Cognitive Impairment after Lacunar Stroke and the Risk of Recurrent Stroke and Death.

INTRODUCTION: Patients with poststroke cognitive impairment appear to be at higher risk of recurrent stroke and death. However, whether cognitive impairment after lacunar stroke is associated with recurrent stroke and death remains unclear. We assessed whether global or domain-specific cognitive impairment after lacunar stroke is associated with recurrent stroke and death. METHODS: We considered patients from the Secondary Prevention of Small Subcortical Strokes (SPS3) trial with a baseline cognitive exam administered in English by certified SPS3 personnel, 14-180 days after qualifying lacunar stroke. We considered a baseline score of ≤86 on the Cognitive Assessment Screening Instrument to indicate global cognitive impairment, <10 on the Clock Drawing on Command test to indicate executive function impairment, and domain-specific summary scores in the lowest quartile to indicate memory and nonmemory impairment. We used Cox proportional hazards models to estimate the association between poststroke cognitive impairment and subsequent risk of recurrent stroke and death. RESULTS: The study included 1,528 participants with a median enrollment time of 62 days after qualifying stroke. During a mean follow-up of 3.9 years, 11.4% of participants had recurrent stroke and 8.2% died. In the fully adjusted models, memory impairment was independently associated with an increased risk of recurrent stroke (hazard ratio, 1.48; 95% confidence interval [95% CI]: 1.04-2.09) and death (hazard ratio, 1.87; 95% CI: 1.25-2.79). Global impairment (hazard ratio, 1.66; 95% CI: 1.06-2.59) and nonmemory impairment (hazard ratio, 1.74; 95% CI: 1.14-2.67) were associated with an increased risk of death. DISCUSSION/CONCLUSION: After lacunar stroke, memory impairment was an independent predictor of recurrent stroke and death, while global and nonmemory impairment were associated with death. Cognitive screening in lacunar stroke may help identify populations at higher risk of recurrent stroke and death.

mtDNA Copy Number Contributes to All-Cause Mortality of Lacunar Infarct in a Chinese Prospective Stroke Population.

The study aimed to investigate the relationship between mtDNA copy number and the risk of all-cause mortality in stroke. One thousand four hundred eighty-four stroke patients were documented including 273 deaths (127 thrombosis, 52 lacunar, 94 hemorrhage). Patients in the third quartile had the lowest mortality rates in overall stroke and the three subtypes. The lowest quartile of mtDNA copy number (Q1 < 85.85) indicated an increased risk of all-cause mortality in stroke patients (adjusted HR, 1.52; 95% CI, 1.08-2.14; p = 0.017). In the subtype analysis, the risk of all-cause mortality appeared only in lacunar infarct, and the patients in the Q1 (< 87.76) and Q4 (> 150.61) mtDNA copy number groups showed significantly higher risks of HRs (Q1, adjusted HR, 3.87, 95% CI, 1.52-9.83; Q4, adjusted HR, 3.08, 95% CI, 1.16-8.18). Stroke patients with lacunar infarct in mtDNA copy number < 87.76 or > 150.61 were at a high risk of poor outcomes in all-cause mortality.

Cerebral Small Vessel Disease Burden and All-Cause Mortality: Mayo Clinic Florida Familial Cerebrovascular Diseases Registry.

GOAL: Cerebral small vessel disease (CSVD) leads to cognitive decline, gait disturbances, mood changes, and an increased risk of stroke. The goal of this study is to describe the relationship between a composite radiographic CSVD score and all-cause mortality. MATERIALS AND METHODS: Data were collected from a prospective registry of patients with and without cerebrovascular disease from November 2010 through April 2018. The radiographic Total CSVD Score (tSVD) ranges from 0 (minimal disease) to 4 (severe disease), based on detection of lacunar infarcts, cerebral microbleeds, perivascular spaces, and subcortical or periventricular white matter hyperintensities. All-cause mortality served as the primary endpoint. The independent relationship between CSVD burden and all-cause mortality was assessed using Cox regression models with significance being P < .05. FINDINGS: Four hundred and forty-nine patients were included (mean age, 63 years; 50.1% [225 of 449] women). The hazard ratio for mortality significantly increased with advancing score (1.92, P = .014 score 1; 2.92, P < .001 score 2; 4.23, P < .001 combined scores 3 and 4). Significance remained despite adjustment for coexistent cerebrovascular risk factors aside from age. CONCLUSIONS: The clinically practical tSVD score may serve as a predictor for all-cause mortality in populations with high disease prevalence. Continued investigations are needed to better understand the effects of risk factor modification on mortality and pathogenesis with the goal of developing disease modifying therapies.

The Value of the CHADS2 and CHA2DS2-VASc Score for Predicting the Prognosis in Lacunar Stroke with or without Atrial Fibrillation Patients.

BACKGROUND: The CHADS2 and CHA2DS2-VASc scoring systems have been proved efficacy to stratify stroke and thromboembolism risk in patients with atrial fibrillation (AF). Whether CHADS2 and CHA2DS2-VASc score has predictive value for the prognosis in lacunar stroke (LS) patients remains unclear. METHODS: A total of 763 consecutive patients with LS (mean age: 66 ± 12 years; 464 male) were enrolled in this study between January 2013 and December 2014. Patients were divided into LS without AF (LS; n = 679) and LS with AF (LS-AF; n = 84) groups. Measures of performance for the risk scores were evaluated at predicting mortality and restroke in LS-AF and LS without AF patients. All patients were evaluated with respect to clinical features and in-hospital clinical results. RESULTS: During the mean follow-up period of 20 ± 5.8 months, 29 patients (3.8%) experienced all-cause death, 105 patients (13.8%) experienced recurrence of ischemic stroke. Multivariate analysis revealed that CHADS2 and CHA2DS2-VASc score were independently associated with all-cause death (all P < .05). On receiver operating characteristic curve analysis, area under the curve (AUC) for CHADS2 score was .942 with a similar accuracy of the CHA2DS2-VASc score (AUC: .908) in predicting mortality in LS-AF patients. Kaplan-Meier curves were conducted according to the cut-off value of CHA2DS2-VASc score. When CHADS2 score greater than or equal to 4 point or CHA2DS2-VASc score greater than or equal to 5 point, the mortality in LS-AF patients was significantly higher compared with those CHADS2 score less than 4 point or CHA2DS2-VASc score less than 5 point. However, after adjusting for clinical covariates, CHADS2 and CHA2DS2-VASc score could not predict both mortality and restroke in LS without AF patients. CONCLUSIONS: The CHADS2 and CHA2DS2-VASc score have excellent predictive value for mortality in LS-AF patients but could not predict both mortality and restroke in LS without AF patients.

Treatment Approaches to Lacunar Stroke.

Lacunar strokes are appropriately named for their ability to cavitate and form ponds or "little lakes" (Latin: lacune -ae meaning pond or pit is a diminutive form of lacus meaning lake). They account for a substantial proportion of both symptomatic and asymptomatic ischemic strokes. In recent years, there have been several advances in the management of large vessel occlusions. New therapies such as non-vitamin K antagonist oral anticoagulants and left atrial appendage closure have recently been developed to improve stroke prevention in atrial fibrillation; however, the treatment of small vessel disease-related strokes lags frustratingly behind. Since Fisher characterized the lacunar syndromes and associated infarcts in the late 1960s, there have been no therapies specifically targeting lacunar stroke. Unfortunately, many therapeutic agents used for the treatment of ischemic stroke in general offer only a modest benefit in reducing recurrent stroke while adding to the risk of intracerebral hemorrhage and systemic bleeding. Escalation of antithrombotic treatments beyond standard single antiplatelet agents has not been effective in long-term lacunar stroke prevention efforts, unequivocally increasing intracerebral hemorrhage risk without providing a significant benefit. In this review, we critically review the available treatments for lacunar stroke based on evidence from clinical trials. For several of the major drugs, we summarize the adverse effects in the context of this unique patient population. We also discuss the role of neuroprotective therapies and neural repair strategies as they may relate to recovery from lacunar stroke.

IL-1α and IL-6 predict vascular events or death in patients with cerebral small vessel disease-Data from the SHEF-CSVD study.

PURPOSE: The natural clinical course of cerebral small vessel disease (CSVD) was not thoroughly described. The aim of this single center cohort study was to establish biochemical predictors of vascular events and death in CSVD patients during a 24-month follow-up. PATIENTS AND METHODS: A total of 130 functionally independent patients with marked MRI features of CSVD and recent lacunar stroke (n = 52,LS), vascular Parkinsonism (n = 28,VaP) or dementia (n = 50,VaD) were prospectively recruited. Serum markers of endothelial dysfunction, inflammation and hemostasis were determined at baseline. The primary outcome was defined as occurrence of death or any vascular events during the observation. RESULTS: The mean age was 72 ± 8.1 years, and 37.6% of the patients were women. The mean follow-up time was 22.3 ± 4.3 months, and 84.6% of patients had extensive white matter lesions on baseline MRI. The overall mortality rate was 6.9%, and vascular events or death occurred in 27% of the patients. Kaplan-Meier survival curves revealed no significant differences between CSVD groups (log rank p = 0.49). Cox regression analysis revealed that IL-1α (HR 1.4; 95%CI 1.09-1.8), IL-6 (1.4;1.1-2.2), hs-CRP (1.1;1.06-1.9), homocysteine (1.4;1.1-1.8), fibrinogen (1.4;1.05-2), and d-dimer (2.7;1.6-4.5) were significantly associated with the primary outcome. IL-1α (1.3;1.07-1.8), IL-6 (1.4;1.02-2.2), d-dimer (2.8;1.6-5) and homocysteine (1.4;1.1-1.8) remained significant after adjusting for age, sex and CSVD radiological markers. CONCLUSIONS: Our study demonstrated the important prognostic role of various circulation markers of inflammation in individuals with different clinical signs and radiological markers of CSVD. The strongest association occurred between IL-1α, IL-6 and recurrent stroke, other vascular events and death.

Assessment of Homocysteine as a Diagnostic and Early Prognostic Biomarker for Patients with Acute Lacunar Infarction.

BACKGROUND: Although increasing evidence has demonstrated that elevated homocysteine (Hcy) levels may be an important contributor for the development of cerebral infarction, rare studies focused on its diagnostic and early prognostic roles in acute lacunar infarction. METHODS: A total of 197 patients with acute lacunar infarction and 192 to form the control group were prospectively recruited between January 2013 and February 2017. Early neurological deterioration was defined as an increase of ≥2 points in National Institutes of Health Stroke Scale or the decrease in Barthel index (BI) score at discharge. RESULTS: Univariate and multivariate logistic regression analyses revealed that higher levels of fibrinogen and Hcy were independently clinical predictors associated with lacunar infarction. Receiver operating characteristic curves analysis demonstrated that the diagnosis value of Hcy was superior to fibrinogen, with the area under the curve of 0.881 and 0.688 respectively. Using the optimal cutoff value of 15.5 µmol/L of Hcy, a sensitivity of 65% and a specificity of 100% were achieved for predicting lacunar infarction. Hcy was only significantly related with BI reduction in the males (30.5 [15.5-65.5] vs. 18 [15-24], p = 0.034) in the univariate analysis but not in the females and the multivariate analysis. CONCLUSIONS: Serum Hcy may be an independent diagnostic and not an early prognostic biomarker for patients with acute lacunar infarction.

Multiple Silent Lacunes Are Associated with Recurrent Ischemic Stroke.

BACKGROUND: Silent lacunes are a common finding on brain imaging in ischemic stroke patients, but the prognostic significance of these lesions is uncertain. We aimed at investigating the association of silent lacunes and the risk of ischemic stroke recurrence, death, and cardiovascular events in a cohort of patients with incident ischemic stroke and no atrial fibrillation (AF). METHODS: We included 786 patients (mean age 59.5 (SD 14.0); 42.9% females) in a registry-based, observational cohort study on patients with first-ever ischemic stroke. On brain MRI we assessed the number of silent lacunes as none, single, or multiple and we calculated stratified incidence rates of the outcomes. Cox proportional hazard ratios (HRs) adjusted for age, gender, congestive heart failure, hypertension, diabetes, and vascular disease were calculated with no silent lacunes as reference. In additional analyses, we further adjusted for white matter hyperintensities. Patients were followed up until death or recurrence of ischemic stroke. RESULTS: In 81 (10.3%) patients, a single silent lacune was present, and in 87 (11.1%) patients, multiple silent lacunes were present. Patients with at least one silent lacune were older (mean age 66.1 vs. 57.7, p < 0.001) and were more often hypertensive (60.1 vs. 43.4%, p < 0.001) compared to patients with no silent lacunes. During a median follow-up time of 2.9 (interquartile range 3.1) years, we observed 53 recurrent ischemic strokes, 76 deaths, and 96 cardiovascular events. Incidence rates per 100 person-years of ischemic stroke recurrence were 1.6, 2.5, and 5.0 for none, single, and multiple silent lacunes respectively. Corresponding incidence rates were 2.6, 2.4, and 4.4 for death, and 3.4, 4.0, and 6.6 for cardiovascular events respectively. Adjusted HRs of ischemic stroke recurrence were 1.53 (0.67-3.49) and 2.52 (1.25-5.09) for a single and multiple silent lacunes, respectively. Further adjustment for white matter hyperintensities maintained positive association although not significant. Corresponding adjusted HRs were 0.56 (0.25-1.25) and 0.65 (0.33-1.25) for death and 1.16 (0.61-2.22) and 1.51 (0.86-2.66) for cardiovascular events. CONCLUSIONS: In this large cohort of patients with incident ischemic stroke and no AF, an increasing number of silent lacunes was associated with increasing incidence rates of ischemic stroke recurrence. In the adjusted Cox proportional hazard analyses, the presence of multiple silent lacunes was significantly associated with an increased risk of ischemic stroke recurrence. The risk of death or cardiovascular events was not significantly influenced by the presence of silent lacunes.

Comparison of risk factors, severity and outcome between lacunar and non-lacunar stroke in a tertiary care center in Sri Lanka: a descriptive study.

This study compares demography, risk factors and outcome of lacunar (LAC) and non-lacunar (non-LAC) strokes from the prospective hospital based stroke registry at Colombo South Teaching Hospital from 1st March 2012 to 30th June 2013. Data on admission, discharge and at 28 days after discharge were analysed. There were 229 ischaemic stroke (IS) patients. Average age was 65.7 years (SD 12.2, range 34-94) and 116 (50.7%) were males. LAC (n=130, 56.8%) were common than non-LAC (n=99, 43.2%). There were 75 (64.7%) males and 55 (48.7%) females in the LAC group (adjusted OR 2.1, 95% CI 1.08-4.29). Atrial fibrillation was less frequent among LAC stroke (OR 0.3, 95% CI 0.09-0.99). Hypertension, diabetes, smoking, dyslipidaemia did not differ in the two groups. Lower NIHSS (5.34 Vs 6.6, p= 0.053), higher GCS (14.7 Vs 13.3, p=0.001) were seen in LAC. Disability (MRS, Barthel index) on discharge, at 28 days and mortality during hospital stay and within 28 days was lower in the LAC group (p <0.001).

Clinical characteristics of acute lacunar stroke in young adults.

INTRODUCTION: Acute lacunar stroke in subjects under 55 years of age has been poorly characterized. METHODS: We assessed the clinical features of lacunar stroke in 51 patients aged ≤55 years (84.5% men, mean standard deviation [SD] age 49.8 [5.2] years) collected from a prospective hospital-based stroke registry in Barcelona, Catalonia, Spain. RESULTS: This subset of young lacunar stroke patients accounted for only 5.2% of all lacunar strokes, 1.2% of all ischemic strokes, and 1.1% of all acute strokes included in the registry over a 24-year period. In the multivariate analysis, factors independently associated with acute lacunar stroke in patients aged ≤55 years were alcohol consumption (>60 g/day) (odds ratio [OR] = 6.67), heavy smoking (>20 cigarettes/day) (OR = 3.02), obesity (OR = 2.81), essential etiology (OR = 2.73), and headache at stroke onset (OR = 2.45). CONCLUSION: Characterization of the clinical profile of acute lacunar stroke in younger patients contributes to a better knowledge of the full clinical expression of this ischemic stroke subtype.

Incidence and survival of lacunar infarction in a southern Chinese population: A 7-year prospective study.

OBJECTIVE: Little attention has been paid to the epidemiological characteristics of lacunar infarction (LAC) in China before. This study aimed to examine the incidence and survival of LAC in a southern Chinese population. METHODS: From 2004-2010 in Changsha, two communities with a registered population of ∼100 000 were selected and data from first-ever ischaemic stroke (IS) cases were prospectively collected. Then the epidemiological characteristics of LAC and non-LAC were evaluated. RESULTS: During the study period, the age-standardized incidence increased at an annual rate of 0.7% (p < 0.001) for LAC and 2.0% (p < 0.001) for non-LAC. The mean annual age-standardized incidence of LAC and non-LAC was 28.2/100 000 and 45.0/100 000, respectively. Compared with non-LAC patients, the prevalence of hypertension, diabetes and hyperlipidemia was significantly higher in patients with LAC (p < 0.05). Although the 30-day fatality rate was significantly lower in patients with LAC than non-LAC (0.5% vs. 14.9%, p < 0.001), there was no significant difference in survival between the two groups (96.7% vs. 95.2%, p = 0.203) after excluding the patients who died within 1 year of stroke onset. CONCLUSION: LAC is a common stroke sub-type in southern China and the long-term prognosis is not benign.

Gender differences and woman-specific trends in acute stroke: results from a hospital-based registry (1986-2009).

OBJECTIVE: We assessed gender differences and women-specific secular trends in stroke. METHODS: Data from 2318 women and 2274 men with first-ever stroke collected from the Sagrat Cor Hospital Stroke Registry of Barcelona between 1986 and 2009 were analyzed. RESULTS: Patient's age increased significantly from a mean of 74.5 years in 1986-1992 to 81.2 years in 2004-2009 (P < 0.001). Patients aged ≥ 85 years increased from 18.5% to 38.5% (P = 0.0001) as were patients with hypertension, atrial fibrillation, and cardioembolic stroke. The in-hospital death decreased from 17.6% to 11% (P = 0.02), median length of hospital from 14 to 9 days (P = 0.0001) and prolonged hospital stay (> 12 days) from 59.7% to 33.7% (P = 0.0001). Lacunar infarction was more frequent in men (21.5% vs. 16.2%, P = 0.0003) and cardioembolic infarction in women (26% vs. 15.6%, P = 0.0001). Acute stroke in women continues to be a severe disease with high risk of death in the immediate post-stroke phase (13.5%) and low probability of early full neurological recovery (13.9% vs. 11.8%, P = 0.029). CONCLUSION: Women differ from men in the distribution of risk factors and stroke subtype, stroke severity, and outcome. An increase in the patient's age, hypertension, atrial fibrillation and cardioembolic infarction, as well as a decrease mortality and length of hospitalization over a 24-year period was recorded.

Factors associated with severity of leukoaraiosis in first-ever lacunar stroke and atherosclerotic ischemic stroke patients.

BACKGROUND: Leukoaraiosis (LA) is an indicator of small vessel disease, but little is known about the relationship between the severity of LA and etiologic subtype of ischemic stroke. Our study aimed to investigate the factors associated with the severity of LA and the relationship between the severity of LA and etiologic subtype of ischemic stroke. METHODS: A total of 791 patients with first-ever ischemic stroke within 7 days were enrolled in our study. We evaluated cranial magnetic resonance imagings including severity of LA in periventricular and deep white matter, severity of silent lacunar infarcts (SLIs), etiologic subtype of ischemic stroke, and topographic patterns of acute cerebral infarcts. Severity of LA was graded as grade 0 when Fazekas scores = 0, grade 1 when Fazekas scores ranged from 1 to 2, and grade 2 when Fazekas scores were greater than or equal to 3. Multivariable ordinal logistic regression was used to analyze the factors associated with the severity of LA. RESULTS: A total of 748 patients (94.6%) had LA, the numbers and proportions of grade 0, grade 1, and grade 2 LA were 43 patients (5.4%), 413 patients (52.2%), and 335 patients (42.4%), respectively. In multivariable ordinal logistic regression analysis, increasing age, higher diastolic blood pressure, admission National Institutes of Health Stroke Scale scores less than or equal to 3, presence of SLIs, and small artery occlusion (SAO) subtype of ischemic stroke were found to be independently associated with higher grade of LA. CONCLUSIONS: LA is prevalent in first-ever ischemic stroke patients. Severe LA is more frequently associated with higher grades of SLIs and ischemic stroke due to SAO.

Predictors of mortality in patients with lacunar stroke in the secondary prevention of small subcortical strokes trial.

BACKGROUND AND PURPOSE: The Secondary Prevention of Small Subcortical Stroke trial (SPS3) recruited participants meeting clinical and radiological criteria for symptomatic lacunes. Individuals randomized to dual antiplatelet therapy with clopidogrel and aspirin had an unanticipated increase in all-cause mortality compared with those assigned to aspirin. We investigated the factors associated with mortality in this well-characterized population. METHODS: We identified independent predictors of mortality among baseline demographic and clinical factors by Cox regression analysis in participants of the SPS3 trial. Separately, we examined the effect on mortality of nonfatal bleeding during the trial. RESULTS: During a mean follow-up of 3.6 years, the mortality rate was 1.78% per year for the 3020 participants (mean age, 63 years). Significant independent predictors of mortality at study entry were age, diabetes mellitus, history of hypertension, systolic blood pressure (hazard ratio [HR], 1.3 per 20 mm Hg increase), serum hemoglobin<13 g/dL (HR, 1.6), renal function (HR, 1.3 per estimated glomerular filtration rate decrease of 20 mL/min), and body mass index (HR, 1.8 per 10 kg/m2 decrease). Participants with ischemic heart disease (P=0.01 for interaction) and normotensive/prehypertensive participants (P=0.03 for interaction) were at increased risk if assigned to dual antiplatelet therapy. Nonfatal major hemorrhage increased mortality in both treatment arms (HR, 4.5; 95% confidence interval, 3.1-6.6; P<0.001). CONCLUSIONS: Unexpected interactions between assigned antiplatelet therapy and each of ischemic heart disease and normal/prehypertensive status accounted for increased mortality among patients with recent lacunar stroke given dual antiplatelet therapy. Despite extensive exploratory analyses, the mechanisms underlying these interactions are uncertain. CLINICAL TRIAL REGISTRATION URL: http://www.SPS3ClinicalTrials.gov. Unique identifier: NCT00059306.

Lacunar infarction, mortality over time and mortality relative to other ischemic strokes.

OBJECTIVES: Determine the overall mortality after lacunar infarction and compare it to the overall mortality afterothrombotic and cardioembolic strokes. Determine the pattern of increased mortality over time after lacunar infarction. METHODS: The clinical literature was searched for articles providing mortality data on lacunar infarction having at least 5 years of post stroke follow up. Three such articles were identified two of which also had post stroke mortality data on the other two types of ischemic stroke, atherothrombotic and cardioembolic stroke. Degree of overall increased mortality was determined for all three stroke types and increased mortality over time was determined for lacunar infarction as well. Standard mortality methodology was used and expectant mortality was determined using appropriate population life tables. Average overall mortality ratios (MR) and average overall excess deaths per thousand per year (EDR) were determined by weighting for the number of entrants in each study. RESULTS: The average overall MR for lacunar infarction = 159%, for atherothrombotic stroke = 213% and for cardioembolic stroke = 322%. The mortality ratios for lacunar infarction for the following post-stroke intervals were: 1-5 years = 166%; 6-10 years = 153%; and 11-14 years = 106%. CONCLUSIONS: Lacunar infarction from onset is associated with moderately increased overall mortality relative to the general population. Post-stroke mortality risks from atherothrombotic and cardioembolic strokes are significantly higher.

Visit-to-visit systolic blood pressure variability predicts all-cause and cardiovascular mortality after lacunar infarct.

BACKGROUND AND PURPOSE: Both blood pressure (BP) and its variability (BPV) are established risk factors for development of atherosclerotic disease and are associated with an increased risk for cardiovascular and all-cause mortality. The prognostic implications of outpatient clinic visit-to-visit BPV amongst patients with lacunar infarction are nevertheless unknown. METHODS: The clinical outcome of 281 patients with lacunar infarction was prospectively followed up. The average BP and BPV, as determined by the standard deviation of the systolic and diastolic BP, were recorded during a mean 13 ± 6 outpatient clinic visits. RESULTS: The mean age of the population was 70 ± 10 years. After a mean 78 ± 18 months follow-up, 65 patients died (23%), 31% (20/65) due to cardiovascular causes; 14% and 7% developed recurrent stroke and acute coronary syndrome. After adjusting for age, sex, mean systolic and diastolic BP, cardiovascular risk factors and comorbidities, patients with a systolic BPV of the third tertile had significantly higher risk of all-cause mortality [hazard ratio (HR) 1.97, 95% confidence interval (CI) 1.02-3.80, P = 0.04) and cardiovascular mortality (HR 7.64, 95% CI 1.65-35.41, P < 0.01) than those with systolic BPV of the first tertile. Nevertheless, systolic BPV did not predict recurrent stroke or acute coronary syndrome. Diastolic BPV did not predict various adverse clinical outcomes. CONCLUSIONS: Visit-to-visit systolic BPV predicts long-term all-cause and cardiovascular mortality after lacunar infarct, independent of conventional risk factors including average BP control.

Five-year prognosis after mild to moderate ischemic stroke by stroke subtype: a multi-clinic registry study.

BACKGROUND AND PURPOSE: Mild to moderate ischemic stroke is a common presentation in the outpatient setting. Among the various subtypes of stroke, lacunar infarction (LI) is generally very common. Currently, little is known about the long-term prognosis and factors associated with the prognosis between LI and non-LI. This study aims to compare the risk of death and acute cardiovascular events between patients with LI and non-LI, and identify potential risk factors associated with these outcomes. METHODS: A total of 710 first-ever ischemic stroke patients (LI: 474, non-LI: 263) from 18 clinics were recruited consecutively from 2003 to 2004. They were prospectively followed-up until the end of 2008. Hazard ratios and 95% confidence intervals were calculated using multivariable Cox proportional hazards regression. RESULTS: After a 5-year follow up, 54 deaths and 96 acute cardiovascular events occurred. Recurrent stroke was the most common cause of death (19 cases, 35.18%) and new acute cardiovascular events (75 cases, 78.13%). There were no significant differences between patients with LI and non-LI in their risks of death, new cardiovascular events, and recurrent stroke after adjusting for age, sex, hypertension, diabetes, cardiac diseases, body mass index, dyslipidemia, smoking, alcohol consumption, ADL dependence, and depressive symptoms. Among the modifiable risk factors, diabetes, hypertension, ADL dependency, and symptoms of depression were independent predictors of poor outcomes in patients with LI. In non-LI patients, however, no modifiable risk factors were detected for poor outcomes. CONCLUSION: Long-term outcomes did not differ significantly between LI and non-LI patients. Detecting and managing vascular risk factors and depression as well as functional rehabilitation may improve the prognoses of LI patients.

Mood problems increase the risk of mortality in patients with lacunar infarcts: the SMART-MR study.

OBJECTIVE: A relationship between depression and mortality has been well established, but underlying mechanisms remain unclear. We investigated the influence of cerebral small vessel disease (CSVD), characterized by white matter lesions (WMLs) and lacunar infarcts, on the relationship between mood mortality during 6 years follow-up. METHODS: Mood problems were assessed with the mental component summary of the 36-item Short-Form Medical Outcomes Study in 1110 patients with symptomatic atherosclerotic disease (mean age 59 years). Volumetric WML estimates were obtained with 1.5-T magnetic resonance imaging; lacunar infarcts were scored visually. Cox regression models were adjusted for age, sex, vascular risk, physical functioning, antidepressants and infarcts. We adjusted for CSVD to examine whether it may be an intermediate or confounding factor. Second, we added interaction terms to investigate whether associations differed between patients with CSVD (absent/present). RESULTS: Patients in the lowest quartile of mental functioning, representing most severe mood problems, were at higher, although not significant, risk of death (hazard ratio [HR] = 1.47, 95% confidence interval [CI] = 0.94-2.30) compared with patients in higher quartiles. Adjustment for CSVD did not change this association. Lacunar infarcts, not WML, modified the association of mood problems with mortality (p value for interaction = .01); mood problems strongly increased the risk of mortality in patients with lacunar infarcts (HR = 2.75, 95% CI = 1.41-5.38) but not in those without it (HR = 0.78, 95% CI = 0.39-1.57). CONCLUSIONS: Patients with lacunar infarcts may be especially vulnerable for the effect of mood problems on mortality.

Are stroke occurrence and outcome related to weather parameters? Results from a population-based study in northern portugal.

BACKGROUND: Changes in meteorological parameters have been associated with cardiovascular mortality and stroke. The high incidence of stroke in Portugal may be modelled by short- or long-term weather changes whose effect may be different across stroke types and severity. METHODS: Data include all patients with a first-ever-in-a-lifetime stroke registered in a population of 86,023 residents in the city of Porto from October 1998 to September 2000. Specific stroke types were considered and ischaemic stroke (IS) subtype was defined according to the Oxfordshire Community Stroke Projet classification and the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Information on daily temperature, humidity and air pressure was obtained from the National Meteorological Office. The Poisson distribution was used to model the daily number of events as a function of each weather parameter measured over different hazard periods, and the binomial model to contrast effects across subgroups. Differential effects of meteorological parameters and hazard periods upon stroke occurrence and outcome were analysed in a stepwise model. RESULTS: Among the 462 patients registered, 19.6% had a primary intracerebral haemorrhage (PICH) and 75.3% an IS. Among patients with IS, 21.6% were total anterior circulation infarcts (TACIs), 19.8% partial anterior circulation infarcts (PACIs), 19.5% posterior circulation infarcts (POCIs) and 39.1% were lacunar infarcts (LACIs). The aetiology of IS was large artery atherosclerosis in 6.9%, cardioembolism in 23.3% and small artery occlusion in 35.6%. The incidence of PICH increased by 11.8% (95% CI: 3.8-20.4%) for each degree drop in the diurnal temperature range in the preceding day. The incidence of IS increased by 3.9% (95% CI: 1.6-6.3%) and cardioembolic IS by 5.0% (95% CI: 0.2-10.1%) for a 1°C drop in minimum temperature in the same hazard period. The incidence of TACIs followed the IS pattern while for PACIs and POCIs there were stronger effects of longer hazard periods and no association was found for LACIs. The relative risk of a fatal versus a non-fatal stroke increased by 15.5% (95% CI: 6.1-25.4%) for a 1°C drop in maximum temperature over the previous day. CONCLUSIONS: Outdoor temperature and related meteorological parameters are associated with stroke occurrence and severity. The different hazard periods for temperature effects and the absence of association with LACIs may explain the heterogeneous effects of weather on stroke occurrence found in community-based and hospital admission studies. Emergency services should be aware that specific weather conditions are more likely to prompt calls for more severe strokes.

Cerebral small vessel disease and risk of death, ischemic stroke, and cardiac complications in patients with atherosclerotic disease: the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study.

BACKGROUND AND PURPOSE: Cerebral small vessel disease may be related to vascular and nonvascular pathology. We assessed whether lacunar infarcts and white matter lesions on MRI increased the risk of vascular and nonvascular death and future vascular events in patients with atherosclerotic disease. METHODS: Brain MRI was performed in 1309 patients with atherosclerotic disease from the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study. Infarcts were scored visually and volumetric assessment of white matter lesion was performed. Patients were followed for a median of 4.5 years (range, 0.2 to 7.1 years) for death, ischemic stroke, and ischemic cardiac complications. RESULTS: Cox regression models showed that presence of lacunar infarcts (n=229) increased the risk of vascular (hazard ratio, 2.6; 95% CI, 1.4 to 4.9) and nonvascular death (hazard ratio, 2.7; 95% CI, 1.3 to 5.3), adjusted for age, sex, vascular risk factors, nonlacunar infarcts, and white matter lesion. These risks were similar for patients with silent lacunar infarcts. White matter lesion volume (relative to total intracranial volume) increased the risk of vascular death (hazard ratio per milliliter increase, 1.03; 95% CI, 1.01 to 1.05) and white matter lesions in the upper quintile compared with lower quintiles increased risk of ischemic stroke (hazard ratio, 2.6; 95% CI, 1.3 to 4.9). CONCLUSIONS: Cerebral small vessel disease, with or without a history of cerebrovascular disease, is associated with increased risk of death and ischemic stroke in patients with atherosclerotic disease.