Aims Carotid intima media thickness (cIMT) is an intermediate phenotype of early atherosclerosis that independently predicts vascular events. It is often suggested that cIMT be used as a screening ...tool to select subjects with an elevated event risk. Whether cIMT adds information to traditional risk models has so far received little investigation. Methods and results The 10-year follow-up of 4904 subjects from the Carotid Atherosclerosis Progression Study (CAPS) without pre-existing vascular disease included cardiovascular events and total mortality. Using Cox models and reclassification statistics, we investigated the usefulness of cIMT in individual risk prediction beyond the Framingham and the SCORE models, using risk strata of 0–5, 5–10, 10–20, and ≥20% over 10 years. Carotid intima media thickness was significantly and independently predictive for cardiovascular events. Compared with a model using the Framingham risk factors, a second model that included the common carotid-IMT led to the reclassification of 357 subjects (8.1%). In 107 subjects (30.0%), this reclassification was correct as confirmed with the actual outcome over 10 years. Net reclassification improvement was −1.41% (P = NS); integrated discrimination improvement was 0.04% (P = NS). More subjects were shifted to lower than to higher risk categories by the inclusion of cIMT. Analyses including other endpoint definitions, other carotid segments, and the SCORE risk model for baseline prediction did not result in consistently better risk prediction with cIMT. Conclusion Despite cIMT being predictive for cardiovascular endpoints, it did not consistently improve the risk classification of individuals. Carotid intima media thickness may not be useful for the risk stratification of individuals in the general population.
Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque ...further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.
Intima-media thickness (IMT) is increasingly used as a surrogate end point of vascular outcomes in clinical trials aimed at determining the success of interventions that lower risk factors for ...atherosclerosis and associated diseases (stroke, myocardial infarction and peripheral artery diseases). The necessity to promote further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is expressed through this updated consensus. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is based on physics, technical and disease-related principles as well as agreements on how to perform, interpret and document study results. Harmonization of carotid image acquisition and analysis is needed for the comparison of the IMT results obtained from epidemiological and interventional studies around the world. The consensus concludes that there is no need to 'treat IMT values' nor to monitor IMT values in individual patients apart from exceptions named, which emphasize that inside randomized clinical trials should be performed. Although IMT has been suggested to represent an important risk marker, according to the current evidence it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of randomized clinical trials incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.
Transcranial sonography (TCS) shows characteristic hyperechogenicity of the substantia nigra (SN) in patients with Parkinson's disease (PD). Although this feature is well established, sufficient ...observer reliability and diagnostic accuracy are prerequisites for advancements of this method.
The authors investigated both aspects in a cross-sectional study with four blinded TCS raters in 22 PD patients and 10 healthy controls.
As expected, the authors found significant bilateral SN hyperechogenicity in PD patients. Quantitative computerised SN planimetry had a substantial intra- (intraclass correlation coefficient (ICC) 0.97 and 0.93 respectively for both hemispheres) and inter-rater reliability (ICC 0.84 and 0.89), while visual semiquantitative echogenicity grading of the SN revealed a moderate intrarater (weighted kappa 0.80 ipsilateral and 0.74 contralateral) and slight (0.33) to fair (0.51) inter-rater reliability only. Diagnostic accuracy measured as the area under the curve of receiver-operating characteristics plots was highest in TCS of the SN opposite the clinically most affected body side (planimetry 0.821, echogenicity grading 0.792) with a hyperechogenic area of 0.24 cm(2) as the optimum cut-off value for the differentiation between PD and controls (sensitivity 79%, specificity 81%).
The data demonstrate that the observer variability of SN planimetry is low in the hands of experienced investigators. This approach also offers adequate diagnostic accuracy. The authors conclude that reliable SN TCS data on PD can be achieved in clinical routine and multicentre trials when standardised analysis protocols and certain quality criteria of brain parenchyma sonography are met.
A serum marker for malignant cerebral astrocytomas could improve both differential diagnosis and clinical management of brain tumour patients. To evaluate whether the serum concentration of glial ...fibrillary acidic protein (GFAP) may indicate glioblastoma multiforme (GBM) in patients with single supratentorial space-occupying lesions, we prospectively examined 50 consecutive patients with histologically proven GBM, World Health Organization (WHO) grade IV, 14 patients with anaplastic astrocytoma (WHO grade III), 4 patients with anaplastic oligodendroglioma, 13 patients with diffuse astrocytoma (WHO grade II), 17 patients with a single cerebral metastasis and 50 healthy controls. Serum was taken from the patients before tumour resection or stereotactic biopsy. Serum GFAP levels were determined using a commercially available ELISA test and were detectable in 40 out of the 50 GBM patients (median: 0.18 μg/l; range: 0–5.6 μg/l). The levels were significantly elevated compared with those of the non-GBM tumour patients and healthy controls (median: 0 μg/l; range: 0–0.024 μg/l; P < 0.0001, respectively). Non-GBM tumour patients and all healthy subjects showed zero serum GFAP levels. There was a significant correlation between tumour volume (Spearman Rho, CC = 0.47; 95% confidence interval, 0.2–0.67; P < 0.001), tumour necrosis volume (CC = 0.49; 95% confidence interval, 0.2–0.72; P = 0.004), the amount of necrotic GFAP positive cells (CC = 0.61; 95% confidence interval, 0.29–0.81; P = 0.007) and serum GFAP level among the GBM patients. A serum GFAP level of >0.05 μg/l was 76% sensitive and 100% specific for the diagnosis of GBM in patients with a single supratentorial mass lesion in this series. Therefore, it can be concluded that serum GFAP constitutes a diagnostic biomarker for GBM. Future studies should investigate whether serum GFAP could also be used to monitor therapeutic effects and whether it may have a prognostic value.
Abstract Objective There is controversy over whether or not chronic HIV infection contributes to atherosclerosis. We investigated the relationship between HIV infection, antiretroviral medication and ...ultrasound evidence of early atherosclerosis in the context of vascular risk factors. Design A case–control design with 292 HIV-positive subjects and 1168 age- and sex-matched controls. Methods We assessed vascular risk factors, blood pressure, serum lipids and carotid intima media thickness (IMT) in cases and controls. With multivariate regression models, we investigated the effects of HIV status and antiretroviral medication on IMT. Results The common carotid artery (CCA) IMT value was 5.70% (95% confidence interval 3.08–8.38%, p < 0.0001) or 0.044 mm 0.021–0.066 mm ( p = 0.0001) higher in HIV-positives, adjusted for multiple risk factors. In the carotid bifurcation (BIF), the IMT values were 24.4% 19.5–29.4% or 0.250 mm 0.198–0.303 mm higher in HIV patients ( p < 0.0001). An investigation of antiretroviral substances revealed higher CCA- and BIF-IMT values in patients receiving combination antiretroviral therapy (HAART). Conclusions HIV infection and HAART are independent risk factors for early carotid atherosclerosis. Assuming a risk ratio similar to that in large population-based cohorts, the observed IMT elevation suggests that vascular risk is 4–14% greater and the “vascular age” 4–5 years higher in HIV-positive subjects. The underlying mechanisms remain to be clarified.
Background: Biomarkers of stroke are an evolving field of clinical research. A serum marker which can differentiate between haemorrhagic and ischaemic stroke in the very early phase would help to ...optimise acute stroke management. Objective: To examine whether serum glial fibrillary acidic protein (GFAP) identifies intracerebral haemorrhage (ICH) in acute stroke patients. Methods: A pilot study assessing 135 stroke patients admitted within six hours after symptom onset. Diagnosis of ICH (n = 42) or ischaemic stroke (n = 93) was based on brain imaging. GFAP was determined from venous blood samples obtained immediately after admission, using a research immunoassay. Results: GFAP was detectable in the serum of 39 patients (34 of 42 (81%) with ICH, and five of 93 (5%) with ischaemic stroke). Serum GFAP was substantially raised in patients with ICH (median 11 ng/l, range 0 to 3096 ng/l) compared with patients with ischaemic stroke (median 0 ng/l, range 0 to 14 ng/l, p<0.001). Using receiver operating characteristic curve analysis, a cut off point of 2.9 ng/l provided a sensitivity of 0.79 and a specificity of 0.98 for the identification of ICH in acute stroke (positive predictive value 0.94, negative predictive value 0.91; p<0.001). Conclusions: Serum GFAP can reliably detect ICH in the acute phase of stroke. Further evaluation of the usefulness of GFAP as an early diagnostic marker of ICH is now required, with the aim of optimising cause specific emergency management.
A 69-year-old female patient who had been physically and mentally healthy was admitted to our emergency department because of acute onset of amnesia.
Inconspicuous diagnostic findings led to the ...diagnosis of transient global amnesia (TGA). Furthermore bradycardia and elevated troponins were detected. Because of these findings a cardiologic workup was performed resulting in the diagnosis of Tako-Tsubo cardiomyopathy.
The patient recovered completely from TGA as well as from the slight reduction of the left-ventricular ejection fraction as part of the Tako-Tsubo cardiomyopathy.
There are similarities of the two diseases Tako-Tsubo cardiomyopathy and TGA concerning triggers as well as reversibility. Patients presenting with symptoms suggestive for TGA should be considered to undergo additional cardiologic evaluation.
The clinical efficacy of filter devices in internal carotid artery (ICA) stent placement has been a matter of controversy. The aim of this retrospective study was to assess the number and extent of ...cerebral emboli, as represented by new lesions on diffusion-weighted MR imaging (DWI), in patients treated with filter-protected carotid stent placement.
Standard DWI (B0 = 1000) was performed within 48 hours before and 48 hours after filter-protected carotid stent placement in 50 patients with symptomatic, high grade (>70%), atherosclerotic ICA stenosis. Number, extent, and vascular territory of new DWI lesions after stent placement were assessed by consensus of 2 experienced neuroradiologists. Multifactorial statistical analysis was performed to determine risk factors associated with DWI lesions.
New punctate DWI lesions with a median diameter of 2 mm were detected in 14 of 50 cases in the territory of the stented ICA and in 7 of 50 cases in other vascular territories. Median lesion load was 1 lesion (range, 1-15) per positive case in the stented ICA and 1 lesion (range, 1-7) in other vascular territories. All DWI lesions were clinically asymptomatic. Because of 1 hyperperfusion syndrome with temporary brain swelling, the 30-day stroke and death rate was 2%. Age >or =70 years was the only significant predictor for new DWI lesions, whereas sex, degree and site of stenosis, vascular risk factors, and stent and filter type showed no significant correlation.
New DWI lesions after filter-protected carotid stent placement are substantially more frequent in the ipsilateral ICA territory compared with other vascular territories. Therefore, intraluminal filters cannot completely protect the brain from procedure-related embolization. However, individual lesion load and the risk of clinically relevant ischemia is low.
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