Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment.

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I² = 30.7%) and 1.20 (1.18-1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I² = 8.4%) and 1.14 (1.12-1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls.

A Network-Wide Stroke Team Program Reduces Time to Treatment for Endovascular Stroke Therapy in a Regional Stroke-Network.

BACKGROUND AND PURPOSE: Driven by the positive results of randomized, controlled trials of endovascular stroke therapies (EVT) in stroke patients with large vessel occlusion, different approaches to speed up the workflow for EVT candidates are currently being implemented worldwide. We aimed to assess the effect of a simple stroke network-wide workflow improvement project, primarily focusing on i.v. thrombolysis, on process times for patients undergoing EVT. METHODS: In 2015, we conducted a network-wide, peer-to-peer acute stroke workflow improvement program for i.v. thrombolysis with the main components of implementing a binding team-based algorithm at every stroke unit of the regional network, educating all stroke teams about non-technical skills and providing a stroke-specific simulation training. Before and after the intervention we recorded periprocedural process times, including patients undergoing EVT at the 3 EVT-capable centers (January - June 2015, n = 80 vs. July 2015 - June 2016, n = 184). RESULTS: In this multi-centric evaluation of 268 patients receiving EVT, we observed a relevant shortening of the median time from symptom onset to EVT specifically in patients requiring secondary transfer by almost an hour (300 min, 25-75% interquartile range [IQR] 231-381 min to 254 min, IQR 215.25-341 min; p = 0.117), including a reduction of the median door-to-groin time at the EVT-capable center in this patient group by 15.5 min (59 min, IQR 35-102 min to 43.5 min, IQR 27.75-81.25 min; p = 0.063). In patients directly admitted to an EVT-capable center, the median door-to-groin interval was reduced by 10.5 min (125 min, IQR 83.5-170.5 min to 114.5 min, IQR 66.5-151 min; p = 0.167), but a considerable heterogeneity between the centers was observed (p < 0.001). CONCLUSIONS: We show that a simple network-wide workflow improvement program primarily directed at fast i.v. thrombolysis also accelerates process times for EVT candidates and is a promising measure to improve the performance of an entire stroke network.

Dysphagia risk assessment in acute left-hemispheric middle cerebral artery stroke.

BACKGROUND AND PURPOSE: Bedside evaluation of dysphagia may be challenging in left middle cerebral artery (MCA) stroke due to frequently existing aphasia. Here we analyse the predictive value of common bedside screening tests and of two items of cortical dysfunction, aphasia and buccofacial apraxia (BFA), for the detection of dysphagia. METHODS: We prospectively examined 67 consecutive patients with clinical and imaging evidence of acute (<72 h) left MCA stroke. Dysphonia, dysarthria, abnormal volitional cough and abnormal gag reflex were assessed followed by a standardized 50-ml water-swallowing test determining the symptoms cough and voice change after swallow. Aphasia and BFA were assessed according to defined criteria. Fibre-optic endoscopic evaluation of swallowing (FEES) was performed for validation of dysphagia. RESULTS: 41 (61%) patients had FEES-proven dysphagia. Abnormal gag reflex, abnormal volitional cough, cough after swallow, aphasia and BFA were significantly more frequent in dysphagic as compared to non-dysphagic patients, while dysphonia, dysarthria and voice change after swallow were not. Aphasia and BFA had the highest sensitivity (97 and 78%, respectively) and high negative predictive values (89 and 68%, respectively) for dysphagia. Multivariate regression analysis did not identify an independent predictor of dysphagia. CONCLUSIONS: In left MCA stroke, the sensitivity and specificity of common bedside dysphagia screening methods are low. In contrast, aphasia and BFA have a high sensitivity and high negative predictive power, presumably due to the neuro-anatomical overlap between cortical regions involved in swallowing, speech production, imitation and voluntary movement control.

Clinical usefulness of carotid ultrasound to improve stroke risk assessment: ten-year results from the Carotid Atherosclerosis Progression Study (CAPS).

BACKGROUND AND PURPOSE: To prevent strokes it is essential to correctly classify people according to their risk of stroke. The aim of the present study was to assess whether carotid ultrasound improves the stroke risk prediction in asymptomatic individuals. METHODS: The baseline visit of the Carotid Atherosclerosis Progression Study (CAPS) included assessment of conventional risk factors and carotid ultrasound. During the 10-year follow-up of 4995 subjects, strokes, transient ischaemic attacks (TIA) and deaths were recorded. We assessed the additional usefulness of carotid ultrasound compared to the Framingham Stroke Risk Score (FSRS) with reclassification statistics using four risk categories. RESULTS: Most risk models were not improved by carotid ultrasound. For individual stroke prediction, intima-media thickness (IMT) or plaque of the internal carotid arteries were more useful than common carotid or bifurcational IMT. The model predicting 'any stroke or death' was significantly improved when ultrasound parameters were included - 339 subjects (7.2%) were reclassified to another risk category (122 were shifted to a higher, 217 to a lower risk category); 182 (53.7%) were correctly reclassified. The net reclassification improvement (NRI) was 7.7% (p = 0.029) and the integrated discrimination improvement (IDI) was 0.73% (p = 0.023). CONCLUSIONS: When carotid ultrasound is not restricted to the common carotid artery but includes the internal carotid segments, the inclusion of ultrasound data into stroke risk models may improve the risk classification of individuals. Further validation in primary prevention cohorts is warranted.

Prevalence of asymptomatic carotid artery stenosis in the general population: an individual participant data meta-analysis.

BACKGROUND AND PURPOSE: In the discussion on the cost-effectiveness of screening, precise estimates of severe asymptomatic carotid stenosis are vital. Accordingly, we assessed the prevalence of moderate and severe asymptomatic carotid stenosis by age and sex using pooled cohort data. METHODS: We performed an individual participant data meta-analysis (23 706 participants) of 4 population-based studies (Malmö Diet and Cancer Study, Tromsø, Carotid Atherosclerosis Progression Study, and Cardiovascular Health Study). Outcomes of interest were asymptomatic moderate (> or =50%) and severe carotid stenosis (> or =70%). RESULTS: Prevalence of moderate asymptomatic carotid stenosis ranged from 0.2% (95% CI, 0.0% to 0.4%) in men aged <50 years to 7.5% (5.2% to 10.5%) in men aged > or =80 years. For women, this prevalence increased from 0% (0% to 0.2%) to 5.0% (3.1% to 7.5%). Prevalence of severe asymptomatic carotid stenosis ranged from 0.1% (0.0% to 0.3%) in men aged <50 years to 3.1% (1.7% to 5.3%) in men aged > or =80. For women, this prevalence increased from 0% (0.0% to 0.2%) to 0.9% (0.3% to 2.4%). CONCLUSIONS: The prevalence of severe asymptomatic carotid stenosis in the general population ranges from 0% to 3.1%, which is useful information in the discussion on the cost-effectiveness of screening.

Risk assessment of symptomatic intracerebral hemorrhage after thrombolysis using DWI-ASPECTS.

BACKGROUND AND PURPOSE: Pretreatment lesion size on diffusion-weighted imaging (DWI) is a risk factor for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment. Here, we investigated whether the Alberta Stroke Programme Early CT Score (ASPECTS) applied to DWI images (DWI-ASPECTS) predicts sICH risk accurately. METHODS: In this retrospective multicenter study, prospectively collected data of 217 patients with anterior circulation stroke treated with intravenous or intraarterial thrombolysis within 6 hours after symptom onset were analyzed. Pretreatment DWI-ASPECTS scores were assessed by 2 independent investigators. For bleeding risk analysis, DWI-ASPECTS scores were either categorized into 0 to 7 (n=105) or 8 to 10 (n=112) or in 3 groups of similar sample size (DWI-ASPECTS 0 to 5 [n=69], 6 to 7 [n=70], and 8 to 10 [n=78]). RESULTS: DWI-ASPECTS scores correlated well with the DWI lesion volume (r=0.77, P<0.001, Spearman Rank test). Interobserver reliability for the assessment of DWI-ASPECTS was moderate (weighted kappa 0.441 [95% CI 0.373 to 0.509]). Twenty-three (10.6%) patients developed sICH. The sICH rate was significantly higher in patients with DWI-ASPECTS scores 0 to 7 (n=21, 15.1%) as compared to patients with DWI-ASPECTS scores 8 to 10 (n=2, 2.6%, P=0.004). sICH risk was 20.3%, 10%, and 2.6% in the 0 to 5, 6 to 7, and 8 to 10 DWI-ASPECTS groups, respectively. DWI-ASPECTS remained an independent prognostic factor for sICH after adjustment for clinical baseline variables (age, NIHSS, time to thrombolysis). CONCLUSIONS: DWI-ASPECTS predicts sICH risk after thrombolysis and may be helpful to contributing to quick sICH risk assessment before thrombolytic therapy.

Effects of poor bone window on the assessment of cerebral autoregulation with transcranial Doppler sonography - a source of systematic bias and strategies to avoid it.

BACKGROUND: The consequences of poor insonation conditions on autoregulation parameters assessed with transcranial Doppler (TCD) are unclear. METHODS: We present two new complementary methods to assess the quality of a TCD signal. Inserting a thin aluminium foil between TCD probe and skin makes a simple model to artificially worsen a good insonation window. Validation studies are presented. We assessed insonation quality and cerebral autoregulation parameters with transfer function analysis and cross correlation in 46 healthy volunteers with and without the aluminium foil model. The same studies were operated on 45 patients with good insonation windows, naïve, after worsening the bone window and during constant infusion of an ultrasound contrast agent. For studying reproducibility, we assessed autoregulation twice in 30 patients with poor bone windows, with and without constant contrast infusion. RESULTS: Both methods to measure insonation quality are valid and reproducible. The aluminium foil model realistically simulates a natural poor bone window, reducing the signal quality (e.g. energy of the signal spectrum from 33.4+/-3.5 to 26.2+/-2.5 dB, p<0.001). Thereby, the autoregulation parameters are systematically biased (e.g. phase difference from 37.3+/-10.1 degrees to 25.9+/-15.1 degrees , p<0.001); while with the use of an ultrasound contrast agent this can be largely compensated (phase difference 35.7+/-10.7 degrees , p<0.001). The reproducibility is significantly improved (ICC from 0.76 to 0.90, p<0.05). CONCLUSIONS: Poor bone windows can cause considerable bias in TCD autoregulation parameters. This bias might be avoided by the use of ultrasound contrast agents, which may greatly improve the credibility of TCD autoregulation assessment in elderly patients.

Assessment of cerebral autoregulation with transcranial Doppler sonography in poor bone windows using constant infusion of an ultrasound contrast agent.

Cerebral autoregulation is an important pathophysiological and prognostic parameter for a variety of neurologic conditions. It can be assessed quickly and safely using transcranial Doppler sonography (TCD). In elderly patients, poor insonation conditions decrease the number of examinable patients and can cause a systematic bias in autoregulation parameters. The aim of this study was to investigate whether a constant infusion of an ultrasound contrast agent (Levovist((R))) can counteract these effects. We examined two cohorts of unselected neurologic patients. In 45 patients with good insonation windows (cohort 1), we used a thin aluminium foil between the skin and the TCD probe to artificially decrease the insonation quality. We determined two parameters of cerebral autoregulation (phase difference [PD] and a cross-correlation coefficient [Mx]) in native patients, with aluminium foil and with aluminium foil and a constant infusion of Levovist. In 30 patients with poor insonation windows (cohort 2), we measured the autoregulation twice, with and without an infusion of Levovist, to assess the reproducibility of the autoregulation parameters. In cohort 1, the foil model significantly decreased the Doppler signal quality, i.e., the mean spectrum energy decreased from 33.9 +/- 2.7 dB to 26.3 +/- 2.4 dB (p < 0.001). This introduced a significant bias to all autoregulation parameters (PD: decreased from 38.2 +/- 10.0 degrees to 27.9 +/- 12.5 degrees (p < 0.001); Mx: decreased from 0.308 +/- 0.170 to 0.254 +/- 0.162 (p < 0.01)). Both effects were compensated largely by a constant infusion of Levovist (300 mg/min). In cohort 2, infusion of the contrast agent at the same rate increased insonation quality, too, but to a lesser degree (27.4 +/- 2.4 dB to 32.0 +/- 3.7 dB, p < 0.001). This smaller increase did not cause a significant change in the autoregulation parameters, but the reproducibility of the PD was significantly improved (intraclass coefficient coefficient [ICC] 0.76, 95% confidence interval [0.59-0.87] in native poor bone window compared with ICC 0.90, 95% confidence interval [0.81-0.95] with infusion of the contrast agent). Our data show that constant infusion of an ultrasound contrast agent during the assessment of cerebral autoregulation can avoid potential bias introduced by poor insonation conditions. Furthermore, infusion of the contrast agent can improve reproducibility and contribute to the credibility of autoregulation assessment in the elderly. (E-mail: matthias.lorenz@em.uni-frankfurt.de).

Influence of temporal insonation window quality on the assessment of cerebral autoregulation with transcranial Doppler sonography.

Cerebral autoregulation can be assessed quickly and noninvasively using transcranial Doppler sonography (TCD). A poor transtemporal insonation window is a common limitation in TCD examinations. The effects of insonation quality on TCD autoregulation measurements have never been investigated. We developed two methods to quantitatively measure insonation quality. We also validated a model to artificially worsen the insonation window. This involves inserting a thin aluminium foil between the TCD probe and the skin. Forty-six healthy volunteers underwent TCD examination before and after artificial reduction of the transtemporal insonation quality. Two autoregulation parameters, the phase difference (PD) and a cross-correlation coefficient (Mx), were calculated from the recordings. The aluminium foil model realistically simulates poor insonation conditions, producing a decrease in the signal power from 36.4 +/- 2.8 dB to 32.0 +/- 1.5 dB. In corrupted insonation windows, the PD is artificially low (native: 34.2 +/- 9.3 degrees , corrupted: 29.9 +/- 9.7 degrees , p = 0.002), but the Mx is not significantly different. Insonation quality may introduce a systematic bias of clinically relevant magnitude into TCD-based cerebral autoregulation studies. This must be considered when studies of elderly patients are planned. This article discusses strategies to account for this bias.