Carotid Plaque Calcification Research Articles

Presence of calcified carotid plaque predicts vascular events: The Northern Manhattan Study

Objective The prognostic implications of carotid plaque calcification (CPC) relative to subsequent vascular events are unclear. Our aim was to determine the association between CPC and risk of vascular events in a prospective multi-ethnic cohort. Methods CPC was assessed among 1118 stroke-free subjects (mean age 68 ± 8 years; 59% women; 59% Hispanic, 22% black, 19% white) from the Northern Manhattan Study using high-resolution B-mode ultrasound. CPC was defined by presence of any acoustic shadowing associated with carotid plaque, producing a reduction in echo amplitude due to intervening structures with high attenuation. Using Cox proportional hazards models, hazard ratios (HR) were estimated for the combined vascular outcome, defined as ischemic stroke (IS), myocardial infarction (MI) or vascular death (VD). Results Carotid plaque was present in 637 (57%) subjects. CPC was present in 225 subjects (20% of total cohort; 35% of those with plaque). During a mean follow-up time of 2.7 years, the combined vascular outcome occurred among 52 subjects (20 IS, 22 MI, and 24 VD). Adjusting for demographics, major vascular risk factors, and carotid intima media thickness, those with CPC (in comparison to those without plaque) had a significantly increased risk of the combined vascular outcome (HR 2.5, 95% CI 1.0–5.8). Conclusions In this population-based cohort, the presence of calcified carotid plaque, as assessed by high-resolution B-mode ultrasound, was an independent predictor of vascular events. It may serve as a simple and non-invasive marker of increased atherosclerotic risk and further aid in vascular risk stratification.

Composition of the Stable Carotid Plaque

Calcification has been associated with carotid plaque stability; however, an acceptable in vivo method to define plaques based on this component remains to be developed. The purpose of our study was to compare calcified and noncalcified volumes of carotid artery culprit symptomatic plaques with asymptomatic plaques using multidetector computed tomography. We identified 102 patients with > or =50% stenosis using NASCET criteria by multidetector computed tomography angiography between January 2004 and May 2006, which included 35 symptomatic (stenosis: 82.0+/-11.9%) and 67 asymptomatic patients (stenosis: 79.4+/-10.8%). Total plaque volume, noncalcified plaque volume, calcified plaque volume, and calcified/total ratio were measured for the 102 index plaques causing stenosis. In a model including age, stenosis, and cardiovascular risk factors, calcified plaque volume/total plaque volume was significantly inversely associated with the occurrence of symptoms (P=0.012; odds ratio, 0.047; 95% CI, 0.004 to 0.511). There was a notable overlap in the calcified plaque volume/total plaque volume ratio between 0% and 45% for symptomatic and asymptomatic plaques. However, calcification >45% of the total plaque was very specific: 97.1% (34/35) for absence of symptoms (sensitivity: 28.4% 19/67). No significant association between total plaque volume, noncalcified plaque volume, or calcified plaque volume and symptomatology was found. The proportion of carotid plaque calcification, rather than absolute volume, is associated with stability in patients with stenosis. Specifically, for a subset of patients, plaque calcification >45% of the total volume may represent a clinically useful cutoff. The carotid plaque calcium ratio, determined by multidetector computed tomography volume measurements, may help noninvasively risk stratify patients with asymptomatic stenosis.

Coincident Linkage of Type 2 Diabetes, Metabolic Syndrome, and Measures of Cardiovascular Disease in a Genome Scan of the Diabetes Heart Study

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality in type 2 diabetes, but the relationship between CVD and type 2 diabetes is not well understood. The Diabetes Heart Study is a study of type 2 diabetes-enriched families extensively phenotyped for measures of CVD, type 2 diabetes, and metabolic syndrome. A total of 977 Caucasian subjects from 358 pedigrees (575 type 2 diabetic relative pairs) with at least two individuals with type 2 diabetes and, where possible, unaffected siblings were included in a genome scan. Qualitative traits evaluated in this analysis are with or without the presence of coronary calcified plaque (CCP) and with or without carotid calcified plaque (CarCP) measured by electrocardiogram-gated helical computed tomography. In addition, prevalent CVD was measured using two definitions: CVD1, based on self-reported history of clinical CVD (393 subjects), and CVD2, defined as CVD1 and/or CCP >400 (606 subjects). These discrete traits (type 2 diabetes, metabolic syndrome, CVD1, CVD2, CCP, and CarCP) frequently coincide in the same individuals with concordance ranging from 42.9 to 99%. Multipoint nonparametric linkage analysis revealed evidence for coincident mapping of each trait (type 2 diabetes, metabolic syndrome, CVD1, CVD2, CCP, and CarCP) to three different genomic regions: a broad region on chromosome 3 (70-160 cM; logarithm of odds [LOD] scores ranging between 1.15 and 2.71), chromosome 4q31 (peak LOD 146 cM; LOD scores ranging between 0.90 and 2.41), and on chromosome 14p (peak LOD 23 cM; LOD scores ranging between 1.43 and 2.31). Ordered subset analysis (OSA) suggests that the linked chromosome 3 region consists of at least two separate loci on 3p and 3q. In addition, OSA based on lipid measures and other traits identify family subsets with significantly stronger evidence of linkage (e.g., CVD2 on chromosome 3 at 87 cM subsetting on low HDL with an initial LOD of 2.19 is maximized to an LOD of 7.04 in a subset of 25% of the families and CVD2 on chromosome 14 at 22 cM subsetting on high triglycerides with an initial LOD of 1.99 maximized to an LOD of 4.90 in 44% of the families). When subjects are defined as affected by the presence of each trait (type 2 diabetes, metabolic syndrome, CVD1, and CCP), significant evidence for linkage to the 3p locus is observed with a peak LOD of 4.13 at 87 cM. While the correlated nature of the traits makes it unclear whether these loci represent distinct type 2 diabetes, metabolic syndrome, or CVD loci or single loci with pleiotropic effects, the coincident linkage suggests that identification of the underlying genes may help clarify the relationship of diabetes, metabolic syndrome, and CVD.

Association of protein tyrosine phosphatase-N1 polymorphisms with coronary calcified plaque in the Diabetes Heart Study.

Individuals with type 2 diabetes are at increased risk of cardiovascular disease (CVD) mortality and display increased levels of subclinical CVD. Genetic variation in PTPN1, a diabetes susceptibility gene, was investigated for a role in diabetic atherosclerosis. The PTPN1 gene encodes protein tyrosine phosphatase-1B, which is ubiquitously expressed and plays a role in the regulation of several signaling pathways. Subclinical atherosclerosis was assessed in 590 Caucasian participants with type 2 diabetes in the Diabetes Heart Study using B-mode ultrasound measurement of carotid intima-media thickness (IMT) and computed tomography measurement of carotid calcified plaque (CarCP) and coronary calcified plaque (CorCP). Twenty-three single nucleotide polymorphisms (SNPs) in PTPN1 were genotyped and assessed for association with IMT, CarCP, and CorCP. A total of 12 SNPs within a block of linkage disequilibrium encompassing the coding sequence of PTPN1 were significantly associated with CorCP (P values from <0.0001 to 0.043) and 3 SNPs also within the block approached significance (P values from 0.058 to 0.066). In addition, a nine-SNP haplotype (GACTTCAGO) was also associated with increased CorCP under a dominant model (P = 0.01). No association was detected with IMT or CarCP. The associated SNPs and haplotype are the same as those observed to be associated with type 2 diabetes, insulin resistance, and fasting glucose in previous studies. With the inclusion of the most likely haplo-genotype for each individual, the heritability estimate of CorCP increased from 0.53 +/- 0.1 to 0.57 +/- 0.1 (P = 8.1 x 10(-10)), suggesting a modest but detectable effect of this gene on the phenotype of CorCP in type 2 diabetic patients.

The impact of ethnicity and sex on subclinical cardiovascular disease: the Diabetes Heart Study

African-Americans with type 2 diabetes and access to adequate healthcare are at lower risk of clinical coronary artery disease than are white diabetic patients. We evaluated whether ethnic differences in subclinical cardiovascular disease, coronary and carotid artery calcified plaque and carotid artery intima-medial thickness (IMT) were present in members of The Diabetes Heart Study families. In a bi-racial cohort of 1,180 individuals from families enriched for members with type 2 diabetes, we calculated coronary and carotid artery calcified plaque using fast-gated helical computed tomography, and measured carotid artery IMT and clinical risk factor profiles. Generalised estimating equations were used to test for an association between measures of subclinical cardiovascular disease and ethnicity and sex. After adjustment for age, ethnicity and kidney function, African-Americans had significantly lower amounts of coronary artery calcified plaque (mean+/-SE) (866+/-158 vs 1,915+/-135, respectively; p=0.0466) and carotid artery calcified plaque (179+/-51 vs 355+/-27, respectively; p=0.0240) relative to whites, despite having increased carotid IMT (0.71+/-0.01 vs 0.67+/-0.004 cm, respectively; p=0.0007), and higher blood pressure, albuminuria and HbA1c. Sex-specific analyses revealed that African-American men had significantly lower coronary and carotid artery calcified atheroma than white men. In women, ethnic differences in calcified carotid artery plaque, but not coronary artery plaque, were observed. In families enriched for members with type 2 diabetes, African-American men had markedly lower levels of coronary and carotid artery calcified plaque than white men, despite increased carotid artery IMT and conventional risk factors. These findings suggest that susceptibility to subclinical cardiovascular disease differs markedly according to ethnicity and sex.

Detection of Carotid Atherosclerotic Plaque Ulceration, Calcification, and Thrombosis by Multicontrast Weighted Magnetic Resonance Imaging

A 62-year-old man presented to the emergency department with a chief complaint of severe headache and decreased vision in his left eye. Initial physical examination demonstrated a new-onset left homonymous hemianopsia, which warranted a stroke workup. The patient’s head CT was significant for a 2.3×3.7-cm acute hemorrhage in the right posterior parietal and occipital lobes. Conventional angiography was performed and interpreted as >90% stenosis of both internal carotid arteries without ulceration. The remainder of the work-up, including …

Calcified Carotid Atherosclerotic Plaque Is Associated Less with Ischemic Symptoms Than Is Noncalcified Plaque on MDCT

Risk assessment based on plaque vulnerability would be valuable in the management of asymptomatic carotid stenosis. The purpose of this study was to compare plaque morphology in symptomatic and asymptomatic patients with significant extracranial carotid artery stenosis using MDCT angiography. We identified 31 patients with greater than 60% carotid artery stenosis on MDCT angiography using the criteria of the North American Symptomatic Carotid Endarterectomy Trial Collaborators. We analyzed plaque density by blinded review in Hounsfield units in the atherosclerotic plaques of 15 symptomatic and 21 asymptomatic stenotic vessels for classification as soft, intermediate, or calcified. Data were analyzed using multiple logistic regression. Even with age, traditional cardiovascular risk factors, and treatment taken into account, we found that calcified plaques were 21 times less likely to be symptomatic than noncalcified plaques (95% confidence interval for odds ratio, 0.003, 0.749; p = 0.030). No significant predictive value was found between soft (p = 0.23) or intermediate (p = 0.18) plaque morphology for the occurrence of symptoms. MDCT angiography may help risk-stratify patients with asymptomatic carotid artery stenosis. Extracranial carotid artery calcified plaques causing stenosis are significantly less likely to be symptomatic and thus may be more stable than noncalcified plaques. This finding may have implications for the interpretation of calcification of atherosclerotic plaque in other vascular beds.

Degree of carotid plaque calcification in relation to symptomatic outcome and plaque inflammation

Objective We undertook this study to quantitate differences in the degree of calcification between symptomatic and asymptomatic plaques removed at carotid endarterectomy (CEA) and to determine associated extent of plaque macrophage infiltration, a histopathologic feature of plaque instability. Methods CEA plaques (n = 48) were imaged at 1.25-mm intervals with spiral computed tomography (CT; 10-15 images per plaque). Indications for CEA were transient ischemic attack (n = 16), stroke (n = 5), amaurosis (n = 4), and critical asymptomatic stenosis (n = 23). The percent area calcification for each plaque was determined in spiral CT serial sections and averaged for each plaque. In 31 of 48 plaques macrophage infiltration was quantitated in corresponding histologic sections with immunohistochemical techniques. Results The mean (± SD) age of patients with symptomatic and asymptomatic plaques was 66 ± 7 years vs 71 ± 7 years, respectively, and degree of stenosis was 76% versus 82%, respectively ( P = .05). Atherosclerosis risk factors were similar between groups. Percent plaque area calcification was twofold greater in asymptomatic versus symptomatic plaques (48% ± 19% vs 24% ± 20%, respectively; P < .05). At receiver operating characteristic curve analysis, 80% of symptomatic plaques were below and 87% of asymptomatic plaques were above a cutoff point of 30% plaque area calcification. Macrophage burden was greater in the symptomatic plaques than in the asymptomatic plaques (52% vs 23%; P < .03). A strong inverse relationship between the degree of plaque calcification and macrophage infiltration was found in critical carotid stenoses ( r = −0.87; P < .001). Conclusions Symptomatic plaques are less calcified and more inflamed than asymptomatic plaques. Regardless of clinical outcome, a strong inverse correlation was found between the extent of carotid plaque calcification and the intensity of plaque fibrous cap inflammation as determined by the degree of macrophage infiltration. Carotid plaque calcification is associated with plaque stability, and is a potential spiral CT in vivo quantitative marker for cerebrovascular ischemic event risk.

Calcified plaque of the extracranial carotid arteries in comparison with traditional risk factors as a predictor for relevant coronary artery stenoses

Intima-media thickness (IMT) of carotid arteries, measured by vascular ultrasound, has widely been used as a surrogate marker for coronary atherosclerosis. As recent studies showed significant but only weak correlation between IMT and coronary artery stenoses, this study evaluated calcified plaques in the extracranial carotid arteries as a reasonable marker for coronary artery disease. 139 patients underwent cardiac catheterization with selective coronary angiography and ultrasound examination (B-mode, standard Doppler, color Doppler) of the carotid arteries. In case of calcified plaques number and distribution among the extracranial cerebral arteries were determined (Figure 1). Coronary angiograms were analyzed for disease severity and extent (number of main vessels with > 50% stenosis). Besides the traditional vascular risk factors hypertension, diabetes, smoking and hypercholesterolemia as well as body mass index, age and sex were analyzed. Calcified plaques of carotid arteries were significantly correlated (r = 0.502, p < 0.001) with coronary artery stenoses as well as hypercholesterolemia (r = 0.410, p < 0.001), increasing age (r = 0.406, p < 0.001) and diabetes (r = 0.290, p < 0.001) in contrast to hypertension (r = 0.125, p = 0.075), smoking status (r = -0.043, p = 0.311), body mass index (r = -0.122, p = 0.083) and male sex (r = -0.103, p = 0.114) (Table 1). The number of calcified plaques was significantly correlated (r = 0.568, p < 0.001) with severity and extent of coronary artery disease, too (Figure 2). For two and more calcified plaques sensitivity concerning coronary artery stenoses was 80%, specificity 75%, positive predictive value 83%, negative predictive value 73% (Table 2). Multiple stepwise regression analysis was performed for all eight variables (calcified plaques, hypercholestrolemia, diabetes, hypertension, smoking status, age, sex, body mass index). Including calcified plaques the predictive value of all factors was higher (r = 0.644 to r = 0.607). Determination of calcified carotid plaques by ultrasound is useful to improve the predictive value of risk factor-based multivariate models based on traditional risk factors.

Carotid plaque morphology and clinical events.

Studies have suggested that B-mode ultrasonography can be used to determine carotid plaque composition and that specific plaque characteristics are associated with a worse clinical outcome. However, histological studies examining the relationship between carotid plaque morphology and clinical outcome have reported conflicting findings. Furthermore, few investigators have described plaque morphology in quantifiable terms. This study examines the association between the volume of carotid plaque constituents and preoperative ischemic neurological symptoms. Constituents examined were chosen based on their potential for identification by current diagnostic imaging modalities such as ultrasound or MRI. Atherosclerotic plaques from 43 patients undergoing carotid endarterectomy were examined histologically, with sections obtained every 0.5 to 1 mm. The lesions were examined for the presence and quantity of fibrous intimal tissue, intraplaque hemorrhage, lipid core, necrotic plaque core, and calcification. The quantity of each constituent was compared in plaques removed from symptomatic patients with those excised from asymptomatic individuals. Differences were analyzed with a Kolmogorov-Smirnov statistic. There was no difference between plaques removed from asymptomatic and symptomatic patients with regard to the presence and volume of fibrous intimal tissue, intraplaque hemorrhage, the lipid core, the necrotic core, or calcification. In patients with highly stenotic carotid lesions who are undergoing carotid endarterectomy, gross plaque composition is similar regardless of preoperative symptom status. Given this similarity, it is unlikely that differences in the volume of intraplaque hemorrhage, lipid core, necrotic core, or calcification in atherosclerotic carotid plaques explain their embolic history.

Diabetic macroangiopathy in the elderly

Autopsy cases from Annual Report of Autopsy Cases published by the Japan Society of Pathology showed an increase of myocardial infarction from 13.2% in the years 1958-65 to 26.6% in the years 1983-85. However, cerebral infarction and hemorrhage showed no definite increase during the period. Frequency of diabetes mellitus was extremely increased among the cases of myocardial infarction who were admitted to our hospital. Arteriographic characteristics of coronary atherosclerosis in diabetics consist of multiple tight stenoses in one major artery and two or three arterial obstructions. Carotid arterial blood flow and plaque formation and calcification of the arteries were examined by doppler imaging technology and B-mode (5 MHz) real time ultrasound using ultrasonographic equipment in diabetic patients. Both blood flow volume and blood flow velocity in the elderly patients with diabetes mellitus (over 65 years old) were significantly reduced compared with those in the younger patients with diabetes mellitus (7.4 +/- 0.4 vs. 8.5 +/- 0.2 in blood flow volumes. p < 0.01; 12.4 +/- 0.8 in blood flow velocities. p < 0.01). Plaque formation and calcification of carotid arteries were significantly more frequent in the elderly patients with diabetes mellitus than in the younger patients with diabetes mellitus (p < 0.05). Asymptomatic cerebral infarction was studied in 37 diabetic patients by brain magnetic resonance imaging (MRI) in the absence of prior stroke. T2 weighted MRI imaging showed 27 patients among 37 patients (73%) to suffer from lacunar infarction. Hyperintensities were seen in the brain stem (28.6%), white matter (62.9%), basal ganglia (60.0%), and paraventricular areas (PVH) (20.0%).(ABSTRACT TRUNCATED AT 250 WORDS)