Intimal Thickening Of Coronary Arteries Research Articles

Identification of clinical risk factors for coronary artery lesions in children with Kawasaki disease: a retrospective cohort study.

Coronary artery lesions are the most severe complications of Kawasaki disease. Despite recent advances, evidence of the association between risk factors and coronary artery lesion is lacking. In this study, we demonstrated the potential clinical indicators that could assist to evaluate the prevalence of coronary artery lesion among paediatric patients with Kawasaki disease. We retrospectively enrolled 260 paediatric patients with Kawasaki disease. Patients with coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries were included in this study. Medical records of each patient were collected. Logistic regression analysis was performed to explore risk factors and the occurrence of coronary artery lesion in patients with Kawasaki disease. Respectively, 64 (24.6%), 39 (15%), and 56 patients (21.5%) of the participants had coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries. Univariate analysis revealed that age, gender, duration of fever, time of initial use of intravenous immunoglobulin, erythrocyte sedimentation rate, white blood cell counts, time of platelet increase, the maximum value of platelet, albumin, and immunoglobulin G level was associated with coronary artery lesion. In multivariable logistic analysis, those younger and mainly males were associated with all three outcomes of coronary artery lesion, lower serum albumin levels, and later initial use of intravenous immunoglobulin were linked to a higher risk of coronary dilation and coronary aneurysm. The potential risk factors that could be used to estimate the occurrence of coronary artery lesion in Kawasaki disease patients are young age, male, lower serum albumin lever, and later initial use of intravenous immunoglobulin. However, long-term follow-up and multi-centre studies are required to verify our findings in the future.

Vasa vasorum enhancement on optical coherence tomography in Kawasaki disease.

Patients with Kawasaki disease (KD) prone to develop coronary artery aneurysm (CAA) with unknown etiology. We aimed to disclose the relationship between vasa vasorum (VV) and intimal thickening using optical coherence tomography (OCT) in KD. Forty-three coronary artery branches of 21 patients with KD were examined by OCT. The coronary arteries were classified into three groups: the CAA group (n = 9) in which CAAs remained since the acute phase, the regressed group (n = 16) in which CAAs were regressed, and the no CAA group (n = 18). The number and distribution of VV, and intimal thickening in coronary arteries were evaluated on OCT. Intimal thickening was significantly more severe in the CAA and regressed groups than in the no CAA group (median: 481, 474, and 218 μm, p = 0.001 and p < 0.001, respectively). The number of VV in the regressed group was significantly higher than that in the CAA and no CAA groups. The numbers of adventitial VV and internal VV were positively correlated with the intimal thickness (R = 0.64, p < 0.001; R = 0.62, p < 0.001, respectively). In the no CAA group, no internal VV were observed. VV enhances according to intimal thickening, suggesting that VV may have some link to the healing process, such as CAA regression and intimal thickening. Kawasaki disease (KD) is a vasculitis syndrome developing coronary artery aneurysm, however its etiology still remains unclear. Coronary artery imaging using optical coherence tomography (OCT) can reveal coronary arterial wall pathology, however OCT studies are limited in patients with KD. Using OCT, we disclosed the closed relationship between vasa vasorum enhancement and regressed coronary arterial lesions. Vasa vasorum enhancement is involved in the pathomechanism of the convalescent phase of KD.

Myocardial Bridge and Atherosclerosis, an Intimal Relationship.

This review investigates the relationship between myocardial bridges (MBs), intimal thickening in coronary arteries, and Atherosclerotic cardiovascular disease. It focuses on the role of mechanical forces, such as circumferential strain, in arterial wall remodeling and aims to clarify how MBs affect coronary artery pathology. MBs have been identified as influential in modulating coronary artery intimal thickness, demonstrating a protective effect against thickening within the MB segment and an increase in thickness proximal to the MB. This is attributed to changes in mechanical stress and hemodynamics. Research involving arterial hypertension models and vein graft disease has underscored the importance of circumferential strain in vascular remodeling and intimal hyperplasia. Understanding the complex dynamics between MBs, mechanical strain, and vascular remodeling is crucial for advancing our knowledge of coronary artery disease mechanisms. This could lead to improved management strategies for cardiovascular diseases, highlighting the need for further research into MB-related vascular changes.

OPTICAL COHERENCE TOMOGRAPHY IN CHILDREN: DEVELOPMENT OF A PROTOCOL FOR THE STANDARDIZED QUANTITATIVE ANALYSIS OF CORONARY ARTERIES

Optical coherence tomography (OCT) is a high-resolution intravascular imaging technique that has shown promise for the early detection of intimal thickening of coronary arteries in pediatric heart transplant recipients. The potential utility of OCT as a diagnostic and/or prognostic tool is currently unclear due to a lack of a standardized approach to analyse OCT images in this population. We established the OCT Core Imaging Laboratory at BC Children’s Hospital to develop a standardized protocol for the quantitative analysis of OCT images. Our study population included n=30 pediatric cardiac transplant recipients who had OCT imaging of the coronary arteries performed as part of standard of care at BC Children’s Hospital (St Jude Medical, now Abbott). We deemed a ‘pullback’ analyzable if ≥10mm of the segment was of good image quality (defined as ≥75% of cross-section visible without artifact). We evenly selected 10-20 cross-sectional frames ≥1 mm apart, avoiding bifurcations. Using the device-manufacturer’s software, we applied digital planimetry to trace the lumen-intima border, the internal elastic lamina, and the external elastic lamina for each cross-sectional frame. Cross-sectional areas (CSA, mm2) were derived for the lumen, the intima and the media; maximal intimal thickness (mm) was defined as the widest point between the circular markers for the intima and media. We calculated the intima/media (I/M) CSA ratio. For each pullback, we derived summary values from cross-sectional frames for relevant variables as means, medians, 95th percentile (p95) and maximal values. We performed inter-rater and intra-rater reliability analyses by intra-class correlation coefficients and Bland-Atman Analyses. Overall, 82% of analyzable pullbacks met inclusion criteria for our protocol (≥10-20 frames, ≥1 mm apart), resulting in 67 pullbacks from 28 patients analysed. The right coronary artery was most frequently imaged (58%), and more often met inclusion criteria for quantitative analyses (85% vs. 82% overall). Mean vs. median and max vs. p95 summary statistics yielded very similar values for I/M CSA and maximal intimal thickness (all ICC>0.98; difference < 3%), suggesting our protocol provides robust summary values. We registered excellent inter-rater and intra-rater reliability for I/M CSA and maximal intimal thickness (all ICC>0.95; difference < 5%). We provide a systematically developed and rigorously tested protocol for the quantitative analysis of OCT images in children. The novel application of OCT to a pediatric population requires expert image analysis and has the potential to improve the care of pediatric transplant patients who are at risk of structural coronary changes.

Intimal thickening of coronary arteries in the rabbitfish, Chimaera monstrosa L. (Chondrichthyes: Holocephali)

This study is the first to report the occurrence of intimal thickening of coronary arteries in a holocephalan, namely the rabbitfish, Chimaera monstrosa. The sample studied consisted of five hearts from rabbitfish with body weights ranging between 12 g and 1116 g. The specimens were fixed in formalin, in methanol:acetone:water (MAW), or in paraformaldehyde and were examined by brightfield and polarization light microscopy. Coronary arteries from three larger animals displayed focal intimal thickenings, which were located in the left main coronary artery trunk, at the level of the cono-ventricular junction, and in several intramyocardial ventricular arteries. The vascular changes were characterized by myointimal proliferation, breakage or absence of the inner elastic lamina, and, in one case, by increased collagen within the myointimal proliferation. Taking into account the severity of the coronary arterial changes, their location, and the body weight of the affected animals, we conclude that (1) these changes are age-related in the rabbitfish and (2) local intense mechanical tension seems to be an important factor in their formation in this species.

Development of intimal thickening of coronary arteries over the lifetime of Atlantic salmon, Salmo salar L., fed different lipid sources

The objective of the present study was to investigate the development of intimal changes of coronary arteries over the lifetime of farmed Atlantic salmon, Salmo salar L., fed either a 100% fish oil or a 100% vegetable oil blend. The study was performed as a randomized observer blinded controlled trial with parallel group design. At the start of the project, the fish were divided in two groups and sampled at five different time points throughout their life span. The total study sample consisted of 259 healthy fish. Serial sections were taken from the coronary artery lying on the bulbus arteriosus for histopathological evaluation and for area measurements using semi-quantitative and quantitative methods. The earliest onset of vascular changes was detected in fish from both groups in the freshwater stage prior to smoltification. The mean range lesion (MRL), used to describe the severity of the lesions observed, increased significantly for both groups from sea transfer throughout the study period. Comparison of the two groups based on the overall material corrected for time of sampling did not show any difference (P = 0.20) between the two groups with regard to MRL. The percentage lumen loss (PLL) measured by a quantitative method and used as a measure to indicate lesion severity showed an incremental, non-significant increase from week 72 to week 92 and further to week 115 in both diet groups during the seawater phase. Comparison of the groups corrected for time of sampling indicated a difference of PLL in favour of VO (P = 0.02). Heart weight, body weight and body length were all positively and significantly correlated to Log MRL. The partial correlation analysis indicated that heart weight was the most dominant variable in the set. Early vascular changes were found in the major bifurcation of the coronary artery at the apex and beyond the flow divider into the daughter branches. The latter represented the dominant changes and were found throughout the entire lifecycle of the fish. Increasing in size over time they formed pads or cushions that were regularly located close to the outer walls of the bifurcation. The origin of the cells forming the intimal thickening has not been conclusively determined, but immunohistochemical findings indicate a smooth muscle cell origin, possibly of a myointimal type. Our findings suggest there is no correlation between diet and intimal changes. The severity of the changes, MRL and PLL, of the coronary vessels correlate with heart weight and fish weight growth and growth rate and mechanical factors are implicated in intimal development, but rather than being induced by external injury due to the location of the coronaries, haemodynamic factors and low shear stress are proposed as the main mechanism behind these changes.

Cardiac Allograft Vasculopathy after Cardiac Transplantation and Hormone Therapy: Positive Effects?

There is a great deal of controversy surrounding the issue of hormone replacement therapy after transplantation. The question whether or not this therapy has effects in cardiac allograft vasculopathy (CAV), the Achilles heel of cardiac transplantation or other unique aspects of allograft function is still unknown. We investigated the long-term effect of 17beta-estradiol as well as phytoestrogen Coumestrol, a synthetically produced phytoestrogen, on the development of CAV and the degree of fibrosis in an ovariectomized female heterotopic chronic allograft model (LEW-F344). We found that, 150 days after transplantation, no significant effect of estrogen application on intimal thickening of coronary arteries was observed. 17beta-estradiol and phytoestrogen Coumestrol did significantly reduce the perivascular immune reaction. However, the immune effect had no consequence on the intensity of CAV. Although neither 17beta-estradiol nor phytoestrogen Coumestrol revealed a positive effect on CAV, the group of animals treated with 17beta-estradiol showed the highest decline in heart function and the most distinct fibrosis. 17beta-estradiol does not affect CAV positively, but worsens cardiac allograft function and leads to increased fibrosis. This is the first study showing a negative effect of 17-beta-estradiol after heart transplantation in the long term.

Egr-1 in vascular smooth muscle cell proliferation in response to allo-antigen

Background Early growth response factor-1 (Egr-1) plays an important role in regulating multiple factors involved in the progression of vascular lesions. This study examined our hypothesis that Egr-1 plays a critical role in the early stage of chronic cardiac allograft rejection and in the proliferation of the smooth muscle cell response to alloantigen. Materials and methods Antisense Egr-1 oligodeoxynucleotide (ODN) was ex vivo gene transfected into the donor hearts from DBA/2 mice, followed by heterotopic allografting into B10.D2 recipients. The allografts were harvested on day 30. Egr-1 and its target molecules, such as platelet-derived growth factor (PDGF)-A, basic fibroblastic growth factor (bFGF), vascular cell adhesion molecule (VCAM)-1, transforming growth factor (TGF)-β and nonmuscle myosin heavy chain B (SMemb), were identified immunohistochemically, and the percentage of the lumen occluded by the intima was calculated. For the cell proliferation assay, sensitized T cells were harvested from B10.D2 recipients as stimulator and then added to the SMCs, which were harvested from DBA/2 mouse aorta. Cellular proliferation was measured and Egr-1 and its target gene expression were examined by real-time RT-PCR. Results Egr-1 and its target genes were expressed in the thickened intima from untreated recipients. Egr-1 antisense ODN inhibited not only Egr-1 expression but also its target genes and significantly suppressed intimal thickening of coronary arteries. Egr-1 antisense ODN also significantly inhibited cell proliferation and expressions of Egr-1 and Egr-1 target genes in a mixed cell culture model. Conclusion We conclude that Egr-1 plays an important role in the formation of the cardiac allograft vasculopathy responding to alloantigens.

Diffuse intimal thickening of coronary arteries in slow coronary flow.

Intravascular ultrasound imaging can detect intimal thickening and is suitable for detection of early atherosclerosis, which cannot be detected by conventional angiography. The aim of the present study was to investigate the epicardial coronary morphology and intracoronary pressure in relation to slow coronary flow (SCF). The study population consisted of 19 patients with SCF [11 (57.9%) females; 55.95 +/- 9.42 years]. Proximal, middle, distal and mean total vessel area, lumen area, intima + media area (IMA), percent IMA, and maximal intima + media (I + M) thickness were calculated and compared to healthy subjects. Proximal, middle, distal and mean I + M thickness, IMA, and % IMA of patients with SCF were found to be significantly higher than those of control subjects. Longitudinally extended massive calcification throughout the epicardial arteries was found in 13 (68.49%) patients with SCF and regional calcification was found in 6 (31.6%) patients with SCF. Proximal and distal pressure gradients of patients with SCF were determined to be 15.84 +/- 12.11 mmHg in the intracoronary pressure measurements. Fractional flow reserve values were significantly lower than the normal population (0.83 +/- 0.13, P < 0.0001). This study indicates that patients with SCF have diffuse intimal thickening, widespread calcification along the vessel wall and atheroma which does not cause luminal irregularities in coronary angiography, and a pressure gradient between proximal and distal segments of epicardial coronary arteries with SCF. Based on these results, we believe that SCF may be a form of diffuse atherosclerosis involving both the microvascular system and epicardial coronary arteries.

Relation Between Vascular Resistance and Intimal Thickness in Patients with Coronary Artery Disease

Background:The intimal thickening of coronary artery was understood as an early process in the beginning of atherosclerosis. However, the implication of intimal thickening as a morphologic change of coronary artery disease, on the coronary vascular hemodynamics has not been explored. Methods:To evaluate the effect of intimal thickening on the coronary vascular hemodynamics, we studied the extent of intimal thickening on intravascular ultrasound (IVUS) and the coronary vascular flow and resistance by using Doppler wire in left anterior descending coronary arteries after successful intervention in 40 patients (29 males, mean age 55±9 years) with coronary artery disease. Mean intimal index and mean lumen cross sectional area were determined by IVUS and coronary flow average peak velocity was obtained by using Doppler wire before and after intracoronary adenosine in distal artery to the stenosis. Coronary flow velocity reserve (CFR), volumetric coronary blood flow (CBF) and coronary vascular resistance index (CVRI) were calculated. Hyperemic pressureto-flow ratio (hyperemic mean aortic pressure/hyperemic volumetric coronary blood flow), ie, an index of minimal coronary vascular resistance (mCVR), was further derived. Results:Intimal index (mean 20.0± 8.3%) was significantly correlated with CVRI (mean 0.33±0.14, r=0.37, p=0.02) and mCVR (mean 0.81± 0.40 mmHg/ml/min, r=0.36, p=0.02). However, there was no correlation with CBF and CFR. Conclusion: The CVRI and mCVR, the indices coronary microvascular resistance, were significantly related to the degree of intimal thickness of coronary artery. The extent of intimal thickness of coronary artery on IVUS study may be related to microvascular integrity. (Korean Circulation J 2001;31(1):54-62)

Diffuse intimal thickening of coronary arteries in patients with coronary spastic angina

OBJECTIVESThe purpose of this study was to evaluate the extent of atherosclerotic changes in angiographically normal coronary arteries using intravascular ultrasound (IVUS) technique in patients with coronary spastic angina.BACKGROUNDNitric oxide activity was shown to be decreased in coronary arteries of patients with coronary spastic angina (CSA). Decrease in nitric oxide causes arterial intimal hyperplasia or thickening. However, it remains unclear whether intimal thickening is diffusely present in coronary arteries of patients with CSA.METHODSThe IVUS study was performed in 26 patients with CSA and with normal coronary angiograms and in 31 control subjects in whom age and gender was matched with those in patients with CSA.RESULTSCompared with control subjects, patients with CSA had significantly larger percent intima + media area (%I + M area), intima + media area and maximal intima + media thickness in all of proximal, middle and distal segments (p < 0.01, respectively). Lumen area was comparable between these groups. The presence of spasm was the most powerful independent predictor of increase in percent intima + media area, in multiple-regression analysis with the traditional risk factors as covariates.CONCLUSIONSIntimal thickening existed entirely in a coronary artery in patients with CSA and with normal angiograms, independently of other traditional risk factors. The diffuse intimal thickening in the spasm coronary arteries is intimately related with coronary spasm.

An aldose redutase inhibitor prevents the intimal thickening in coronary arteries of galactose-fed beagle dogs.

Although increased polyol pathway activity has been implicated in the pathogenesis of diabetic microangiopathy, the relation with diabetic macroangiopathy remains unclear. Galactose feeding is known to stimulate the polyol pathway and to develop abnormalities similar to those in diabetic microangiopathy. Our study was conducted to investigate whether an activation of polyol pathway by long-term treatment with galactose produced morphological changes in coronary arteries of dogs and the effect of an aldose reductase inhibitor, epalrestat, was also studied. Dogs received either normal chow or chow containing 30% galactose with or without epalrestat given orally (20 or 50 mg x kg(-1)). After 44 months, morphometric analyses of coronary arteries were carried out and the galactitol contents in aortas were measured. The ratio of areas of the intimal layer to those of the medial layer, an indicator of intimal thickening, was statistically significantly increased in galactose-fed dogs compared with control dogs. Galactose-fed dogs had a remarkable accumulation of galactitol in their aortas. These morphological and biochemical deficits were reduced by treatment with epalrestat. This report morphologically shows diabetes-like macrovascular abnormalities in galactosaemic animals, suggesting that polyol pathway hyperactivity is closely related to the development of diabetic macroangiopathy, which could be prevented by aldose reductase inhibition.

784-3 Prognostic Significance of Intimal Thickening Detected by Intracoronary Ultrasound in Heart Transplant Recipients

Intracoronary ultrasound (ICUS) is a sensitive tool for the detection of intimal thickening in coronary arteries of heart transplants recipients. However, the prognostic significance of this intimal thickening has not been proven. During a one year period, 90 transplant recipients had ICUS examination at the time of their annual angiogram. For each ICUS study an intimal index (II), defined as the ratio of the plaque area to the area within the media, was measured for the most diseased segment imaged. The angiogram at the time of ICUS was reviewed for the presence of visually apparent coronary artery disease (V-CADI· Those patients (n = 19) with V-CAD present at the time of ICUS were excluded from the study. The time since transplantation for the 71 pts without V-CAD ranged from 1 to 15 yrs, with a mean of 4.2 yrs and median of 3.9 yrs. The subsequent annual follow-up angiograms of the 71 patients without V-CAD at the time of ICUS were reviewed for the development of V-CAD. Mean duration of angiographic follow-up was 2.0 yrs (range 1–3 yrs). V-CAD developed on follow-up angiograms in 13 of the 71 pts. Mean time to development of V-CAD was 1.5 yrs. Forty-six patients had II &lt; 0.3, 4 (9%) of whom subsequently developed V-CAD. Twenty-five patients had II ≥ 0.3, 9 (36%) of whom developed V-CAD. Odds ratio for future V-CAD between pts with II &lt; 0.3 and II 2: 0.3 was 5.9 (95% CI 1.8 to 19.0, difference significant at p &lt; 0.01 by Fisher's Exact test). In a subgroup of 22 patients more than 5 years post transplantation at the time of ICUS, 12 had II &lt; 0.3 and 10 had II 2 ≥ 0.3. In this subgroup none of the 12 pts with II &lt; 0.3 developed V-CAD and only 1 of the 10 with II &gt; 0.3 developed V-CAD (difference not significant). Conclusion — Among patients more than 1 year and less than 5 years post-transplantation without visually apparent angiographic coronary artery disease, the presence of moderate to severe intimal thickening by ICUS is predictive of the future development of angiographically apparent CAD. Intimal thickening as detected by ICUS is of prognostic significance in patients with angiographically silent transplant coronary artery disease.

体位強制による動脈硬化症(予報)

Wistar rats were placed in an orthostatic state 3 hours every day for 11 months.Arteriosclerotic intimal thickening of the small coronary arteries accompanied by small infarctions of the myocardium were detected. Neither necrotic nor PN-like lesions were seen.Blood pressure increased gradually and showed levels of 180mmHg at the end of the experiment.Further studies are necessary to determine the cause of intimal thickening of coronary arteries, that is, whether it derives from orthostatic circulation or from a hypertensive condition following orthostatic experiment.