Associations of Thrombotic and Bleeding Risks With Plaque Morphology

Abstract

Background: Plaque morphology evaluation using optical coherence tomography (OCT) is vital for planning an optimized strategy for percutaneous coronary intervention (PCI), and an assessment of thrombotic risk (TR) and bleeding risk (BR) is crucial in managing patients who have undergone PCI. We examined the association of TR and BR with plaque morphology in patients with coronary artery disease (CAD).

Methods and Results: We conducted a multicenter prospective observational study and enrolled 325 patients with CAD who underwent PCI with OCT (median age 70 years, 19% women). The calcium index, which is equivalent to the calcium plaque volume, was assessed using OCT. Nondeformable calcified plaque was defined as a calcium score ≥3, the threshold for necessitating aggressive lesion modification. The TR and BR were evaluated using CREDO-Kyoto risk scores. The calcium index and prevalence of nondeformable calcified plaque increased significantly with increasing TR and BR scores. The TR and BR scores were significantly associated with higher calcium index after adjustment for confounders (TR score: β, 0.757; 95% confidence interval [CI], 0.568–0.946; P<0.001 and BR score: β, 0.623; 95% CI, 0.374–0.871; P<0.001). Both the calcium index and prevalence of nondeformable calcified plaque were highest in patients with both high TR and BR.

Conclusions: The TR and BR scores were associated with significant calcification and nondeformable calcified plaques in patients with CAD.

Central Figure

Data of 325 patients with CAD who underwent PCI were collected from the Yamagata OCT registry. TR and BR scores were assessed by CREDO-Kyoto risk score. Plaque morphology was evaluated by OCT before PCI. Calcium index is higher in patients with higher TR and BR scores. Patients with both high TR and high BR most frequently have nondeformable calcified plaques compared with those without it. BR, bleeding risk; CAD, coronary artery disease; TR, thrombotic risk; OCT, optical coherence tomography; PCI, percutaneous coronary intervention.

Cardiovascular disease is the leading cause of death worldwide. Despite advancements in percutaneous coronary intervention (PCI) and medicine, coronary artery disease (CAD) remains the major cause of cardiovascular deaths.^1–3 Coronary artery calcification detected using computed tomography, a well-known marker of atherosclerotic plaque burden, is reportedly associated with poor clinical outcomes.^4–6 Because calcified plaques are associated with an increased risk of stent underexpansion, thrombosis, and target lesion revascularization,⁷ predicting the requirement for aggressive lesion modification prior to PCI is clinically important.

Assessment of the Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) thrombotic risk (TR) and bleeding risk (BR) scores is recommended before PCI to predict the risk of thrombotic and bleeding events.⁸ The coexistence of high TR and BR is not uncommon and is reportedly associated with worse clinical outcomes in patients with CAD.⁹ However, the relationship of TR and BR with plaque morphology has not been thoroughly investigated.

Evaluation of plaque morphology using optical coherence tomography (OCT) is essential for planning an optimized PCI strategy.^10–13 OCT has high resolution for assessing detailed plaque morphology at the microscopic level, particularly for calcified plaque.¹⁴ In the present study, we used OCT to examine the association of the TR and BR scores with plaque morphology.

Methods

Ethics Statement

All procedures were performed in accordance with the ethical, institutional, and/or national research committee guidelines of the centers at which the study was conducted, and complied with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Institutional Ethics Committee of the Yamagata University School of Medicine (no. 2022-17). All patients provided written informed consent prior to PCI.

Study Participants

For this study, we adopted a multicenter, prospective, cross-sectional design. Patients who had undergone OCT before PCI were enrolled and included patients diagnosed with chronic coronary syndrome (CCS) or acute coronary syndrome (ACS) between January 2022 and September 2024. Patient data were extracted from the ongoing “Yamagata OCT Registry”. Data were collected from 5 institutions in Japan: the Japanese Red Cross Ishinomaki Hospital, Okitama Public General Hospital, Nihonkai General Hospital, Yamagata Prefectural Central Hospital, and Yamagata University Hospital. For analysis, all OCT images and clinical data obtained from the 5 centers were forwarded to the cardiovascular imaging laboratory at Yamagata University School of Medicine (Yamagata, Japan).

Of the 412 enrolled patients, 48 with in-stent restenosis and 39 with poor OCT image quality were excluded, so 325 patients were included in this study. The site investigators determined the culprit vessel based on clinical and angiographic information and/or left ventricular regional wall motion abnormalities. In cases of multivessel disease in which the culprit vessel was not apparent, the choice was made based on lesions showing evidence of recent plaque disruption in patients presenting with ACS or the most severe lesion in those with CCS. All selected lesions were subsequently confirmed using OCT.

Cardiovascular Risk Factors

Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or antihypertensive medication use. Diabetes mellitus (DM) was defined as a fasting blood sugar level ≥126 mg/dL, glycosylated hemoglobin A1c ≥6.5% (National Glycohemoglobin Standardization Program) or antidiabetic medication use. Dyslipidemia was defined as high-density lipoprotein cholesterol <40 mg/dL, low-density lipoprotein cholesterol ≥140 mg/dL, triglyceride ≥150 mg/dL or lipid-lowering medication use.

TR and BR Scores

The components of the CREDO-Kyoto score for TR in patients who underwent PCI include severe chronic kidney disease (CKD) defined as estimated glomerular filtration rate <30 mL/min/1.73 m² or hemodialysis, lower extremity artery disease (LEAD), heart failure (HF), atrial fibrillation (AF), anemia defined as hemoglobin level <11 g/dL, age ≥75 years, DM, and chronic total coronary artery occlusion. The CREDO-Kyoto risk score for BR includes severe CKD, LEAD, HF, AF, low platelet count (<10⁵/μL), prior ACS, and malignancies.⁸ High TR (HTR) and high BR (HBR) were defined as a CREDO-Kyoto TR score ≥4 and BR score ≥3, respectively.

OCT Analysis

Two independent investigators (D.K. and T.M.), blinded to the patient data, analyzed all OCT images using an offline review workstation (St. Jude Medical). Discordance was resolved by consensus with a third reviewer. In total, 325 target lesions were imaged using OCT. Calcium deposits were identified as heterogeneous areas of high and low reflectivity with low signal attenuation and sharply demarcated borders. The arc of each calcium deposit was assessed at 1 mm cross-sectional intervals. Calcium deposit length was measured longitudinally. The calcium index, equivalent to calcium volume, was calculated as the product of the mean calcium arc and length.¹⁵ The calcium score was calculated by adding 2 points for maximum angle >180°, 1 point for maximum thickness (at the slice with the maximum angle) >0.5 mm, and length >5 mm. Nondeformable calcified plaque, defined as a calcium score ≥3, is a strong predictor for suboptimal stent expansion.⁷ We defined nodular calcification as protruding mass with an irregular surface, high backscattering, and signal attenuation covered by an intact fibrous cap.¹⁶

Statistical Analysis

The normality of continuous variables was confirmed using the Shapiro-Wilk test. The results are expressed as the mean±standard deviation (SD) for continuous variables and the number (percentage) for categorical variables. Skewed values were presented as median (interquartile range [25–75th percentile]). Normally distributed variables were compared using Student’s t-test, and nonnormally distributed variables were compared using the Mann-Whitney U test. Categorical variables were compared using the chi-squared test or Fisher’s exact test, as appropriate. Differences among groups were analyzed using Tukey’s honest significant difference test. Because of the nonnormal distribution, differences in OCT parameters among the groups were analyzed using the Kruskal-Wallis test. The P value for trend was calculated using the Jonckheere-Terpstra test for continuous variables or the Cochran-Armitage test for categorical variables. In the multivariable analysis, generalized linear models with identity links for continuous dependent variables or logit links for categorical dependent variables were employed. Confounders were selected based on P<0.10 in the univariable analysis in addition to prespecified confounders, including sex, history of DM, clinical presentation (ACS or not), and statin treatment. Statistical significance was defined as a two-sided P value <0.05. Statistical analyses were performed using the R software version 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Baseline Patient Characteristics

A total of 325 lesions in 325 patients were imaged using OCT (Figure 1). The baseline characteristics of the patients are shown in Table 1. The median patient age was 70 years, 19.1% were women, and 21.3% presented with ACS. ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina pectoris were observed in 25, 16, and 28 patients, respectively. The median CREDO-Kyoto TR and BR scores were 1.0 and 1.0, respectively. The prevalences of all components of the TR and BR scores are shown in Supplementary Table 1. Overlapping factors of TR and BR, such as severe CKD, LEAD, HF, and AF, were identified in 36 (11%), 71 (22%), 63 (19%), and 31 (9.5%) patients, respectively. Specific factors for TR, such as anemia, age ≥75 years, and DM, were identified in 32 (10%), 100 (31%), and 160 (49%) patients, respectively. Specific factors for BR, such as low platelet count, prior ACS, and malignancy, were identified in 3 (1%), 98 (30%), and 43 (13%) patients, respectively. The calcium index was significantly higher in patients with severe CKD, LEAD, HF, anemia, age ≥75 years, and DM, all of which were components of the TR score (Figure 2).

Figure 1.

Flowchart of the present study and summary of the CREDO-Kyoto thrombotic and bleeding risk scores. ACS, acute coronary syndrome; CKD, chronic kidney disease; Hb, hemoglobin; LEAD, lower extremity artery disease; OCT, optical coherence tomography; PCI, percutaneous coronary intervention.

Table 1.

Baseline Characteristics of Patients With Coronary Artery Disease

Variable	All patients (n=325)
Age, years	70 (64–76)
Women, n (%)	62 (19.1)
Body mass index, kg/m2	23.8 (22.1–26.5)
Clinical presentation, n (%)
ACS	69 (21.2)
CCS	256 (78.8)
STEMI/NSTEMI/UAP	25/16/28
PCI procedure
DES use	290 (89)
DCB use	30 (9.2)
RA/OA/IVL use	39 (12)
Risk factors, n (%)
Hypertension	252 (77.5)
Dyslipidemia	222 (68.3)
Current smoker	40 (12.3)
Hemodialysis, n (%)	32 (9.8)
Prior PCI, n (%)	163 (50.2)
Prior CABG, n (%)	13 (4.0)
The CREDO-Kyoto risk score criteria, n (%)
Severe CKD	36 (11.1)
LEAD	71 (21.8)
Heart failure	63 (19.4)
AF	31 (9.5)
Anemia	32 (9.8)
Age ≥75 years	100 (30.7)
Diabetes mellitus	160 (49.2)
Low platelets (<105/μL)	3 (0.9)
Prior ACS	98 (30.2)
Malignancies	43 (13.2)
BR score	1 (0–3)
TR score	1 (1–3)
Laboratory data
LDL-C, mg/dL	86 (66–109)
HDL-C, mg/dL	46 (40–55)
Triglyceride, mg/dL	113 (81–160)
HbA1c, %	6.3 (5.8–7)
eGFR, mL/min/1.73 m2	68.6 (55–73.6)
Medication before PCI, n (%)
P2Y12 inhibitor	258 (79.4)
Aspirin	255 (78.5)
ACEi/ARB/ARNI	212 (65.2)
β-blocker	144 (44.3)
Statin	260 (80.0)
DOAC/warfarin	36 (11.1)

Data are given as n (%), or median (IQR). ACEi, angiotensin-converting enzyme inhibitor; ACS, acute coronary syndrome; AF, atrial fibrillation; ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor-neprilysin inhibitor; BR, bleeding risk; CABG, coronary artery bypass grafting; CCS, chronic coronary syndrome; CKD, chronic kidney disease; DCB, drug-coated balloon; DES, drug-eluting stent; DOAC, direct oral anticoagulant; eGFR, estimated glomerular filtration rate; HbA1c, glycosylated hemoglobin; HDL-C, high-density lipoprotein cholesterol; IQR, interquartile range; IVL, intravascular lithotripsy; LDL-C, low-density lipoprotein cholesterol; LEAD, lower extremity artery disease; NSTEMI, non-ST-segment elevation myocardial infarction; OA, orbital atherectomy; PCI, percutaneous coronary intervention; RA, rotational atherectomy; STEMI, ST-segment elevation myocardial infarction; TR, thrombotic risk; UAP, unstable angina pectoris.

Figure 2.

Comparisons of calcium index in the settings of severe CKD (A), LEAD (B), HF (C), AF (D), anemia defined as hemoglobin level <11 g/dL (E), age ≥75 years (F), DM (G), low Plt count (H), prior ACS (I), and malignancies (J). ACS, acute coronary syndrome; AF, atrial fibrillation; CKD, chronic kidney disease; DM, diabetes mellitus; HF, heart failure; LEAD, lower extremity artery disease; Plt, platelet.

Association of TR and BR Scores With Calcium Index

In this study, the median calcium index was 535, and was significantly higher in the patients with higher TR and BR scores (Figure 3A,B). Similarly, the prevalence of nondeformable calcified plaque was significantly higher in patients with higher TR and BR scores (Figure 3C,D). Of note, the calcium index was significantly higher in the patients with higher TR and BR scores (Supplementary Figure) in patients without severe CKD. The other OCT findings are presented in Table 2 and Table 3. The association of these scores with OCT features of plaque vulnerability was observed only for lipid-rich plaque. Patients with a TR score ≥4 or BR score ≥3 had a significantly lower prevalence of lipid-rich plaque than those with TR and BR scores of 0. These associations were consistent irrespective of clinical presentation (Supplementary Tables 2,3).

Figure 3.

Association of the TR and BR scores with (A,B) the calcium index and (C,D) the prevalence of nondeformable calcified plaque. BR, bleeding risk; TR, thrombotic risk.

Table 2.

Association Between TR Score and OCT Features

	TR score					P value
	0 (n=73)	1 (n=90)	2 (n=50)	3 (n=42)	≥4 (n=70)
Qualitative analysis, n (%)
TCFA	22 (30.1)	18 (20.0)	13 (26.0)	9 (21.4)	19 (27.1)	0.606
Lipid-rich plaque	62 (84.9)	67 (74.4)	41 (82.0)	31 (73.8)	43 (61.4)*	0.017
Macrophage	56 (76.7)	65 (72.2)	36 (72.0)	32 (76.2)	42 (60.0)	0.205
Microvessels	38 (52.1)	49 (54.4)	28 (56.0)	18 (42.9)	29 (41.4)	0.347
Cholesterol crystal	31 (42.5)	39 (43.3)	20 (40.0)	14 (33.3)	21 (30.0)	0.402
Layered plaque	47 (64.4)	55 (61.1)	27 (54.0)	23 (54.8)	39 (55.7)	0.704
Multilayered plaque	9 (12.3)	14 (15.6)	5 (10.0)	3 (7.1)	7 (10.0)	0.644
Thrombus	16 (21.9)	18 (20.0)	4 (8.0)	3 (7.1)	6 (8.6)	0.027
Ruptured plaque	15 (20.5)	18 (20.0)	4 (8.0)	2 (4.8)	8 (11.4)	0.044
Nodular/sheet calcification, n	2/6	4/16	7/8	3/15	16/21	<0.001
Nondeformable calcified plaque	8 (11.0)	20 (22.2)	15 (30.0)	18 (42.9)*	37 (52.9)*,†	<0.001
Quantitative analysis
Maximal lipid arc, °	213 (155–301)	191 (85–284)	222 (149–295)	238 (85–360)	195 (0–287)	0.126
Maximal calcification arc, °	49 (0–98)	104 (38–169)*	114 (57–251)*	163 (78–256)*	186 (101–336)*,†	<0.001
Maximal layer arc, °	146 (0–240)	119 (0–227)	44 (0–201)	115 (0–242)	49 (0–204)	0.121
Lipid index	1,250 (625–2,049)	823 (260–2,113)	1,253 (418–2,753)	1,056 (171–2,595)	1,058 (0–2,726)	0.194
Calcium index	95 (0–465)	503 (54–1,554)*	621 (140–1,566)*	842 (290–2,281)*	1,593 (506–4,097)*,†,‡	<0.001
Layer index	509 (0–1,285)	381 (0–1,250)	121 (0–1,027)	269 (0–1,151)	119 (0–981)	0.146
Macrophage grade	7 (2–17)	6 (0–15)	5 (0–18)	6 (2–14)	7 (0–17)	0.847
MLA, mm2	1.2 (0.9–1.7)	1.5 (1.0–2.0)	1.4 (1.0–1.8)	1.5 (1.1–1.8)	1.3 (1.0–2.1)	0.136
Area stenosis, %	77.3 (71.5–83.5)	76.2 (68.0–81.6)	75.5 (67.0–82.0)	75.8 (70.2–82.2)	76.2 (67.9–82.2)	0.244

*P<0.05 vs. 0; ^† vs. 1; ^‡ vs. 2. MLA, minimal lumen area; OCT, optical coherence tomography; TCFA, thin-cap fibroatheroma; TR, thrombotic risk.

Table 3.

Association Between BR Score and OCT Features

	BR score				P value
	0 (n=101)	1 (n=83)	2 (n=58)	≥3 (n=83)
Qualitative analysis, n (%)
TCFA	22 (21.8)	25 (30.1)	17 (29.3)	17 (20.5)	0.361
Lipid-rich plaque	76 (75.2)	70 (84.3)	45 (77.6)	53 (63.9)†	0.022
Macrophage	73 (72.3)	64 (77.1)	43 (74.1)	51 (61.4)	0.136
Microvessels	55 (54.5)	38 (45.8)	35 (60.3)	34 (41.0)	0.086
Cholesterol crystal	40 (39.6)	37 (44.6)	22 (37.9)	26 (31.3)	0.368
Layered plaque	59 (58.4)	55 (66.3)	31 (53.4)	46 (55.4)	0.393
Multilayered plaque	17 (16.8)	8 (9.6)	5 (8.6)	8 (9.6)	0.285
Thrombus	27 (26.7)	8 (9.6)*	3 (5.2)*	9 (10.8)*	<0.001
Ruptured plaque	19 (18.8)	14 (16.9)	7 (12.1)	7 (8.4)	0.200
Nodular/sheet calcification, n	4/16	4/10	3/15	21/25	<0.001
Nondeformable calcified plaque	20 (19.8)	14 (16.9)	18 (31.0)	46 (55.4)*,†,‡	<0.001
Quantitative analysis
Maximal lipid arc, °	199 (92–276)	230 (157–319)	233 (119–360)	165 (0–287)†	0.233
Maximal calcification arc, °	92 (30–166)	71 (13–144)	127 (63–258)*,†	188 (92–324)*,†	<0.001
Maximal layer arc, °	133 (0–240)	144 (0–230)	44 (0–200)	72 (0–199)	0.073
Lipid index	921 (257–2,080)	1,358 (536–2,271)	1,281 (366–2,731)	743 (0–2,542)	0.274
Calcium index	413 (30–1,061)	283 (12–887)	641 (174–1,811)	1,626 (357–3,699)*,†	<0.001
Layer index	438 (0–1,323)	435 (0–1,179)	121 (0–1,191)	147 (0–882)	0.138
Macrophage grade	6 (0–14)	7 (2–19)	8 (0–14)	5 (0–17)	0.972
MLA, mm2	1.2 (0.9–1.9)	1.4 (0.9–1.9)	1.5 (1.1–1.8)	1.4 (1.1–2.2)	0.008
Area stenosis, %	76.6 (69.6–84.0)	77.6 (70.7–83.0)	76.1 (68.3–82.1)	75.4 (67.8–81.4)	0.057

*P<0.05 vs. 0; ^† vs. 1; ^‡ vs. 2. Abbreviations as in Tables 1,2.

Multivariable Analyses

Univariable analysis showed that the TR and BR scores were significantly associated with the calcium index and nondeformable calcified plaques (Supplemental Tables 4,5). Multivariable analysis showed that both the TR and BR scores were associated with a higher calcium index after adjustment for confounders (TR score: β, 0.545; 95% confidence interval [CI], 0.267–0.824; P<0.001 and BR score: β, 0.342; 95% CI, 0.045–0.638; P=0.025; Table 4). Similarly, both TR and BR scores were associated with the presence of nondeformable calcified plaques after adjusting for confounders (TR score: odds ratio [OR], 1.444; 95% CI, 1.146–1.825; P=0.002 and BR score: OR, 1.484; 95% CI, 1.138–1.947; P=0.004; Table 4). On the other hand, these scores were not significantly associated with lipid-rich plaque. Instead, low-density lipoprotein cholesterol was significantly associated with lipid-rich plaque after adjusting for confounders (Supplementary Table 6).

Table 4.

Multivariable Analysis for the Factors Related to Calcium Index or Nondeformable Calcified Plaque

Variable	Univariable analysis			Multivariable analysis
	β	95% CI	P value	β	95% CI	P value
(A) Calcium index
TR score	0.756	0.566, 0.945	<0.001	0.545	0.267, 0.824	<0.001
BR score	0.624	0.375, 0.872	<0.001	0.342	0.045, 0.638	0.025
(B) Nondeformable calcified plaque
TR score	1.673	1.408, 2.003	<0.001	1.444	1.146, 1.825	0.002
BR score	1.802	1.455, 2.253	<0.001	1.484	1.138, 1.947	0.004

A generalized linear model with identity links was conducted for the associations of BR score or TR score with log-transformed calcium index (A) or nondeformable calcified plaque (B). Multivariable models included sex, clinical presentation, hypertension, smoking status (current smoker or not), age ≥75 years, diabetes mellitus, LDL-C, eGFR, and statin treatment. CI, confidence interval; OR, odds ratio. Other abbreviations as in Table 1.

OCT Characteristics in Patients With HTR and HBR

Among the patients, 225 had neither HTR nor HBR, 47 had either, and 53 (16.3%) had both (Supplementary Table 7). The calcium index was higher and nondeformable calcified plaques more prevalent in patients with both HTR and HBR among the 3 groups (Figure 4A,B). The other OCT findings are summarized in Supplementary Table 8. There was no association of HTR or HBR with OCT features of plaque vulnerability. These associations were consistent in the subgroups of CCS or ACS presentation (Supplementary Table 9).

Figure 4.

The association of HTR and HBR with (A) the calcium index and (B) the prevalence of nondeformable calcified plaque. HTR, high thrombotic risk; HBR, high bleeding risk.

Discussion

The findings of the present study were: (1) the calcium index, equivalent to calcified plaque volume, was higher in patients with higher TR and BR scores; (2) nondeformable calcified plaques were more prevalent as patients had higher TR or BR scores; and (3) patients with both HTR and HBR had a higher calcium index and most frequently had nondeformable calcified plaques compared with those without or with HTR or HBR alone.

The present study identified a low frequency of lipid-rich plaques and higher calcium index as the common plaque morphology in patients with higher TR and BR scores. A recent report indicated that the calcium index represents calcium plaque volume and that the median calcium index in nonculprit lesions of ACS was 97.¹⁷ In the present study, the median calcium index was 535. The high number of patients with CCS and the assessment of plaque morphology at the culprit lesions could account for this relatively high value. Notably, the significant associations of both TR and BR scores with the degree of calcification, and their weak associations with plaque vulnerability were consistent, irrespective of the clinical presentation. Calcified plaques are reportedly less common as an underlying etiology of ACS, but are associated with more severe pan-vascular atherosclerosis and worse clinical outcomes than other etiologies, such as plaque rupture and erosion.¹⁸ Thus, the findings of the present study suggest that the TR and BR scores increase in parallel with the development of advanced atherosclerosis.

We found that the TR score criteria correlated well with a higher calcium index, whereas the specific criteria for BR, such as low platelet count, prior ACS, and malignancies, were not. Accumulating evidence indicates that patients with CKD, LEAD or HF have a high risk of both thrombotic and bleeding events.^19–24 In the present study, overlapping risk factors, such as severe CKD, LEAD, and HF, were associated with more severely calcified plaques. Patients with higher coronary artery calcium scores (CACS), assessed by the Agatston score using computed tomography, reportedly have more extensive CAD,²⁵ worse renal function,²⁶ a higher risk for HF,²⁷ and a higher risk of bleeding and thrombotic events than those with lower CACS, in line with our findings. These observations indicate that the degree of coronary calcification is a marker not only of atherosclerosis but also of biological age, subclinical organ injury, and disease burden, eventually increasing the risk of thrombotic and bleeding events.^26,28

Because intracoronary images acquired through OCT are valuable for determining the necessity of aggressive lesion modification,²⁹ we also examined the associations of TR and BR scores with nondeformable calcified plaques. The CREDO-Kyoto risk scores were developed to determine the intensity of dual-antiplatelet therapy (DAPT) using data from 3 Japanese registries. It was reported in 1 study that 8.5% of patients with HTR and HBR had a high risk of bleeding and thrombotic events.⁹ In the present study, 16% of the patients had both HTR and HBR, and of them, 60% had nondeformable calcified plaques. These findings underscore a critical challenge in managing patients with CAD: the frequent overlap of HTR and HBR is linked to a higher prevalence of severely calcified plaques, which further complicates the prevention of future cardiovascular and bleeding events. Several studies have consistently demonstrated that suboptimal stent expansion is the strongest predictor of target lesion failure.^30,31 Nondeformable calcified plaque, defined as a calcium score ≥3, is reportedly associated with suboptimal stent expansion and delayed intimal coverage,^7,32 necessitating a longer duration of DAPT. Thus, evaluating plaque morphology using OCT facilitates more tailored management of patients with CAD to lower the risk of thrombosis,³³ which might benefit patients with higher TR and BR scores.

Study Limitations

Because OCT analysis requires coronary blood flow, patients with chronic total occlusion were not enrolled because of the difficulty in obtaining sufficient image quality for OCT analysis. Second, because the mechanism of neoatherosclerosis differs from that of de novo lesions, we did not analyze lesions related to in-stent restenosis. Third, all the patients in this study were enrolled in Japan. Consequently, the generalizability of our results to other populations with different ethnic backgrounds may be limited. Fourth, regarding the use of OCT as the in vivo gold standard, it should be noted that although OCT is a valuable tool, some of its features have not yet been fully validated by histology, and caution should be exercised in their interpretation. Fifth, we registered only patients who underwent PCI with OCT, so we could not eliminate the possibility of selection bias. Lastly, this study did not include data regarding clinical outcomes, because the Yamagata OCT registry was basically designed to evaluate clinical outcomes after 1,000 patients’ data were collected.

Conclusions

TR and BR scores were related to a higher calcium index. The coexistence of HTR and HBR was related to severely calcified plaques, which fulfills the requirement for aggressive lesion modification. This knowledge may serve as the basis for planning an optimized PCI strategy.

Acknowledgment

This study was partly supported by Abbot Medical Japan.

Disclosure

Authors have no conflicts of interest.

IRB Information

The Ethical Review Committee of Yamagata University Faculty of Medicine (no.2022-17).

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circrep.CR-25-0133

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