Management of patent foramen ovale; findings from a nationwide survey.

OBJECTIVES: Several clinical trials have provided evidence supporting the transcatheter closure of patent foramen ovale (PFO) in selected patients following a cryptogenic stroke. However, it remains unknown to what extent these guidelines have been implemented in everyday clinical practice and the familiarity of physicians from different specialties with PFO closure. The aim of our nationwide survey is to explore the implementation of transcatheter PFO occlusion in Greek clinical practice. MATERIALS AND METHODS: Attending level cardiologists, internal medicine physicians and neurologists involved in the management of PFO-related strokes working in Greece were invited to complete an online questionnaire. The questionnaire consisted of 19 questions and was designed to obtain comprehensive data on provider demographics, PFO characteristics, and specific clinical scenarios. RESULTS: A total of 51 physicians (56.9 % cardiologists, 25.5 % neurologists and 17.6 % internal medicine physicians) completed the survey, resulting in a response rate of 53 %. Cardiologists, internal medicine physicians and neurologists agree on several issues regarding PFO closure, such as PFO closure as first line treatment, management of patients with DVT or prior decompression sickness, and post-closure antithrombotic treatment, but different approaches were reported regarding closure in patients with thrombophilia treated with oral anticoagulation (p=0.012) and implantable loop recorder placement for atrial fibrillation exclusion (p=0.029 and p=0.020). CONCLUSIONS: Our findings show that cardiologists, internal medicine physicians and neurologists agree in numerous issues, but share different views in the management of patients with thrombophilia and rhythm monitoring duration. These results highlight the significance of collaboration among physicians from different medical specialties for achieving optimal results.

External Performance of the HAVOC Score for the Prediction of New Incident Atrial Fibrillation.

Background and Purpose- The HAVOC score (hypertension, age, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, coronary artery disease) was proposed for the prediction of atrial fibrillation (AF) after cryptogenic stroke. It showed good model discrimination (area under the curve, 0.77). Only 2.5% of patients with a low-risk HAVOC score (ie, 0-4) were diagnosed with new incident AF. We aimed to assess its performance in an external cohort of patients with embolic stroke of undetermined source. Methods- In the AF-embolic stroke of undetermined source dataset, we assessed the discriminatory power, calibration, specificity, negative predictive value, and accuracy of the HAVOC score to predict new incident AF. Patients with a HAVOC score of 0 to 4 were considered as low-risk, as proposed in its original publication. Results- In 658 embolic stroke of undetermined source patients (median age, 67 years; 44% women), the median HAVOC score was 2 (interquartile range, 3). There were 540 (82%) patients with a HAVOC score of 0 to 4 and 118 (18%) with a score of ≥5. New incident AF was diagnosed in 95 (14.4%) patients (28.8% among patients with HAVOC score ≥5 and 11.3% among patients with HAVOC score 0-4 [age- and sex-adjusted odds ratio, 2.29 (95% CI, 1.37-3.82)]). The specificity of low-risk HAVOC score to identify patients without new incident AF was 88.7%. The negative predictive value of low-risk HAVOC score was 85.1%. The accuracy was 78.0%, and the area under the curve was 68.7% (95% CI, 62.1%-73.3%). Conclusions- The previously reported low rate of AF among embolic stroke of undetermined source patients with low-risk HAVOC score was not confirmed in our cohort. Further assessment of the HAVOC score is warranted before it is routinely implemented in clinical practice.

Supraventricular Extrasystoles on Standard 12-lead Electrocardiogram Predict New Incident Atrial Fibrillation after Embolic Stroke of Undetermined Source: The AF-ESUS Study.

BACKGROUND: The diagnosis of covert atrial fibrillation (AF) remains a major challenge to guide secondary prevention of patients with embolic stroke of undetermined source (ESUS). AIMS: We analyzed consecutive ESUS patients from 3 prospective stroke registries to assess whether the presence of supraventricular extrasystoles (SVE) on standard 12-lead electrocardiogram (ECG) is associated with the detection of AF (primary outcome), stroke recurrence and death (secondary outcomes) during follow-up. METHODS: We measured the number of SVEs in all available ECGs of patients hospitalized for ESUS. Multivariate stepwise regression with forward selection of covariates assessed the association between SVE (classified in 4 groups according to their number per 10 seconds of ECG: no SVE, >0-1SVEs, >1-2SVEs, and >2SVEs) and outcomes during follow-up. The Kaplan-Meier product limit method estimated the 10-year cumulative probabilities of outcomes in each SVE group. We calculated the negative prognostic value (NPV) of the presence of any SVE to predict new AF, defined as the probability that AF will not be detected during follow-up if there is no SVE. RESULTS: Among 853 ESUS patients followed for 2857 patient-years (median age: 67 years, 43.0% women), 226 (26.5%) patients had at least 1 SVE at the standard 12-lead ECGs performed during hospitalization. AF was detected in 125 (14.7%) of patients in the overall population during follow-up: 8.9%, 22.5%, 28.1%, and 48.3% in patients with no SVE, greater than 0-1SVE, greater than 1-2SVE and greater than 2SVE respectively. In multivariate regression analysis, compared to patients with no SVEs, the corresponding hazard-ratios were 1.80 [95% confidence intervals (95%CI):1.06-3.05], 2.26 (95%CI:1.28-4.01) and 3.19 (95%CI:1.93-5.27). The NPV of the presence of any SVE for the prediction of new AF was 91.4%. There was no statistically significant association of SVE with the risk of ischemic stroke recurrence and death. CONCLUSIONS: In ESUS patients without SVEs during hospitalization, the probability that AF will not be detected during a follow-up of 3.4 years is more than 91%.

External Validation of the PREMISE Score in the Athens Stroke Registry.

BACKGROUND: A simple score was proposed recently for Predicting Early Mortality from Ischemic Stroke (PREMISE) derived from the Austrian Stroke Unit Registry. This score could be useful in clinical practice and research. However, its generalizability is uncertain, as it was validated internally only. AIMS: We aimed to validate the PREMISE score externally. METHODS: The analysis was performed in the Athens Stroke Registry. The PREMISE score was calculated as described in the original publication. The outcome was death within 7 days after stroke. Logistic regression analysis was used to estimate the relative death risk in different strata of the PREMISE score using the lowest values of the score (ie, 0-4) as the reference category. We assessed the score's calibration by the Hosmer-Lemeshow goodness-of-fit test and its discriminatory power by calculating the area under the receiver operating characteristics curve (AUC). RESULTS: In 2608 consecutive patients (median age 71 years, 38.8% women) with acute ischemic stroke treated in the stroke unit, mortality increased with increasing PREMISE score from .1% (95% confidence intervals [95% CI]: 0%-.2%) in patients with a score of 0-4 to 28.2% (95% CI: 14.1%-42.3%) in patients with a score of ≥10. The risk for death was more than 6 times higher in patients with a PREMISE score of ≥10 compared to patients with 0-4 points (odds ratio [OR]:6.21, 95% CI:4.13-8.29). Τhe PREMISE score showed excellent calibration (Hosmer-Lemeshow χ2: .01, P= .99) and good discriminatory power (AUC .873, 95% CI: .844-.901). CONCLUSIONS: The present study confirms the prognostic accuracy of the PREMISE score in an independent cohort of patients with acute ischemic stroke treated in the stroke unit.

Renal Function and Risk Stratification of Patients With Embolic Stroke of Undetermined Source.

Background and Purpose- We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods- We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results- In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99-1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87-1.73) or categorical covariate (likelihood-ratio test 2.59, P=0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR ≥90, 16.6% for eGFR 60-89, 21.7% for eGFR 45-59, 19.2% for eGFR 30-44, and 24.9% for eGFR <30 (likelihood-ratio test 2.59, P=0.63). The results were similar for the outcome of death. Conclusions- The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.

Muscle microcirculation alterations and relation to dipping status in newly diagnosed untreated patients with arterial hypertension-A pilot study.

OBJECTIVE: The importance of abnormalities observed in the microcirculation of patients with arterial hypertension (AH) is being increasingly recognized. The authors aimed to evaluate skeletal muscle microcirculation in untreated, newly diagnosed hypertensive patients with NIRS, a noninvasive method that evaluates microcirculation. METHODS: We evaluated 34 subjects, 17 patients with AH (13 males, 49±13 years, BMI: 26±2 kg/m2 ) and 17 healthy controls (12 males, 49±15 years, BMI: 25±3 kg/m2 ). The thenar muscle StO2 (%) was measured by NIRS before, during and after 3-minutes vascular occlusion to calculate OCR (%/min), EF (%/min), and RHT (minute). The dipping status of hypertensive patients was assessed. RESULTS: The RHT differed between AH patients and healthy subjects (2.6±0.3 vs 2.1±0.3 minutes, P<.001). Dippers had higher EF than nondippers (939±280 vs 710±164%/min, P=.05). CONCLUSIONS: The study suggests an impaired muscle microcirculation in newly diagnosed, untreated AH patients.

Convexity Subarachnoid Hemorrhage Due to Cardioembolic Stroke in a Woman with Thyrotoxicosis: Α Case Report.

BACKGROUND: Non-traumatic convexity subarachnoid hemorrhage (cSAH) is a rarely reported condition with a wide spectrum of etiologies. Cerebral ischemia secondary to extracranial or intracranial atherosclerotic disease has been identified as a relatively uncommon cause of cSAH. CASE REPORT: We report a case of cSAH caused by cardioembolic stroke. A 69-year old female patient developed suddenly left-sided face and body weakness and numbness and visual neglect on the left. She was newly detected with paroxysmal atrial fibrillation on the ground of thyrotoxicosis. Brain magnetic resonance imaging revealed ischemia of embolic pattern with cSAH. Further evaluation excluded other cause of hemorrhage. Dilation of leptomeningeal collateral vessels and rupture of pial vessels in distal cortical arteries may caused cSAH. Full anticoagulation was initiated. After one month, her condition improved significantly (NIHSS from 6 to 2). CONCLUSIONS: cSAH may be a rare complication of cardioembolic stroke.

Risk Stratification for Recurrence and Mortality in Embolic Stroke of Undetermined Source.

BACKGROUND AND PURPOSE: The risk of stroke recurrence in patients with Embolic Stroke of Undetermined Source (ESUS) is high, and the optimal antithrombotic strategy for secondary prevention is unclear. We investigated whether congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke or transient ischemic attack (TIA; CHADS2) and CHA2DS2-VASc scores can stratify the long-term risk of ischemic stroke/TIA recurrence and death in ESUS. METHODS: We pooled data sets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. Cox regression analyses were performed to investigate if prestroke CHADS2 and congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or TIA, vascular disease, age 65-74 years, sex category (CHA2DS2-VASc) scores were independently associated with the risk of ischemic stroke/TIA recurrence or death. The Kaplan-Meier product limit method was used to estimate the cumulative probability of ischemic stroke/TIA recurrence and death in different strata of the CHADS2 and CHA2DS2-VASc scores. RESULTS: One hundred fifty-nine (5.6% per year) ischemic stroke/TIA recurrences and 148 (5.2% per year) deaths occurred in 1095 patients (median age, 68 years) followed-up for a median of 31 months. Compared with CHADS2 score 0, patients with CHADS2 score 1 and CHADS2 score >1 had higher risk of ischemic stroke/TIA recurrence (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.41-4.00 and HR, 2.72; 95% CI, 1.68-4.40, respectively) and death (HR, 3.58; 95% CI, 1.80-7.12, and HR, 5.45; 95% CI, 2.86-10.40, respectively). Compared with low-risk CHA2DS2-VASc score, patients with high-risk CHA2DS2-VASc score had higher risk of ischemic stroke/TIA recurrence (HR, 3.35; 95% CI, 1.94-5.80) and death (HR, 13.0; 95% CI, 4.7-35.4). CONCLUSIONS: The risk of recurrent ischemic stroke/TIA and death in ESUS is reliably stratified by CHADS2 and CHA2DS2-VASc scores. Compared with the low-risk group, patients in the high-risk CHA2DS2-VASc group have much higher risk of ischemic stroke recurrence/TIA and death, approximately 3-fold and 13-fold, respectively.

Embolic Stroke of Undetermined Source and Detection of Atrial Fibrillation on Follow-Up: How Much Causality Is There?

BACKGROUND: There is increasing debate whether atrial fibrillation (AF) episodes during follow-up in patients with embolic stroke of undetermined source (ESUS) are causally associated with the event. AF-related strokes are more severe than strokes of other etiologies. In this context, we aimed to compare stroke severity between ESUS patients diagnosed with AF during follow-up and those who were not. We hypothesized that, if AF episodes detected during follow-up are indeed causally associated with the index event, stroke severity in the AF group should be higher than the non-AF group. METHODS: Dataset was derived from the Athens Stroke Registry. ESUS was defined by the Cryptogenic Stroke/ESUS International-Working-Group criteria. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Cumulative probabilities of recurrent stroke or peripheral embolism in the AF and non-AF ESUS groups were estimated by Kaplan-Meier analyses. RESULTS: Among 275 ESUS patients, AF was detected during follow-up in 80 (29.1%), either during repeated electrocardiogram monitoring (18.2%) or during hospitalization for stroke recurrence (10.9%). NIHSS score was similar between the two groups (5 [2-13] versus 5 [2-14], P = .998). More recurrent strokes or peripheral embolisms occurred in the AF group compared with the non-AF group (42.5% versus 13.3%, P = .001). CONCLUSIONS: Stroke severity is similar between ESUS patients who were diagnosed with AF during follow-up and those who were not. Given that AF-related strokes are more severe than strokes of other etiologies, this finding challenges the assumption that the association between ESUS and AF detected during follow-up is as frequently causal as regarded.

Embolic Strokes of Undetermined Source in the Athens Stroke Registry: An Outcome Analysis.

BACKGROUND AND PURPOSE: Information about outcomes in Embolic Stroke of Undetermined Source (ESUS) patients is unavailable. This study provides a detailed analysis of outcomes of a large ESUS population. METHODS: Data set was derived from the Athens Stroke Registry. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group criteria. End points were mortality, stroke recurrence, functional outcome, and a composite cardiovascular end point comprising recurrent stroke, myocardial infarction, aortic aneurysm rupture, systemic embolism, or sudden cardiac death. We performed Kaplan-Meier analyses to estimate cumulative probabilities of outcomes by stroke type and Cox-regression to investigate whether stroke type was outcome predictor. RESULTS: 2731 patients were followed-up for a mean of 30.5±24.1months. There were 73 (26.5%) deaths, 60 (21.8%) recurrences, and 78 (28.4%) composite cardiovascular end points in the 275 ESUS patients. The cumulative probability of survival in ESUS was 65.6% (95% confidence intervals [CI], 58.9%-72.2%), significantly higher compared with cardioembolic stroke (38.8%, 95% CI, 34.9%-42.7%). The cumulative probability of stroke recurrence in ESUS was 29.0% (95% CI, 22.3%-35.7%), similar to cardioembolic strokes (26.8%, 95% CI, 22.1%-31.5%), but significantly higher compared with all types of noncardioembolic stroke. One hundred seventy-two (62.5%) ESUS patients had favorable functional outcome compared with 280 (32.2%) in cardioembolic and 303 (60.9%) in large-artery atherosclerotic. ESUS patients had similar risk of composite cardiovascular end point as all other stroke types, with the exception of lacunar strokes, which had significantly lower risk (adjusted hazard ratio, 0.70 [95% CI, 0.52-0.94]). CONCLUSIONS: Long-term mortality risk in ESUS is lower compared with cardioembolic strokes, despite similar rates of recurrence and composite cardiovascular end point. Recurrent stroke risk is higher in ESUS than in noncardioembolic strokes.

ASTRAL score predicts 5-year dependence and mortality in acute ischemic stroke.

BACKGROUND AND PURPOSE: The ASTRAL score was externally validated showing remarkable consistency on 3-month outcome prognosis in patients with acute ischemic stroke. The present study aimed to evaluate ASTRAL score's prognostic accuracy to predict 5-year outcome. METHODS: All consecutive patients with acute ischemic stroke registered in the Athens Stroke Registry between January 1, 1998, and December 31, 2010, were included. Patients were excluded if admitted >24 hours after symptom onset or if any ASTRAL score component was missing. End points were 5-year unfavorable functional outcome, defined as modified Rankin Scale 3 to 6, and 5-year mortality. For each outcome, the area under the receiver operating characteristics curve was calculated; also, a multivariate Cox proportional hazards analysis was performed to investigate whether the ASTRAL score was an independent predictor of outcome. The Kaplan-Meier product limit method was used to estimate the probability of 5-year survival for each ASTRAL score quartile. RESULTS: The area under the receiver operating characteristics curve of the score to predict 5-year unfavorable functional outcome was 0.89, 95% confidence interval 0.88 to 0.91. In multivariate Cox proportional hazards analysis, the ASTRAL score was independently associated with 5-year unfavorable functional outcome (hazard ratio, 1.09; 95% confidence interval, 1.08-1.10). The area under the receiver operating characteristics curve for the ASTRAL score's discriminatory power to predict 5-year mortality was 0.81 (95% confidence interval, 0.78-0.83). In multivariate analysis, the ASTRAL score was independently associated with 5-year mortality (hazard ratio, 1.09, 95% confidence interval, 1.08-1.10). During the 5-year follow-up, the probability of survival was significantly lower with increasing ASTRAL score quartiles (log-rank test <0.001). CONCLUSIONS: The ASTRAL score reliably predicts 5-year functional outcome and mortality in patients with acute ischemic stroke.

Association of home and ambulatory blood pressure variability with left ventricular mass index in chronic kidney disease patients.

Increased blood pressure (BP) variability is associated with the development of target organ damage. However, the optimal type and index of BP variability (BPV) regarding their prognostic significance is unclear. The aim of our study was to compare the association of ambulatory and home BPV with the left ventricular mass index (LVMI) in patients with chronic kidney disease (CKD). From a total of 1560 consecutive subjects, 137 hypertensive patients with CKD underwent home and ambulatory BP monitoring and echocardiographic measurements. The variability of home BP monitoring was quantified by using the standard deviation (SD), coefficient of variation (CV), and morning minus evening BP values. Ambulatory BPV was quantified using the SD, CV, and the time rate (TR) of BP variation. The univariate analysis demonstrated that day-to-day systolic SD and the 24-h TR of systolic BP (SBP) variation were significantly associated with the LVMI. The multivariate linear regression analysis showed a significant and independent association of the LVMI with the 24-h TR of SBP variation (B = 9.204, 95% CI: 1.735-16.672; p = 0.016). A 0.1-mmHg/min increase in the 24-h TR of SBP variation was associated with an increment of 9.204 g/m2 in the LVMI, even after adjustment for BP and other vascular risk factors. In conclusion, ambulatory BPV but not home BPV was associated with the LVMI in CKD patients. The 24-h TR of SBP variation was the only BPV index associated with the LVMI, independent of average BP values.

Characteristics and outcomes of Embolic Stroke of Undetermined Source according to stroke severity.

BACKGROUND AND AIMS: Patients with embolic strokes of undetermined source (ESUS) usually present with mild symptoms. We aimed to compare the baseline characteristics between mild and severe ESUS, identify predictors for severe ESUS, and assess outcomes of patients with severe ESUS. METHODS: In the AF-ESUS (AF-ESUS) dataset, we stratified ESUS severity using the median National Institutes of Health Stroke Scale (NIHSS) score on admission as cut-off. We performed multivariable stepwise regression analyses to identify independent predictors of severe ESUS and to assess the association between ESUS severity and stroke recurrence, death, and new incident atrial fibrillation (AF) on follow-up. The 10-year cumulative probabilities of outcome incidence were estimated by the Kaplan-Meier product limit method. RESULTS: In 772 patients (median NIHSS: 6 (interquartile range: 3-12)), 414 (53.6%) patients had severe ESUS (i.e. NIHSS ≥6). Female sex was the only independent predictor for severe ESUS (odds ratio: 1.72 (1.27-2.33)). The rates of recurrence (3.3%/year vs. 3.4%/year, adjusted-hazard ratio: 1.09 (0.73-1.62)) and new incident AF (13.5% vs. 17.0%, adjusted odds ratio: 0.67 (0.44-1.03)) were similar between severe and mild ESUS, but mortality was higher (5.4%/year vs. 3.7%/year, adjusted-hazard ratio: 1.51 (1.05-2.16)) in severe ESUS. The 10-year cumulative probability for stroke recurrence was similar between severe and mild ESUS (38.1% (29.2-48.6) vs. 36.6% (27.8-47.0), log-rank test: 0.01, p = 0.920). The 10-year cumulative probability of death was higher in patients with severe ESUS compared with mild ESUS (40.5% (32.5-50.0) vs. 34.0% (26.0-43.6) respectively; log-rank test: 4.54, p = 0.033). CONCLUSIONS: Women have more severe ESUS compared with men. Patients with severe ESUS have similar rates of stroke recurrence and new incident AF, but higher mortality compared with mild ESUS.

Left atrial diameter thresholds and new incident atrial fibrillation in embolic stroke of undetermined source.

BACKGROUND AND PURPOSE: We analyzed consecutive patients with embolic stroke of undetermined source (ESUS) from three prospective stroke registries to compare the prognostic performance of different LAD thresholds for the prediction of new incident AF. METHODS: We calculated the sensitivity, specificity, positive prognostic value (PPV), negative prognostic value (NPV) and Youden's J-statistic of different LAD thresholds to predict new incident AF. We performed multivariate stepwise regression with forward selection of covariates to assess the association between the LAD threshold with the highest Youden's J-statistic and AF detection. RESULTS: Among 675 patients followed for 2437 patient-years, the mean LAD was 38.5 ± 6.8 mm. New incident AF was diagnosed in 115 (17.0%) patients. The LAD threshold of 40mm yielded the highest Youden's J-statistic of 0.35 with sensitivity 0.69, specificity 0.66, PPV 0.27 and NPV 0.92. The likelihood of new incident AF was nearly twice in patients with LAD > 40 mm compared to LAD ≤ 40 mm (HR:1.92, 95%CI:1.24-2.97, p = 0.004). The 10-year cumulative probability of new incident AF was higher in patients with LAD>40 mm compared to LAD ≤ 40 mm (53.5% and 22.4% respectively, log-rank-test: 28.2, p < 0.001). The annualized rate of stroke recurrence of 4.0% in the overall population did not differ significantly in patient above vs. below this LAD threshold (HR:0.96, 95%CI:0.62-1.48, p = 0.85). CONCLUSIONS: The LAD threshold of 40 mm has the best prognostic performance among other LAD values to predict new incident AF after ESUS. The diagnostic yield of prolonged cardiac rhythm monitoring in patients with LAD ≤ 40 mm seems low; therefore, such patients may have lower priority for prolonged cardiac monitoring.

Impact of prehypertension on common carotid artery intima-media thickness and left ventricular mass.

BACKGROUND AND PURPOSE: Prehypertension has been recently introduced by JNC 7 as a new blood pressure (BP) category, associated with increased target-organ damage. Subclinical atherosclerosis by means of common artery intima-media thickness (CCA-IMT) has been incompletely investigated in prehypertensive patients. The aim of our study was to assess the extent of CCA-IMT and left ventricular mass (LVM) in prehypertensive adults in comparison to normotensive and untreated hypertensive subjects. METHODS: From a total of 5221 consecutive patients screened to our Hypertension Unit we selected 896 consecutive individuals according to prespecified inclusion criteria, who underwent 24-hour ambulatory BP monitoring, carotid artery ultrasonographic, and echocardiographic measurements. Patients who received antihypertensive treatment during the BP monitoring were excluded. According to the office BP levels, patients were divided into 3 subgroups: normotensives (office BP <120/80 mm Hg), prehypertensives (120/80 mm Hgor=140/90 mm Hg). Statistical analyses were performed by means of 1-way ANOVA, chi(2) test, and ANCOVA. RESULTS: According to the office BP levels, the distribution of the study population was: normotensives (14.4%), prehypertensives (23.7%), and hypertensives (61.9%). Prehypertensive patients had higher CCA-IMT (P=0.038) and LVM (P=0.030) values than normotensive subjects, even after adjustment for baseline characteristics. Greater CCA-IMT values were observed in hypertensive patients in comparison to prehypertensives (P=0.002). CONCLUSIONS: Prehypertensive patients had higher CCA-IMT and LVM than their normotensive counterparts. Prehypertension status is cross-sectionally associated with subclinical atherosclerosis and target-organ damage.

Prevalence and Overlap of Potential Embolic Sources in Patients With Embolic Stroke of Undetermined Source.

Background We aimed to assess the prevalence and degree of overlap of potential embolic sources (PES) in patients with embolic stroke of undetermined source (ESUS). Methods and Results In a pooled data set derived from 3 prospective stroke registries, patients were categorized in ≥1 groups according to the PES that was/were identified. We categorized PES as follows: atrial cardiopathy, atrial fibrillation diagnosed during follow-up, arterial disease, left ventricular disease, cardiac valvular disease, patent foramen ovale, and cancer. In 800 patients with ESUS (43.1% women; median age, 67.0 years), 3 most prevalent PES were left ventricular disease, arterial disease, and atrial cardiopathy, which were present in 54.4%, 48.5%, and 45.0% of patients, respectively. Most patients (65.5%) had >1 PES, whereas only 29.7% and 4.8% of patients had a single or no PES, respectively. In 31.1% of patients, there were ≥3 PES present. On average, each patient had 2 PES (median, 2). During a median follow-up of 3.7 years, stroke recurrence occurred in 101 (12.6%) of patients (23.3 recurrences per 100 patient-years). In multivariate analysis, the risk of stroke recurrence was higher in the atrial fibrillation group compared with other PES, but not statistically different between patients with 0 to 1, 2, or ≥3 PES. Conclusions There is major overlap of PES in patients with ESUS. This may possibly explain the negative results of the recent large randomized controlled trials of secondary prevention in patients with ESUS and offer a rationale for a randomized controlled trial of combination of anticoagulation and aspirin for the prevention of stroke recurrence in patients with ESUS. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02766205.

Carotid plaques and detection of atrial fibrillation in embolic stroke of undetermined source.

OBJECTIVE: To investigate the association between the presence of ipsilateral nonstenotic carotid plaques and the rate of detection of atrial fibrillation (AF) during follow-up in patients with embolic strokes of undetermined source (ESUS). METHODS: We pooled data of all consecutive ESUS patients from 3 prospective stroke registries. Multivariate stepwise regression assessed the association between the presence of nonstenotic carotid plaques and AF detection. The 10-year cumulative probabilities of AF detection were estimated by the Kaplan-Meier product limit method. RESULTS: Among 777 patients followed for 2,642 patient-years, 341 (38.6%) patients had an ipsilateral nonstenotic carotid plaque. AF was detected in 112 (14.4%) patients in the overall population during follow-up. The overall rate of AF detection was 8.5% in patients with nonstenotic carotid plaques (2.9% per 100 patient-years) and 19.0% in patients without (5.0% per 100 patient-years) (unadjusted hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.37-0.84). The presence of ipsilateral nonstenotic carotid plaques was associated with lower probability for AF detection (adjusted HR 0.57, 95% CI 0.34-0.96, p = 0.03). The 10-year cumulative probability of AF detection was lower in patients with ipsilateral nonstenotic carotid plaques compared to those without (34.5%, 95% CI 21.8-47.2 vs 49.0%, 95% CI 40.4-57.6 respectively, log-rank-test: 11.8, p = 0.001). CONCLUSIONS: AF is less frequently detected in ESUS patients with nonstenotic carotid plaques compared to those without. CLINICALTRIALSGOV IDENTIFIER: NCT02766205.

A tool to identify patients with embolic stroke of undetermined source at high recurrence risk.

OBJECTIVE: A tool to stratify the risk of stroke recurrence in patients with embolic stroke of undetermined source (ESUS) could be useful in research and clinical practice. We aimed to determine whether a score can be developed and externally validated for the identification of patients with ESUS at high risk for stroke recurrence. METHODS: We pooled the data of all consecutive patients with ESUS from 11 prospective stroke registries. We performed multivariable Cox regression analysis to identify predictors of stroke recurrence. Based on the coefficient of each covariate of the fitted multivariable model, we generated an integer-based point scoring system. We validated the score externally assessing its discrimination and calibration. RESULTS: In 3 registries (884 patients) that were used as the derivation cohort, age, leukoaraiosis, and multiterritorial infarct were identified as independent predictors of stroke recurrence and were included in the final score, which assigns 1 point per every decade after 35 years of age, 2 points for leukoaraiosis, and 3 points for multiterritorial infarcts (acute or old nonlacunar). The rate of stroke recurrence was 2.1 per 100 patient-years (95% confidence interval [CI] 1.44-3.06) in patients with a score of 0-4 (low risk), 3.74 (95% CI 2.77-5.04) in patients with a score of 5-6 (intermediate risk), and 8.23 (95% CI 5.99-11.3) in patients with a score of 7-12 (high risk). Compared to low-risk patients, the risk of stroke recurrence was significantly higher in intermediate-risk (hazard ratio [HR] 1.78, 95% CI 1.1-2.88) and high-risk patients (HR 4.67, 95% CI 2.83-7.7). The score was well-calibrated in both derivation and external validation cohorts (8 registries, 820 patients) (Hosmer-Lemeshow test χ2: 12.1 [p = 0.357] and χ2: 21.7 [p = 0.753], respectively). The area under the curve of the score was 0.63 (95% CI 0.58-0.68) and 0.60 (95% CI 0.54-0.66), respectively. CONCLUSIONS: The proposed score can assist in the identification of patients with ESUS at high risk for stroke recurrence.

Factors influencing white-coat effect.

BACKGROUND: The transient blood pressure (BP) rise during clinical visits is usually referred to as white-coat effect (WCE). The aim of the present study was to investigate factors that may influence the WCE. METHODS: A total of 2004 subjects underwent office BP measurements and 24-h ambulatory BP monitoring (ABPM) on the same day. The WCE was estimated as the difference between office and average daytime ambulatory BP (ABP). According to the office and daytime BP values, the study population was divided into normotensives (NTs), white-coat hypertensives (WCHs), masked hypertensives (MHTs), and sustained hypertensives (SHTs). Statistical analyses were performed using one-way analysis of variance and multiple linear regression models. RESULTS: The mean systolic and diastolic WCE was 9 +/- 16 and 7 +/- 12 mm Hg, respectively. In the entire group of patients, multiple linear regression models revealed independent determinants of systolic WCE in the following rank order: office systolic BP (SBP) (beta = 0.727; P < 0.001), female gender (beta = 0.166; P < 0.001), daytime SBP variability (beta = 0.128; P < 0.001), age (beta = 0.039, P = 0.020), and smoking (beta = 0.031, P = 0.048). A 1.0 mm Hg increase in daytime SBP variability correlated with an increment of 0.589 mm Hg (95% confidence intervals, 0.437-0.741) in the systolic WCE. The regression analyses for diastolic WCE revealed the same factors as independent determinants. A 1.0 mm Hg increase in daytime diastolic BP (DBP) variability was independently associated with an increment of 0.418 mm Hg (95% confidence intervals, 0.121-0.715) in the diastolic WCE. CONCLUSIONS: Factors such as gender, age, smoking, office BPV and daytime BPV may exert an important influence on the magnitude of the WCE.

20-year trends of characteristics and outcomes of stroke patients with atrial fibrillation.

Background The accurate knowledge of secular trends in prevalence, characteristics and outcomes of patients with ischemic stroke and atrial fibrillation allows better projections into the future. Aim We aimed to report the overall, age- and sex-specific secular trends of characteristics and outcomes of patients with acute ischemic stroke (AIS) and atrial fibrillation between 1993 and 2012 in the Athens Stroke Registry. Methods We used Joinpoint regression analysis to calculate the average annual percent changes and 95% confidence intervals. Results Among 3314 stroke patients, 1044 (31.5%) had atrial fibrillation. Between 1993 and 2012, there was an average annual reduction of 0.8% (95% CI: -1.5%; 0.0%) in the proportion of atrial fibrillation patients among all AIS patients, whereas the proportion of newly diagnosed atrial fibrillation patients among all atrial fibrillation patients increased annually by an average of 7.1% (95% CI: 5.4%;8.9%). Among all atrial fibrillation patients, there was an average annual reduction of 2.9% (95% CI: -2.7; -3.2%) in the proportion of previously known atrial fibrillation patients, followed by an annual average reduction of 2.4% (95% CI: -1.2; -3.6%) in the proportion of previously known atrial fibrillation patients not receiving any antithrombotic treatment at admission. During that period, there was an increase in the average annual proportion of previously known atrial fibrillation patients treated with anticoagulants (6.4%, 95% CI: 1.2;11.9%) and aspirin (2.3%, 95% CI: -0.4;5.0%) at admission; an average annual increase in the proportion of atrial fibrillation patients who were prescribed anticoagulant was apparent both for patients with mRS<4 (3.5%) and mRS: 4-5 (7.2%), while the proportion of atrial fibrillation patients who were prescribed aspirin or no antithrombotic at discharge was annually reduced (5.8% for mRS<4; 1.6% for mRS: 4-5 and 7.1% for mRS<4;5.3% for mRS: 4-5 respectively). Stroke recurrences were annually reduced by an average of 5.8% (95% CI: -8.6; -3.0%), along with cardiovascular events (6.5%, 95% CI: -8.3; -4.7%) and deaths (7.9%, 95% CI: -9.2; -6.5%). Conclusions Between 1993 and 2012, the proportion of atrial fibrillation patients on proper antithrombotic treatment and the rate of newly diagnosed atrial fibrillation increased significantly. Rates of stroke recurrence, cardiovascular events, and mortality reduced significantly.