Evidence of a chronic systemic cause of instability of atherosclerotic plaques - ScienceDirect

The Lancet

Volume 355, Issue 9197, 1 January 2000, Pages 19-24

The Lancet

https://doi.org/10.1016/S0140-6736(99)04470-0 Get rights and content

Summary

Background

Major thrombotic and embolic complications of atherosclerosis are closely associated with irregularity and rupture of atheromatous plaques in both the carotid and coronary arteries. Plaque instability is partly determined by local factors, but systemic factors, such as infection, autoimmunity, or genes, may also be important. If plaque stability is influenced by systemic factors that are present in only a proportion of patients, some individuals should be more prone to rupture of plaques than others-ie, irregular plaques should occur in multiple vascular beds in some individuals more frequently than would be expected by chance alone.

Methods

We studied 5393 carotid bifurcation angiograms from 3007 patients with a recently symptomatic carotid stenosis. We assessed the extent to which plaque-surface irregularity at the symptomatic carotid artery was associated with irregularity at a distant site, the contralateral carotid artery, and the extent to which plaque irregularity at these sites was associated with previous myocardial infarction or subsequent non-stroke vascular death (due mainly to coronary-artery disease).

Findings

Patients with plaque-surface irregularity (n=1897) in the symptomatic carotid artery were more likely than those with smooth plaque (n=110) to have irregularity in the contralateral carotid artery (odds ratio 2·21 [95% CI 1·62–3·01], p < 0·001). Patients with irregular plaques in both arteries were more likely to have had a previous myocardial infarction than patients with smooth plaques (hazard ratio 1·82 [1·23–2·64], p < 0·001), and were more likely to have a non-stroke vascular death on follow-up (hazard ratio 1·67 [1·15–2·44], p=0·007). However, there was no difference in the risk of non-vascular death (hazard ratio 0·92 [0·57–1·45], p=0·5). These associations were not explicable on the basis of differences in traditional vascular risk factors.

Interpretation

These data suggest that some individuals have a systemic predisposition to irregularity and rupture of atherosclerotic plaques that is independent of traditional vascular risk factors. This finding supports the hypothesis that other systemic factors are important in the cause of plaque instability.

Introduction

The development of atherosclerosis is a chronic process that is caused, or at least accelerated, in part by hypertension, cigarette smoking, diabetes, and hyperlipidaemia.¹ However, the risks of the major thrombotic and thromboembolic complications of atherosclerosis appear to be related more to the stability of atheromatous plaques than to the extent of disease. Stable angina is associated with smooth fibrous coronary-artery plaques, whereas unstable angina, acute myocardial infarction, and sudden cardiac death are almost invariably associated with irregular or ruptured plaques.2, 3, 4 Similarly, in patients with carotid-artery atherosclerotic disease, plaque irregularity and rupture are closely associated with the occurrence of cerebral ischaemic events,5, 6 and patients with irregular or ulcerated plaques on carotid angiography have a higher risk of ischaemic stroke irrespective of the degree of stenosis of the vessel lumen.7, 8

The factors that influence the stability of plaques are uncertain. Local factors, such as sheer stress or vessel and plaque anatomy, are important,⁹ but there is evidence that systemic factors may also be involved. Plaque instability is associted with inflammation and haemorrhage within plaques,10, 11 and there is evidence that these processes may be induced by autoimmunity and infection.12, 14 If plaque stability is influenced by systemic factors—infection, autoimmunity, or genes—and these factors are present in just a proportion of individuals, some individuals with atherosclerotic vascular disease will be more prone to instability and rupture of plaques, and so clinical complications, than others. Unstable plaques would be present at multiple sites in certain individuals more frequently than would be expected by chance alone. To test this hypothesis, we studied plaque-surface morphology on 5393 carotid bifurcation angiograms from 3007 patients with a symptomatic carotid stenosis in the European carotid surgery trial.¹⁵ We assessed the extent to which plaque-surface irregularity at one site, the symptomatic carotid artery, was associated with irregularity at a distant site, the contralateral carotid artery, and the extent to which plaque irregularity at these sites was associated with previous myocardial infarction and subsequent myocardial infarction and non-stroke vascular death (due mainly to coronary-artery disease).

Section snippets

Patients

We studied the carotid angiograms of patients randomly allocated treatment in the European Carotid Surgery Trial (ECST), the methods and results of which have been published previously.¹⁵ Briefly, patients with ocular or carotid-territory cerebral ischaemia, and who had evidence of carotid bifurcation stenosis on an angiogram, were randomly assigned carotid endarterectomy and best medical treatment or best medical treatment alone. Baseline clinical data were recorded and patients were followed

Results

There were no differences in baseline clinical characteristics between patients in whom a contralateral carotid angiogram was available for study (2386) and those in whom it was not (621). The mean degree of carotid stenosis of the arteries studied was 58·4% (SD 20·8) for the symptomatic artery and 46·7% (17·4) for the contralateral artery. There was a weak correlation between the degree of stenosis on the two sides (r=0·2, p < 0·001). Observers A and B agreed on the classification of

Discussion

We have shown that patients with angiographic plaque-surface irregularity in one carotid artery are more likely than would be expected by chance to have irregular plaques in the other carotid artery. These patients are more likely than patients with smooth plaques to have had a previous myocardial infarction and are more likely to die as a consequence of a subsequent acute myocardial infarction or other non-stroke vascular disorders, and to have sudden cardiac deaths. Since acute myocardial

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It is thought that the progression of vulnerable plaque is due in part to neovascularization, and plaque vulnerability is a useful approach for classifying cardiovascular risk. The aim of this retrospective study was to evaluate the correlation between carotid intraplaque neovascularization (IPN) detected on contrast-enhanced ultrasound and the progression of coronary lesions in patients undergoing percutaneous coronary intervention (PCI).
Contrast-enhanced ultrasound and angiography were performed in 131 patients undergoing PCI. All patients had angiograms obtained ≥12 months after PCI, and progression was defined using those angiograms. On the basis of angiographic images, patients were divided into progression and nonprogression groups. IPN was graded from 0 to 3 according to each plaque's microbubble appearance and extent, detected using contrast-enhanced ultrasound. The plaque with the highest IPN was used for analysis. Logistic regression and receiver operating characteristic analyses were applied to evaluate risk factors for predicting the progression of coronary lesions in patients undergoing PCI.
In the progression group, the numbers of patients with IPN values of 0, 1, 2, and 3 were one (3.3%), nine (30.0%), 16 (53.3%), and four (13.3%), respectively. Significant differences were found in maximum plaque height and IPN between groups. IPN and maximum plaque height were independent risk contributors to coronary lesion progression in patients undergoing PCI. The sensitivity, specificity, positive predictive value, and negative predictive value of IPN of 1.5 and to predict the progression of coronary lesions were 67%, 91%, 68%, and 89%, respectively. The area under the curve was 0.822.
Carotid plaque neovascularization was correlated with the progression of coronary lesions in patients undergoing PCI. IPN is a clinically useful tool for detecting the progression of coronary lesions and for risk stratification, especially in patients >60 years old.
Cerebrovascular diseases
2023, Medicine (Spain)
La enfermedad cerebrovascular es una de las principales causas de mortalidad y discapacidad a nivel mundial. Conocer su etiología y los factores de riesgo es importante para poder efectuar un adecuado diagnóstico y tratamiento. Dado que en el ictus «tiempo es cerebro», es precisa una cadena asistencial que garantice una rápida atención y permita el acceso de los pacientes a las unidades de ictus y a las terapias de reperfusión en aquellos con infarto cerebral.
Cerebrovascular disease is one of the main causes of mortality and disability worldwide. Knowing its etiology and risk factors is important in order to provide an adequate diagnosis and treatment. Given that «time is brain» when a stroke occurs, a chain of healthcare is needed that guarantees rapid care, allows patients to access care in stroke units, and permits patients with cerebral infarction to receive reperfusion treatment.
Echolucency of carotid plaque is useful for selecting high-risk patients with chronic coronary artery disease who benefit from intensive lipid-lowering therapy
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Ultrasound assessment of the carotid artery provides prognostic information on coronary events. This study examined whether ultrasound assessments of plaque echolucency of the carotid artery are useful for identifying patients with coronary artery disease (CAD) who are at high risk but could benefit from lipid-lowering therapy for secondary prevention.
Ultrasound assessment of carotid plaque echolucency with integrated backscatter (IBS) analysis was performed in 393 chronic CAD patients with low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dL on statin therapy. All patients were prospectively followed up for a maximum of 96 months or until the occurrence of one of the following coronary events: cardiac death, nonfatal myocardial infarction, or unstable angina pectoris requiring unplanned revascularization.
During the follow-up period, 45 coronary events occurred. Patients were stratified by IBS (≤-16.3 or >-16.3 dB, median value) and LDL-C level (<70 or 70–99 mg/dL). Multivariate Cox proportional hazards analysis showed that patients with lower IBS and LDL-C 70–99 mg/dL had significantly higher probabilities of coronary events compared with those with higher IBS and LDL-C <70 mg/dL, after adjustment for a baseline model of risk factors (hazard ratio 5.15; 95% confidence interval 1.21–22.0, p = 0.03). In contrast, patients with lower IBS and LDL-C <70 mg/dL had an improved prognosis comparable with those with higher IBS. Addition of LDL-C levels to the baseline model of risk factors improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI) in patients with lower IBS (NRI, 0.44, p = 0.04; and IDI, 0.035, p < 0.01), but not in those with higher IBS.
Evaluation of echolucency of the carotid artery was useful for selecting CAD patients at high risk of secondary coronary events but who could benefit from lipid-lowering therapy.
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Patients with peripheral artery disease (PAD) are at high risk of cardiovascular events, including myocardial infarction (MI), stroke, and cardiovascular death. However, the impact of PAD on prognosis in Japanese patients with acute MI remains unclear.
The Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET) is a prospective multicenter registry that registered 3283 patients with acute MI. Among them, 2970 patients with available data of PAD were divided into the following 4 groups: 2513 patients without prior MI or PAD (None group), 320 patients with only prior MI (Prior MI group), 100 patients with only PAD (PAD group), and 37 patients with both previous MI and PAD (Both group). The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina.
The 3-year cumulative incidence of the primary endpoint was 26.9% in None group, 41.4% in Prior MI group, 48.0% in PAD group, and 60.3% in Both group (p < 0.001). In multivariate analysis, hazard ratio using None group as reference was 1.55 (95% confidence intervals 1.25–1.91; p < 0.001) for MI group, 2.26 (1.61–3.07; p < 0.001) for PAD group, and 2.52 (1.52–3.90; p < 0.001) for Both group.
Concomitant PAD was associated with poor prognosis in Japanese patients with acute MI.
Carotid intraplaque neovascularization predicts atherosclerotic renal artery stenosis in patients with carotid artery stenosis
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This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with atherosclerotic renal artery stenosis (ARAS) in patients with normal kidney function.
We investigated carotid IPN using CEUS in 198 consecutive patients with normal kidney function with and without ARAS. IPN was graded on the basis of the presence and location of microbubbles within each plaque (0, no visible microbubbles in the plaque; 1, moderate microbubbles confined to the shoulder and/or adventitial side of the plaque; and 2, extensive microbubbles throughout the plaque). The grades of each plaque were averaged to obtain an overall score per patient. ARAS was determined angiographically. We found that a higher CEUS-assessed carotid IPN score was associated with ARAS (Odd Ratio, OR: 7.281; 95% Confidence Interval, 95% CI: 3.246–16.336; P < 0.001). Furthermore, an IPN score >1.75 predicted severe stenosis with a sensitivity of 81% and specificity of 58%. Compared with using the IPN score alone, the addition of the homocysteine (HCY) cutoff value (>22.5 mmol/L) resulted in a stronger predictive value (Area Under Curve, AUC: 0.893 vs 0.834; P < 0.001) for severe ARAS.
Carotid plaque neovascularization combined with HCY levels is predictive of severe ARAS in patients with normal kidney function. CEUS-assessed carotid IPN is clinically useful for stratification of ARAS in patients with normal kidney function.
New Quantitative Digital Image Analysis Method of Histological Features of Carotid Atherosclerotic Plaques
2019, European Journal of Vascular and Endovascular Surgery
Atherosclerosis and its thrombotic complications are major causes of morbidity and mortality worldwide. Plaque stability assessment is considered to be important for both clinical and fundamental applications. The current gold standard method to investigate plaque stability is performed by histological assessment of plaque features using semi-quantitative classifications. However, these assessments can be limited by subjectivity and variability. Thus, the aim was to develop a new digital image analysis method to measure quantitatively individual plaque features that is more precise than existing semi-quantitative methods.
A quantitative method was developed using Image Pro Primer software. Carotid plaque specimens were obtained from patients who underwent carotid endarterectomy and categorised according to stability (definitely stable, probably stable, probably unstable, definitely unstable) based on the gold standard semi-quantitative method that assesses 10 histological plaque features. Using the new quantitative method, plaque features (n = 15) from each stability grade were then analysed by two independent raters. For the semi-quantitative analysis, quadratic weighted Cohen's kappa was used to test intra- and inter-rater reliability, while for the quantitative analysis, intraclass correlation coefficients (ICCs) were assessed.
Intra-rater reliability demonstrated almost perfect agreement between both methods (Cohen's kappa range 0.831–0.969, ICC range 0.848–1.000). However, inter-rater reliability demonstrated mainly fair to moderate agreement (Cohen's kappa range 0.341–0.778) for the semi-quantitative analysis, while the digital image analysis method performed most optimally regarding reproducibility, yielding high ICCs close to 1 (ICC range 0.816–0.999). Using quantitative measurements, a statistically significant proportion of the individual plaque features (p < .05) were re-classified from one grade to another (shift by one) under the semi-quantitative classification.
A new quantitative digital image analysis was developed for the accurate assessment of histological plaque features, which demonstrated higher precision than the gold standard semi-quantitative methods, as measured by between and within rater analysis. Moreover, quantitative image analysis of histological plaque features provided more detailed insight into plaque morphology and composition.

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