Stroke-associated pneumonia according to mCDC criteria: impact on prognosis and antibiotic therapy.

Objective: The modified Centers for Disease Control and Prevention (mCDC) criteria have been proposed for diagnosing and managing stroke-associated pneumonia (SAP). The objective was to investigate the impact of SAP on stroke outcome depending on whether or not it conforms to mCDC criteria. Our secondary objective was to identify the responsible factors for antibiotic initiation in stroke patients. Methods: We conducted a prospective, multicenter, observational study of ischemic stroke patients with moderate to severe stroke (NIHSS≥4) admitted within 24 h. For 7 days, mCDC criteria were assessed daily, and infections and antibiotics were recorded. Pneumonias were divided into those fulfilling mCDC criteria (mCDC-SAP) or not (other pneumonias, OPn). The effect of each type of pneumonia on 3-month outcome was evaluated in separated logistic regression models. Factors associated with antibiotic initiation were explored using a random forest analysis. Results: Of the 342 patients studied, infections were diagnosed in 72 (21.6%), including 39 (11.7%) cases of pneumonia. Of them, 25 (7.5%) fulfilled mCDC criteria. Antibiotics were used in 92% of mCDC-SAP and 64.3% of OPn. In logistic regression analysis, mCDC-SAP, but not OPn, was an independent predictor of poor outcome [OR, 4.939 (1.022-23.868)]. The random forest analysis revealed that fever had the highest importance for antibiotic initiation. Interpretation: The mCDC criteria might be useful for detecting clinically relevant SAP, which is associated with poor outcomes. Isolated signs of infection were more important for antibiotic initiation than compliance with pre-defined criteria. Therefore, adherence to mCDC criteria might result in antibiotic saving without compromising clinical outcome.

Silent brain infarcts, peripheral vascular disease and the risk of cardiovascular events in patients with hypertension.

BACKGROUND AND AIMS: We aimed to study the relationship between cerebral small vessel disease (cSVD) lesions, as markers of subclinical target organ damage (TOD) in the brain, and incident cardiovascular events (CVE). METHODS: Data from the ISSYS (Investigating Silent Strokes in hYpertensives Study), which is a longitudinal and observational study conducted in patients with hypertension aged 50-70 years, and stroke-free at the inclusion. At the baseline visit, participants underwent a clinical interview, a brain MRI, urine and blood sampling collection and vascular testing studies. Therefore, we obtained markers of TOD from the brain [white matter hyperintensities, silent brain infarcts (SBI), cerebral microbleeds and enlarged perivascular spaces (EPVS)], from kidney (microalbuminuria, glomerular filtration) and regarding large vessels [ankle-to-brachial index (ABI), carotid-femoral pulse wave velocity]. Survival analyses were used to assess the relationship between these predictors and the incidence of cardiovascular events (CVE). RESULTS: We followed-up 964 individuals within a median time of 5 years (4.7-5), representing 4377.1 persons-year. We found 73 patients presenting incident CVE, which corresponds to a rate of 8.2%. We found ABI less than 0.9 [hazard ratio, 2.2; 95% confidence interval (CI) 1.17-4.13, P value = 0.014] and SBI (hazard ratio, 2.9; 95% CI 1.47-5.58, P value = 0.002) independently associated with higher risk of incident CVE. The inclusion of both variables in a clinical model resulted in an increased discrimination of individuals with new CVE of 4.72%, according to the integrated discrimination index. CONCLUSION: Assessment of SBI and ABI less than 0.9 may refine the cardiovascular risk stratification in patients with hypertension.

Antidepressant use and stroke or mortality risk in the elderly.

BACKGROUND AND PURPOSE: Current evidence on antidepressant-related stroke or mortality risk is inconsistent. Because the elderly have the highest exposure to antidepressants, the aim was to quantify their association with stroke and mortality risks in this vulnerable population. METHODS: Persons over 65 years old and registered in the Information System for Research in Primary Care of Catalonia during 2010-2015 comprised the study population. Antidepressant exposure was categorized into current-users, recent-users, past-users and antidepressant non-users (controls). The effect of antidepressant exposure on stroke or death, whichever came first, was analyzed by Cox regression adjusted for established risk factors. RESULTS: Of the 1,068,117 participants included, 20% had antidepressant reimbursements during follow-up, 17% had a stroke and 3% died. The risk of experiencing stroke or death was higher in antidepressant current-users (hazard ratio [HR] 1.04; 95% confidence interval [CI] 1.02-1.06), recent-users (HR 3.34; 95% CI 3.27-3.41) and past-users (HR 2.06; 95% CI 2.02-2.10) compared to antidepressant non-users. Antidepressant current-use was associated with increased stroke (HR 1.56; 95% CI 1.50-1.61) but decreased mortality risk (HR 0.93; 95% CI 0.91-0.94). During antidepressant recent-use and past-use, both stroke and mortality risks were significantly increased compared to no antidepressant use. CONCLUSIONS: Antidepressant use may be associated with increased stroke risk in the elderly. When using antidepressants in this population, the potential risks should be considered.

Effect of late-onset epilepsy on cognitive functioning in patients with small vessel disease.

RATIONALE: Late-onset epilepsy (LOE) often has underlying cerebrovascular cause and has been associated with neurocognitive deficits and dementia. Nevertheless, the interplay between these factors has not been studied thus far. Hence, we conducted a retrospective cross-sectional study aimed to explore how unprovoked epileptic seizures along with vascular-related factors contribute to neurocognitive impairments in patients with cerebral small vessel disease. METHODS: Twenty-seven patients with LOE aged > 60 years with concomitant cerebral small vessel disease (cSVD) and a matched group of cSVD without epilepsy were cognitively assessed. Demographic, clinical, and vascular information were obtained and vascular burden score was calculated for each patient. Multiple linear regression models were used to explore the relationship between epilepsy and cognitive measures adjusting for demographic and vascular risk factors. RESULTS: Compared with cSVD, cSVD-LOE group showed a poorer performance on verbal memory measures, visuomotor tracking and speed processing and phonetic fluency. In the multiple regression analysis, the presence of epilepsy was found to be the major predictor for verbal memory dysfunction, specifically in verbal short recall (p = 0.008) and verbal learning (p < 0.001). No interactions between vascular burden and epilepsy were found. CONCLUSION: Patients who had cSVD with concurrent LOE showed poorer performance on memory function compared with patients with cSVD without epilepsy, and they showed a different cognitive profile from that typically manifested by patients with cSVD. The presence of epilepsy, but not seizure localization nor vascular burden, was the major contributor to the decrease in verbal memory.

Diabetes, Albuminuria and the Kidney-Brain Axis.

Cognitive decline and kidney disease are significant public health problems that share similar characteristics and risk factors. The pathophysiology of the kidney-brain axis is not completely understood, and studies analysing the relationship between the biomarkers of kidney damage and cognitive impairment show different results. This article focuses on the epidemiological and clinical aspects concerning the association of albuminuria, a marker for endothelial dysfunction and microvascular disease, and cognitive impairment in patients with chronic kidney disease, diabetic kidney disease and end-stage kidney disease. Most studies show a positive relationship between albuminuria and cognitive impairment in all groups, but evidence in type 2 diabetes (T2D) patients is limited. We briefly discuss the mechanisms underlying these associations, such as damage to the microvascular circulation, leading to hypoperfusion and blood pressure fluctuations, as well as increased inflammation and oxidative stress, both in the brain and in the kidneys. Further clinical and epidemiological studies developed to understand the interplay between the kidneys and brain diseases will hopefully lead to a reduction in cognitive impairment in these patients.

Genome-wide transcriptome study in skin biopsies reveals an association of E2F4 with cadasil and cognitive impairment.

CADASIL is a small vessel disease caused by mutations in NOTCH3 that lead to an odd number of cysteines in the EGF-like repeat domain, causing protein misfolding and aggregation. The main symptoms are migraine, psychiatric disturbances, recurrent strokes and dementia, being executive function characteristically impaired. The molecular pathways altered by this receptor aggregation need to be studied further. A genome-wide transcriptome study (four cases paired with three healthy siblings) was carried out, in addition to a qRT-PCR for validation purposes (ten new cases and eight new controls). To study the expression profile by cell type of the significant mRNAs found, we performed an in situ hybridization (ISH) (nine cases and eight controls) and a research in the Single-nuclei Brain RNA-seq expression browser (SNBREB). Pathway analysis enrichment was carried out with Gene Ontology and Reactome. Neuropsychological tests were performed in five of the qRT-PCR cases. The two most significant differentially expressed mRNAs (BANP, p-value = 7.23 × 10-4 and PDCD6IP, p-value = 8.36 × 10-4) were selected for the validation study by qRT-PCR. Additionally, we selected two more mRNAs (CAMK2G, p-value = 4.52 × 10-3 and E2F4, p-value = 4.77 × 10-3) due to their association with ischemic neuronal death. E2F4 showed differential expression in the genome-wide transcriptome study and in the qRT-PCR (p = 1.23 × 10-3), and it was upregulated in CADASIL cases. Furthermore, higher E2F4 expression was associated with worse executive function (p = 2.04 × 10-2) and attention and information processing speed (IPS) (p = 8.73 × 10-2). In situ hibridization showed E2F4 expression in endothelial and vascular smooth vessel cells. In silico studies indicated that E2F4 is also expressed in brain endothelial cells. Among the most significant pathways analyzed, there was an enrichment of vascular development, cell adhesion and vesicular machinery terms and autophagy process. E2F4 is more highly expressed in the skin biopsy of CADASIL patients compared to controls, and its expression is present in endothelial cells and VSMCs. Further studies are needed to understand whether E2F4 could be useful as a biomarker, to monitor the disease or be used as a therapeutic target.

Ambulatory Blood Pressure Levels in the Prediction of Progression of Cerebral Small Vessel Disease.

OBJECTIVES: We aimed to study the value of ambulatory blood pressure monitoring (ABPM) in predicting the global progression of cerebral small vessel disease (cSVD). DESIGN: Longitudinal cohort study. SETTING: Data from the population-based Investigating Silent Strokes in Hypertensives study. PARTICIPANTS: Individuals with hypertension who were 50 to 70 years of age and stroke free at baseline. In baseline and follow-up visits, patients underwent magnetic resonance imaging and ABPM. MEASUREMENTS: Ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels were studied as continuous variables and dichotomized according to good or poor control on the basis of 125/75 (24 hours), 130/80 (day), and 110/65 (night) mm Hg cutoff values. Whole cSVD progression was qualitatively scored with 1 point when an incident lesion (incident lacunar infarcts, deep cerebral microbleeds, white matter hyperintensities, and basal ganglia enlarged perivascular spaces) was detected. The score ranged from 0 to 4. RESULTS: We followed up 233 participants with a median age of 65 years within 4 years. A total of 61 (26.2%) and 23 (9.9%) subjects showed cSVD progression in one and two or more markers, respectively. Baseline ambulatory SBP and DBP and nighttime pulse pressure (PP) values were positively correlated with the number of incident cSVD lesions. Interestingly, patients without incident lesions showed greater differences between office and ambulatory BP, thus suggesting an increased white coat effect. Poor DBP control, nighttime PP, and DBP white coat effect were independently associated with cSVD progression. The inclusion of these metrics in a clinical model resulted in a significant increase in the prediction of incident lesions (integrated discrimination improvement = 9.09%; P value <.001). CONCLUSION: ABPM may help assess cSVD risk of progression, especially by the identification of poor BP control, masked hypertension, and increased nighttime PP. J Am Geriatr Soc 68:2232-2239, 2020.

Nighttime hypoxia affects global cognition, memory, and executive function in community-dwelling individuals with hypertension.

STUDY OBJECTIVES: The objective of this study was to determine which respiratory and architectural sleep parameters are related to cognitive function and cognitive status (mild cognitive impairment [MCI] versus normal cognitive aging [NCA]) in community-dwelling individuals with hypertension. Additionally, it aimed to determine whether the results changed in the presence or absence of vascular brain lesions (silent brain infarcts and extensive white matter hyperintensities [WMHs]). METHODS: In a cohort of individuals with hypertension and without previous stroke or dementia, we conducted in-hospital polysomnography including electroencephalography, electro-oculography, electromyography, and magnetic resonance imaging to assess silent brain infarcts and WMHs. Cognitive testing was carried out with a screening test (Dementia Rating Scale version 2 [DRS-2]) and a complete cognitive visit. RESULTS: This study included 158 participants with a median age of 65.0 years; 32.3% were females, and the median apnea-hypopnea index was 22.3 events/h. MCI was diagnosed in 24 study participants, and the rest had NCA. Regarding respiratory parameters, total DRS-2 scores (ß; 95% CI) 0.121; 0.026, 0.215 were positively associated with mean O2 saturation, whereas total (-0.022; -0.036, -0.009), executive function (-0.016; -0.026, -0.006) and memory (-0.017; -0.029, -0.004) DRS-2 scores were all negatively associated with the percent of time with oxygen saturation < 90% after correcting for education, vascular risk factors, and magnetic resonance imaging lesions. Regarding sleep architecture, Attention DRS-2 scores (0.0153; 0.001, 0.306) were independently associated with total sleep time. Similar results were obtained in the absence of silent brain infarcts or WMHs in the stratified analysis. None of the sleep parameters were associated with cognitive status. CONCLUSIONS: Low oxygen saturation contributes to cognitive performance, and this effect appears even in the absence of vascular brain lesions in individuals with hypertension.

Kidney function changes and their relation with the progression of cerebral small vessel disease and cognitive decline.

AIMS: We aimed to study whether worsening in markers of kidney function parallels the progression in cerebral small vessel disease (cSVD) and cognitive decline. METHODS: Data from the ISSYS (Investigating Silent Strokes in Hypertensives Study), a longitudinal population-based study in hypertensives aged 50-70 and dementia and stroke-free at baseline. At both visits, patients underwent a brain MRI, a cognitive diagnosis (normal aging or mild cognitive impairment, [MCI]) and urine and blood sampling collection. We assessed the incidence of infarcts and cerebral microbleeds, and the progression of white matter hyperintensities at periventricular (PVH) and deep areas. We determined changes in albumin-creatinine ratio and estimated glomerular filtration rate (eGFR). These changes were dichotomized into microalbuminuria at follow-up -either in subjects with or without baseline microalbuminuria- and significant decline in eGFR -lowest quintile of eGFR change (-10.57 mL/min/1.73m2)-. RESULTS: 360 patients were followed-up for 4 years. 80 (23%) patients presented microalbuminuria at follow-up and 68 (20.1%) experienced a significant eGFR decline. Considering cSVD change, we found a relationship between microalbuminuria at follow-up and progression in PVH (ß = 0.31, P-value = .01). Regarding cognitive decline, presence of microalbuminuria at follow-up related to a steeper decrease in memory function (ß = -0.36, P-value<.01). Moreover, patients with significant decline in eGFR were at higher risk of incident MCI (OR = 3.54, P-value = .02). These associations were independent of progression of cSVD. CONCLUSION: The worsening in markers of kidney function paralleled the decrease in cognition and the progression of cSVD, and this may be explained by common shared underlying risk factors.

Perampanel: A therapeutic alternative in refractory status epilepticus associated with MELAS syndrome.

To our knowledge, there are no reports of status epilepticus (SE) associated with mitochondrial diseases and treated with perampanel (PER). We present three cases of patients with refractory SE associated with MELAS syndrome who responded favorably to PER. All cases were diagnosed as non-convulsive SE (focal without impairment of level of consciousness). After an initial treatment with other anti-seizure drugs, PER was added in all cases (8, 16 and 12 mg) and cessation of SE was observed within the next 4-8 hours. All the cases involved a stroke-like lesion present on brain MRI. In our patients, PER was an effective option in SE associated with MELAS syndrome.

Cognitive Impact of Cerebral Small Vessel Disease Changes in Patients With Hypertension.

Hypertension is one of the principal risk factors for cerebral small vessel disease progression and cognitive impairment. We aimed to investigate how changes in cerebral small vessel disease lesions relate to cognitive decline and incident mild cognitive impairment in hypertensive patients. Data were obtained from the ISSYS cohort (Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study)-a longitudinal population-based study on hypertensive patients aged 50 to 70 years without dementia and stroke at baseline. Patients underwent a brain magnetic resonance imaging, a cognitive screening test, and cognitive diagnosis (normal aging or mild cognitive impairment) at baseline and follow-up. We evaluated incident lacunar infarcts and cerebral microbleeds. Changes in the periventricular and deep white matter hyperintensities (WMH) were qualitatively defined as none, minor, or marked. We followed up 345 patients (median age, 65 [61-68]; 55.4% men) for 3.95 (3.83-4.34) years. Incident mild cognitive impairment was diagnosed in 9.1% of the sample. Considering the progression of cerebral small vessel disease, the prevalence of incident infarcts was 6.1% and that of incident cerebral microbleeds was 5.5%; progression of periventricular WMH was 22% and that of deep WMH was 48%. Patients with marked progression of periventricular WMH showed a significant decrease in global cognition compared with patients without progression (adjusted mean [SE], -0.519 [0.176] versus 0.057 [0.044], respectively; P value=0.004) and a higher risk of incident mild cognitive impairment (OR, 6.184; 95% CI, 1.506-25.370; P value=0.011). Therefore, our results indicate that hypertensive patients with progression of periventricular WMH have higher odds of cognitive impairment, even in the early stages of cognitive decline.

Prognosis of post-stroke status epilepticus: Effects of time difference between the two events.

PURPOSE: This study aimed to investigate the prognosis of patients with status epilepticus (SE) following stroke, focusing on the timing of SE after the event and other unexplored variables. METHODS: All consecutive patients experiencing post-stroke SE (PSSE) in our center were included (2011-2016). We analyzed SE- and stroke-related factors in relation to the patients' outcome. RESULTS: 95 patients with PSSE (54 ischemic and 41 hemorrhagic stroke) were analyzed; 40 were women (42.1%) and mean age was 72.7 ±â€¯13.56 years. 51(53.7%) showed prominent motor symptoms, 49(51.6%) needed >2 antiepileptic drugs, and 27(28.4%) required anesthetics. Median duration of SE was 12 h (1-240). Median time from stroke to SE was 15 days (0-532). At discharge, logistic regression identified SE within 72 h after stroke (p = 0.004), baseline mSTESS (p = 0.009), and lesion volume (p = 0.001) as independent factors predicting mortality. Female sex (p = 0.019), SE duration >12 h (p = 0.005), temporal lobe involvement (p = 0.029), and stroke-to-SE time <90 days (p < 0.0001) were independent predictors of functional decline. At long-term follow-up, SE occurring within 72 h after stroke (p = 0.0001), SE duration (p = 0.004), and baseline mSTESS score (p = 0.012) remained as predictive of mortality. CONCLUSIONS: The timing of SE after stroke is associated with different consequences: mortality was higher when SE occurred within the first 72 h after stroke and this risk persisted at follow-up, whereas risk of functional decline was higher when SE occurred during the first 3 months. Other factors such as the mSTESS score and SE duration were associated with outcome at both discharge and long-term follow-up.

Obstructive sleep apnea and silent cerebral infarction in hypertensive individuals.

Obstructive sleep apnea syndrome is very prevalent in hypertensive subjects. Moreover, obstructive sleep apnea syndrome activates multiple processes that might be associated with silent cerebral infarct independently of established risk factors. Our aim is to estimate the frequency of obstructive sleep apnea syndrome in hypertensive patients with and without silent cerebral infarct, and to determine whether obstructive sleep apnea syndrome is an independent risk factor of silent cerebral infarct and/or lacunar silent cerebral infarct in patients with hypertension. In this matched cross-sectional study performed in hypertensive subjects, each patient with silent cerebral infarct detected by magnetic resonance imaging was matched with two patients without silent cerebral infarct. Polysomnographic studies were performed, and the apnea-hypopnea index was calculated. Severe obstructive sleep apnea syndrome was considered in those with apnea-hypopnea index >30. One-hundred and eighty-three patients, 61 with silent cerebral infarct and 122 without silent cerebral infarct, were evaluated. The mean age was 64.1 ± 4.5 years, and 72.1% were men. The frequency of severe obstructive sleep apnea syndrome was 44.3% in patients with silent cerebral infarct and 38.5% in the control group. An adjusted conditional logistic regression model did not show a significant increased risk of silent cerebral infarct in patients with severe obstructive sleep apnea syndrome (odds ratio 1.362; 95% confidence interval: 0.659-2.813; P = 0.404). Forty-three patients (70.5%) of the silent cerebral infarct were lacunar. The presence of severe obstructive sleep apnea syndrome was significantly higher in lacunar silent cerebral infarct when compared with patients without lacunar infarcts (55.8% versus 35.7%, P = 0.019), being independently associated on an adjusted logistic regression model (odds ratio 2.177; 95% confidence interval: 1.058-4.479; P = 0.035). In conclusion, severe obstructive sleep apnea syndrome is highly prevalent among hypertensive subjects, and is independently associated with lacunar silent cerebral infarct.

Dementia Rating Scale-2 normative data for middle-and older-aged Castilian speaking Spaniards.

OBJECTIVES: The Dementia Rating Scale-2 (DRS-2) is frequently used as a dementia screening tool in clinical and research settings in Spain. The present study describes DRS-2 Total and subscale scores in community-dwelling Spaniards, aged 50-71, and provides normative data for its use in Castilian Spanish-speaking individuals. METHODS: The sample consisted of 798 individuals who participated in an observational study on essential hypertension. Mean age was 62.8 years (SD = 5.4), mean education was 8.6 years (SD = 3.4) with 47.9% females. Almost all of them were receiving blood pressure-lowering drugs (93%) and most of them had fairly well-managed blood pressure control (M systolic/diastolic blood pressure = 142.3/77.0 ± 16.0/9.2 mm Hg). We applied a previously described method of data normalization from the Mayo's Older Americans Normative Studies to obtain the Castilian Spanish DRS-2 norms. RESULTS: Worse performance on Total and subscale scores was associated with older age (p < .05) and fewer years of education (p < .001). Women obtained lower raw Total scores than men (131.68 ± 7.2 vs. 133.10 ± 6.90, p < .005), but had fewer years of education (7.96 ± 3.33 vs. 9.17 ± 3.45, p < .001). This gender difference disappeared after correcting for age and years of education. Total and subscale scores are presented adjusted by age, and normative data are shown for Total scores adjusted by age and years of education. CONCLUSIONS: These norms are useful for studying cognitive status and cognitive decline in research and clinical settings in Castilian Spanish-speaking populations.

Long-Term Treatment with Citicoline Prevents Cognitive Decline and Predicts a Better Quality of Life after a First Ischemic Stroke.

Stroke, as the leading cause of physical disability and cognitive impairment, has a very significant impact on patients' quality of life (QoL). The objective of this study is to know the effect of citicoline treatment in Qol and cognitive performance in the long-term in patients with a first ischemic stroke. This is an open-label, randomized, parallel study of citicoline vs. usual treatment. All subjects were selected 6 weeks after suffering a first ischemic stroke and randomized into parallel arms. Neuropsychological evaluation was performed at 1 month, 6 months, 1 year and 2 years after stroke, and QoL was measured using the EuroQoL-5D questionnaire at 2 years. 163 patients were followed during 2 years. The mean age was 67.5 years-old, and 50.9% were women. Age and absence of citicoline treatment were independent predictors of both utility and poor quality of life. Patients with cognitive impairment had a poorer QoL at 2 years (0.55 vs. 0.66 in utility, p = 0.015). Citicoline treatment improved significantly cognitive status during follow-up (p = 0.005). In conclusion, treatment with long-term citicoline is associated with a better QoL and improves cognitive status 2 years after a first ischemic stroke.

Prevalence and associated factors of silent brain infarcts in a Mediterranean cohort of hypertensives.

Silent brain infarcts (SBIs) are detected by neuroimaging in approximately 20% of elderly patients in population-based studies. Limited evidence is available for hypertensives at low cardiovascular risk countries. Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study (ISSYS) is aimed to assess the prevalence and risk factors of SBIs in a hypertensive Mediterranean population. This is a cohort study in randomly selected hypertensives, aged 50 to 70 years old, and free of clinical stroke and dementia. On baseline, all participants underwent a brain magnetic resonance imaging to assess prevalence and location of silent infarcts, and data on vascular risk factors, comorbidities, and the presence of subclinical cardiorenal damage (left ventricular hypertrophy and microalbuminuria) were collected. Multivariate analyses were performed to determine SBIs associated factors. A total of 976 patients (49.4% men, mean age 64 years) were enrolled, and 163 SBIs were detected in 99 participants (prevalence 10.1%; 95% CI, 8.4%-12.2%), most of them (64.4%) located in the basal ganglia and subcortical white matter. After adjustment, besides age and sex, microalbuminuria and increasing total cardiovascular risk (assessed by the Framingham-calibrated for Spanish population risk function) were independently associated with SBIs. Male sex increased the odds of having SBIs in 2.5 as compared with females. Our results highlight the importance of considering both global risk assessment and sex differences in hypertension and may be useful to design future preventive interventions of stroke and dementia.

Triflusal and aspirin in the secondary prevention of atherothrombotic ischemic stroke: a very long-term follow-up.

BACKGROUND: The mean follow-up in the clinical trials of antiplatelet drugs in the secondary prevention of ischemic atherothrombotic stroke ranges from 1 to 5.5 years. Thus, the safety and efficacy of these drugs in the very long term is not totally documented. We have assessed the safety and effectiveness of triflusal and aspirin for a very long-term period in the secondary prevention of patients with ischemic atherothrombotic stroke. METHODS: Patients with atherothrombotic ischemic stroke, including TIA, who participated in randomized clinical trials of triflusal versus aspirin were included in the study. The period of recruitment was between 1983 and 1999. After finishing their participation in the clinical trials, patients were followed up in the Neurology Department of our hospital. All patients were treated with aspirin or triflusal during a mean period of 17.2 years. Groups were comparable with respect to sex, age, risk factor and etiology of the stroke. Adverse events and vascular events (including stroke recurrence, ischemic heart disease and vascular death) that appeared throughout the study were registered. Statistical analysis was performed using the statistical package SPSS 15.0 for Windows. Kaplan-Meier curves and the log-rank test were used to compare treatments. RESULTS: A total of 441 patients (305 men) with a mean age (±SD) of 51.1±12.4 years were included in the study; 288 patients (65.3%) were treated with triflusal and 153 with aspirin. There were no statistically significant differences between aspirin and triflusal concerning new vascular events (72.5 vs. 60.4%; p=0.28), stroke recurrence (49.7 vs. 46.5%; p=0.53), ischemic heart events (54.9 vs. 55.6%; p=0.90), vascular death (25.5 vs. 24%; p=0.73) and global mortality (42.5 vs. 42%; p=0.92). The incidence of serious bleeding (upper digestive tract hemorrhage and cerebral hemorrhage) was 18.3% in aspirin-treated patients and 5.5% in triflusal-treated patients (p<0.001). In reference to other adverse events, no significant differences were found between aspirin and triflusal. CONCLUSIONS: In the secondary prevention of ischemic stroke, very long-term treatment with triflusal or aspirin seems to have a similar efficacy, but triflusal is safer with a lower hemorrhagic risk. Triflusal may be an alternative therapy, particularly in patients who present aspirin resistance.

Investigating silent strokes in hypertensives: a magnetic resonance imaging study (ISSYS): rationale and protocol design.

BACKGROUND: Silent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patients based on population studies. They are five times more frequent than stroke in general population, and increase significantly both with advancing age and hypertension. Moreover, they are independently associated with the risk of future stroke and cognitive decline.Despite these numbers and the clinical consequences of silent brain infarcts, their prevalence in Mediterranean populations is not well known and their role as predictors of future cerebrovascular and cardiovascular events in hypertensive remains to be determined.ISSYS (Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study) is an observational cross-sectional and longitudinal study aimed to: 1- determine the prevalence of silent cerebrovascular infarcts in a large cohort of 1000 hypertensives and to study their associated factors and 2-to study their relationship with the risk of future stroke and cognitive decline. METHODS/DESIGN: Cohort study in a randomly selected sample of 1000 participants, hypertensive aged 50 to 70 years old, with no history of previous stroke or dementia.On baseline all participants will undergo a brain MRI to determine the presence of brain infarcts and other cerebrovascular lesions (brain microbleeds, white matter changes and enlarged perivascular spaces) and will be also tested to determine other than brain organ damage (heart-left ventricular hypertrophy, kidney-urine albumin to creatinine ratio, vessels-pulse wave velocity, ankle brachial index), in order to establish the contribution of other subclinical conditions to the risk of further vascular events. Several sub-studies assessing the role of 24 hour ambulatory BP monitoring and plasma or genetic biomarkers will be performed.Follow-up will last for at least 3 years, to assess the rate of further stroke/transient ischemic attack, other cardiovascular events and cognitive decline, and their predictors. DISCUSSION: Improving the knowledge on the frequency and determinants of these lesions in our setting might help in the future to optimize treatments or establish new preventive strategies to minimize clinical and socioeconomic consequences of stroke and cognitive decline.

Factors influencing haemorrhagic transformation in ischaemic stroke.

Haemorrhagic transformation (HT) of ischaemic infarction occurs when an area of brain infarction is stained with blood products, mainly red blood cells. An abnormally permeable blood-brain barrier resulting from ischaemia of the capillary endothelium allows this extravasation of blood products. HT is part of the natural history of some forms of ischaemic infarction, especially cerebral embolism, but it can be precipitated or enhanced by therapeutic interventions used in the acute phase of ischaemic stroke. The old view of HT after cerebral embolism as a generally asymptomatic change in a tissue that is already necrotic has been challenged by observations from therapeutic thrombolysis that suggest that HT can have a negative effect on patients' outcomes. Understanding of the risk factors for and the underlying mechanisms and clinical variability of HT in the context of acute therapeutic interventions in ischaemic stroke could help in the early detection of this complication, in determining the safety of recanalisation approaches, and in setting the stage for future research into the prevention or treatment of HT in patients with acute ischaemic stroke.