Progression Of Carotid Artery Disease Research Articles

Knowledge fields and emerging trends about extracellular matrix in carotid artery disease from 1990 to 2021: analysis of the scientific literature

BackgroundStroke is a heavy burden in modern society, and carotid artery disease is a major cause. The role of the extracellular matrix (ECM) in the development and progression of carotid artery disease has become a popular research focus. However, there is no published bibliometric analysis to derive the main publication features and trends in this scientific area. We aim to conduct a bibliometric analysis to reveal current status of ECM in carotid artery disease and to predict future hot spots.MethodsWe searched and downloaded articles from the Web of Science Core Collection with “Carotid” and “Extracellular Matrix” as subject words from 1990 to 2021. The complete bibliographic data were analyzed by Bibliometrics, BICOMB, gCLUTO and CiteSpace softwares.ResultsSince 1990, the United States has been the leader in the number of publications in the field of ECM in carotid artery disease, followed by China, Japan and Germany. Among institutions, Institut National De La Sante Et De La Recherche Medicale Inserm, University of Washington Seattle and Harvard University are in the top 3. “Arteriosclerosis Thrombosis and Vascular Biology” is the most popular journal and “Circulation” is the most cited journal. “Clowes AW”, “Hedin Ulf” and “Nilsson Jan” are the top three authors of published articles. Finally, we investigated the frontiers through the strongest citation bursts, conducted keyword biclustering analysis, and discovered five clusters of research hotspots. Our research provided a comprehensive analysis of the fundamental data, knowledge organization, and dynamic evolution of research about ECM in carotid artery disease.ConclusionsThe field of ECM in carotid artery disease has received increasing attention. We summarized the history of the field and predicted five future hotspots through bibliometric analysis. This study provided a reference for researchers in this fields, and the methodology can be extended to other fields.

Comparison of Parameters for Assessment of Carotid Stiffness and Their Association with Carotid Atherosclerosis in Rural Australian Adults: A Pilot Study.

Carotid stiffness has been associated with the development and progression of carotid artery disease and is an independent factor for stroke and dementia. There has also been a lack of comparison of different ultrasound-derived carotid stiffness parameters and their association with carotid atherosclerosis. This pilot study aimed to investigate the associations between carotid stiffness parameters (derived via ultrasound echo tracking) and the presence of carotid plaques in Australian rural adults. In cross-sectional analyses, we assessed forty-six subjects (68 ± 9 years; mean ± SD) who underwent carotid ultrasound examinations. Carotid stiffness was assessed by a noninvasive echo-tracking method, measuring and comparing multiple carotid stiffness parameters, including stroke change in diameter (ΔD), stroke change in lumen area (ΔA), β- stiffness index, pulse wave velocity beta (PWV-β), compliance coefficient (CC), distensibility coefficient (DC), Young's elastic modulus (YEM), Peterson elastic modulus (Ep), and strain. Carotid atherosclerosis was assessed bilaterally by the presence of plaques in the common and internal carotid arteries, while carotid stiffness was assessed at the right common carotid artery. β-stiffness index, PWV-β, and Ep were significantly higher (p = 0.006, p = 0.004, p = 0.02, respectively), whilst ΔD, CC, DC, and strain were lower among subjects with carotid plaques (p = 0.036, p = 0.032, p = 0.01, p = 0.02, respectively) comparing to subjects without carotid plaques. YEM and ΔA did not significantly differ among the groups. Carotid plaques were associated with age, history of stroke, coronary artery disease, and previous coronary interventions. These results suggest that unilateral carotid stiffness is associated with the presence of carotid plaques.

Effect of the Neutrophil/Lymphocyte Ratio on Outcome after Carotid Endarterectomy and Carotid Artery Disease Progression

Effect of the Neutrophil/Lymphocyte Ratio on Outcome after Carotid Endarterectomy and Carotid Artery Disease Progression

P5510High plasma sRAGE is associated with slower carotid intima media thickness progression and lower risk for first-time coronary events and mortality

Abstract Background/Introduction The receptor for advanced glycation end products (RAGE) and the extracellular matrix metalloproteinase inducer (EMMPRIN) are immune receptors for pro-inflammatory mediators. These receptors can also be found in a soluble form in the circulation. Soluble RAGE (sRAGE) has shown atheroprotective properties in animal studies, by acting as a decoy receptor for its ligands. Whether sEMMPRIN has similar roles is unknown. Purpose The purpose of our study was to investigate the associations between sRAGE and sEMMPRIN in plasma and the progression of vascular disease, incident coronary events and mortality in the general population. Methods We measured baseline sRAGE and sEMMPRIN in 4612 cardiovascular disease-free middle aged individuals from a population-based cohort. Measurements of intima media thickness (IMT) in the common carotid artery were performed at inclusion and after a median of 16.5 years. Incident major adverse coronary events (MACE) and mortality were recorded during a follow-up period of 21 years. Results sRAGE was negatively correlated with the progression of carotid IMT, independently of traditional cardiovascular risk factors, kidney function and hsCRP. Additionally, sRAGE was associated with decreased risk for MACE [HR=0.91 (0.83–0.99); p=0.031] and total mortality [HR=0.92 (0.87–0.99); p=0.017] in multivariate Cox regression analyses. We found no correlations between EMMPRIN, IMT progression or prognosis. Conclusion We show that individuals with high levels of circulating sRAGE have a slower rate of carotid artery disease progression, and a lower risk for coronary events and mortality. These findings support further research into the potential atheroprotective properties of sRAGE. Acknowledgement/Funding This study was supported by grants from the Swedish Research Council, Marianne and Marcus Wallenberg Foundation, Swedish Heart and Lung Foundation

Matrix Metalloproteinases 2 and 9 are CAD More Relevant Biomarkers Than -1, -8, and -12 to Separate CAD from Non-CAD Patients

Background: Atherosclerotic Carotid Artery Disease (CAD) is a frequent cause of mortality worldwide. The discovery of biomarkers that evidenced CAD progression would help with cardiovascular risk reduction. Extracellular Matrix Metalloproteinases (MMPs) have been associated with plaque progression, lesion aggravation, and rupture. Objective: This study evaluated that MMPs serum optical-densities and digestive gel-activity are associated with CAD. Methods: This cross-sectional study evaluated 65 outpatients presenting CAD (n=31) or not (n=34). The Carotid disease was evidenced by Doppler echography. ELISA and SDS-PAGE zymography were performed to determine MMPs serum optical-densities and proteolytic-activity. Principal Component Analysis (PCA) was performed to identify the most relevant MMPs (MMP-1, 2, 8, 9 and 12). Results: MMP-2 and MMP-9 showed lower serum optical-densities in CAD (MMP-2, p = 0.0246; and MMP-9, p < 0.0001), but higher digestive enzymatic activity when compared to non-CAD samples (p < 0.0001). PCA analysis strengthens the singling out of those individual MMPs as predictors of choice to differentiate CAD from non-CAD patients as opposed to others MMPs. Analysis of the loadings showed MMP-2 and MMP-9 as the most important independent variables to separate CAD from non-CAD patients. Conclusion: MMP-2 and MMP-9 are more relevant biomarkers for CAD than the other MMPs analyzed.

High Plasma sRAGE (Soluble Receptor for Advanced Glycation End Products) Is Associated With Slower Carotid Intima-Media Thickness Progression and Lower Risk for First-Time Coronary Events and Mortality.

Objective- RAGE (receptor for advanced glycation end products) and EMMPRIN (extracellular matrix metalloproteinase inducer) are immune receptors for proinflammatory mediators. These receptors can also be found in a soluble form in the circulation. Soluble RAGE (sRAGE) has shown atheroprotective properties in animal studies, possibly by acting as a decoy receptor for its ligands. Whether sEMMPRIN (soluble EMMPRIN) has similar roles is unknown. We hypothesized that sRAGE and sEMMPRIN might be associated with vascular disease progression, incident coronary events, and mortality. Approach and Results- We measured baseline sRAGE and sEMMPRIN in 4612 cardiovascular disease-free individuals from the population-based Malmö Diet and Cancer cohort. Measurements of intima-media thickness in the common carotid artery were performed at inclusion and after a median of 16.5 years. sRAGE was negatively correlated with carotid intima-media thickness progression, independently of traditional cardiovascular risk factors, kidney function, and hsCRP (high sensitive C-reactive protein). Additionally, sRAGE was associated with decreased risk for major adverse coronary events (hazard ratio=0.90 [0.82-0.97]; P=0.009) and mortality (hazard ratio=0.93 [0.88-0.99]; P=0.011) during a follow-up period of 21 years. The relationship with mortality was independent of all considered potential confounders. We found no correlations between EMMPRIN, intima-media thickness progression, or prognosis. Conclusions- Individuals with high levels of circulating sRAGE have a slower rate of carotid artery disease progression and a better prognosis. Although its predictive value was too weak to promote sRAGE as a useful clinical biomarker in the population, the findings support further research into the potential anti-inflammatory and atheroprotective properties of this soluble receptor.

Effect of lipid parameters on carotid artery disease progression in patients undergoing carotid endarterectomy and unoperated patients with non-severe carotid artery stenosis

Objectives: We aim to evaluate the relationship between serum lipid indices and carotid artery stenosis (CAS). Methods: This retrospective observational study included patients who underwent carotid endarterectomy (CEA) and unoperated patients who have CAS less than 50%. CAS was diagnosed with history and physical examination followed by doppler ultrasonography, coronary and carotid angiography. All data retrieved retrospectively from the hospital medical files. Non-high-density lipoprotein-cholesterol (non-HDL-C) level was calculated by removing HDL-C from total cholesterol. In addition, low-density lipoprotein-cholesterol (LDL-C)/HDL-C ratio, non-HDL-C/HDL-C ratio, and triglyceride (TG)/HDL-C ratio were assessed. Results: CEA group (77.5% male, mean age: 71.35 ± 8.35 years) included 40 patients who underwent CEA, and there were 32 patients who have less than 50% CAS in unoperated group (68.8% male, mean age: 63.94 ± 9.92 years). The development of CAS was not significantly correlated with LDL-C/HDL-C ratio (p = 0.119), non-HDL-C/HDL-C ratio (p = 0.227) and TG/HDL-C ratio (p = 0.768). Advanced age and presence of coronary artery disease were identified as an independent predictor of the development of CAS. For predicting development of CAS, there were 50.0% sensitivity and 65.6% specificity for LDL-C/HDL-C ratio and non-HDL-C/ HDL-C ratio (area under the curve [AUC]: 0.592, log rank p = 0.183, AUC: 0.583, log rank p = 0.227, respectively). Conclusions: We found that lipid ratios were not an independent predictors of the development of CAS. But, we think that AUC values which were above 0.5 for lipid ratios are may be important development of CAS.

Progression of carotid artery disease could stratify a risk of coronary artery disease patients with type 2 diabetes.

Introduction Diabetic population has been defined as high-risk one. Those patients (pts) with diabetes and present coronary artery disease, due to actual risk scores have been defined as high-risk pts. Current guidelines propose imaging techniques for improvement of prognosis of high-risk pts. However, class of recommendation is not IA. We assessed an incremental value of carotid ultrasound in prognosis of pts with coronary artery disease and type 2 diabetes. Patients and methods In this cohort study, pts with coronary artery disease and present type 2 diabetes 264 pts were included. They were prospectively followed up for 31.5 + 10.4 months. Carotid ultrasound was used for detection of progression of carotid artery disease. Coronary artery disease in pts was confirmed with angiography. Results Cohort follow-up revealed: progression of IMT in 86.8% of pts, progression of carotid stenosis in 17.8% and occurrence of plaque in 41.8% of these pts. New cardiovascular (CV) events were registered in 145 pts with incidence of 0.55 events per pt. Multivariate analysis found as independent factors: change of IMT for total CV events (OR 2.30), change of IMT per year for new angina (OR 4.84) and occurrence of carotid plaque for onset of stroke (OR 2.14).

Anti-ApoA-I IgG antibodies are not associated with carotid artery disease progression and first-time cardiovascular events in middle-aged individuals.

IgG antibodies against apolipoprotein A-I (ApoA-I) have been found to be elevated in subjects from the general population with clinically manifest cardiovascular disease and in myocardial infarction patients with an adverse prognosis. Here, we investigated whether these antibodies are prospectively associated with carotid artery disease progression and with the risk for first-time cardiovascular events in individuals with no previous history of cardiovascular disease. We selected 383 subjects from the cardiovascular cohort of Malmö Diet and Cancer study who suffered a coronary event during a median follow-up period of 15.4 (10.3-16.4)years and 395 age- and sex-matched controls. None of the study participants had a previous history of coronary artery disease or stroke. Anti-ApoA-I IgG were measured by ELISA in serum samples collected at baseline. Intima-media thickness (IMT) was measured in the common carotid artery and in the carotid bifurcation at baseline and after 15.9 (±1.5)years. We found no associations between anti-ApoA-I IgG and carotid artery IMT at baseline or with IMT progression during follow-up. In Cox proportional hazards analyses adjusted for traditional cardiovascular risk factors, the hazard ratio (HR 95%CI) for the primary outcome, incident coronary events, was 0.97 (0.75-1.25), P=0.782, in subjects with anti-ApoA-I IgG within the highest tertile compared with the lowest tertile. Similarly, we did not find any associations with the secondary outcome, incident first-time stroke. Serum autoantibodies against ApoA-I do not correlate with disease progression and adverse events in cardiovascular disease-free individuals from the general population.

Progression of carotid artery disease could stratify a risk of coronary artery disease pts with type 2 diabetes

Progression of carotid artery disease could stratify a risk of coronary artery disease pts with type 2 diabetes

Carotid artery disease progression and related neurologic events after carotid endarterectomy

During the last decade, there has been a dramatic improvement in best medical treatment for patients with vascular disease. Yet, there is a paucity of contemporary long-term data for restenosis and contralateral internal carotid artery (ICA) progression. This study assessed ipsilateral and contralateral disease progression and cerebrovascular events after carotid endarterectomy (CEA). A consecutive cohort of CEAs between January 1, 2000, and December 31, 2010, was retrospectively analyzed. End points were restenosis ≥50% and ≥70%, contralateral carotid disease progression (50%-69%, 70%-99%, or occlusion) and stroke. Survival analysis and Cox regression models were used to assess the effect of baseline predictors. During the 11-year study period, 1639 patients underwent 1782 CEAs (50.0% patch closure, 23.9% primary closure, 26.1% eversion, and 2.5% combined with coronary artery bypass grafting). The combined stroke/death rate was 2.6% overall and 1.8% in the asymptomatic cohort. The rate of restenosis ≥50% at 2, 5, and 10years was 8.5%, 15.6%, 27.2%, and the rate for restenosis ≥70% was 3.4%, 6.5%, 10.2%, respectively. Restenosis ≥50% was predicted by hypertension (hazard ratio [HR], 2.09; P= .027), female gender (HR, 1.43; P= .042), and younger age (≤65years; HR, 1.56; P= .016), but not by statins, surgical technique, symptoms, or other baseline risk factors. Restenoses remained asymptomatic in 125 of 148 (84.5%). Progression of contralateral ICA disease at 2, 5, and 10years was estimated at 5.4%, 15.5%, and 46.8%, respectively. Contralateral progression was only predicted by smoking (HR, 1.74; P=.008). The stroke rate in patients with disease progression of the contralateral ICA was not different compared with those without progression (7.0% vs 3.3%; P= .063). Any-stroke rates at 2, 5, and 10years were 4.6%, 7.3%, and 15.7%, respectively. Predictors were symptomatic lesion (HR, 1.48; P= .039), renal insufficiency, defined as a glomerular filtration rate (GFR) of 30 to 59 vs<30mL/min/1.73m2 (HR, 0.34; P= .009) or GFR ≥60 vs GFR<30mL/min/1.73m2 (HR, 0.55; P= .109), and statin use (HR, 0.59; P= .006). Restenosis or contralateral disease progression after CEA, to a level that might warrant consideration for treatment, is very low. The potentially associated stroke rates are also very low and not clearly related to disease progression. With the exception of the postoperative duplex, surveillance within short intervals of<1 or 2years cannot be justified.

Progression of carotid-artery disease in type 2 diabetic patients: a cohort prospective study.

In order to assess the progression of carotid-artery disease in type 2 diabetic cohort (n=207 patients), the dynamic change in carotid intima-media thickness (CIMT) and the occurrence of plaques were followed for a period of 31.35±10.59 months. The mean CIMT at the beginning of the study was 0.9178±0.1447 mm, with a maximal value of 1.1210±0.2366 mm. The maximal value of CIMT changed by 0.07 mm/year. Progression of CIMT was noted in 86.8% and its regression in 7.8% of patients. The occurrence of carotid plaques was detected in 41.8% of patients. Multiple regression analysis revealed the maximal value of CIMT to be associated with diastolic blood pressure, despite mean CIMT being predicted by body mass index. The presence of peripheral arterial disease and hypo-high-density lipoproteinemia were found to be predictors for the occurrence of carotid plaques. Our data have clinical implications in predicting risk factors for the progression of carotid-artery disease in type 2 diabetic patients for their appropriate management.

Longitudinal assessment of carotid atherosclerosis after Radiation Therapy using Computed Tomography: A case control Study.

To study the carotid artery plaque composition and its volume changes in a group of patients at baseline and 2 years after head and neck radiation therapy treatment (HNXRT). In this retrospective study, 62 patients (41 males; mean age 63 years; range 52-81) who underwent HNXRT and 40 patients (24 males; mean age 65) who underwent surgical resection of neoplasm and did not undergo HNXRT were assessed, with 2-year follow-up. The carotid artery plaque volumes, as well as the volume of the sub-components (fatty-mixed-calcified), were semiautomatically quantified. Mann-Whitney and Wilcoxon tests were used to test the hypothesis. In the HNXRT group, there was a statistically significant increase in the total volume of the carotid artery plaques (from 533 to 746 mm(3); p = 0.001), in the fatty plaques (103 vs. 202 mm(3); p = 0.001) and mixed plaque component volume (328 vs. 419 mm(3); p = 0.034). A statistically significant variation (from 21.8 % to 27.6 %) in the percentage of the fatty tissue was found. Results of this preliminary study suggest that HNXRT promotes increased carotid artery plaque volume, particularly the fatty plaque component. HNXRT increases carotid plaque volume. Plaque volume increase is mainly due to increase.in fatty plaque component. Patients who undergo HNXRT have a progression of carotid artery disease.

Long-Term Carotid Artery Disease Progression and Related Neurologic Events Following Carotid Endarterectomy

Long-Term Carotid Artery Disease Progression and Related Neurologic Events Following Carotid Endarterectomy

The role of C-reactive protein genetic variability in the onset of carotid artery disease and renal function impairment in patients with diabetes mellitus type 2

The role of diabetes mellitus (DM) in cardiovascular disease is well established and currently is considered as an equivalent of coronary artery disease. Studies have also reported that DM is associated with the prevalence of occlusive carotid artery disease (AD) [ [1] Kuebler T.W. Bendick P.J. Fineberg S.E. et al. Diabetes mellitus and cerebrovascular disease: prevalence of carotid artery occlusive disease and associated risk factors in 482 adult diabetic patients. Diabetes Care. 1983; 6: 274-278 Crossref PubMed Scopus (21) Google Scholar ] as well as the grade carotid artery stenosis [ [2] Göksan B. Erkol G. Bozluolcay M. Ince B. Diabetes as a determinant of high-grade carotid artery stenosis: evaluation of 1,058 cases by Doppler sonography. J Stroke Cerebrovasc Dis. 2001; 10: 252-256 Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar ]. In addition, DM is related to impaired renal function via several mechanisms [ [3] Vallon V. Thomson S.C. Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney. Annu Rev Physiol. 2012; 74: 351-375 Crossref PubMed Scopus (237) Google Scholar ]. During the last years novel data have arisen for the role of genetics in the initiation and progression of carotid AD [ 4 Pessi T. Eklund C. Huhtala H. et al. CRP and FCGR2A genes have an epistatic effect on carotid artery intima-media thickness: the Cardiovascular Risk in Young Finns Study. Int J Immunogenet. 2009; 36: 39-45 Crossref PubMed Scopus (6) Google Scholar , 5 Jylhävä J. Eklund C. Pessi T. et al. Genetics of C-reactive protein and complement factor H have an epistatic effect on carotid artery compliance: the Cardiovascular Risk in Young Finns Study. Clin Exp Immunol. 2009; 155: 53-58 Crossref PubMed Scopus (16) Google Scholar , 6 Bleil M.E. Ferrell R.E. Sutton-Tyrrell K. Muldoon M.F. Manuck S.B. Apolipoprotein E polymorphism and preclinical carotid artery disease in untreated hypertensive men. Eur J Cardiovasc Prev Rehabil. 2006; 13: 98-100 Crossref PubMed Scopus (4) Google Scholar , 7 Losito A. Selvi A. Jeffery S. Afzal A.R. Parente B. Cao P.G. Angiotensin-converting enzyme gene I/D polymorphism and carotid artery disease in renovascular hypertension. Am J Hypertens. 2000; 13: 128-133 Crossref PubMed Scopus (16) Google Scholar , 8 Diamantopoulos E.J. Andreadis E. Kakou M. et al. Atherosclerosis of carotid arteries and the ace insertion/deletion polymorphism in subjects with diabetes mellitus type 2. Int Angiol. 2002; 21: 63-69 PubMed Google Scholar ] as well as for impaired renal function [ 9 Hung A.M. Ikizler T.A. Griffin M.R. et al. CRP polymorphisms and chronic kidney disease in the third national health and nutrition examination survey. BMC Med Genet. 2011; 12: 65 Crossref PubMed Scopus (11) Google Scholar , 10 Cooper Worobey C. Fisher N.D. Cox D. Forman J.P. Curhan G.C. Genetic polymorphisms and the risk of accelerated renal function decline in women. PLoS One. 2009; 4: e4787 Crossref PubMed Scopus (12) Google Scholar ]. However, scarce data exist regarding genetic polymorphisms in patients with diabetes mellitus and their role in carotid artery disease and renal function. Thus, in the present study we examined the potential role of a single nucleotide polymorphism (SNP) on C-reactive protein (CRP) gene in the onset of carotid AD and impaired renal function in patients with diabetes mellitus type 2.

Development of 3D ultrasound techniques for carotid artery disease assessment and monitoring

Quantitative measurements of carotid plaque burden are used to monitor patients and evaluate established interventions as well as new treatment options. Three-dimensional ultrasound (3D US) techniques were developed to noninvasively monitor the progression of carotid artery disease in both symptomatic and asymptomatic patients. Three-dimensional carotid US images were acquired and reconstructed, and methods for quantitative assessment were developed. The measurement of intima-media thickness (IMT) based on two-dimensional ultrasound (2D US) images was extended to a 3D vessel-wall-plus- plaque thickness (VWT), obtained by computing the distance between the carotid wall and lumen surfaces on a point-by-point basis. VWT measurements were superimposed on the arterial wall to produce 3D VWT maps. VWT changes were determined by comparing the 3D VWT maps obtained at two different time points. To facilitate the visualization and interpretation of the VWT and VWT-Change maps, a technique to flatten these maps was developed. Carotid remodeling involving changes in both arterial wall and plaque thickness was assessed with VWT maps obtained from in vivo 3D ultrasound images. 3D carotid ultrasound image evaluation with VWT mapping provides a feasible means for the analysis of plaque burden volumes and changes.

A prospective evaluation of C-reactive protein in the progression of carotid artery stenosis

Our institution previously reported an association between elevated C-reactive protein (CRP) and carotid artery stenosis. Based on this finding, we sought to further evaluate the association of CRP levels with ultrasound progression of carotid artery stenosis, and/or clinical events. A prospective observational study of patients evaluated for carotid artery stenosis was performed at a tertiary medical center from 2003-2007. Patients underwent serial lab draws for serum CRP, as well as serial duplex ultrasounds of their carotid bifurcations. Examinations were performed at 6-month intervals. Initial risk factors and CRP levels were evaluated with univariate statistics. Ultrasound progression of disease was evaluated with Kaplan-Meier curves and Cox regression analysis. During the study period, 271 patients completed study requirements with a mean follow-up of 37 (+/-6) months. Initial duplex examination revealed 114 (41%) of patients had 0% to 15%, 94 (35%) had 16% to 49%, and 63 (23%) had 50% to 79% stenosis of the carotid bifurcation. Sixty-three patients (23%) demonstrated progression of disease by ultrasound examination, 27 (10%) progressed to carotid endarterectomy, and three (1%) experienced a stroke during follow-up. Mean CRP levels were higher among patients that progressed on duplex examination (6.7 +/- 1.28 vs 4.6 +/- 0.4 mg/dl, P < .05). Kaplan-Meier analysis revealed a significant difference in freedom from progression of carotid artery disease for patients with 1(st) and 3(rd) quartile CRP levels (log-rank test P < .05). Adjusting for diabetes, hyperlipidemia, hypertension, coronary artery disease, aspirin or other anti-inflammatory uses, and statin therapy, 4(th) quartile CRP was independently associated with disease progression (OR 1.8, 95% CI; 1.03-2.99, P < .05). High CRP levels predict ultrasound progression of disease in patients with carotid artery stenosis. In addition, CRP levels may provide additional information to help guide ultimate therapy for evaluation and follow-up of patients with borderline lesions identified by duplex exam.

Platelet Degranulation Is Associated With Progression of Intima-Media Thickness of the Common Carotid Artery in Patients With Diabetes Mellitus Type 2

Platelets play a key role in atherogenesis and thromboembolic complications in patients with type 2 diabetes. We prospectively examined the relationship between systemic platelet activation and progression of carotid wall thickness within 1 year in 105 patients with type 2 diabetes. The intima-media thickness (IMT) of the common carotid artery was measured bilaterally at study entry and after 1 year. Platelet activation was assessed with the use of immunologic markers of platelet activation (CD62P, CD63, and CD40L) and flow cytometry. The prevalence for progression of atherosclerotic carotid disease in this population was 55.2%. We found that platelet degranulation (CD63 and CD40L) correlated with progression of IMT within 1 year (CD63: r=0.231, P=0.022; CD40L: r=0.230, P=0.029). Diabetic patients with progression of IMT had a significantly increased expression of CD63 compared with patients with stable carotid disease (mean intensity of immunofluorescence; median, interquartile range: 17.1 [12.4, 25.8] versus 11.9 [7.7, 19.8]; P=0.004). Multivariate logistic regression analysis revealed that degranulation of platelet CD63 is a predictor for progression of IMT independently of classical cardiovascular risk factors and hemoglobin A1c in diabetic patients (P=0.017). Enhanced systemic platelet degranulation is associated with progression of carotid artery disease in type 2 diabetes.

Basic mechanisms of stroke prevention with lipid-lowering therapy.

Cholesterol-lowering therapy has not been considered an important risk factor for stroke; however, lipid-lowering therapies reduce cerebrovascular events in patients with coronary heart disease (CHD). The basic mechanisms of cerebrovascular protection have emphasized reduced atheroemboli from the left ventricle and aortic arch, delayed carotid artery disease progression, stabilization of vulnerable carotid atherosclerotic plaque, and improvement in cerebral blood flow.

Psychological stress and the progression of carotid artery disease.

We examined the relation between cardiovascular reactivity (the response of the cardiovascular system to psychological stress) and the severity and progression of carotid atherosclerosis. Using duplex ultrasonography, we measured the change in the area of all detectable plaques in the extracranial carotid arteries during 2 years. Cardiovascular reactivity was assessed by measuring changes in hemodynamics during a frustrating cognitive task (the Stroop Color Word Interference Task). Established risk factors for atherosclerosis were measured by interviewing patients, a physical examination, and blood assays for 351 subjects with a wide range of types of atherosclerotic disease. Atherosclerotic plaques were present in the carotid arteries of 273 (78%) subjects. In a forward stepwise multiple regression analysis, it was found that greater age (beta = 0.46), a history of hypertension (beta = 0.20), use of lipid level-lowering agents (beta = 0.18), a longer history of smoking (beta = 0.13), a larger cholesterol:high-density lipoprotein ratio (beta = 0.13), a smaller change in heart rate during the task (beta = -0.12), and a higher resting systolic blood pressure (SBP; beta = 0.11) were associated significantly with a greater plaque area (R2 = 0.35). In 136 untreated subjects who were followed up for 2 years, a greater change in SBP during the task (beta = 0.28), a higher total cholesterol: high-density lipoprotein ratio (beta = 0.23), a shorter resting preejection period (beta = -0.19), and a lower body mass index (beta = -0.17) were significant predictors of the change in atherosclerosis, after controlling for age and initial plaque area in a stepwise multiple regression analysis (R2 = 0.24). These results support the hypothesis that hemodynamic responses under conditions of mental stress may influence the progression of atherosclerosis.