Progression from normal vessel wall to atherosclerotic plaque: lessons from an optical coherence tomography study with follow-up of over 5 years.

The initial process of atherosclerotic development has not been systematically evaluated. This study aimed to observe atherosclerotic progression from normal vessel wall (NVW) to atherosclerotic plaque and examine local factors associated with such progression using > 5-year long-term follow-up data obtained by serial optical coherence tomography (OCT). A total of 49 patients who underwent serial OCT for lesions with NVW over 5 years (average: 6.9 years) were enrolled. NVW was defined as a vessel wall with an OCT-detectable three-layer structure and intimal thickness ≤ 300 µm. Baseline and follow-up OCT images were matched, and OCT cross sections with NVW > 30° were enrolled. Cross sections were diagnosed as "progression" when the NVW in these cross sections was reduced by > 30° at > 5-year follow-up. Atherogenic progression from NVW to atherosclerotic plaque was observed in 40.8% of enrolled cross sections. The incidence of microchannels in an adjacent atherosclerotic plaque within the same cross section (6.7 vs. 3.3%; p = 0.046) and eccentric distribution of atherosclerotic plaque (25.0 vs. 12.6%; p < 0.001) at baseline was significantly higher in cross sections with progression than in those without. Cross sections with progression exhibited significantly higher NVW intimal thickness at baseline than cross sections without progression (200.1 ± 53.7 vs. 180.2 ± 59.6 µm; p < 0.001). Multivariate analysis revealed that the presence of microchannels in an adjacent atherosclerotic plaque, eccentric distribution of atherosclerotic plaque, and greater NVW intimal thickness at baseline were independently associated with progression at follow-up. The presence of microchannels in an adjacent atherosclerotic plaque, eccentric distribution of atherosclerotic plaque, and greater NVW intimal thickness were potentially associated with initial atherosclerotic development from NVW to atherosclerotic plaque.

Efficacy of optical frequency domain imaging in detecting peripheral artery disease: the result of a multi-center, open-label, single-arm study.

Optical frequency domain imaging (OFDI) is a high-resolution intracoronary imaging modality with fast automated longitudinal pullback. We aimed to evaluate the ability of performing OFDI from the superficial femoral artery (SFA) to the below-knee (BK) artery. This clinical trial was a multi-center, single-arm, open-label study. The primary endpoint was to obtain a clear image of the intra-vascular lumen from the SFA to the BK artery, specifically > 270° visualization of the blood vessel lumen with > 16/21 cross sections. The proportion of the clear image (≥ 85%) was regarded as confirmatory of the ability of OFDI to visualize the vessel lumen. Overall, 20 patients were enrolled. The proportion of the primary endpoint was 90% (18/20), and the pre-specified criterion was successfully attained. The proportion of the clear image assessed by the operator was 100% (20/20), and an additional statistical analysis for the proportion of the visualization, > 270°, of the blood vessel lumen revealed a significantly higher cut-off value than that for the pre-specified criterion, 85% (p = 0.0315). There were three adverse events not related to OFDI. OFDI achieved acceptable visualization of the vessel lumen without any adverse event related to it. After regulatory approval based on the present study, OFDI will be available as a new option of endovascular imaging for peripheral artery diseases in daily practiceTrial registration: This study was registered in the Japanese Registry of Clinical Trials (jRCT 2052190025, https://jrct.niph.go.jp/latest-detail/jRCT2052190025 ).

Vascular Response Occurring at 3 Months After Everolimus-Eluting Cobalt-Chromium Stent Implantation in Patients With ST-Segment Elevation Myocardial Infarction vs. Stable Coronary Artery Disease.

BACKGROUND: Second-generation drug-eluting stents (DES) reduce the incidence of stent thrombosis, even in patients with ST-segment elevated myocardial infarction (STEMI). However, the early local vascular healing after DES implantation in STEMI lesions, which mainly concerns stent thrombosis, is still unclear.Methods and Results:We attempted to determine early local vascular healing 3 months after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation in STEMI lesions relative to stable coronary artery disease (CAD) lesions. This prospective, multicenter study analyzed 96 total lesions (STEMI=49, stable CAD=51) by frequency domain-optical coherence tomography (FD-OCT) performed post-procedure and at the 3-month follow-up. Although CoCr-EES implanted in STEMI were almost entirely covered at 3 months, they had a relatively high incidence of uncovered struts compared with stable CAD (5.5% vs. 1.6%, P<0.001). Intrastent thrombus in the 2 groups was primarily resolved at the 3-month follow-up (STEMI: 91.7%→26.5%, stable CAD: 74.5%→11.8%). Regarding irregular protrusion, complete resolution was observed in stable CAD (21.6%→0%), while a few stents remained in STEMI (79.2%→8.2%). Although there were almost no changes for the serial change of average lumen area in STEMI, there were slight but significant decreases in stable CAD [STEMI 0.08 (-0.44, 0.55) mm2, stable CAD -0.35 (-0.55, 0.11) mm2; P=0.009]. CONCLUSIONS: Although strut coverage after CoCr-EES implantation for STEMI lesions was slightly delayed, the healing process appeared to be acceptable in both STEMI and stable CAD.

Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents.

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI.

Stentless percutaneous coronary intervention with directional coronary atherectomy and drug-coated balloon angioplasty in worsening angina patients with metal allergies.

Metal allergy is a concern in percutaneous coronary intervention (PCI) with stent implantation because of its potential association with poor cardiovascular outcomes, such as stent thrombosis and recurrent in-stent restenosis requiring revascularization. Although stentless PCI with drug-coated balloon (DCB) angioplasty is theoretically useful for patients with metal allergies, DCB angioplasty alone for huge plaques in large vessels may yield inadequate luminal enlargement and coronary deep dissection, leading to insufficient results. Directional coronary atherectomy (DCA) is effective to reduce plaque volume. However, the efficacy of DCA followed by DCB (DCA/DCB) angioplasty in patients with metal allergies has never been described. We present two cases wherein stentless PCI with DCA/DCB angioplasty was an alternative revascularization strategy for patients with metal allergy and concomitant worsening angina pectoris involving proximal left anterior descending artery stenoses. Preoperative evaluation using coronary computed tomography angiography in Case 1 and intravascular ultrasound in Case 2 was useful to determine the possible use of the DCA/DCB procedure for huge plaques in large vessels. Learning objective: Revascularization for patients with metal allergy with worsening angina pectoris due to stenoses of the proximal main arteries is often challenging because of the necessity to avoid stent implantation. As stentless percutaneous coronary intervention (PCI) is theoretically useful in such settings, PCI with directional coronary atherectomy (DCA)/drug-coated balloon angioplasty can be one of the treatable strategies. Preoperative evaluation of plaque morphology for the suitability of DCA procedure is important.

Rare complications of Guideplus guide-extension catheter during complex percutaneous coronary intervention.

Guide-extension catheters (GECs) are effective in providing reinforced backup support and coaxial alignment, leading to successful complex percutaneous coronary intervention (PCI). However, several GEC-associated complications have been reported, including coronary injuries, thrombotic events, and GEC fractures. The Guideplus GEC (Guideplus II ST; Nipro, Osaka, Japan) has a higher crossability due to its unique hydrophilic-coated soft cylinder, which is frequently used in complex PCI for diffuse, tortuous, and heavily calcified lesions. We describe two cases of Guideplus GEC-associated complications during complex PCI: Case 1 with a radiopaque marker dislodgement and Case 2 with a stent dislodgment. In both cases, the Guideplus GEC was used within 7-Fr guiding catheters, employing the mother-and-child technique. A large inner-catheter gap between these catheters caused by a positioning bias due to arterial bends (the aortic arch in Case 1 and brachiocephalic arterial bends in Case 2) may have caused these complications due to its interference with coronary devices (the trapping balloon in Case 1, and the scoring balloon in Case 2). Early cognition and management of these potential Guideplus GEC-associated complications are important to prevent further deterioration. Learning objectives: The Guideplus guide-extension catheter (GEC) with a hydrophilic-coated soft cylinder can deliver coronary devices to complex lesions owing to its high crossability. However, delivering coronary devices with the Guideplus GEC should be carefully performed because a large inner-catheter gap between Guideplus GEC and a guiding catheter may occur if a proximal port of the Guideplus GEC is located at an arterial bend. In such settings, Guideplus GEC-associated complications must be carefully observed, including radiopaque marker dislodgement and stent dislodgement.

A serial optical frequency-domain imaging study of early and late vascular responses to bioresorbable-polymer sirolimus-eluting stents for the treatment of acute myocardial infarction and stable coronary artery disease patients: results of the MECHANISM-ULTIMASTER study.

The purpose of this study was to assess early and late vascular healing in response to bioresorbable-polymer sirolimus-eluting stents (BP-SESs) for the treatment of patients with ST-elevation myocardial infarction (STEMI) and stable coronary artery disease (CAD). A total of 106 patients with STEMI and 101 patients with stable-CAD were enrolled. Optical frequency-domain images were acquired at baseline, at 1- or 3-month follow-up, and at 12-month follow-up. In the STEMI and CAD cohorts, the percentage of uncovered struts (%US) was significantly and remarkably decreased during early two points and at 12-month (the STEMI cohort: 1-month: 18.75 ± 0.78%, 3-month: 10.19 ± 0.77%, 12-month: 1.80 ± 0.72%; p < 0.001, the CAD cohort: 1-month: 9.44 ± 0.78%, 3-month: 7.78 ± 0.78%, 12-month: 1.07 ± 0.73%; p < 0.001 respectively). The average peri-strut low-intensity area (PLIA) score in the STEMI cohort was significantly decreased during follow-up period (1.90 ± 1.14, 1.18 ± 1.25, and 1.01 ± 0.72; p ≤ 0.001), whereas the one in the CAD cohort was not significantly changed (0.89 ± 1.24, 0.67 ± 1.07, and 0.64 ± 0.72; p = 0.59). In comparison with both groups, differences of %US and PLIA score at early two points were almost disappeared or close at 12 months. The strut-coverage and healing processes in the early phase after BP-SES implantation were significantly improved in both cohorts, especially markedly in STEMI patients. At 1 year, qualitatively and quantitatively consistent neointimal coverage was achieved in both pathogenetic groups.

Open-label multicenter registry on the outcomes of peripheral arterial disease treated by balloon angioplasty with optical frequency domain imaging in superficial femoral artery and popliteal artery (OCEAN-SFA study).

Although balloon angioplasty for femoropopliteal artery lesions has been associated with restenosis rates of up to 60% at 12 months, the mechanism of restenosis has not been fully evaluated. The aim of this study was to evaluate the relationship between the vascular features observed on optical frequency domain imaging (OFDI) before and after balloon angioplasty of femoropopliteal artery lesions, and restenosis at 6 months. This study was a prospective multicenter single arm study. OFDI was performed before and after balloon angioplasty and plaque characteristics and vascular features, along with de novo lesions, were assessed. The primary outcome was the presence or absence of restenosis 6 months after balloon angioplasty. Residual platelet reactivity was assessed according to VerifyNow platelet reactivity units (PRUs). The number of patients completing 6 months of follow-up was 47, of which 14 had developed restenosis. Maximum thickness of the dissection flap (odds ratio (OR) 2.71; 95% confidence interval [0.9-8.0]; p = 0.071) and lesion length were identified as risk factors for restenosis (OR 1.015; 95% confidence interval [0.001-0.029]; p = 0.039). The mean PRU at the time of treatment in patients with restenosis was significantly higher than in those without restenosis (286.3 ± 82.6 vs. 208.5 ± 03.6, p = 0.026). Long lesions and major dissection on OFDI after balloon angioplasty for femoropopliteal artery lesions increase restenosis at 6 months. In addition, high residual platelet reactivity at the time of EVT may also be a risk factor for restenosis.Clinical Trial Registration Number UMIN000021120.

Comparison of the 9-Month Intrastent Condition and 30-Month Clinical Outcomes After Resolute Zotarolimus-Eluting Stent Implantation Between Standard-Duration and 1-Month Dual Antiplatelet Therapy Followed by Prasugrel Monotherapy.

Background: In this study we investigated the efficacy and safety of very short duration (1-month) dual antiplatelet therapy (DAPT) followed by prasugrel monotherapy. In particular, we compared intrastent conditions using optical coherence tomography (OCT) after second-generation drug-eluting stent implantation between standard-duration and 1-month DAPT followed by prasugrel monotherapy. Methods and Results: Between May 2015 and February 2018, 120 consecutive patients who underwent elective Resolute zotarolimus-eluting stent implantation were enrolled and divided into those receiving standard-duration or 1-month (1M) DAPT followed by prasugrel monotherapy; 47 patients (n=55 stents) and 46 patients (n=54 stents) in the standard and 1M groups, respectively, completed the protocol. The primary endpoint was the prevalence of abnormal intrastent tissue at the 9-month examination, as observed by OCT. The secondary endpoint was the presence of composite adverse events, including all-cause death, myocardial infarction, stent thrombosis, target lesion and vessel revascularization, and major and minor bleeding. The prevalence of abnormal intrastent tissue was similar between the standard and 1M groups (1.6% vs. 1.5%, respectively; non-inferiority P<0.01). There was a tendency for fewer composite events in the 1M than standard group at the 30-month follow-up examination (28.3% vs. 44.7%, respectively; P=0.41). Conclusions: In conclusion, 1M DAPT followed by prasugrel monotherapy after second-generation drug-eluting stent implantation was not inferior to standard-duration DAPT in terms of intrastent thrombus formation and composite adverse events.

Open-Label Multicenter Registry on the Outcomes of In-Stent Restenosis Treated by Balloon Angioplasty with Optical Frequency Domain Imaging in the Superficial Femoral Artery (ISLAND-SFA Study).

Objectives: Balloon angioplasty for in-stent restenosis (ISR) in the superficial femoral artery (SFA) has a high recurrent restenosis rate; however, its mechanism has not been fully and precisely evaluated using high-resolution intravascular imaging. Thus, we aimed to evaluate the relationship between vascular features obtained by optical frequency domain imaging (OFDI) and recurrent restenosis at 6 months. Methods: This was a prospective multicenter single-arm study. OFDI was performed before and after balloon angioplasty, and vascular features were assessed. A multi-layered ISR pattern detected by OFDI was defined as several signal-poor appearances with a high-signal band adjacent to the luminal surface. The primary outcome was defined as recurrent restenosis 6 months after balloon angioplasty. Results: Given that this study was terminated early, only 18 patients completed the 6-month follow-up; of these, 8 developed restenosis. Recurrent restenosis at 6 months tended to be related to a multi-layered ISR pattern (odds ratio (OR), 6.67; 95% confidence interval (CI), 0.81-54.96; p=0.078) and the minimum lumen area (MLA) after balloon angioplasty (OR, 0.71; 95%CI, 0.48-1.04; p=0.077). Conclusion: A multi-layered ISR pattern and MLA after balloon angioplasty detected by OFDI might be risk factors for recurrent ISR in the SFA.

Efficacy of optical frequency-domain imaging in detecting peripheral artery disease: a single-center open-label, single-arm study protocol.

Intravascular optical coherence tomography is a high-resolution intracoronary imaging modality, providing a microscopic image of intravascular features. However, it has lower penetration depth than intravascular ultrasound. Recently, a second-generation optical frequency-domain imaging (OFDI) technique has been developed to provide greater penetration depth and faster pullback speed. However, there is little evidence supporting the efficacy of OFDI in patients with peripheral artery disease (PAD) undergoing endovascular treatment (EVT). We aimed to evaluate the ability of OFDI to visualize vessel walls from the superficial femoral artery (SFA) to the below-knee (BK) arteries, as well as the coronary arteries. This clinical trial is a single-center, single-arm, open-label study to be conducted in Japan. A total of 20 patients will be enrolled in this study. The primary endpoint is to obtain a clear image of the intravascular features of the SFA and BK arteries, specifically the visualization of ≥ 270° of the vessel lumen in ≥ 16 out of 21 cross sections. Obtaining clear images in ≥ 85% of cases will be regarded as confirmation of the ability of OFDI to visualize vessel walls from the SFA to the BK arteries. This is the first clinical trial to be conducted accordance with good clinical practice to expand the indications of OFDI for PAD patients undergoing EVT in Japan. The result of this study will help provide another imaging option during EVT in daily practice.

Correction to: Efficacy of optical frequency­domain imaging in detecting peripheral artery disease: a single­center open­label, single­arm study protocol.

In the original publication of the article, the author group was published without full names and one of the co-authors' name was published incorrectly. The full names of author group and correct co-authors' name are given in this Correction.

Efficacy of alirocumab for reducing plaque vulnerability: Study protocol for ALTAIR, a randomized controlled trial in Japanese patients with coronary artery disease receiving rosuvastatin.

BACKGROUND: Although a recent clinical trial demonstrated that alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, significantly reduces the incidence of acute coronary events, the impact of alirocumab on plaque stabilization remains uncertain. The Efficacy of ALirocumab for Thin-cap fibroatheroma in patients with coronary Artery disease estImated by optical coherence tomogRaphy (ALTAIR) study will investigate the effect of alirocumab on thin-cap fibroatheroma (TCFA) in Japanese patients who underwent recent percutaneous coronary intervention (PCI). METHODS AND DESIGN: ALTAIR is a phase IV, open-label, randomized, parallel-group, single-center study involving blinded optical coherence tomography (OCT) image analysis in Japanese adults hospitalized for PCI and having suboptimal control of low-density lipoprotein cholesterol (LDL-C) levels (>70mg/dL) despite statin therapy. Patients will be randomized (1:1) to the alirocumab arm (alirocumab 75mg every 2 weeks added to rosuvastatin 10mg/day) or the standard-of-care arm (rosuvastatin 10mg/day, with initiation and/or dose adjustment of non-statin lipid-lowering to achieve an LDL-C target of <70mg/dL). OCT imaging will be conducted at baseline and at week 36 (post-treatment). The primary objective is to compare the alirocumab and standard-of-care arms regarding the change in TCFA fibrous-cap thickness after 9 months of treatment. CONCLUSION: The outcomes of ALTAIR (ClinicalTrials.gov identifier: NCT03552432) will provide insights into the effect of alirocumab on plaque vulnerability following PCI in patients with suboptimal LDL-C control despite stable statin therapy.

Vascular response to paclitaxel-eluting nitinol self-expanding stent in superficial femoral artery lesions: post-implantation angioscopic findings from the SHIMEJI trial (Suppression of vascular wall Healing after IMplantation of drug Eluting peripheral stent in Japanese patients with the Infra inguinal lesion: serial angioscopic observation).

The aim of this study was to elucidate the vascular responses to paclitaxel-eluting stent (Zilver PTX stent) in superficial femoral artery lesion at different elapsed times using angioscopy. Patients who received Zilver PTX stent implantation from five centers were enrolled. We performed angioscopic examinations at 2, 6, and 12 months after implantation and evaluated neointimal coverage (NIC) grade, intra-stent thrombus (IS-Th) grade, and presence of yellow plaque. NIC grade 0 was defined as stent struts exposed; grade 1, struts transparently visible although covered; grade 2, struts embedded in the neointima, but translucent; and grade 3, struts fully embedded and invisible. IS-Th was graded as follows: grade 0 (none), 1 (focal), and 2 (diffusely spread). Angioscopic follow-up evaluation was performed at 2 months (25 patients, 42 lesions), 6 months (18 patients, 23 stents), and 12 months (14 patients, 24 stents) after stent implantation. Dominant NIC grade significantly increased over time; however, 16.3% of the cases had NIC grade 1 or 2 at 12 months. IS-Th grade decreased; however IS-Th and yellow plaque were persistently observed in 62.5% and 83.3% cases, respectively, at 12 months. An ongoing healing response was observed at 12 months after implantation; however, thrombogenic findings were noted. Prolonged dual antiplatelet therapy could potentially enhance the clinical utility of Zilver PTX.

Impaired Cholesterol-Uptake Capacity of HDL Might Promote Target-Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation.

Background We evaluated the importance of high-density lipoprotein (HDL) functionality for target-lesion revascularization in patients treated with coronary stents using a rapid cell-free assay system to evaluate the functional capacity of HDL to accept additional cholesterol (cholesterol-uptake capacity; CUC). Methods and Results From an optical coherence tomography (OCT) registry of patients treated with coronary stents, 207 patients were enrolled and their HDL was functionally evaluated by measuring the CUC. Follow-up OCT was performed (median duration, 24.5 months after stenting) to evaluate the presence of neoatherosclerosis. Clinical follow-up was performed to assess target-lesion revascularization for a median duration of 42.3 months after stent implantation. Neoatherosclerosis was identified in 37 patients (17.9%). Multivariate logistic regression analysis revealed that a decreased CUC was independently associated with neoatherosclerosis (odds ratio, 0.799; P<0.001). The CUC showed a significant inverse correlation with incidence of target-lesion revascularization (odds ratio, 0.887; P=0.003) and with lipid accumulation inside stents, suggesting that neoatherosclerosis contributes to the association between CUC and target-lesion revascularization. Conclusions Impaired HDL functionality, detected as decreased CUC, might lead to future stent failure by provoking atherogenic changes of the neointima within stents. Both quantitative and qualitative assessments of HDL might enable the improved prediction of clinical outcomes after stent implantation.

Potent effect of prasugrel on acute phase resolution of intra-stent athero-thrombotic burden after percutaneous intervention to acute coronary syndrome.

BACKGROUND: Recent studies suggested protruding thrombus and atheroma after stent placement could be a substrate for subsequent adverse ischemic events. Although protruded atherothrombotic burden can be assessed as intra-stent tissue (IST) by optical coherence tomography (OCT), the effects of potent antiplatelet therapy on the acute phase resolution of IST in patients with acute coronary syndrome (ACS) was unknown. METHODS: Ninety-six consecutive ACS patients with multi-vessel disease were enrolled in this prospective registry. In combination with aspirin, either clopidogrel or prasugrel was selected according to the date of enrolment. OCT examination was done immediately after percutaneous coronary intervention (post-PCI) and 10 days after index PCI (follow-up acute phase) to calculate averaged IST score as semi-quantitative measures of IST. High residual platelet reactivity (HRPR) was defined as platelet reactivity units (PRU)≥240 by VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, CA, USA). RESULTS: Thirty two patients (38 stents) were enrolled in the prasugrel group and sixty four patients (72 stents) in the clopidogrel group. Averaged IST scores post-PCI were similar between the two groups (0.68±0.41 vs. 0.68±0.40, p=0.99), which decreased in all of the prasugrel group and in 87.5% of the clopidogrel group (p=0.02). Consequently, changes in averaged IST score (delta averaged IST score) were significantly greater in the prasugrel group compared to those in the clopidogrel group (-0.411±0.288 vs. -0.299±0.270, p=0.045). The frequency of HRPR was significantly lower in the prasugrel group (10.0% vs 32.4%, p=0.028). CONCLUSIONS: Prasugrel plus aspirin achieved greater acute phase reduction of IST than clopidogrel plus aspirin, which might underlie the clinical benefit of potent antiplatelet therapy in ACS. (UMIN000018751).

Impact of CD14++CD16+ monocytes on coronary plaque vulnerability assessed by optical coherence tomography in coronary artery disease patients.

BACKGROUND AND AIMS: This study examined the impact of CD14++CD16+ monocytes on coronary plaque vulnerability, as assessed by optical coherence tomography (OCT), and investigated their association with daily glucose fluctuation. Although increased CD14++CD16+ monocyte levels have been reported to increase cardiovascular events, their impact on coronary plaque vulnerability in coronary artery disease (CAD) patients with or without diabetes mellitus (DM) remains unclear. METHODS: This prospective observational study included 50 consecutive patients with CAD, receiving lipid-lowering therapy and undergoing coronary angiography and OCT. Patients were divided into 3 tertiles according to the CD14++CD16+ monocyte percentages assessed by flow cytometry. Standard OCT parameters were assessed for 97 angiographically intermediate lesions (diameter stenosis: 30-70%). Daily glucose fluctuation was analyzed by measuring the mean amplitude of glycemic excursion (MAGE). RESULTS: CD14++CD16+ monocytes negatively correlated with fibrous cap thickness (r = -0.508, p < 0.01). The presence of thin-cap fibroatheroma (TCFA) was increased stepwise according to the tertile of CD14++CD16+ monocytes (0 [tertile 1] vs. 5 [tertile 2] vs. 10 [tertile 3], p < 0.01). CD14++CD16+ monocytes were a significant determinant of TCFA (OR 1.279, p = 0.001). In non-DM patients, a significant relationship was found between CD14++CD16+ monocytes and MAGE (r = 0.477, p = 0.018). CONCLUSIONS: CD14++CD16+ monocytes were associated with coronary plaque vulnerability in CAD patients with well-regulated lipid levels both in DM and non-DM patients. Cross-talk between glucose fluctuation and CD14++CD16+ monocytes may enhance plaque vulnerability, particularly in non-DM patients. CD14++CD16+ monocytes could be a possible therapeutic target for coronary plaque stabilization.