Elisa Cuadrado-Godia

Statin Therapy and Outcome After Ischemic Stroke Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials

Background and Purpose— Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. Methods— The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (⩽72 hours after stroke), and (2) thrombolysis-treated patients. Results— The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29–1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9–1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62–0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, 0.67–0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0–2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02–1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90–1.44; 4012 patients). Conclusion— In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed.

High Risk of Early Neurological Recurrence in Symptomatic Carotid Stenosis

Background and Purpose— Few data are available on very early stroke recurrence evaluated within the first hours after onset of symptoms and outcome for unselected patients with first-ever mild stroke or TIA and symptomatic carotid stenosis ≥50%. Methods— One hundred sixty-three patients with symptomatic carotid stenosis and initial mild stroke (121) or TIA (42) were evaluated within 6 hours from onset of symptoms in a single tertiary hospital. Neurological recurrence (NR) was defined as a clearly defined new neurological event (TIA or stroke) or an increase of 4 points in the initial NIHSS. The NR rate was determined at 72 hours, 7 days, and 14 days. Disability was defined as a score of 3 to 6 on the modified Rankin scale at 14 days. Results— Forty-five patients (27.6%) had NR, including 6 patients with 2 episodes in different time periods: 34 (20.9%) within the first 72 hours; 11 (6.7%) between 72 hours and 7 days; and 6 (3.7%) at 14 days. Only carotid stenosis ≥70% was associated with NR; diabetes was marginally associated. At 2 weeks, 19 patients (11.7%) had disability; 14 of them experienced NR in the first 72 hours. Conclusions— Patients with first-ever mild stroke or TIA and symptomatic carotid stenosis are at high risk for NR, especially within the first 72 hours. Our results suggest the necessity of testing pharmacological or interventional strategies for use during the hyperacute stroke phase in these patients.

Weather as a Trigger of Stroke

Background: The conclusions of previous studies show little agreement concerning the relationship between weather and the incidence of stroke. We analyse the relationship between daily meteorological conditions and daily as well as seasonal stroke incidence. Methods: 1,286 consecutive strokes assessed during 3 years (2001–2003) from the reference area of Hospital del Mar were classified as intracerebral haemorrhage (ICH) (n = 243) or ischaemic stroke (IS) (n = 1,043). IS was divided in non-lacunar stroke (NLS) (n = 732) and lacunar stroke (LS) (n = 311). Daily meteorological data were obtained from ‘Observatori Fabra’ of Barcelona: atmospheric pressure (AP), relative humidity, maximum, minimum, and mean temperatures, and the variation of all these measures compared with the previous day. Results: Total stroke (TS) incidence showed little association with AP (coefficient of confidence, CC: –0.072; p = 0.022), but was higher with the AP variations (CC: 0.127; p < 0.001). NLS were related to AP falls (OR: 2.41; p < 0.001) whilst ICHs were associated with AP rises (OR: 2.07; p = 0.01). NLS and temperature showed an inverse correlation; however, it lost its significance after adjusting for AP variations. The daily incidences of NLS and ICH were higher in autumn and in winter, but depended strongly on the daily variations of AP. No other associations were found. Conclusions: The incidences of NLS and ICH are related to AP changes compared with the previous day. AP changes largely explain the seasonal and daily variations in the incidence of stroke. These data may help to explain the controversy in previous studies and to promote studies focused on the trigger mechanisms of stroke.

Hyperlipidemia and Reduced White Matter Hyperintensity Volume in Patients with Ischemic Stroke

Background and Purpose— White matter hyperintensity (WMH), or leukoaraiosis, is a radiologic finding generally assumed to reflect diseased small cerebral vasculature. WMH has significant functional impact through its relation to cognitive decline and risk of ischemic and hemorrhagic stroke. Accumulating evidence suggests that some manifestations of small-vessel disease such as intracerebral hemorrhage are associated with low levels of cholesterol. We sought to determine the relation between hyperlipidemia and WMH severity in patients with acute ischemic stroke (AIS). Methods— We analyzed 2 independent, hospital-based AIS cohorts. Demographic and clinical data were collected prospectively. WMH was measured using semiautomated volumetric image analysis and a semiquantitative visual grading scale. Univariate and multivariable regression analyses were used to assess the relation between WMH severity and study variables. Results— A total of 631 and 504 subjects in the first and second cohorts, respectively, were included. In univariate analyses, advancing age and hypertension were associated with severity of WMH (P<0.001) in both cohorts. In the multivariable analysis, after controlling for age, sex, and significant risk factors in the univariate and age-adjusted analyses, patients with a history of hyperlipidemia had less severe WMH in both cohorts (P<0.01). Conclusions— Results from 2 independent cohorts demonstrate that AIS patients with a history of hyperlipidemia have less severe WMH at the time of stroke. These data support the hypothesis that hyperlipidemia may play a relatively protective role in cerebral small-vessel disease.

Acute stroke unit care and early neurological deterioration in ischemic stroke

ObjectiveTo evaluate the impact that monitored acute stroke unit care may have on the risk of early neurological deterioration (END), and 90-day mortality and mortality-disability.MethodsNon-randomized prospective study with consecutive patients with acute ischemic stroke (AIS) admitted to a conventional care stroke unit (CCSU), from May 2003 to April 2005, or to a monitored acute stroke unit (ASU) from May 2005 to April 2006. END was defined as an increase in the NIHSS score ≥ 4 points in the first 72 hours after admission.ResultsEND was detected in 19.6 % of patients (11.2 % of patients admitted to the ASU and 23.8 % to the CCSU; p < 0.0001). Patients admitted to the ASU received more treatment with intravenous rtPa (13.5 % versus 4.2 %; p < 0.0001), had a shorter length of stay (9.1 [11.0] d versus 13.1 [10.4] d; p < 0.0001), lower 90-day mortality (10.2 % versus 17.3 %; p = 0.02), and lower mortality-disability at 90-days (28.4 % versus 40.2 %; p = 0.004) than those admitted to the CCSU. Multivariable analysis showed that ASU admission was a protector for END (OR: 0.37; 95 % CI: 0.23–0.62). On admission, higher NIHSS (OR: 1.06; 95 % CI: 1.03–1.10), higher glycaemia (OR: 1.003; 95 % CI: 1.001–1.006), and higher systolic pressure (OR: 1.01; 95 % CI: 1.002–1.017) were independent predictors of END.ConclusionsEND prevention by ASU care might be a key factor contributing to better outcome and decrease of length of stay in patients admitted to monitored stroke units.

Early Arterial Study in the Prediction of Mortality After Acute Ischemic Stroke

Background and Purpose— The purpose of this study was to evaluate the value of the initial arterial study as a predictor of 90-day mortality in patients with acute ischemic stroke. Methods— A total of 1220 unselected patients assessed during the first 24 hours after stroke onset were prospectively studied. Initial stroke severity was evaluated by the National Institutes of Health Stroke Scale and dichotomized in mild (National Institutes of Health Stroke Scale ≤7) and severe (National Institutes of Health Stroke Scale >7). Severe arterial stenosis (≥70%) or arterial occlusion in the symptomatic territory was determined by a Doppler study and also by additional explorations (carotid duplex, MR or CT angiography) in the first 24 hours after admission. The following variables were also analyzed: age, gender, previous functional status, smoking, hypertension, hyperlipidemia, diabetes mellitus, peripheral arterial disease, ischemic heart disease, heart failure, atrial fibrillation, previous stroke, and prior use of antithrombotic or statins. Ninety-day mortality was the end point of the study. Results— Ninety-day mortality was 15.7%. A total of 25.5% of all deaths were in patients with mild stroke. In addition to well-known factors related to mortality (age, stroke severity, ischemic heart disease, heart failure, and previous disability), severe arterial stenosis/occlusion was the factor with the highest relationship with 90-day mortality (adjusted OR: stenosis 2.13, occlusion 4.42, both 3.36). Arterial stenosis/occlusion was a higher predictor of 90-day mortality in patients with mild (adjusted OR: 5.38) than severe stroke (adjusted OR: 3.05). Conclusions— Severe arterial stenosis/occlusion in the early arterial study was highly related with 90-day mortality in an unselected series of patients with stroke. These data achieve special relevance in patients with initial mild stroke.

Outcomes of a contemporary cohort of 536 consecutive patients with acute ischemic stroke treated with endovascular therapy.

Background and Purpose— We sought to assess outcomes after endovascular treatment/therapy of acute ischemic stroke, overall and by subgroups, and looked for predictors of outcome. Methods— We used data from a mandatory, population-based registry that includes external monitoring of completeness, which assesses reperfusion therapies for consecutive patients with acute ischemic stroke since 2011. We described outcomes overall and by subgroups (age ⩽ or >80 years; onset-to-groin puncture ⩽ or >6 hours; anterior or posterior strokes; previous IV recombinant tissue-type plasminogen activator or isolated endovascular treatment/therapy; revascularization or no revascularization), and determined independent predictors of good outcome (modified Rankin Scale score ⩽2) and mortality at 3 months by multivariate modeling. Results— We analyzed 536 patients, of whom 285 received previous IV recombinant tissue-type plasminogen activator. Overall, revascularization (modified Thrombolysis In Cerebral Infarction scores, 2b and 3) occurred in 73.9%, 5.6% developed symptomatic intracerebral hemorrhages, 43.3% achieved good functional outcome, and 22.2% were dead at 90 days. Adjusted comparisons by subgroups systematically favored revascularization (lower proportion of symptomatic intracerebral hemorrhages and death rates and higher proportion of good outcome). Multivariate analyses confirmed the independent protective effect of revascularization. Additionally, age >80 years, stroke severity, hypertension (deleterious), atrial fibrillation, and onset-to-groin puncture ⩽6 hours (protective) also predicted good outcome, whereas lack of previous disability and anterior circulation strokes (protective) as well as and hypertension (deleterious) independently predicted mortality. Conclusions— This study reinforces the role of revascularization and time to treatment to achieve enhanced functional outcomes and identifies other clinical features that independently predict good/fatal outcome after endovascular treatment/therapy.

Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage

Background and Purpose— Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome. Methods— We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured genetic variants. Contribution to heritability was separately estimated for the APOE (encoding apolipoprotein E) gene, an established genetic risk factor, and for the rest of the genome. Analyzed phenotypes included ICH risk, admission hematoma volume, and 90-day mortality. Results— ICH risk heritability was estimated at 29% (SE, 11%) for non-APOE loci and at 15% (SE, 10%) for APOE. Heritability for 90-day ICH mortality was 41% for non-APOE loci and 10% (SE, 9%) for APOE. Genetic influence on hematoma volume was also substantial: admission volume heritability was estimated at 60% (SE, 70%) for non-APOEloci and at 12% (SE, 4%) for APOE. Conclusions— Genetic variation plays a substantial role in ICH risk, outcome, and hematoma volume. Previously reported risk variants account for only a portion of inherited genetic influence on ICH pathophysiology, pointing to additional loci yet to be identified.

Outcome of intracerebral haemorrhage patients pre‐treated with statins

Background:  Statins treatment may have potential clinical impact in vascular disease beyond cholesterol lowering. Its benefits have been documented in cerebral ischaemia and in subarachnoid haemorrhage. In intracerebral haemorrhage (ICH), experimental models in statin‐treated animals have better outcome than non‐treated ones, but in humans the relationship is unclear. We investigated whether patients treated with statins before the onset of intracerebral haemorrhage have a better outcome at 3 months than patients without statins pre‐treatment.

Steno-occlusive arterial disease and early neurological deterioration in acute ischemic stroke.

Aim: To evaluate the influence that steno-occlusive arterial disease may have on the development of early neurological deterioration (END) in a large series of patients with acute ischemic stroke. Methods: We studied a prospective cohort of 1,093 patients admitted to a single tertiary hospital with presence of neurological symptoms in the first 24 h after stroke onset. END was defined as any increase in the National Institutes of Health Stroke Scale score ≧4 points in the first 72 h. The arterial study assessed the presence of arterial occlusion or significative stenosis in the symptomatic territory. Additionally, age, initial stroke severity, blood pressure, glucose levels, vascular risk factors, lacunar stroke and prior use of antithrombotic treatment were also analyzed in a multivariable analysis. Results: END was detected in 179 patients (16.3%). Steno-occlusive disease (adjusted OR 3.60), initial blood pressure and abdominal obesity were independently associated with END. Both arterial stenosis (adjusted OR 2.33) or occlusions (adjusted OR 3.65) were associated with END. The higher adjusted OR (5.49) was obtained for steno-occlusive arterial disease in the vertebrobasilar system. Conclusions: An early arterial study may provide key data for the selection of patients with higher risk of END after acute ischemic stroke.