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Plaque rupture occurs if stress within coronary lesions exceeds the protection exerted by the fibrous cap overlying the necrotic lipid core. However, very little is known about the biomechanical stress exerting this disrupting force. Employing optical coherence tomography (OCT), we generated plaque models and performed finite-element analysis to simulate stress distributions within the vessel wall in 10 ruptured and 10 non-ruptured lesions. In ruptured lesions, maximal stress within fibrous cap (peak cap stress [PCS]: 174 ± 67 vs. 52 ± 42 kPa, p<0.001) and vessel wall (maximal plaque stress [MPS]: 399 ± 233 vs. 90 ± 95 kPa, p=0.001) were significantly higher compared to non-ruptured plaques. Ruptures arose in the immediate proximity of maximal stress concentrations (angular distances: 21.8 ± 30.3° for PCS vs. 20.7 ± 23.7° for MPS); stress concentrations excellently predicted plaque rupture (area under the curve: 0.940 for PCS, 0.950 for MPS). This prediction of plaque rupture was superior to established vulnerability features such as fibrous cap thickness or macrophage infiltration. In conclusion, OCT-based finite-element analysis effectively assesses plaque biomechanics, which in turn predicts plaque rupture in patients. This highlights the importance of morpho-mechanic analysis assessing the disrupting effects of plaque stress., Competing Interests: AM, EL, RD, KB, NM, SR, MB No competing interests declared, (© 2021, Milzi et al.)

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased cardiovascular risk related at least in part to a more vulnerable plaque phenotype. However, patients with T2DM exhibit also an increased risk following percutaneous coronary intervention (PCI). It is unknown if plaque vulnerability of a treated lesion influences cardiovascular outcomes in patients with T2DM. In this study, we aimed to assess the association of plaque morphology as determined by optical coherence tomography (OCT) with cardiovascular outcome following PCI in high-risk patients with T2DM., Methods: 81 patients with T2DM and OCT-guided PCI were recruited. Pre-interventional OCT and systematic follow-up of median 66.0 (IQR = 8.0) months were performed., Results: During follow-up, 24 patients (29.6%) died. The clinical parameters age (HR 1.16 per year, 95% CI 1.07-1.26, p < 0.001), diabetic polyneuropathy (HR 3.58, 95% CI 1.44-8.93, p = 0.006) and insulin therapy (HR 3.25, 95% CI 1.21-8.70, p = 0.019) predicted mortality in T2DM patients independently. Among OCT parameters only calcium-volume-index (HR 1.71 per 1000°*mm, 95% CI 1.21-2.41, p = 0.002) and lesion length (HR 1.93 per 10 mm, 95% CI 1.02-3.67, p = 0.044) as parameters describing atherosclerosis extent were significant independent predictors of mortality. However, classical features of plaque vulnerability, such as thickness of the fibrous cap, the extent of the necrotic lipid core and the presence of macrophages had no significant predictive value (all p = ns)., Conclusion: Clinical parameters including those describing diabetes severity as well as OCT-parameters characterizing atherosclerotic extent but not classical features of plaque vulnerability predict mortality in T2DM patients following PCI. These data suggest that PCI may provide effective plaque sealing resulting in limited importance of local target lesion vulnerability for future cardiovascular events in high-risk patients with T2DM.

Background: Coronary calcification is associated with high risk for cardiovascular events. However, its impact on plaque vulnerability is incompletely understood. In the present study we defined the intrinsic calcification angle (ICA) as the angle externally projected by a vascular calcification and analyzed its role as novel feature of coronary plaque vulnerability in patients with type 2 diabetes., Methods: Optical coherence tomography was used to determine ICA in 219 calcifications from 56 patients with stable coronary artery disease (CAD) and 143 calcifications from 36 patients with acute coronary syndrome (ACS). We then used finite elements analysis to gain mechanistic insight into the effects of ICA., Results: Minimal (139.8 ± 32.8° vs. 165.6 ± 21.6°, p < 0.001) and mean ICA (164.1 ± 14.3° vs. 176.0 ± 8.4°, p < 0.001) were lower in ACS vs. stable CAD patients. Mean ICA predicted ACS with very good diagnostic efficiency (AUC = 0.840, 95% CI 0.797-0.882, p < 0.001, optimal cut-off 175.9°); younger age (OR 0.95 per year, 95% CI 0.92-0.98, p = 0.002), male sex (OR 2.18, 95% CI 1.41-3.38, p < 0.001), lower HDL-cholesterol (OR 0.82 per 10 mg/dl, 95% CI 0.68-0.98, p = 0.029) and ACS (OR 14.71, 95% CI 8.47-25.64, p < 0.001) were determinants of ICA < 175.9°. A lower ICA predicted ACS (OR for 10°-variation 0.25, 95% CI 0.13-0.52, p < 0.001) independently from fibrous cap thickness, presence of macrophages or extension of lipid core. In finite elements analysis we confirmed that lower ICA causes increased stress on a lesion's fibrous cap; this effect was potentiated in more superficial calcifications and adds to the destabilizing role of smaller calcifications., Conclusion: Our clinical and mechanistic data for the first time identify ICA as a novel feature of coronary plaque vulnerability.

Background: The presence of plaque macrophages and microcalcifications are acknowledged features of plaque vulnerability. Experimental data suggest that microcalcifications promote inflammation and macrophages foster microcalcifications. However, co-localization of plaque macrophages and calcification (ColocCaMa) in coronary segments and its impact on plaque phenotype and lesion vulnerability is unexplored., Methods: Plaque morphology including ColocCaMa of calcified coronary target segments in patients with stable coronary artery disease (n = 116) was analyzed using optical coherence tomography (OCT) prior to coronary intervention. Therefore we considered macrophages co-localized with calcification if their distance in an OCT frame was <100μm and OCT-defined microcalcifications with a calcium arc <22.5°., Results: ColocCaMa was present in 29/116(25.0%) coronary segments. Calcium burden was greater (calcium volume index:1731±1421°*mm vs. 963±984°*mm, p = 0.002) and calcifications were more superficial (minimal thickness of the fibrous cap overlying the calcification 35±37μm vs. 64±72μm, p = 0.005) in the presence of ColocCaMa. Segments with ColocCaMa demonstrated a higher incidence of newly suggested features of plaque vulnerability, with a 3.5-fold higher number of OCT-defined microcalcifications (0.7±1.0 vs. 0.2±0.6, p = 0.022) and a 6.7-fold higher incidence of plaque inflammation (macrophage volume index:148.7±248.3°*mm vs. 22.2±57.4°*mm, p<0.001). Clinically, intima-media thickness (IMT) in carotid arteries was increased in patients with ColocCaMa (1.02±0.30mm vs. 0.85±0.18, p = 0.021). In a multivariate model, IMT (OR1.76 for 100μm, 95%CI 1.16-2.65, p = 0.007), HDL-cholesterol (OR0.36 for 10mg/dl, 95%CI 0.16-0.84, p = 0.017), calcium volume index (OR1.07 for 100°*mm, 95%CI 1.00-1.14, p = 0.049), macrophage volume index (OR5.77 for 100°*mm, 95%CI 2.04-16.3, p = 0.001) and minimal luminal area (OR3.41, 95%CI 1.49-7.78, p = 0.004) were independent predictors of ColocCaMa., Conclusion: Plaque macrophages co-localize with calcifications in coronary target segments and this is associated with high-risk morphological features including microcalcifications and macrophage infiltration as well as with greater calcification burden. Our data may add to the understanding of the relationship between plaque macrophages, vascular calcification and their clinical impact., Competing Interests: The authors have declared that no competing interests exist.

Background: The minimal fibrous cap thickness overlying the necrotic lipid core as well as the presence of macrophages are established characteristics of coronary plaque vulnerability. Recently, the presence of microcalcifications has emerged as a novel feature of vulnerable lesions. However, clinical and plaque morphological predictors of microcalcifications are unknown., Methods: In patients with stable coronary artery disease, analysis of plaque morphology (n = 112) was performed using optical coherence tomography prior to coronary intervention to assess predictors of microcalcifications., Results: Microcalcifications were present in 21/112 (18.7%) lesions. Segments with microcalcifications showed a higher total number of calcifications per lesion (6.7 ± 3.0 vs. 3.2 ± 2.5, p < 0.001), a lower percent area stenosis (70.9 ± 11.1 vs. 76.2 ± 9.7%, p = 0.028), and a higher frequency of macrophage infiltration (66.7 vs. 37.4%, p = 0.014). In lesions with vs. without microcalcifications, macrophage infiltration was characterized by a wider macrophage angle (31.1° ± 34.4° vs. 13.7° ± 20.6°, p = 0.003), a higher macrophage index (105.6 ± 269.0 vs. 31.6 ± 66.5° mm, p = 0.020), and an increased frequency of calcium-macrophage co-localization (47.6 vs. 15.6%, p = 0.001). In multivariable logistic regression analysis, the total number of calcifications per lesion (OR 1.53, 95% CI 1.23-1.91, p < 0.001), average macrophage angle (OR 1.28 for 10°-variation, 95% CI 1.03-1.60, p = 0.024), and percent area stenosis (OR 0.59 for 10% increase, 95% CI 0.34-1.04, p = 0.070) were independent predictors for the presence of microcalcifications, whereas the latter did not reach statistical significance., Conclusion: Microcalcifications are related to a less advanced stenosis severity and to extensive plaque inflammation, but not to clinical parameters. Our data may add to the understanding and role of microcalcifications in coronary artery lesions.

Background: Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular events, which usually arise from the rupture of a vulnerable coronary plaque. The minimal fibrous cap thickness (FCT) overlying a necrotic lipid core is an established predictor for plaque rupture. Recently, coronary calcification has emerged as a relevant feature of plaque vulnerability. However, the impact of T2DM on these morphological plaque parameters is largely unexplored. Therefore, this study aimed to compare differences of coronary plaque morphology in patients with and without T2DM with a particular focus on coronary calcification., Methods: In 91 patients (T2DM = 56, non-T2DM = 35) with 105 coronary de novo lesions (T2DM = 56, non-T2DM = 49) plaque morphology and calcification were analyzed using optical coherence tomography (OCT) prior to coronary intervention., Results: Patients with T2DM had a lower minimal FCT (80.4 ± 27.0 µm vs. 106.8 ± 27.8 µm, p < 0.001) and a higher percent area stenosis (77.9 ± 8.1% vs. 71.7 ± 11.2%, p = 0.001) compared to non-diabetic subjects. However, patients with and without T2DM had a similar total number of calcifications (4.0 ± 2.6 vs. 4.2 ± 3.1, p = ns) and no significant difference was detected in the number of micro- (0.34 ± 0.79 vs. 0.31 ± 0.71), spotty (2.11 ± 1.77 vs. 2.37 ± 1.89) or macro-calcifications (1.55 ± 1.13 vs. 1.53 ± 0.71, all p = ns). The mean calcium arc (82.3 ± 44.8° vs. 73.7 ± 31.6), the mean thickness of calcification (0.54 ± 0.13 mm vs. 0.51 ± 0.15 mm), the mean calcified area (0.99 ± 0.72 mm 2 vs. 0.78 ± 0.49 mm 2 ), the mean depth of calcification (172 ± 192 μm vs. 160 ± 76 μm) and the cap thickness overlying the calcification (50 ± 71 μm vs. 62 ± 61 μm) did not differ between the diabetic and non-diabetic groups (all p = ns)., Conclusion: T2DM has an impact on the minimal FCT of the coronary target lesion, but not on localization, size, shape or extent of calcification. Thus, the minimal FCT overlying the necrotic lipid core but not calcification is likely to contribute to the increased plaque vulnerability observed in patients with T2DM.

Background: Annexin A5 (anxA5) is involved in processes which are crucial in atherogenesis. However, anxA5's relationship with atherosclerotic lesion extension and plaque composition in high-risk patients with type 2 diabetes remains unclear. Thus, we characterized the association between circulating anxA5 levels with atherosclerotic burden and coronary plaque composition in diabetes mellitus patients., Methods: Intima-media thickness was determined in 96 diabetes mellitus patients with stable coronary artery disease. Furthermore, intracoronary optical coherence tomography was performed in 106 lesions to determine plaque composition., Results: AnxA5 plasma levels of patients with intima-media thickening were higher (3.49 ± 2.19 ng/mL) compared to patients with normal intima-media thickness (2.24 ± 1.67 ng/mL, p = 0.002). Furthermore, anxA5 was associated with intima-media thickening on univariable [odds ratio = 1.445 (1.106-1.889), p = 0.007] and multivariable [odds ratio = 1.643 (1.166-2.314), p = 0.005] logistic regression analysis when adjusted for multiple cardiovascular risk factors and biomarkers. Furthermore, receiver operating characteristic analysis demonstrated that anxA5 predicted intima-media thickening with low-moderate diagnostic efficiency [area under the curve = 0.700 (0.592-0.808)]. In contrast, there was no association between anxA5 levels and coronary plaque composition as assessed by optical coherence tomography including the presence of lipid, calcified, fibrous plaque or the minimal thickness of the fibrous cap overlying the necrotic lipid core ( p = ns)., Conclusion: Circulating anxA5 levels are associated with carotid intima-media thickness but not coronary plaque composition in high-risk patients with diabetes mellitus.

Background: Insufficient stent expansion, vessel wall injury, and tissue prolapse, all frequently unrecognized by coronary angiography, are predictors of future major adverse cardiac event (MACE) after percutaneous coronary intervention (PCI). Optical coherence tomography (OCT) provides accurate visualization of these features of inadequate stent deployment, whereas reduced fractional flow reserve (FFR) values after PCI indicate functional significance of a residual intrastent stenosis., Objective: To investigate the relationship of OCT-derived intrastent lumen dimensions and FFR-derived hemodynamic relevance immediately after coronary stent implantation and to evaluate the clinical impact of these parameters at follow-up., Methods: In 66 stable patients with a coronary de novo lesion, treated by stent implantation, post-stenting FFR and OCT data were compared and related to MACE at follow-up., Results: There was a significant correlation between remaining OCT-derived intrastent percent area stenosis (%AS) and post-stent FFR (r² = 0.491; P<.001). According to receiver operating characteristic (ROC) analysis, both final FFR and intrastent %AS predicted MACE at 20 months (FFR: area under the curve [AUC] = 0.768; 95% confidence interval [CI], 0.562-0.973; and optimal cut-off = 0.905; %AS: AUC = 0.807; 95%CI, 0.613-1.000; and optimal cut-off = 16.85%) with moderate diagnostic efficiency. Intrastent %AS (16.60 ± 4.75% vs 7.01 ± 3.49%; P<.001) and the 20-month cumulative incidence of MACE (35.9% vs 5.3%; P=.01) were significantly greater in patients with FFR ≤0.905 (n = 26; 39.4%) compared with FFR >0.905 (n = 40; 60.6%)., Conclusion: OCT-derived residual intrastent %AS is associated with decreased FFR following stent implantation and both are predictors for clinical outcome at follow-up.

Background: Fractional flow reserve (FFR) measurements accurately assess functional relevance in intermediate grade coronary lesions. A significant relationship between hemodynamic stenosis severity and optical coherence tomography (OCT)-derived intraluminal dimensions has recently been demonstrated. However, morphologic thresholds to identify significant stenoses are variable and exploration of this correlation in patients with diabetes mellitus (DM) remains currently incomplete. This study aimed at comparing the diagnostic value of intraluminal parameters as determined by OCT to predict FFR ≤0.8 in lesions of patients with versus without DM., Methods: In 100 patients (DM = 56, non-DM = 44) with 142 coronary de novo lesions (DM = 80, non-DM = 62) of intermediate grade as determined by quantitative coronary angiography, we performed OCT and FFR. Stenoses were defined functionally relevant if FFR was ≤0.8., Results: FFR measurements in the overall study cohort, the DM and the non-DM group correlated significantly with minimal lumen area (MLA) [overall: r (2) = 0.339, DM: r (2) = 0.341, non-DM: r (2) = 0.355 (all p < 0.001)], percent area stenosis [overall: r (2) = 0.352, DM: r (2) = 0.376, non-DM: r (2) = 0.351 (all p < 0.001)] and minimal lumen diameter [overall: r (2) = 0.333, DM: r (2) = 0.277, non-DM: r (2) = 0.417 (all p < 0.001)] without differing statistically between diabetic and non-diabetic patients (p = ns). Receiver operating characteristic analysis demonstrated that among OCT-derived parameters, MLA predicted FFR ≤0.8 with the best diagnostic efficiency and with similar cut-off values for all patients [area under the curve (AUC) = 0.836, 95% confidence interval (CI) = 0.772-0.901, cut-off value = 1.64 mm(2)] as well as for diabetic (AUC = 0.840, 95% CI = 0.754-0.927, cut-off value = 1.59 mm(2)) and non-diabetic subjects (AUC = 0.833, 95% CI = 0.734-0.932, cut-off value = 1.64 mm(2))., Conclusion: In both, diabetic and non-diabetic patients, FFR and OCT-derived intraluminal measurements are significantly correlated and OCT predicts hemodynamically relevant coronary stenosis with moderate diagnostic efficiency.

Objective: To compare optical coherence tomography (OCT)-derived plaque characteristics of coronary target lesions between diabetic patients with acute coronary syndrome (ACS) versus stable angina pectoris (SAP)., Background: In vivo assessment of plaque composition of coronary culprit lesions in a cardiovascular high-risk population with diabetes mellitus is incompletely elucidated., Methods: 102 diabetic patients with coronary de novo lesions were enrolled and categorized into an ACS-group (40 patients) and a SAP-group (62 patients) according to their clinical presentation. Assessment of clinical data, angiographic, and OCT imaging including the analysis of plaque composition and lipid content of the target lesions were performed prior to percutaneous coronary intervention and compared between the two groups., Results: Plaque characteristics of patients in the ACS-group compared with the SAP-group showed a higher incidence of lipid-rich plaque [33 (82.5%) vs. 25 (40.3%)], thin-capped fibroatheroma [29 (72.5%) vs. 10 (16.1%)], macrophage infiltration [32 (80.0%) vs. 21 (33.9%)], thrombus [23 (57.5%) vs. 2 (3.2%)], and plaque rupture [27 (67.5%) vs. 2 (3.2%)] (all P < 0.001). Moreover, there was a wider lipid arc (174.5 ± 33.8° vs. 122.9 ± 43.9°), a longer lipid plaque length (6.52 ± 2.04 mm vs. 3.73 ± 2.16 mm), a greater lipid volume index (1117.2 ± 349.9 vs. 504.8 ± 379.3), and a smaller minimal fibrous cap thickness (51.52 ± 9.14 µm vs. 80.33 ± 26.71 µm) within lipid-rich lesions of ACS patients (all P < 0.001)., Conclusion: Diabetic patients with ACS exhibit more vulnerable plaque features in coronary culprit lesions compared with diabetic patients with SAP. This may provide rationale for a specific therapeutic strategy either by pharmacological plaque stabilization or coronary intervention in any lesion with vulnerable plaque morphology in patients with diabetes., (© 2013 Wiley Periodicals, Inc.)

Background: Patients with type 2 diabetes are at a high risk for acute cardiovascular events, which usually arise from the rupture of a vulnerable coronary lesion characterized by specific morphological plaque features. Thus, the identification of vulnerable plaques is of utmost clinical importance in patients with type 2 diabetes. However, there is currently no scoring system available to identify vulnerable lesions based on plaque characteristics. Thus, we aimed to characterize the diagnostic value of optical coherence tomography (OCT) - derived lesion characteristics to quantify plaque vulnerability both as individual parameters and when combined to a score in patients with type 2 diabetes., Methods: OCT was performed in the coronary culprit lesions of 112 patients with type 2 diabetes. The score, which quantifies plaque vulnerability, was defined as the predicted probability that a lesion is the cause for an acute coronary syndrome (ACS) (vs. stable angina (SAP)) based on its specific plaque morphology., Results: Multivariable logistic regression analysis demonstrated that plaque vulnerability was independently predicted by the minimal fibrous cap thickness overlying a lesion's lipid core (odds ratio (OR) per 10 μm 0.478, p = 0.002), the medium lipid arc (OR per 90° 13.997, p < 0.001), the presence of macrophages (OR 4.797, p = 0.015) and the lipid plaque length (OR 1.290, p = 0.098)., Conclusion: This is the first study to present a score to quantify lesion vulnerability in patients with type 2 diabetes. This score may be a valuable adjunct in decision-making and useful in guiding coronary interventions.

Patients with type 2 diabetes are at increased risk for post-PCI complications including stent thrombosis and restenosis. Stent edge dissections (SEDs) have been associated with these complications. This study assessed incidence and predictors of SEDs in patients with type 2 diabetes using optical coherence tomography (OCT). Intravascular lesion parameters and plaque morphology were investigated pre- and post-PCI using OCT in 73 type 2 diabetic patients with 90 lesions and 166 visible stent edges. We detected 42 (25.3 %) SEDs in 166 stent edges and 37 (41.1 %) SEDs in 90 lesions. More SEDs occurred if the border of the stent had been placed within diseased vessel segments with predominantly fibrous (42.9 %) and fibrocalcific (40.5 %) plaques compared to healthy vessel wall morphology (p < 0.001). Furthermore, the lumen eccentricity of the stent at its edges (SAE) (16.00 ± 6.07 vs. 13.11 ± 5.22 %, p < 0.003) and the stent-edge-to-lumen-area-ratio (1.26 ± 0.27 vs. 0.99 ± 0.20, p < 0.001) were both significantly larger in the presence of SEDs. All of the above parameters were significant predictors for SEDs on uni- and multivariate logistic regression analysis (all p < 0.01), suggesting that the lumen eccentricity of the SAE, the stent-edge-to-lumen-area-ratio and diseased vessel wall morphology of the reference segment adjacent to the stent edge are independent risk factors for the presence of SEDs. These results suggest that diseased vessel wall morphology at the stent edges may promote the occurrence of SEDs and that avoidance of longitudinal and transverse mismatch between stent and vessel could be important to reduce SEDs in cardiovascular high-risk patients with type 2 diabetes.

Background: Patients with type 2 diabetes are at increased risk for both, left ventricular (LV)-dilatation and myocardial infarction (MI) following the rupture of a vulnerable plaque. This study investigated the to date incompletely understood relationship between plaque vulnerability and LV-dilatation using optical coherence tomography (OCT) and cardiac magnetic resonance imaging (CMR) in patients with type 2 diabetes and stable coronary artery disease., Methods: CMR was performed in 58 patients with type 2 diabetes, in which 81 coronary lesions were investigated using OCT., Results: A decreased minimal fibrous cap thickness (FCT) of coronary lesions was associated with an increase of several CMR-derived parameters including LV-end diastolic volume (LVEDV, r = 0.521, p < 0.001), LV-end diastolic diameter (r = 0.502, p < 0.001) and LV-end systolic volume (r = 0.467, p = 0.001). Similar results were obtained for mean FCT., Conclusion: These data suggest that vulnerability of coronary lesions is associated with LV-dilatation in high risk patients with type 2 diabetes. CMR may be a useful adjunct to the risk-stratification in this population. Future studies are warranted to investigate potential mechanisms linking plaque vulnerability and LV-dilatation.

Background: The relationship between functional relevance and optical coherence tomography (OCT)-derived measurements of coronary lesions is incompletely understood and of critical importance, particularly in cardiovascular high-risk patients with type 2 diabetes., Objective: To investigate the association between functional relevance of intermediate grade coronary stenoses as assessed by fractional flow reserve (FFR) and OCT-derived lesion parameters in patients with diabetes., Methods: In 46 diabetic patients with stable coronary artery disease, FFR and OCT were performed in 62 coronary lesions with intermediate severity as determined by quantitative coronary angiography. Among lesions haemodynamic relevance was defined as FFR≤0.8., Results: There was a significant association between FFR and OCT-derived minimal lumen area (r(2)=0.379) and minimal lumen diameter (r(2)=0.268), all p<0.001. Receiver operating curve (ROC)-analysis demonstrated an OCT-derived minimal lumen area <1.59 mm(2) and minimal lumen diameter <1.31 mm to be optimal cut-off values to predict FFR≤0.8. Furthermore, in lipid-rich plaques FFR was significantly associated with minimal fibrous cap thickness (FCT, r(2)=0.399). Minimal FCT in lesions with FFR≤0.8 was significantly smaller (60.7±15.0 µm) compared with those lesions with FFR>0.8 (106.0±13.0 µm, p<0.001). ROC-analysis revealed that 0.81 is the ideal FFR cut-off to identify lesions with a minimal FCT≤80 µm (accuracy 97.3%, sensitivity 100%, specificity 93.8%, area under the curve 0.943 (95% CI 0.836 to 1.000))., Conclusions: Haemodynamic relevance of intermediate grade lesions in patients with type 2 diabetes is closely related to (1) intraluminal measurements, which are smaller than previously described in non-diabetic cohorts and to (2) minimal FCT. Furthermore, FFR may be useful to identify vulnerable (minimal FCT≤80 µm) lesions among those with intermediate severity in lipid-rich plaques.