Takahisa Noto

Association Between Virtual Histology Intravascular Ultrasound Findings and Subsequent Coronary Events in Patients With Acute Coronary Syndrome

Virtual histology intravascular ultrasound (VH-IVUS) was employed to compare coronary plaque characteristics between acute coronary syndrome (ACS) patients with and without subsequent coronary events.It is critical to predict subsequent coronary events in patients treated for ACS. Coronary artery events sometimes occur in lesions that do not receive intervention.VH-IVUS was performed in 57 patients with ACS to analyze 83 non-culprit lesions. Characteristics of plaques in the non-culprit lesions were determined. Patients were followed-up for 4.8 ± 1.8 years.During the follow-up period, ACS and stable angina pectoris occurred in 7 patients in whom 13 non-culprit lesions had been analyzed. Seventy non-culprit lesions in 50 patients who did not experience subsequent coronary events were also analyzed. Plaque area was greater in 7 patients who had subsequent coronary events than in those who did not (11.5 ± 3.1 versus 9.1 ± 3.6 mm(3)/mm, P = 0.03). However, there was no significant difference in plaque burden between the two groups (57.1 ± 8.9 versus 55.6 ± 8.7%, P = 0.18). Areas of dense calcium (DC) and necrotic core (NC) were greater in patients who had subsequent coronary events than in those who did not (0.6 ± 0.5 versus 0.2 ± 0.3 mm(3)/mm, P < 0.001, and 1.8 ± 1.0 versus 1.0 ± 0.8 mm(3)/mm, P < 0.01, respectively). When DC area was larger (≥ 3.4% of the plaque area), the cumulative coronary event rate increased significantly (28.6 versus 6.5%, P < 0.01). This was also true for NC area (≥ 20.9%, 31.4 versus 5.1%, P < 0.01).Area size of DC or NC in non-culprit plaques may be associated with subsequent coronary events in patients with ACS.

Impaired macrophage production of anti-atherosclerotic interleukin-10 induced by coronary intraplaque hemorrhage in patients with acute coronary syndrome and hyperglycemia

BACKGROUND Coronary intraplaque hemorrhage (IPH) accelerates atherosclerosis. Extracellular hemoglobin (Hb) released by IPH is cleared by macrophages with CD163 receptors. This process provokes secretion of the anti-atherosclerotic cytokine interleukin (IL)-10. The present study aimed to investigate the relationship between macrophage accumulation and IL-10 production provoked by IPH in plaques obtained from acute coronary syndrome (ACS) patients with hyperglycemia. METHODS In 50 ACS patients, atherothrombotic debris was retrieved during percutaneous coronary intervention (PCI). The debris was stained with antibodies to CD163, glycophorin A (GPA, a marker of IPH) and IL-10. %CD163 was defined as the ratios of CD163-positive cells to all cells. %IL-10 and %GPA were defined as the ratio of positively stained areas per total tissue area. Based on glycosylated Hb [HbA1c (NGSP)] ≥ 6.5%, fasting blood sugar (FBS) ≥ 126 mg/dL, and insulin resistance (HOMA-IR>2.5), patients were divided into a diabetes mellitus (DM) group (N = 18, HbA1c ≥ 6.5% or FBS ≥ 126 mg/dL), an insulin resistance (IR) group (N = 15, HOMA-IR>2.5, HbA1c<6.5%, and FBS< 126 mg/dL), and a normal (NR) group (N = 17). RESULTS Compared to the NR group, %GPA and %CD163 were increased in the DM and IR groups. %IL-10 was similar among the three groups. However, %IL-10/%CD163 ratios were decreased in the DM (2.5 ± 0.6, P = 0.01) and IR (2.7 ± 0.8, P = 0.02) groups compared to the NR group (5.8 ± 4.7). Only in the NR group was there a significant correlation between %IL-10 and %CD163. CONCLUSIONS Impairment of the anti-inflammatory effect provoked by IPH contributes to premature atherosclerosis even in the IR group.

Enhanced Expression of Hemoglobin Scavenger Receptor CD163 in Accumulated Macrophages Within Filtered Debris Between Acute Coronary Syndromes and Stable Angina Pectoris

Coronary intraplaque hemorrhage up-regulates hemoglobin scavenger receptor CD163 expression on macrophages, and has an association with vulnerable plaque development. During percutaneous coronary intervention, mechanical plaque disruption exposes potentially embolic atheromatous contents from culprit plaque.In 37 patients with stable angina pectoris (SAP, n = 20) or acute coronary syndrome (ACS, n = 17), atherothrombotic debris was collected using a filter-based distal embolic protection device. We immunohistochemically determined CD14-positive macrophages and CD163-positive macrophages in filtered debris. We also examined the relation of CD14- and CD163-positive macrophages with culprit plaque volume and components evaluated with ultrasonic tissue characterization (VH-IVUS).The only significant difference in clinical characteristics between the two groups was in hs-CRP. In ACS, the percentage of CD14- and CD163-positive macrophages to the whole cells (%CD14 and %CD163, respectively) was significantly higher than that in SAP (20.1 ± 8.2 versus 8.8 ± 6.8%, P < 0.001 and 32.6 ± 18.9 versus 9.0 ± 3.8%, P < 0.001, respectively). In IVUS indices of culprit plaque, the remodeling index was significantly higher in ACS than in SAP. However, necrotic core component (%NC) in ACS was significantly higher than that in SAP. Furthermore, fibrotic component (%Fibrous) in ACS was significantly lower than that in SAP (56.1 ± 4.7 versus 60.1 ± 3.3%, P = 0.03). %CD14 and %CD163 had a significant positive correlation with %NC (%CD14: r = 0.40, P = 0.01 and %CD163: r = 0.45, P = 0.01), but only %CD163 was negatively correlated with %Fibrous (%CD163: r = -0.48, P = 0.01).These findings suggest that the presence of CD14- and CD163-positive macrophages may reflect plaque inflammation, NC expansion, and plaque vulnerability in patients with coronary heart disease.

Impact of preinterventional plaque composition and eccentricity on late-acquired incomplete stent apposition after sirolimus-eluting stent implantation: an intravascular ultrasound radiofrequency analysis.

ObjectivesThe present study aimed to investigate differences in plaque morphology and components in between the target coronary artery lesion with and without late-acquired incomplete stent apposition (LISA) using radiofrequency analysis (virtual histology) of intravascular ultrasound data. BackgroundIncomplete stent apposition is frequently observed in patients with very late stent thrombosis after sirolimus-eluting stent implantation. MethodsThe study group consisted of 70 coronary artery lesions in 43 patients who underwent elective coronary stenting for stable angina pectoris. Virtual histology intravascular ultrasound was performed at the implantation of stent and 12-month follow-up. LISA was defined as a separation of stent struts from the intimal surface of the arterial wall that had not been present at the time of stent implantation. The plaque eccentricity index (EI) was calculated as (lumen radius+maximal plaque thickness)/(lumen radius+minimal plaque thickness). ResultsAt 12-month follow-up, LISA occurred in 15 plaques (LISA group). Compared with the non-LISA group, the LISA group had significantly longer stents, a higher EI, smaller amount of fibro-fatty component (7.7±4.2 vs. 12.5±7.0%, P=0.01) and larger amount of necrotic core component (16.6±9.8 vs. 11.1±6.4%, P=0.06). Multivariate logistic regression analysis revealed that amount of necrotic core and plaque EI were independent positive predictors for LISA (odds ratio=1.4, 95% confidence interval=1.1–1.6, P=0.04 and 11.2, 1.9–64.9, P<0.01, respectively). ConclusionPlaques with increased amounts of necrotic core and higher eccentricity are associated with subsequent LISA after sirolimus-eluting stent implantation.