Nikolaos Zakopoulos

The Athens Stroke Registry: Results of a Five-Year Hospital-Based Study

The advent and wide application of new technology, especially noninvasive techniques, has enabled physicians to more completely investigate and clarify the etiopathogenic mechanisms of stroke. Such data have not been available until recently for Southeastern Europe. In addition, during the last decades, strategies for the modification of risk factors and primary prevention may have changed the prevalence of each subgroup of stroke as well. We investigated 1,042 consecutive patients who had first strokes, during a period of 5 years (from June 1992 to May 1997) and classified them prospectively based on etiopathogenic mechanisms. Patients with transient ischemic attacks and subarachnoid hemorrhage were excluded. There were 613 male and 429 female patients, with a mean age of 70.2 ± 11.9 years. Forty-six percent of the patients arrived within 3 h from stroke onset. The probable mechanisms were: large-artery atherosclerosis, 156 (15%); lacunes, 177 (17%); cardioembolic, 335 (32.1%); infarct of unknown cause, 182 (17.5%); miscellaneous causes, 35 (3.3%), and intracerebral hemorrhage (ICH), 157 (15.1%). In the cardioembolic group, nonvalvular atrial fibrillation (NVAF) was the probable cause in 225 patients, especially in patients older than 75 years (65%). The overall hospital mortality was 15.2% (from 0.6% for lacunar stroke to 34% for ICH). In our population, cardioembolism is the most frequent subtype of stroke. NVAF is the most likely source, especially in older patients.

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.

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.

Time rate of blood pressure variation is associated with impaired renal function in hypertensive patients

Objectives The rate of blood pressure (BP) variation has been positively associated with intima–media thickness of common carotid arteries and left ventricular mass. We evaluated the association between the rate of BP variation derived from ambulatory blood pressure monitoring (ABPM) data analysis and impaired renal function. Methods Twenty-four-hour ABPM was performed in 803 untreated hypertensive patients. The estimated glomerular filtration rate (eGFR) was assessed using the abbreviated equation of the Modification Diet for Renal Disease study. Patients were divided into two groups: those with an eGFR less than 60 ml/min per 1.73 m2 (group A) and those with an eGFR 60 ml/min per 1.73 m2 or more (group B). Results The 24-h rate of systolic BP variation was significantly (P = 0.004) higher in group A [0.616 mmHg/min; 95% confidence interval (CI) 0.596–0.636] than in group B patients (0.585 mmHg/min; 95% CI 0.578–0.591), even after adjusting for baseline characteristics and ABPM parameters. In the entire study population, the multiple logistic regression models revealed the following variables as independent determinants of impaired renal function: age, male sex, office systolic BP and 24-h rate of systolic BP variation. In this model, the odds ratio for impaired renal function associated with each 0.1 mmHg/min increase in 24-h rate of systolic BP variation was 1.49 (95% CI 1.18–1.88, P = 0.001). Conclusion The 24-h rate of SBP variation is independently associated with impaired renal function. Target-organ damage in hypertensive patients, in addition to BP levels, dipping status and BP variability, may also be related to a steeper rate of BP fluctuations.

Impact of the time rate of blood pressure variation on left ventricular mass

Objectives Blood pressure (BP) changes are steeper in hypertensive than in normotensive individuals, whereas an increased rate of BP fluctuations is associated with medial hypertrophy of the carotid arteries. We evaluated the association between the rate of BP variation derived from ambulatory blood pressure monitoring (ABPM) data analysis and left ventricular mass (LVM). Methods ABPM and echocardiographic measurements of LVM were performed in 365 normotensive, 185 white-coat hypertensive (WCH) and 448 uncomplicated hypertensive individuals. Results The daytime and night-time rate of systolic blood pressure (SBP) and diastolic BP variation were significantly higher in hypertensive than in normotensive (P < 0.001) and WCH (P < 0.05) individuals. In the entire study population multiple linear regression models revealed independent determinants of LVM in the following rank order: body mass index (β + 0.266, P < 0.001), daytime SBP (β + 0.264, P < 0.001), male sex (β +0.220, P < 0.001), age (β + 0.203, P < 0.001), daytime heart rate (HR; β − 0.191, P < 0.001), daytime rate of SBP variation (β + 0.167, P < 0.001), and SBP dipping (β − 0.132, P < 0.001). A 0.1 mmHg/min increase in the daytime rate of SBP variation correlated with an increment of 7.087 g (95% confidence interval 4.775–9.399) in the LVM. The addition of the daytime rate of SBP variation in the multiple regression model for the prediction of LVM significantly increased the adjusted model R2 [R2 change 0.024 (2.4%); P for change < 0.001]. Conclusion Steeper BP variations may produce a greater stress on the left ventricular wall and may have an additive role to body habitus, BP and HR levels in the detection of cardiac hypertrophy. Target-organ damage in hypertensive patients, in addition to BP levels, dipping status and BP variability, may also be related to a steeper rate of BP oscillations.

Comparison of noninvasive oscillometric and intra-arterial blood pressure measurements in hyperacute stroke.

ObjectivesThis study aims to compare automatic oscillometric blood pressure recordings with simultaneous direct intra-arterial blood pressure measurements in hyperacute stroke patients to test the accuracy of oscillometric readings. MethodsA total of 51 first-ever stroke patients underwent simultaneous noninvasive automatic oscillometric and intra-arterial blood pressure monitoring within 3 h of ictus. Casual blood pressure was measured in both arms using a standard mercury sphygmomanometer on hospital admission. Patients who received antihypertensive medication during the blood pressure monitoring were excluded. ResultsThe estimation of systolic blood pressure (SBP) using oscillometric recordings underestimated direct radial artery SBP by 9.7 mmHg (95% confidence interval: 6.5−13.0, P<0.001). In contrast, an upward bias of 5.6 mmHg (95% confidence interval: 3.5−7.7, P<0.001) was documented when noninvasive diastolic blood pressure (DBP) recordings were compared with intra-arterial DBP recordings. For SBP and DBP, the Pearson correlation coefficients between noninvasive and intra-arterial recordings were 0.854 and 0.832, respectively. When the study population was stratified according to SBP bands (group A: SBP≤160 mmHg; group B: SBP>160 mmHg and SBP≤180 mmHg, group C: SBP>180 mmHg), higher mean ΔSBP (intra-arterial SBP−oscillometric SBP) levels were documented in group C (+19.8 mmHg, 95% confidence intervals: 12.2–27.4) when compared with groups B (+8.5 mmHg, 95% confidence intervals: 2.7−14.5; P=0.025) and A (+5.9 mmHg, 95% confidence intervals: 1.8−9.9; P=0.002). ConclusionNoninvasive automatic oscillometric BP measurements underestimate direct SBP recordings and overestimate direct DBP readings in acute stroke. The magnitude of the discrepancy between intra-arterial and oscillometric SBP recordings is even more prominent in patients with critically elevated SBP levels.

Incremental value of arterial wave reflections in the determination of left ventricular diastolic dysfunction in untreated patients with essential hypertension

Systemic arterial stiffness is an indicator of cardiovascular disease and an independent marker of morbidity and cardiovascular mortality. We investigated the association of arterial wave reflections with left ventricular (LV) diastolic dysfunction and their incremental value to other determinants of LV diastolic dysfunction in patients with essential hypertension. In total 143 patients and 20 controls with similar atherosclerotic risk factors were examined by applanation tonometry of the radial artery (Sphygmocor) and echocardiography. Central augmentation index (CAI%) of reflected arterial waves as well as aortic strain (AoS) assessed by echocardiography were estimated. Doppler diastolic abnormalities were defined as proposed by the European Study Group on diastolic heart failure by measurement of E/A ratio (the ratio of the mitral inflow velocities), isovolumic relaxation time, deceleration time and flow propagation velocity. AoS and CAI were impaired in patients compared with controls (4.67±2.94 vs 6.06±4.91% and 145.8±22.7 vs 135.7±20.3%, P<0.01) as well as in patients with LV diastolic dysfunction compared to patients without, (5.52±4.29 vs 10.73±5.77% and 139.5±21.7 vs 124.5±17.0%, P<0.05). The odds ratio (OR) of AoS and CAI for diastolic dysfunction was OR:0.918, 95% confidence interval (CI):0.837–0.99, P=0.04 and OR:1.023, 95%CI:1.023–1.040 P=0.010, respectively. The addition of CAI to the multivariable model including age, LV mass index, AoS and mean arterial pressure increased the power of the model for determination of LV diastolic dysfunction (−2 log likelihood=139.368, change of χ2=4.2, P-value for change=0.04). In untreated patients with newly diagnosed essential hypertension, wave reflections are independent and additive determinants of LV diastolic dysfunction.

Common Carotid Artery Intima-Media Thickness in Patients with Brain Infarction and Intracerebral Haemorrhage

An increase in the intima-media thickness of the common carotid artery (CCA-IMT) is generally considered as an early marker of atherosclerosis and has been associated with a higher risk of stroke and myocardial infarction. There is no evidence of an association between the IMT and cerebral bleeding. We investigated cross-sectionally the diagnostic ability of vascular risk factors, including CCA-IMT, to distinguish between brain infarction (BI) and intracerebral haemorrhage (ICH). Patients suffering from BI (n = 126) had significantly (p < 0.05) higher CCA-IMT when compared to the ICH population (n = 30). The multinomial logistic regression procedure selected CCA-IMT as an independent factor able to discriminate between BI and ICH. The risk of BI versus ICH increased continuously with increasing CCA-IMT. After adjustment for cardiovascular risk factors the odds ratio for BI per 0.1 mm CCA-IMT increase was 1.29 (95% CI: 1.03–1.61). The present results demonstrate the possible predictive power of non-invasive measurement of the CCA-IMT with respect to BI versus ICH and deserve further investigation.