Efstathios Manios

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.

Renal dysfunction in acute stroke: an independent predictor of long-term all combined vascular events and overall mortality

BACKGROUND Acute stroke is the third leading cause of death in western societies after ischemic heart disease and cancer. Although it is an emergency disease sharing the same atherosclerotic risk factors with ischemic heart disease, the association of renal function and stroke is poorly investigated. The present study aims at assessing renal function status in patients with acute stroke and investigate any prognostic significance on the outcome. METHODS This is a prospective study of hospitalized first-ever stroke patients over 10 years. The study population comprised 1350 patients admitted within 24 h from stroke onset and followed up for 1 to 120 months or until death. Patients were divided in 3 groups on the basis of the estimated Glomerular Filtration Rate (eGFR) that was calculated from the abbreviated equation of the Modification Diet for Renal Disease in ml/min/1.73 m(2) of body surface area: Group-A comprised patients who had eGFR > 60, group-B those with 30 <or= eGFR <or= 60 and group-C patients with eGFR < 30. Patients with Acute Kidney Injury (AKI) were excluded from the study. The main outcome measures were overall mortality and the composite new cardiovascular events (myocardial infarction, recurrent stroke, vascular death) among the 3 groups during the follow-up period. RESULTS Almost 1/3 (28.08%) of our acute stroke patients presented with moderate (group B) or severe (group C) renal dysfunction as estimated by eGFR. After adjusting for basic demographic, stroke risk factors and stroke severity on admission, eGFR was an independent predictor of stroke mortality at 10 years. Patients in groups B and C had an increased probability of death during follow-up: Hazard ratio = 1.21 with 95% CI 1.01-1.46, p < 0.05 and Hazard ratio = 1.76 with 95% CI 1.14-2.73, p < 0.05 respectively, compared to patients belonging to group A. The probability of death from any cause was significantly different among groups (log rank test 55.4, p = 0.001) during the follow-up period: in group-A patients it was 62.8 (95% CI 57.6-68.1), in group-B 77.3 (95% CI 68.5-86.1) and in group-C 89.2 (95% CI 75.1-100). During the follow-up period 336 new cardiovascular events occurred. The probability to have a new composite cardiovascular event was also significantly different among the 3 groups (log rank test 21.1, p = 0.001): in group-A patients it was 45.2 (95% CI 38.7-51.7), in group-B 67.4 (95% CI 56.2-78.6) and in group-C 77.6 (95% CI 53.5-100). CONCLUSION Renal function on admission appears to be a significant independent prognostic factor for long term mortality and new cardiovascular morbidity over a 10-year period.

CHADS2, CHA2DS2-VASc, and long-term stroke outcome in patients without atrial fibrillation

Objective: CHADS2 and CHA2DS2-VASc scores are used to assess stroke risk in patients with atrial fibrillation (AF). We investigated whether these scores are associated with stroke outcome in non-AF stroke patients. Methods: Consecutive patients with acute first-ever ischemic stroke but without AF were classified into subgroups according to prestroke CHADS2 and CHA2DS2-VASc scores and followed up for 5 years. The end points were death, stroke recurrence, and a composite of major cardiovascular events. Results: Among 1,756 patients (aged 67.2 ± 12.3 years, 68.2% males), there were 258 (14.7%), 617 (35.3%), and 878 (50.0%) patients with low, intermediate, and high CHADS2 score, respectively. The corresponding figures for CHA2DS2-VASc subgroups were 110 (6.3%), 255 (14.5%), and 1,391 (79.2%). There were significant differences between CHADS2 subgroups in 5-year mortality (log-rank test = 74.5, p < 0.0001), stroke recurrence (log-rank test = 12.3, p = 0.002), and cardiovascular events (log-rank test = 19.4, p < 0.001). Similarly, there were significant differences between CHA2DS2-VASc subgroups in 5-year mortality (log-rank test = 74.5, p < 0.0001), stroke recurrence (log-rank test = 10.6, p = 0.005), and cardiovascular events (log-rank test = 16.4, p < 0.001). Compared with the low-risk group, patients in intermediate- and high-risk CHADS2 subgroups had higher 5-year mortality (hazard ratio [HR]: 2.22 [95% confidence interval {CI}: 1.78–2.77] and 3.66 [95% CI: 2.38–5.62], respectively), stroke recurrence (HR: 1.74 [95% CI: 1.09–2.79] and 1.71 [95% CI: 1.08–2.71], respectively), and cardiovascular events (HR: 1.78 [95% CI: 1.23–2.57] and 1.86 [95% CI: 1.30–2.67], respectively). Compared with the low-risk group, patients in the high-risk CHA2DS2-VASc subgroup also had higher 5-year mortality (HR: 3.56, 95% CI: 1.89–6.70), stroke recurrence (HR: 2.93, 95% CI: 1.30–6.61), and cardiovascular events (HR: 2.71, 95% CI: 1.49–4.95). Conclusions: Prestroke CHADS2 and CHA2DS2-VASc scores predict long-term stroke outcomes in non-AF patients with acute ischemic stroke. These scores may provide a simple way of stroke prognostic risk stratification among non-AF stroke patients.

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.

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 Hg≤office BP<140/90 mm Hg), and hypertensives (office BP ≥140/90 mm Hg). Statistical analyses were performed by means of 1-way ANOVA, &khgr;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.

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.

Factors influencing acute blood pressure values in stroke subtypes.

The aim of this prospective observational study was to determine the association of acute blood pressure values with independent factors (demographic, clinical characteristics, early complications) in stroke subgroups of different aetiology. We evaluated data of 346 first-ever acute (<24 h) stroke patients treated in our stroke unit. Casual and 24-h blood pressure (BP) values were measured. Stroke risk factors and stroke severity on admission were documented. Strokes were divided into subgroups of different aetiopathogenic mechanism. Patients were imaged with CT-scan on admission and 5 days later to determine the presence of brain oedema and haemorrhagic transformation. The relationship of different factors to 24-h BP values (24-h BP) was evaluated separately in each stroke subgroup. In large artery atherosclerotic stroke (n=59), history of hypertension and stroke severity correlated with higher 24-h BP respectively. In cardioembolic stroke (n=87), history of hypertension, stroke severity, haemorrhagic transformation and brain oedema were associated with higher 24-h BP, while heart failure with lower 24-h BP. History of hypertension and coronary artery disease was related to higher and lower 24-h BP, respectively, in lacunar stroke (n=75). In patients with infarct of undetermined (n=57) cause 24-h BP were mainly influenced by stroke severity and history of hypertension. An independent association between higher 24-h BP and history of hypertension and cerebral oedema was documented in intracerebral haemorrhage (n=68). In conclusion, different factors influence acute BP values in stroke subtypes of different aetiology. If the clinical significance of these observations is verified, a differentiated approach in acute BP management based on stroke aetiology may be considered.