sought to correlate the CACS and plaque vulnerability assessed by optical coherence tomography. METHODS:Patients with coronary artery disease who had CACS and optical coherence tomography before percutaneous coronary intervention were included. Patients were divided into 5 groups based on CACS: CACS of 0, 1 to 99, 100 to 399, 400 to 999, and ≥1000. Optical coherence tomography-derived vulnerable features in culprit plaque were compared between the groups. RESULTS:In 460 patients, the prevalence of lipid-rich plaque, macrophage, and cholesterol crystal significantly differed among the 5 groups, being lowest in the patients with a CACS of 0. The prevalence of thin-cap fibroatheroma tended to be lower in those with a CACS of 0. No significant difference in vulnerable features was observed between the 4 groups with CACS >0. In the 2-group comparison between the group with a CACS of 0 and the other 4 groups combined, the prevalence of lipid-rich plaque (60.5% versus 85.9%; P<0.001), macrophage (48.8% versus 74.1%; P<0.001), thin-cap fibroatheroma (16.3% versus 35.0%; P=0.013), and cholesterol crystal (11.6% versus 32.9%; P=0.004) was significantly lower in the patients with CACS of 0. CACS of 0 was independently negatively associated with lipid-rich plaque, macrophage, thin-cap fibroatheroma, and cholesterol crystal after adjustment for patient characteristics. CONCLUSIONS:Patients with a CACS of 0 have a significantly lower prevalence of vulnerable plaque features compared with those with CACS >0 in patients with established coronary artery disease. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.