Nonstenotic Plaques Research Articles

New Frontiers in the Evaluation of Cardiac Patients for Noncardiac Surgery

New Frontiers in the Evaluation of Cardiac Patients for Noncardiac Surgery

Determinants of Carotid Plaque Occurrence

Background: Increased carotid intima media thickness (CIMT) is frequently associated with established modifiable and non-modifiable cardiovascular risk factors, and is thought to be an independent predictor of ischemic cerebrovascular and cardiac events. The presence of carotid plaque is considered an established feature of atherosclerosis. There exist few longitudinal data on the predictive role of CIMT in the occurrence of carotid plaque. Methods: We restudied the survivors of a cohort of the San Daniele Project, a large randomized general population study, investigated in 1990 regarding the prevalence and determinants of carotid atherosclerosis. Using ultrasonography, we determined in 1,193 subjects (548 men and 645 women), the common carotid IMT and the presence of non-stenotic and stenotic plaque. Results: In 795 subjects without plaques or previous ischemic events at baseline, we found in multivariate analysis that CIMT ≧1 mm, age, hypertension and history of smoking are significant predictive elements of the occurrence of a new carotid plaque. The incremental probability of plaque occurrence is greater in midlife. CIMT and age are the most predictive risk factors with ORs of 3.66 (95% CI 1.4–9.4) and 3.02 (95% CI 2.4–3.7), respectively. The ORs for hypertension and smoking account for 1.5 (95% CI 1.1–3.4) and 1.7 (95% CI 1.1–2.8), respectively. Conclusions: Age, hypertension, history of smoking and B-mode detection of CIMT increases in subjects without carotid atherosclerosis and free of previous vascular events predict the occurrence of carotid atherosclerotic plaque.

Usefulness of Follow-Up Low-Density Lipoprotein Cholesterol Level as an Independent Predictor of Changes of Coronary Atherosclerotic Plaque Size as Determined by Intravascular Ultrasound Analysis After Statin ( Atorvastatin or Simvastatin) Therapy

Using serial intravascular ultrasound (IVUS), we identified independent predictors of changes in coronary plaque size in relation to serum lipid levels. One hundred three patients with nonstenotic coronary plaques underwent baseline and 12-month follow-up IVUS studies; 54 patients (52%) were treated with statins. Standard IVUS analyses were performed. Baseline IVUS study showed no statistical differences in mean external elastic membrane, lumen, and plaque/media (P&M) area between statin-treated and nonstatin-treated patients. Although there was an increase in mean P&M cross-sectional area in nonstatin-treated patients, mean P&M cross-sectional area decreased in statin-treated patients (0.11 +/- 0.24 vs -0.20 +/- 0.30 mm(2), p <0.001). There was a positive relation between changes in mean P&M area and follow-up low-density lipoprotein (LDL) cholesterol level (r = 0.430, p <0.001), follow-up total cholesterol level (r = 0.365, p <0.001), changes in LDL cholesterol level (r = 0.312, p = 0.002), and changes in total cholesterol level (r = 0.252, p = 0.012). In multivariate linear regression analysis, the only independent predictor of changes in mean P&M area was follow-up LDL cholesterol level (r = 0.469, p <0.001, 95% confidence interval 0.003 to 0.006). The cut-off value of follow-up LDL cholesterol for no change or a decrease in mean P&M area was <100 mg/dl at regression analysis. In conclusion, the present 12-month follow-up IVUS study showed that follow-up LDL cholesterol level was the only independent predictor of changes in coronary plaque size. When patients achieved a follow-up LDL cholesterol level <100 mg/dl, regression or no progression of coronary plaque was expected. Aggressive lipid-lowering treatments with statins to decrease the follow-up LDL cholesterol level to <100 mg/dl are recommended.

Visualization of graft patency, anatomical course and nonstenotic plaque texture with multislice CT in patients undergoing redo cardiac surgery – important information for the surgeon?

Objectives: Necessary information, which conventional catheter angiography (CA) can only partially provide, includes the precise course of bypass grafts. Therefore, the aim of the study was to evaluate first the ability of ECG-gated MSCT in preoperative identification of patency, second the anatomical course of coronary bypass grafts and third the plaque composition in atherosclerotic vein grafts with still antegrade flow which were predisposed to embolization.

Identification of Culprit Lesions After Transient Ischemic Attack by Combined 18 F Fluorodeoxyglucose Positron-Emission Tomography and High-Resolution Magnetic Resonance Imaging

Carotid endarterectomy is currently guided by angiographic appearance on the assumption that the most stenotic lesion visible at angiography is likely to be the lesion from which future embolic events will arise. However, risk of plaque rupture, the most common cause of atherosclerosis-related thromboembolism, is dictated by the composition of the plaque, in particular the degree of inflammation. Angiography may, therefore, be an unreliable method of identifying vulnerable plaques. In this study, plaque inflammation was quantified before endarterectomy using the combination of 18F fluorodeoxyglucose positron (FDG)-emission tomography (PET) and high-resolution MRI (HRMRI). Twelve patients, all of whom had suffered a recent transient ischemic attack, had a severe stenosis in the ipsilateral carotid artery, and were awaiting carotid endarterectomy underwent FDG-PET and HRMRI scanning. A semiquantitative estimate of plaque inflammation was calculated for all of the lesions identified on HRMRI. In 7 of 12 patients (58%), high FDG uptake was seen in the lesion targeted for endarterectomy. In the remaining 5 patients, FDG uptake in the targeted lesion was low. In these 5 patients, 3 had nonstenotic lesions identified on HRMRI that exhibited a high level of FDG uptake. All 3 of the highly inflamed nonstenotic lesions were located in a vascular territory compatible with the patients' presenting symptoms. Our data suggest that angiography may not always identify the culprit lesion. Combined FDG-PET and HRMRI can assess the degree of inflammation in stenotic and nonstenotic plaques and could potentially be used to identify lesions responsible for embolic events.

Wall shear stress is lower in the carotid artery responsible for a unilateral ischemic stroke

According to the focal nature of atherosclerosis, ischemic stroke is frequently unilateral. Atherosclerotic plaques are favoured by local hemodynamic factors as low wall shear stress and/or elevated circumferential wall tension. Aim of the present study was to investigate the possible association between hemodynamic forces and cerebrovascular disease. Common carotid mean wall shear stress and circumferential wall tension, Peterson's elastic modulus, and blood flow were measured in 25 patients with a recent unilateral large-artery stroke presenting non-stenotic plaques of the carotid arteries (large-artery group), and in 10 patients affected by a recent unilateral cardioembolic stroke without carotid plaques (cardioembolic group). In the large-artery group, atherosclerosis was slightly more evident in the side of cerebral ischemia. All hemodynamic factors were more unfavourable at the affected side in this group (shear stress: 6.2 ± 3.0 versus 8.6 ± 4.0 dynes/cm 2, p < 0.0001; wall tension: (7.3 ± 1.3) × 10 4 versus (6.6 ± 1.3) × 10 4 dynes/cm, p < 0.00001; Peterson's modulus: (16.8 ± 11.9) × 10 5 versus (12.4 ± 5.7) × 10 5 dynes/cm 2, p = 0.06). No difference was detectable in blood flow and in cardioembolic group. The present data demonstrate an unfavourable hemodynamic profile in the common carotid artery supplying the area of a single large-artery stroke and might help to explain the frequent one-sidedness of this disease.

Pathophysiology of Coronary Artery Disease

During the past decade, our understanding of the pathophysiology of coronary artery disease (CAD) has undergone a remarkable evolution. We review here how these advances have altered our concepts of and clinical approaches to both the chronic and acute phases of CAD. Previously considered a cholesterol storage disease, we currently view atherosclerosis as an inflammatory disorder. The appreciation of arterial remodeling (compensatory enlargement) has expanded attention beyond stenoses evident by angiography to encompass the biology of nonstenotic plaques. Revascularization effectively relieves ischemia, but we now recognize the need to attend to nonobstructive lesions as well. Aggressive management of modifiable risk factors reduces cardiovascular events and should accompany appropriate revascularization. We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a "solid-state" stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the "fluid phase" of the blood can also predispose toward ACS. Recent results have established the multiplicity of "high-risk" plaques and the widespread nature of inflammation in patients prone to develop ACS. These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid "stabilization" of other plaques that may produce recurrent events. The concept of "interventional cardiology" must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.

58-Year Old Men with Non-Stenotic Carotid Artery Plaques and the Relationship with Cardiovascular Risk Factors and Future Cardiovascular Events

58-Year Old Men with Non-Stenotic Carotid Artery Plaques and the Relationship with Cardiovascular Risk Factors and Future Cardiovascular Events

Non-stenotic echolucent ultrasound-assessed femoral artery plaques are predictive for future cardiovascular events in middle-aged men

Objectives: The aim of the present study was to examine the relationship between plaque occurrence, plaque size and plaque echogenicity, assessed by B-mode ultrasound, in the femoral artery and the development of clinical cardiovascular disease. Background: The relationship between carotid atherosclerosis assessed by B-mode ultrasound and cardiovascular disease has been thoroughly investigated. In comparison, the femoral arteries have received much less attention. Methods: The femoral artery was examined by high-resolution B-mode ultrasound in 391, 58-year-old men identified by screening in the city of Göteborg, Sweden. Assessment of plaque occurrence, plaque size (no, small, or moderate/large) and plaque characteristics in terms of echogenicity (no, echogenic or echolucent) were performed. Results: Subjects with a plaque present in the femoral artery at study baseline had a three-fold increase in odds ratio (OR 3.04, 95%, CI 1.24–7.42) for having a cardiovascular event during 6.6 years of follow-up compared to subjects without plaque. After adjustment for cardiovascular risk factors (LDL, triglycerides, systolic blood pressure and smoking) there was a borderline significant association between plaque occurrence and cardiovascular disease (OR = 2.64, p = 0.055). Plaque size could be demonstrated to be associated with cardiovascular events ( p = 0.012, for trend). The results also showed that in this group of men, the risk of having a cardiovascular event was to a large extent confined to those with an echolucent plaque at baseline. However, no significant difference in risk prediction was seen between echogenic and echolucent plaques, respectively. Conclusions: This is the first study to show that the presence of non-stenotic plaques in the femoral artery in middle-aged men without prior cardiovascular events has a predictive value for future cardiovascular events. The relationship was attenuated by adjustment for traditional cardiovascular risk factors. Data also indicates that plaque echolucency predicts increased risk.

Role of apoptosis in atherosclerosis and its therapeutic implications.

Atherosclerotic plaques develop as a consequence of the accumulation of circulating lipid and the subsequent migration of inflammatory cells (macrophages and T-lymphocytes) and VSMCs (vascular smooth muscle cells). Advanced plaques consist of a lipid-rich core, separated from the lumen by a fibrous cap composed of VSMCs, collagen and extracellular matrix. Plaque enlargement ultimately narrows the lumen (stenosis) causing angina. However, recent studies have emphasized that acute coronary syndromes (unstable angina/myocardial infarction) are caused by lesion erosion/rupture with superimposed thrombus formation on often small non-stenotic plaques. Thus current therapies work predominantly on stabilization of plaques rather than plaque regression. Apoptosis (programmed cell death) is increasingly observed as plaques develop, although the exact mechanisms and consequences of apoptosis in the development and progression of atherosclerosis are still controversial. Increased endothelial cell apoptosis may initiate atherosclerosis, whereas apoptosis of VSMCs and macrophages localizes in 'vulnerable' lesions, i.e. those most likely to rupture, and at sites of rupture. This review will focus on the regulation of apoptosis of cells within the vasculature, concentrating on the relevance of apoptosis to plaque progression and clinical consequences of vascular cell apoptosis.

Characterization of vulnerable nonstenotic plaque with 16-Slice computed tomography compared with intravascular ultrasound

We compared 16-slice computed tomography with intravascular ultrasound in the detection of unstable component characteristics of nonstenotic plaque responsible for acute coronary syndrome. Computed tomography accurately assessed plaque eccentricity, calcification, and remodeling, and intraplaque hypodensity correlated with intravascular ultrasound echolucent area.

M.650 Non-stenotic echolucent plaques in the carotid arteries in clinically healthy, 58-year old men predict cardiovascular events

M.650 Non-stenotic echolucent plaques in the carotid arteries in clinically healthy, 58-year old men predict cardiovascular events

M.650 Non-stenotic echolucent plaques in the carotid arteries in clinically healthy, 58-year old men predict cardiovascular events

M.650 Non-stenotic echolucent plaques in the carotid arteries in clinically healthy, 58-year old men predict cardiovascular events

Prevalence of diabetes and/or ischaemic heart disease in classes of increasing carotid artery atherosclerosis: an ultrasonographic study.

To evaluate the prevalence of non-diabetic subjects and diabetic patients, with or without ischaemic heart disease (IHD), in different classes of increasing carotid atherosclerotic damage. Using high-resolution B-mode ultrasound, we studied 598 subjects without known cardiovascular disease (CVD) or diabetes, 74 diabetic patients without CVD, 74 non-diabetic subjects with IHD and 36 patients with both diabetes and IHD. Carotid atherosclerosis was classified as: normal; thickened intima-media; non-stenotic plaque; stenotic plaque. Compared with subjects without diabetes or CVD, the frequency of patients with diabetes without known CVD increased significantly from 'normal' to 'stenotic plaque' (4.1%, 6.4%, 13%, 14.8% for normal, thickened intima-media, non-stenotic plaque and stenotic plaque, respectively; P = 0.0057). The same figures were 6%, 7.6%, 10.2%, 23.3% (P = 0.0007) for non-diabetic subjects with IHD, and 0%, 2%, 5.6%, 15.9% (P < 0.0001) for diabetic patients with IHD. No difference was found comparing subjects with diabetes without CVD with non-diabetic patients with IHD (P = 0.56). Using polychotomous logistic regression analysis, diabetic patients without CVD and non-diabetic subjects with IHD showed a similar association with the increasing degree of carotid atherosclerosis (P = 0.59), but significantly stronger compared with subjects without diabetes or CVD (P < 0.03 for both). Diabetic patients without known CVD show an advanced degree of carotid atherosclerotic damage similar to non-diabetic subjects with IHD and significantly higher compared with non-diabetic subjects without CVD. Our data support the need for an aggressive early prevention of CVD in diabetic subjects.

Active and passive smoking, chronic infections, and the risk of carotid atherosclerosis: prospective results from the Bruneck Study.

Susceptibility of the vasculature to the injurious effects of smoking varies substantially, with some smokers developing severe premature atherosclerosis and others remaining free of advanced atheroma until high ages. The present study sought to estimate the contribution of chronic infections to the variability of atherosclerosis severity among smokers. In the community-based Bruneck Study, 5-year changes in carotid atherosclerosis were assessed by high-resolution ultrasound. Early atherogenesis was defined by the development of nonstenotic plaques and advanced atherogenesis by the development/progression of vessel stenosis >40%. The risk of early atherogenesis strongly relied on lifetime smoking exposure and remained elevated long-term after cessation of smoking. Remarkably, current and ex-smokers faced an increased atherosclerosis risk only in the presence of chronic infections (odds ratios [95% CIs], 3.3 [1.8 to 6.2] and 3.4 [1.8 to 6.3]; P<0.001 each), whereas current, past, and nonsmokers without infections did not differ substantially in their estimated risk burden (odds ratios [95% CIs], 1.4 [0.8 to 2.4], 0.9 [0.6 to 1.6], and 1.0 [reference group]). In analogy to first-hand smoking, subjects exposed to environmental tobacco smoke were found to be vulnerable to the manifestation of chronic infection, and only those infected experienced a high atherosclerosis risk. The risk of advanced atherogenesis showed a dose-response relation with the number of daily cigarettes, returned to normal shortly after cessation of smoking, and emerged as independent of infectious illness. Our study provides the first epidemiological evidence that the proatherogenic effects of cigarette smoking are mediated in part by the chronic infections found in smokers. A better understanding of the vascular pathogenetic mechanisms of smoking may offer novel clues for disease prevention supplementary to the primary goal of achieving long-term abstinence.

Interaction of workplace demands and cardiovascular reactivity in progression of carotid atherosclerosis: population based study

Objective: To examine the combined influence of workplace demands and changes in blood pressure induced by stress on the progression of carotid atherosclerosis.Design: Population based follow up study of unestablished...

Socioeconomic Status and Carotid Atherosclerosis

There is a consistent body of evidence that socioeconomic status (SES) is importantly associated with cardiovascular morbidity and mortality. However, little information currently exists on the relationship between SES and early manifestations of atherosclerotic vascular disease. We investigated the association between education, income, and occupation and intima-media thickness (IMT) in a population-based sample of eastern Finnish men. Data from the Kuopio Ischemic Heart Disease Risk Factor Study were used to estimate mean IMT across levels of SES in 1140 men. The association between SES and IMT was examined in relation to atherosclerotic risk factors and was also stratified by degree of atherosclerotic progression and was also stratified by degree of atherosclerotic progression and prevalent cardiovascular disease. There were significant, inverse, graded differences between levels of SES and IMT. For education, the age-adjusted mean IMTs for those with primary schooling or less, some high school, and completed high school or more were 0.96, 0.94, and 0.82 mm, respectively. The difference in mean IMT between the most extreme categories of education corresponds to a 15.4% increase in the risk of myocardial infarction. Similar patterns were found for each measure of SES, although the differences between the highest and lowest levels of SES were attenuated by adjustment for risk factors. In men who had no carotid stenosis or nonstenotic plaque and in men who had no indication of prevalent cardiovascular disease, a graded, inverse association between SES and IMT persisted, even after risk factor adjustment. These findings demonstrate a strong association between SES and atherosclerosis in an unselected population. The results show that this association was mediated by known atherosclerotic risk factors, was evident in the early stages of atherosclerosis, and was apparent in a healthy subgroup. Our findings suggest that the impact of SES is evident early in the natural history of atherosclerotic vascular disease.

Embolus detection in different degrees of carotid disease

Carotid atherosclerotic disease is a major source for artery to artery embolism. Stroke incidence highly depends on the degree of carotid stenosis. TCD monitoring for embolic signals may help to identify patients at high risk for an impeding stroke. This study was performed to correlate the degree of carotid stenosis with the occurrence of embolic signals and the clinical outcome. We performed a bilateral simultaneous TCD study on 4 patient groups with unilateral atherosclerotic disease: We studied patients with non-stenotic ICA plaques (n = 21), 50-75% ICA stenosis (n = 20), 75-95% stenosis (n = 22), and occlusion (n = 13). Minimum insonation time was 45 minutes. Embolic signals were not detected in the control group and patients with a non-stenotic ICA lesion, but in 10% of the patients with 50-75% stenosis, 22% of the patients with a high grade stenosis and 39% of the patients with an ICA occlusion. There is a high specificity (92%) and rather low sensitivity (29%) of these microemboli for past clinical events. The occurrence of embolic signals correlated (p < 0.005) with a history of stroke, TIA or RIND. Microemboli detection may be a valuable tool to identify high risk patients.

Cerebral vasocapacitance in human aging.

To show a relationship between age and cerebral blood flow as well as between age and cerebral vasocapacitance to induced hypercapnia or cerebral reserve percentage, positron emission tomography (PET) with fluorine-18-fluoromethane was used to study 36 normal subjects and 36 patients, all free of stroke, who presented with transient ischemic attacks in a unilateral carotid distribution. Symptomatic-side data have been published elsewhere. All asymptomatic carotid arteries were either normal or had nonstenotic plaque, and subjects were free of intracranial stenoses. Cerebral blood flow and cerebral reserve percentage were calculated for both middle cerebral artery flow territories. Serum hematocrit, expired carbon dioxide tension, and mean arterial blood pressure did not distinguish the two groups of patients or show an age effect. For the 72 normal nonstenotic sides in the volunteers, linear regression showed that while increasing age was significantly related to decreasing cerebral blood flow in the middle cerebral artery, there was no particular relationship between age and decreasing cerebral reserve percentage. In patients, while no overwhelming linear relationships were found between age and decreases in either cerebral blood flow or cerebral reserve percentage, the latter values approached significance as declining cerebral reserve percentage did relate to increasing age. Over a 60-year range in normal subjects, cerebral blood flow declined 37% with age; there was a 21% age-related decrease when normal subjects 50 years and younger were compared to those 50 years and older.(ABSTRACT TRUNCATED AT 250 WORDS)

Biologic characteristics of long-term autogenous vein grafts: a dynamic evolution.

The venous conduit as an arterial substitute has dynamic biologic properties that affect its durability. This study evaluated the morphologic and physiologic characteristics of 72 lower extremity vein grafts functioning at 4.5 to 21.6 years (median 6.6 years). The entire graft was imaged with use of color duplex ultrasonography and then classified as normal (class I), abnormal but not graft-threatening (class II), or abnormal and graft-threatening (class III) for the proximal, middle, and distal thirds. Thirty-one grafts (43%) were classified as normal, whereas 41 (57%) were classified as abnormal, with 58 class II and 15 class III segments. Three types of abnormalities were found by duplex imaging: nonstenotic wall plaques, discrete stenoses, and aneurysmal dilation. Aneurysms developed in five of seven grafts that had required thrombectomy in the distant past (mean of 40 months). There were 70 postoperative revisions in 38 limbs (53%). In 23 (60%) the conduit was revised, in 11 (29%) the revisions corrected progression of native artery atherosclerotic disease, and in 4 (11%) both types of revisions were required. Eleven grafts were revised in the first 30 days to correct technical errors. Eighteen limbs were revised between 1 and 24 months, with 12 (67%) of the revisions correcting stenotic lesions in the conduit or at one of the anastomoses. After 24 months 12 (67%) of 18 limbs were revised to correct progression of occlusive disease in the inflow or outflow vessels. At the time of this study 18 (67%) of the 27 conduits revised for intrinsic lesions were abnormal by color duplex imaging, and they harbored 12 (80%) of the 15-graft-threatening lesions. Autogenous vein remains the most durable arterial conduit, but vigilant surveillance is essential because the atherosclerotic environment continually produces lesions that may imperil the longevity of the graft.