Changes In Fibrous Cap Thickness Research Articles

OR8-3 | Evaluation of the Changes in Fibrous Cap Thickness in Nonculprit Coronary Artery Plaques Using Serial OCT Imaging and Serum Biomarkers

OR8-3 | Evaluation of the Changes in Fibrous Cap Thickness in Nonculprit Coronary Artery Plaques Using Serial OCT Imaging and Serum Biomarkers

Effect of Statin Therapy on Fibrous Cap Thickness in Coronary Plaque on Optical Coherence Tomography - Review and Meta-Analysis.

Statin therapy has been shown to result in coronary plaque regression, but the relationship between statin use and stabilization of coronary plaque has not been elucidated. We conducted a systematic review and meta-analysis to evaluate the effect of statin therapy on fibrous cap thickness (FCT) on optical coherence tomography (OCT).Methods and Results:Nine OCT studies (6 randomized controlled trials and 3 observational studies) were enrolled with a total of 341 patients (390 lesions). Arms of the studies were grouped according to statin type and/or dose. Random effects meta-analysis was used to estimate a pooled mean change in FCT from baseline to follow-up. The overall effect mean FCT change was 67.7 µm (95% CI: 51.4-84.1, I2=95.0%, P<0.001). All statin groups had an increase in FCT, but the magnitude of the increase differed according to the statin. Two homogeneous subgroups with I2=0 were identified: mean FCT change was 27.8 µm (for subgroup atorvastatin 5 mg and rosuvastatin), and 61.9 µm (for subgroup atorvastatin 20 mg, fluvastatin 30 mg, and pitavastatin 4 mg). On meta-regression modeling, statin therapy alone explained most of the change in FCT. Statin therapy induced a significant increase in FCT as assessed on OCT, independent of coronary risk factors and other medications.

Does spotty calcification attenuate the response of nonculprit plaque to statin therapy?: A serial optical coherence tomography study.

The aim of this study was to determine if spotty calcification decreases the response of plaque progression to statin therapy. Previous studies showed that the presence of spotty calcification is a marker of vulnerable plaque. However, the relationship between spotty calcification and plaque progression is not clear. Ninety-six nonculprit lipid-rich plaques in 69 patients who received serial optical coherence tomography (OCT) imaging were included. Plaques were divided into three groups: spotty calcification (n=38), calcified (n=12) and noncalcified (n=46) plaques. Spotty calcification was identified by the presence of a lesion <4mm in length with an arc of calcification <90°. Changes in plaque characteristics and fibrous cap thickness (FCT) at 6 and 12months under statin therapy were analyzed by OCT. The increase of FCT was sustained from baseline to 6 and 12months in three groups: spotty calcification (62.8±20.9, 126.4±84.9, and 169.2±81.6μm, respectively; P<.001), calcified (59.8±17.0, 93.4±51.4, and 155.2±61.7μm, respectively; P<.001) and noncalcified (60.0±17.2, 125.5±62.1, and 161.0±80.5μm, respectively; P<.001). Intensive statin induced a greater change in FCT at 12months than moderate statin in the spotty calcification group (P=0.034). The mean lipid arc decreased significantly at 12months from baseline in the three groups (P=0.004, P=0.023, and P<.001, respectively). Statin therapy was effective for plaque stabilization in plaques with and without spotty calcification. Patients with spotty calcification benefitted more from intensive statin than from moderate statin therapy.

Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study

BackgroundDespite extensive evidence demonstrating the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects remain elusive. ObjectivesThis study assessed changes in plaque morphology using intravascular imaging, with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cell (PBMC) transcriptomics in patients receiving high-dose statin therapy. MethodsIn a prospective study, 85 patients with stable coronary artery disease underwent percutaneous coronary intervention for a culprit lesion, followed by intracoronary multimodality imaging, including optical coherence tomography (OCT) of an obstructive nonculprit lesion. All subjects received 40 mg of rosuvastatin daily for 8 to 12 weeks, when the nonculprit lesion was reimaged and intervention performed. Blood samples were drawn at both times to assess CEC and transcriptomic profile in PBMC. ResultsBaseline OCT minimal fibrous cap thickness (FCT) was 100.9 ± 41.7 μm, which increased to 108.6 ± 39.6 μm at follow-up, and baseline CEC was 0.81 ± 0.14, which increased at follow-up to 0.84 ± 0.14 (p = 0.003). Thin-cap fibroatheroma prevalence decreased from 20.0% to 7.1% (p = 0.003). Changes in FCT were independently associated with CEC increase by multivariate analysis (β: 0.30; p = 0.01). PBMC microarray analysis detected 117 genes that were differentially expressed at follow-up compared to baseline, including genes playing key roles in cholesterol synthesis (SQLE), regulation of fatty acids unsaturation (FADS1), cellular cholesterol uptake (LDLR), efflux (ABCA1 and ABCG1), and inflammation (DHCR24). Weighted coexpression network analysis revealed unique clusters of genes associated with favorable FCT and CEC changes. ConclusionsThe study demonstrated an independent association between fibrous cap thickening and improved CEC that may contribute to morphological changes suggesting plaque stabilization among patients taking intensive statin therapy. Furthermore, the significant perturbations in PBMC transcriptome may help determine the beneficial effects of statin on plaque stabilization. (Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering [YELLOW II]; NCT01837823)

Serial Optical Coherence Tomography and Intravascular Ultrasound Analysis of Gender Difference in Changes of Plaque Phenotype in Response to Lipid-Lowering Therapy

Although the clinical benefit of statins have been demonstrated in both genders, gender differences in the response to statin therapy on plaque morphologic changes have not been reported. A total of 66 nonculprit plaques from 46 patients who had serial image acquisition at baseline, 6months, and 12months by both optical coherence tomography and intravascular ultrasound (IVUS) were included. Patients were treated with atorvastatin 60mg (AT60) or 20mg (AT20). The baseline characteristics were similar between women (n= 16) and men (n= 30) except for age (59.3 ± 6.8 vs 52.5 ± 10.6 years, p= 0.027) and smoking status (12.5% vs 70.0%, p <0.001). The change in fibrous cap thickness (FCT) at 12months was significant in both groups (108.8 ± 87.4μm, p <0.001, 91.3 ± 70.1μm, p <0.001, respectively) without significant difference between the groups (p= 0.437). The percent change in mean lipid arc at 6months was significantly greater in women than that in men (-12.8 ± 18.8% vs-1.56 ± 21.8%, p= 0.040). In women, the percent change of FCT in the AT20 group was similar to that in the AT60 group (182.5 ± 199.5% vs 192.9 ± 149.7%, p= 0.886). However, in men, the percent change of FCT in the AT20 group was significantly smaller than that in the AT60 group (92.2 ± 90.5% vs 225.9 ± 104.3%, p <0.001). No significant change in percent atheroma volume by IVUS was seen at 12months in both women and men. In conclusion, statin therapy was effective in both genders for plaque stabilization at 12-month follow-up. High-intensity statin therapy may be particularly important in men.

Abstract 16064: Effect of Intensive versus Moderate Lipid-Lowering Therapy on the Progression of Coronary Lipid-Rich Plaque: A Prospective, Randomized, Serial Combined Optical Coherence Tomography and Intravascular Ultrasound Study

Background: Despite dramatic improvements in clinical outcome, intravascular ultrasound (IVUS) trials have shown minimal improvement of atheroma volume with statin therapy. Changes in plaque composition rather than plaque volume may contribute to the marked clinical benefit. Objectives: To assess the effect of intensive versus moderate lipid-lowering therapy on fibrous cap thickness (FCT) by optical coherence tomography (OCT) and percent atheroma volume (PAV) by IVUS. Methods: The patients with ≥1 non-treated lipid-rich plaque (LRP) with moderate stenosis were randomized to receive atorvastatin 60 mg (AT60), or atorvastatin 20 mg (AT20). OCT and IVUS imaging were performed at baseline, 6 months and 12 months. The primary endpoint was the change in FCT. The secondary endpoints were the change in PAV and the percent change in normalized total atheroma volume (%NTAV). Sixty-six LRP in 46 patients defined by OCT were studied. Results: Low-density lipoprotein cholesterol (LDL-C) was reduced significantly in both groups at 6 months; however, there was no further reduction at 12 months (Fig A, C). OCT demonstrated a continuous increase in FCT over time in both groups, with greater increase in the AT60 group than the AT20 group at 6 months (139.7±160.9% vs. 68.1±83.9%, p=0.021) and 12 months (211.3±125.4% vs. 120.2±136.9%, p&lt;0.0001) (Fig B, D). IVUS showed no significant changes in PAV and NTAV over time in two groups. The changes in PAV were similar between the two groups at 6 months (-0.48±3.4% in AT60 vs. 0.28±5.2% in AT20, p=0.50) and 12 months (-0.26±4.3% vs. 0.11±4.1%, p=0.73). %NTAV were also comparable between the two groups at 6 months and at 12 months. Conclusions: Intensive atorvastatin therapy induces more rapid and effective stabilization of coronary lipid-rich plaques by increasing FCT, as compared with moderate atorvastatin therapy. IVUS analysis did not show significant change in plaque volume over time in both groups.

Is lipoprotein-associated phospholipase A2 activity correlated with fibrous-cap thickness and plaque volume in patients with acute coronary syndrome?

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a specific biomarker specific for vascular inflammation. Inflammation has a significant association with plaque progression. The fibrous-cap thickness (FCT) is one of the major determinants of plaque vulnerability in atherosclerotic plaques. However, data on the relationship between Lp-PLA2 activity and FCT in lipid plaque are limited. This study aimed to evaluate the in-vivo association between changes in Lp-PLA2 activity and FCT and plaque volume in patients with acute coronary syndrome (ACS). Twenty-four consecutive patients with ACS were enrolled between May 2010 and May 2012. The plaque volume and FCT of nonculprit lipid-rich plaques were assessed by intravascular ultrasound and optical coherence tomography, respectively, at baseline and after 12 months. Lp-PLA2 activity was determined using the colorimetric assay kit. During the 12 months of observation, FCT increased significantly from baseline to follow-up, with a mean percent change of 74.4±46.8%. A significant correlation was observed between changes in Lp-PLA2 activity and changes in FCT (r=-0.56, P=0.006). Changes in plaque volume were also correlated significantly with changes in Lp-PLA2 activity during the study period (r=0.52, P=0.01). Significant associations between serial changes in Lp-PLA2 activity and changes in FCT and plaque volume were observed in patients with ACS.

Relationship Between Arterial and Fibrous Cap Remodeling

Background— Positive arterial remodeling and thin fibrous cap are characteristics of rupture-prone or vulnerable plaque. The natural course of the fibrous cap thickness and the relationship between serial arterial remodeling and changes in fibrous cap thickness are unknown. Therefore, the purpose of this study was to evaluate the relationship between changes in fibrous cap thickness and arterial remodeling by using optical coherence tomography (OCT) and intravascular ultrasound (IVUS) during 6-month follow-up. Methods and Results— Both IVUS and OCT examinations were performed on 108 vessels from 36 patients with ischemic heart disease who underwent percutaneous coronary intervention. Fifty-eight fibroatheromas were selected from 82 nonsignificant, nonculprit lesions (angiographic diameter stenosis, 25% to 75%; plaque burden, &gt;40% by IVUS). Fibroatheroma was defined by OCT as lipid-rich plaque in &gt;1 quadrant that has lipid. Thickness of the fibrous cap was measured by OCT. IVUS and OCT examinations were repeated at 6-month follow-up. Serial changes and relationships between IVUS indices and fibrous cap thickness were investigated. Overall, fibrous cap thickness (98.1±38.9 to 96.9±44.5 μm) as well as IVUS indices did not change significantly within 6 months. The percent changes in fibrous cap thickness correlated negatively and significantly ( r =−0.54; P &lt;0.0001; generalized estimating equation adjusted, r =−0.42; P =0.001) with the percent changes in external elastic membrane cross-sectional area. Conclusions— Arterial remodeling is related to changes in fibrous cap thickness. Positive arterial remodeling is not only an adaptive process, but also related to thinning of the fibrous cap.

The Effect of Lipid and Inflammatory Profiles on the Morphological Changes of Lipid-Rich Plaques in Patients With Non–ST-Segment Elevated Acute Coronary Syndrome: Follow-Up Study by Optical Coherence Tomography and Intravascular Ultrasound

The aim of this study was to determine the relationship between the morphological changes of nonculprit lipid-rich plaques and several clinical profiles in patients with non-ST-segment elevated acute coronary syndrome (NSTEACS). Identification of coronary lesion with morphological characteristics of rupture-prone plaques is still difficult. Eighty-two consecutive patients with NSTEACS who underwent percutaneous coronary intervention were enrolled. The changes in total atheroma volume (TAV) of residual nonculprit lipid-rich plaques and the changes in the corresponding fibrous cap thickness (FCT) were assessed by intravascular ultrasound and optical coherence tomography, respectively, at baseline and after 9 months. The percentage changes in TAV (mm(3)) of lipid-rich plaques and in the corresponding FCT (microm) over the 9-month follow-up period were 3.1 +/- 11% and 15 +/- 17%, respectively. There was no significant correlation between the changes in TAV and those in FCT. The change in TAV showed a significant correlation with reduction of the low-density lipoprotein/high-density lipoprotein (LDL/HDL) ratio (r = 0.42, p < 0.01). In contrast, the change in FCT showed no correlation with LDL/HDL ratio but had a significant positive correlation with changes in high-sensitivity C-reactive protein (r = 0.44, p < 0.01). Furthermore, in multivariate logistic analysis, statin use was an independent predictor of changes in well-stabilized plaques that showed both TAV reduction and FCT increase. The changes in TAV and FCT of coronary plaques over a 9-month observation period were related to 2 different independent factors (i.e., reduction of LDL-cholesterol and high-sensitivity C-reactive protein, respectively). Furthermore, lipid-lowering therapy with statin has the potential to stabilize these parameters by both plaque reduction and FCT.

Association of monocyte subset counts with coronary fibrous cap thickness in patients with unstable angina pectoris

Objectives We examined whether distinct monocyte subsets relate in specific ways to coronary fibrous cap thickness (FCT) in patients with unstable angina pectoris (UAP). Methods Forty patients with UAP who underwent percutaneous coronary intervention were enrolled in this study. The changes in the non-culprit FCT were assessed by optical coherence tomography (OCT) at baseline and after 9 months. The distinct monocyte subsets (CD14 +CD16 −CCR2 + and CD14 +CD16 +CX3CR1 +) were measured by flow cytometry. Results The percent change in FCT showed significantly negative correlation with the percent changes in CD14 +CD16 +CX3CR1 + monocytes, but not CD14 +CD16 −CCR2 + monocytes. In addition, the percent change in CD14 +CD16 +CX3CR1 + monocytes was significantly decreased in the group of patients who received statin treatment compared with the group of patients who did not. Of interest, there was a close relationship between CD14 +CD16 +CX3CR1 + monocytes and levels of C-reactive protein, but not lipid profiles, including low-density lipoprotein cholesterol and low-/high-density lipoprotein cholesterol ratio. Conclusions CD14 +CD16 +CX3CR1 + monocytes may have a role in coronary plaque vulnerability.

Abstract 2549: Natural Course of Lipid-rich Plaques Assessed with Combination of Intra-vascular Ultrasound and Optical Coherence Tomography

Background Identification of coronary lesions with morphological characteristic of “rupture-prone plaques” is not sufficient. We examined the natural history of non-culprit lipid-rich plaques in patients with acute coronary syndrome (ACS). Methods Fifty patients with ACS who underwent percutaneous coronary intervention (PCI) were enrolled. We retrospectively assessed the extent of residual non-culprit lipid-rich plaques and these fibrous cap thickness (FCT) by use of intra-vascular ultrasound (IVUS) and optical coherence tomography (OCT), respectively, at baseline and after 9-months. Results During 9 months follow-up periods, the change in percent area volume (PAV) was 0.42±0.6% and the change in FCT was 14±12%. Percent change in PAV showed a significant positive correlation with percent LDL-C reduction (R=0.52, P&lt;0.01). In contrast, the change in FCT demonstrated no correlation with LDL-C level, but had a significant positive correlation with percent change in high sensitive CRP (R=0.60, P&lt;0.01). And between PAV and FCT changes, no significant correlation was observed. Furthermore, in a multivariable analysis including age, sex, diabetes mellitus, hypertension, several concomitant drugs, only statin-use was the independent predictor for changing well-stabilized plaques, which obtained both PAV reduction and FCT increase. Conclusion The change in PAV and in FCT of coronary plaques during 9-months was related to the two different independent factor (reduction rate of LDL-C and high sensitive CRP, respectively). Furthermore, lipid lowering therapy by use of statin has a potential to stabilize them by both plaque reduction and fibrous cap thickening.