Konstantinos Spengos

U‐shaped relationship between mortality and admission blood pressure in patients with acute stroke

Objective.  To evaluate the relationship between systolic blood pressure (SBP) or diastolic blood pressure (DBP) on admission and early or late mortality in patients with acute stroke.

Time Rate of Blood Pressure Variation Is Associated With Increased Common Carotid Artery Intima-Media Thickness

The extent of target-organ damage has been positively associated with the magnitude of blood pressure (BP) variability in essential hypertension. However, the clinical implications of the rate of BP changes have never been investigated. We evaluated the association between the rate of systolic BP (SBP) variation derived from ambulatory BP monitoring (ABPM) data analysis and the extent of common carotid artery (CCA) intima-media thickness (IMT) in normotensive (n=280) and in uncomplicated hypertensive subjects (n=234). The 24-hour rate of SBP variation was significantly (P<0.001) higher in hypertensive (0.608 mm Hg/min; 95% confidence interval [CI], 0.595 to 0.622) than in normotensive individuals (0.567 mm Hg/min; 95% CI, 0.555 to 0.578), even after adjusting for baseline characteristics, day–night BP changes, 24-hour heart rate (HR), SBP, and HR variability. In the entire group of patients, multiple linear regression models revealed independent determinants of CCA-IMT in the following rank order: age (P<0.001), 24-hour rate of SBP variation (P<0.001), male gender (P=0.004), cholesterol (P=0.009), and smoking (P=0.014). A 0.1 mm Hg/min increase in the 24-hour rate of SBP variation was associated to an increment of 0.029 mm (95% CI, 0.018 to 0.040) in CCA-IMT independent of BP and HR levels, BP and HR variability, and dipping status. The rate of SBP variation during the morning BP surge correlated independently (P<0.001) to larger CCA-IMT values after adjustment for baseline characteristics and other ABPM parameters. Thus, the rate of BP fluctuations is greater in hypertensive patients and correlates to increased CCA-IMT. This finding indicates that steeper BP variations may produce a greater stress on the vessel wall and consequently result in medial hypertrophy of the large arteries.

Association Between Obesity and Mortality After Acute First-Ever Stroke: The Obesity–Stroke Paradox

Background and Purpose— Limited data exist concerning obesity and survival in patients after acute stroke. The objective of this study was to investigate the association between obesity and survival in patients with acute first-ever stroke. Methods— Patients were prospectively investigated based on a standard diagnostic protocol over a period of 16 years. Evaluation was performed on admission, at 7 days, at 1, 3, and 6 months after discharge, and yearly thereafter for up to 10 years after stroke. The study patients were divided into 3 groups according to body mass index (BMI): normal weight (<25 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2). Overall survival during follow-up was the primary end point. The secondary end point was the overall composite cardiovascular events over the study period. Results— Based on our inclusion criteria, 2785 patients were recruited. According to BMI, 1138 (40.9%) patients were of normal weight, 1113 (41.0%) were overweight, and 504 (18.1%) were obese. NIHSS score on admission (mean, 11.28±8.65) was not different among the study groups. Early (first week) survival in obese (96.4%; 95% CI, 94.8%–97.9%) and overweight patients (92.8%; 95% CI, 91.2%–94.4%) was significantly higher compared to that of normal-weight patients (90.2%; 95% CI, 88.4%–92.0%). Similarly, 10-year survival was 52.5% (95% CI, 46.4%–58.6%) in obese, 47.4% (95% CI, 43.5%–51.3%) in overweight, and 41.5% (95% CI, 39.7%–45.0%) in normal-weight patients (log-rank test=17.7; P<0.0001). Overweight (HR, 0.82; 95% CI, 0.71–0.94) and obese patients (HR, 0.71; 95% CI, 0.59–0.86) had a significantly lower risk of 10-year mortality compared to normal-weight patients after adjusting for all confounding variables. Conclusions— Based on BMI estimation, obese and overweight stroke patients have significantly better early and long-term survival rates compared to those with normal BMI.

The VITATOPS (Vitamins to Prevent Stroke) Trial: Rationale and Design of an International, Large, Simple, Randomised Trial of Homocysteine-Lowering Multivitamin Therapy in Patients with Recent Transient Ischaemic Attack or Stroke

Background: Epidemiological studies suggest that raised plasma concentrations of total homocysteine (tHcy) may be a common, causal and treatable risk factor for atherothromboembolic ischaemic stroke. Although tHcy can be lowered effectively with small doses of folic acid, vitamin B12 and vitamin B6, it is not known whether lowering tHcy, by means of multivitamin therapy, can prevent stroke and other major atherothromboembolic vascular events. Purpose: To determine whether vitamin supplements (folic acid 2 mg, B6 25 mg, B12 500 µg) reduce the risk of stroke, and other serious vascular events, in patients with recent stroke or transient ischaemic attacks of the brain or eye (TIA). Methods: An international, multi-centre, randomised, double-blind, placebo-controlled clinical trial. Results: As of November 2001, more than 1,400 patients have been randomised from 10 countries in four continents. Conclusion: VITATOPS aims to recruit and follow up 8,000 patients between 2000 and 2004, and provide a reliable estimate of the safety and effectiveness of dietary supplementation with folic acid, vitamin B12, and vitamin B6 in reducing recurrent serious vascular events among a wide range of patients with TIA and stroke.

Incremental Predictive Value of Carotid Inflammation in Acute Ischemic Stroke

Background and Purpose— Microwave Radiometry (MWR) allows in vivo noninvasive assessment of internal temperature of tissues. The aim of the present study was to evaluate in patients with ischemic stroke and bilateral carotid plaques (1) whether ipsilateral carotid arteries exhibit higher temperature differences (&Dgr;T), as assessed by MWR; (2) the predictive accuracy of MWR in symptomatic carotid artery identification. Methods— Consecutive patients with recent acute anterior circulation ischemic stroke because of large artery atherosclerosis were included in the study. Carotid arteries of all patients were evaluated by carotid ultrasound and MWR. Results— In total, 50 patients were included in the study. Culprit carotid arteries had higher &Dgr;T compared with nonculprit (0.93±0.58 versus 0.58±0.35°C; P<0.001). The addition of &Dgr;T to a risk prediction model based only on ultrasound plaque characteristics increased its predictive accuracy significantly (c-statistic: 0.691 versus 0.768; Pdif=0.05). Conclusions— Culprit carotid arteries show higher thermal heterogeneity compared with nonculprit carotid arteries in patients with acute ischemic stroke and bilateral carotid plaques. MWR has incremental value in culprit carotid artery discrimination.

Validation of the ABCD Score in Identifying Individuals at High Early Risk of Stroke After a Transient Ischemic Attack. A Hospital-Based Case Series Study

Background and Purpose— A simple score derived in the Oxfordshire Community Stroke Project (ABCD score) was able to identify individuals at high early risk of stroke after a transient ischemic attack (TIA) both in a population-based and a hospital-referred clinic cohort. We aimed to further validate the former score in a cohort of hospitalized TIA patients. Methods— We retrospectively reviewed the emergency room and hospital records of consecutive patients hospitalized in our neurological department with a definite TIA according to the World Health Organization (WHO) criteria during a 5-year period. The 6-point ABCD score (age [<60 years=0, ≥60 years=1]; blood pressure [systolic ≤140 mm Hg and diastolic ≤90 mm Hg=0, systolic >140 mm Hg and/or diastolic >90 mm Hg=1]; clinical features [unilateral weakness=2, speech disturbance without weakness=1, other symptom=0]; duration of symptoms [<10 minutes=0, 10 to 59 minutes=1, ≥60 minutes=2]) was used to stratify the 30-day stroke risk. Results— The 30-day risk of stroke in the present case series (n=226) was 9.7% (95% CI, 5.8% to 13.6%). The ABCD score was highly predictive of 30-day risk of stroke (ABCD=0 to 2: 0%, ABCD=3: 3.5% [95% CI, 0% to 8.2%], ABCD=4: 7.6% [95% CI, 1.2% to 14.0%], ABCD=5: 21.3% [95% CI, 10.4% to 33.0%], ABCD=6: 31.3% [95% CI, 8.6% to 54.0%]; log-rank test=23.09; df=6; P=0.0008; P for linear trend across the ABCD score levels <0.00001). After adjustment for stroke risk factors, history of previous TIA, medication use before the index TIA, and secondary prevention treatment strategies, an ABCD score of 5 to 6 was independently (P<0.001) associated with an 8-fold greater 30-day risk of stroke (hazard ratio, 8.01; 95% CI, 3.21 to 19.98). Conclusions— Our findings validate the predictive value of the ABCD score in identifying hospitalized TIA patients with a high risk of early stroke and provide further evidence for its potential applicability in clinical practice.

Common Carotid Artery Intima-Media Thickness and the Risk of Stroke Recurrence

Background and Purpose— Increased common carotid artery intima-media thickness (CCA-IMT) has been associated with an increased risk of myocardial infarction and stroke. We investigated the relationship between CCA-IMT and recurrent stroke in a cohort of ischemic stroke patients. Methods— High-resolution B-mode ultrasonographic measurements of the CCA-IMT were performed in a consecutive series of 238 patients hospitalized in our institution with first-ever ischemic stroke. Stroke risk factors and secondary prevention therapies were documented. Patients were followed-up prospectively and the outcome event of interest was recurrent stroke. Results— During a mean follow-up period of 28.9 months (range: 6 to 60 months), 27 recurrent strokes were documented. Patients who experienced recurrent cerebrovascular events had significantly (P=0.005) higher CCA-IMT values (1.01 mm, 95% CI:0.92 to 1.11 mm) than subjects who were free of stroke recurrence (0.88 mm, 95% CI:0.85 to 0.91 mm). After adjustment for baseline characteristics, risk factors and stroke subtypes and secondary prevention therapies increasing CCA-IMT was found to be an independent predictor of stroke recurrence. For each increment of 0.1 mm in CCA-IMT the probability of experiencing recurrent stroke increased by 18.0% (95% CI:2.0% to 36.0%, P=0.027). Conclusions— Increased CCA-IMT values are associated with a higher risk of long-term 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.

Loss of BRCC3 Deubiquitinating Enzyme Leads to Abnormal Angiogenesis and Is Associated with Syndromic Moyamoya

Moyamoya is a cerebrovascular angiopathy characterized by a progressive stenosis of the terminal part of the intracranial carotid arteries and the compensatory development of abnormal and fragile collateral vessels, also called moyamoya vessels, leading to ischemic and hemorrhagic stroke. Moyamoya angiopathy can either be the sole manifestation of the disease (moyamoya disease) or be associated with various conditions, including neurofibromatosis, Down syndrome, TAAD (autosomal-dominant thoracic aortic aneurysm), and radiotherapy of head tumors (moyamoya syndromes). Its prevalence is ten times higher in Japan than in Europe, and an estimated 6%-12% of moyamoya disease is familial in Japan. The pathophysiological mechanisms of this condition remain obscure. Here, we report on three unrelated families affected with an X-linked moyamoya syndrome characterized by the association of a moyamoya angiopathy, short stature, and a stereotyped facial dysmorphism. Other symptoms include an hypergonadotropic hypogonadism, hypertension, dilated cardiomyopathy, premature coronary heart disease, premature hair graying, and early bilateral acquired cataract. We show that this syndromic moyamoya is caused by Xq28 deletions removing MTCP1/MTCP1NB and BRCC3. We also show that brcc3 morphant zebrafish display angiogenesis defects that are rescued by endothelium-specific expression of brcc3. Altogether, these data strongly suggest that BRCC3, a deubiquitinating enzyme that is part of the cellular BRCA1 and BRISC complexes, is an important player in angiogenesis and that BRCC3 loss-of-function mutations are associated with moyamoya angiopathy.

Embolic Strokes of Undetermined Source in the Athens Stroke Registry: A Descriptive Analysis

Background and Purpose— A new clinical construct termed embolic stroke of undetermined source (ESUS) was recently introduced, but no such population has been described yet. Our aim is to provide a detailed descriptive analysis of an ESUS population derived from a large prospective ischemic stroke registry using the proposed diagnostic criteria. Methods— The criteria proposed by the Cryptogenic Stroke/ESUS International Working Group were applied to the Athens Stroke Registry to identify all ESUS patients. ESUS was defined as a radiologically confirmed nonlacunar brain infarct in the absence of (a) extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the ischemic area, (b) major-risk cardioembolic source, and (c) any other specific cause of stroke. Results— Among 2735 patients admitted between 1992 and 2011, 275 (10.0%) were classified as ESUS. In the majority of ESUS (74.2%), symptoms were maximal at onset. ESUS were of moderate severity (median National Institute Health Stroke Scale score, 5). The most prevalent risk factor was arterial hypertension (64.7%), and 50.9% of patients were dyslipidemic. Among potential causes of the ESUS, covert atrial fibrillation (AF) was the most prevalent: in 30 (10.9%) patients, AF was diagnosed during hospitalization for stroke recurrence, whereas in 50 (18.2%) patients AF was detected after repeated ECG monitoring during follow-up. Also, covert AF was strongly suggested in 38 patients (13.8%) but never recorded. Conclusions— About 10% of patients with first-ever ischemic stroke met criteria for ESUS; covert paroxysmal AF seems to be a frequent cause of ESUS.