Stella-Maria Angelopoulou

Stress hyperglycemia and acute ischemic stroke in-hospital outcome

BACKGROUND AND AIMS Stress hyperglycemia is frequent in patients with acute ischemic stroke. However, it is unclear whether stress hyperglycemia only reflects stroke severity or if it is directly associated with adverse outcome. We aimed to evaluate the prognostic significance of stress hyperglycemia in acute ischemic stroke. METHODS We prospectively studied 790 consecutive patients who were admitted with acute ischemic stroke (41.0% males, age 79.4±6.8years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Stress hyperglycemia was defined as fasting serum glucose levels at the second day after admission ≥126mg/dl in patients without type 2 diabetes mellitus (T2DM). The outcome was assessed with adverse outcome rates at discharge (modified Rankin scale between 2 and 6) and with in-hospital mortality. RESULTS In the total study population, 8.6% had stress hyperglycemia. Patients with stress hyperglycemia had more severe stroke. Independent predictors of adverse outcome at discharge were age, prior ischemic stroke and NIHSS at admission whereas treatment with statins prior to stroke was associated with favorable outcome. When the NIHSS was removed from the multivariate model, independent predictors of adverse outcome were age, heart rate at admission, prior ischemic stroke, log-triglyceride (TG) levels and stress hyperglycemia, whereas treatment with statins prior to stroke was associated with favorable outcome. Independent predictors of in-hospital mortality were atrial fibrillation (AF), diastolic blood pressure (DBP), serum log-TG levels and NIHSS at admission. When the NIHSS was removed from the multivariate model, independent predictors of in-hospital mortality were age, AF, DBP, log-TG levels and stress hyperglycemia. CONCLUSION Stress hyperglycemia does not appear to be directly associated with the outcome of acute ischemic stroke. However, given that patients with stress hyperglycemia had higher prevalence of cardiovascular risk factors than patients with normoglycemia and that glucose tolerance was not evaluated, more studies are needed to validate our findings.

No Association Observed Between Blood Pressure Variability During the Acute Phase of Ischemic Stroke and In-Hospital Outcomes

BACKGROUND Recent data suggest that blood pressure (BP) variability confers increased cardiovascular risk independently of BP. We aimed to evaluate the association between BP variability during the acute phase of ischemic stroke and the in-hospital outcome. METHODS We prospectively studied 608 consecutive patients admitted with acute ischemic stroke (39.5% males, age: 79.1±6.6 years). Variability in BP was assessed with the SD and with the coefficient of variation of systolic (SBP) and diastolic BP (DBP) during the first 2 and the first 3 days of hospitalization. The outcome was assessed with dependency rates at discharge and with in-hospital mortality. RESULTS Patients who were dependent at discharge did not differ from patients who were independent in any index of BP variability. Independent predictors of dependency at discharge were age (relative risk (RR) 1.17, 95% confidence interval (CI) 1.09-1.25, P < 0.001), history of prior ischemic stroke (RR 2.08, 95% CI 1.02-4.24, P = 0.04), and National Institutes of Health Stroke Scale (NIHSS) at admission (RR 1.64, 95% CI 1.44-1.86, P < 0.001). Patients who died during hospitalization did not differ in any index of BP variability from patients who were discharged. DBP at admission was independently and directly associated with in-hospital mortality (RR 1.06, 95% CI 1.03-1.09, P < 0.001). Other independent predictors of in-hospital mortality were history of atrial fibrillation (RR 3.30, 95% CI 1.46-7.49, P = 0.004) and NIHSS at admission (RR 1.18, 95% CI 1.13-1.23, P < 0.001). CONCLUSIONS Our data do not support the hypothesis of an association between BP variability and in-hospital outcomes among patients admitted for ischemic stroke.

Comparative effects of more versus less aggressive treatment with statins on the long-term outcome of patients with acute ischemic stroke.

BACKGROUND AND AIMS There are no studies that compared the effects of different intensities of statin treatment on the long-term outcome of patients with recent ischemic stroke. We aimed to evaluate these effects. METHODS We prospectively studied 436 consecutive patients who were discharged after acute ischemic stroke (39.2% males, age 78.6 ± 6.7 years). Statin treatment was categorized in equipotent doses of atorvastatin. One year after discharge, the functional status was assessed with the modified Rankin scale (mRS). Adverse outcome was defined as mRS between 2 and 6. The occurrence of ischemic stroke, myocardial infarction and death was recorded. RESULT Adverse outcome rates were lower in patients treated with atorvastatin 20 mg/day or more potent doses of statins than in patients treated with atorvastatin 10 mg/day (63.5, 38.2 and 48.2%, respectively; p = 0.004). In binary logistic regression analysis, independent predictors of adverse outcome were the mRS at discharge (relative risk (RR) 2.33, 95% confidence interval (CI) 1.77-3.07, p < 0.001) whereas more aggressive treatment with statins independently predicted favorable outcome (atorvastatin 20 vs. 10 mg/day, RR 0.30, 95% CI 0.11-0.87, p = 0.026; atorvastatin 40 mg/day or more potent dose of statins vs. atorvastatin 10 mg/day, RR 1.66, 95% CI 0.62-4.44, p = NS). The incidence of cardiovascular events and all-cause mortality showed a trend for being lower in patients treated with atorvastatin 40-80 mg/day or rosuvastatin 10-40 mg/day than in those treated with less potent doses of statins. CONCLUSION More aggressive statin treatment improves the long-term functional outcome of patients with acute ischemic stroke more than less aggressive treatment.

Treatment with Clopidogrel Prior to Acute Non-Cardioembolic Ischemic Stroke Attenuates Stroke Severity

Background: Clopidogrel reduces the risk of non-cardioembolic ischemic stroke, but it is unclear whether it affects the severity and outcome of stroke. We aimed at evaluating the effect of prior treatment with clopidogrel on acute non-cardioembolic ischemic stroke severity and in-hospital outcome. Methods: We prospectively studied 608 consecutive patients (39.5% males, age 79.1 ± 6.6 years) who were admitted with acute ischemic stroke. The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Severe stroke was defined as NIHSS ≥21. The outcome was assessed using the dependency rates that prevailed at the time of discharge (i.e. modified Rankin scale between 2 and 5) and with in-hospital mortality. Results: At admission, 397 patients did not have atrial fibrillation or heart valve disease. Among these 397 patients, 69 were receiving monotherapy with clopidogrel prior to stroke, 69 were receiving monotherapy with aspirin and 236 patients were not on any antiplatelet treatment. The prevalence of severe stroke was lower in patients who were receiving clopidogrel than in patients who were receiving aspirin and patients who were not on antiplatelets (1.4, 13.0 and 11.0%, respectively; p < 0.05). Independent predictors of severe stroke at admission were male gender (relative risk (RR) 0.31, 95% CI 0.12-0.78, p < 0.05) and treatment with clopidogrel prior to stroke compared with no antiplatelet treatment (RR 0.13, 95% CI 0.02-0.97, p < 0.05). Treatment with aspirin prior to stroke did not predict severe stroke compared with no antiplatelet treatment (RR 1.24, 95% CI 0.51-2.98, p = NS). The rate of dependency at discharge did not differ between patients who were receiving clopidogrel, patients who were receiving aspirin and those who were not on antiplatelets (57.9, 47.8 and 59.7%, respectively; p = NS). Independent predictors of dependency at discharge were age (RR 1.12, 95% CI 1.05-1.19, p < 0.001) and NIHSS at admission (RR 1.67, 95% CI 1.46-1.92, p < 0.001). In-hospital mortality rate also did not differ between patients who were receiving clopidogrel, patients who were receiving aspirin and those who were not on antiplatelets (4.3, 4.3 and 5.0%, respectively; p = NS). The only independent predictor of in-hospital mortality was NIHSS at admission (RR 1.22, 95% CI 1.14-1.30, p < 0.001). Conclusions: Treatment with clopidogrel prior to acute non-cardioembolic ischemic stroke attenuates the severity of stroke at admission but does not appear to affect the functional outcome at discharge or the in-hospital mortality of these patients.

Acenocoumarol vs. low-dose dabigatran in real-world patients discharged after ischemic stroke.

The aim of this study was to compare the efficacy of dabigatran 110 mg twice daily and acenocoumarol in patients with atrial fibrillation discharged after ischemic stroke. We prospectively studied 436 consecutive patients who were discharged after acute ischemic stroke (39.2% males, age 78.6 ± 6.7 years). Approximately 1 year after discharge, the functional status was assessed with the modified Rankin scale (mRS). Adverse outcome was defined as mRS between 2 and 6. The occurrence of ischemic stroke, myocardial infarction (MI) and death during the 1-year follow-up was also recorded. At discharge, 142 patients had atrial fibrillation. Acenocoumarol and dabigatran 110 mg twice daily were prescribed to 52.1 and 6.3% of these patients, respectively. At 1 year after discharge, there was a trend for patients treated with acenocoumarol to have lower mRS than patients prescribed dabigatran (2.3 ± 2.4 and 4.1 ± 2.2, respectively; P = 0.060). Adverse outcome rates and the incidence of stroke during follow-up did not differ between the two groups. The incidence of MI was almost three times higher in patients prescribed dabigatran than in those prescribed acenocoumarol, but this difference did not reach significance (11.1 and 4.0%, respectively; P = 0.254). The incidence of cardiovascular death was also almost three times higher in the former, but again this difference was not significant (33.3 and 12.2%, respectively; P = 0.237). In real-world patients with acute ischemic stroke, dabigatran 110 mg twice daily is as effective as acenocoumarol in preventing stroke but appears to be associated with worse long-term functional outcome and higher incidence of MI.

Left ventricular hypertrophy assessed by electrocardiogram is associated with more severe stroke and with higher in-hospital mortality in patients with acute ischemic stroke

BACKGROUND AND AIMS Left ventricular hypertrophy (LVH), assessed by electrocardiogram (ECG), is associated with increased risk for stroke. However, few studies that evaluated whether ECG-detected LVH predicts ischemic stroke severity and outcome. We aimed to evaluate these associations. METHODS We prospectively studied 922 patients consecutively admitted with acute ischemic stroke (age 79.6 ± 6.9 years). Stroke severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Severe stroke was defined as NIHSS≥5. LVH was evaluated with the Sokolow-Lyon index and the Cornell voltage-duration product criteria in an ECG obtained at admission. The outcome was assessed with dependency at discharge (modified Rankin scale 2-5) and in-hospital mortality. RESULTS Independent predictors of severe stroke were age (relative risk (RR) per year 1.07, 95% confidence interval (CI) 1.03-1.11, p<0.001), female gender (RR 0.36, 95% CI 0.17-0.76, p<0.01), atrial fibrillation (RR 2.07, 95% CI 1.30-3.29, p<0.005), chronic kidney disease (RR 2.38, 95% CI 1.04-5.44, p<0.05), heart rate (RR per 1/min 1.02, 95% CI 1.01-1.04, p<0.005), glucose levels (RR 1.012, 95% CI 1.006-1.018, p<0.001), high-density lipoprotein cholesterol levels (RR 0.976, 95% CI 0.960-0.993, p<0.005) and LVH defined according to the Cornell voltage-duration product criteria (RR 2.08, 95% CI 1.12-3.86, p<0.05). Independent predictors of dependency at discharge were age (RR per year 1.08, 95% CI 1.03-1.13, p<0.001), past smoking (RR versus no smoking 0.42, 95% 0.19-0.89, p<0.05), history of ischemic stroke (RR 2.13, 95% CI 1.23-3.71, p<0.01) and NIHSS at admission (RR 1.48, 95% CI 1.35-1.63, p<0.001). Independent predictors of in-hospital mortality were glucose levels (RR 1.014, 95% CI 1.003-1.025, p<0.05), NIHSS at admission (RR 1.29, 95% CI 1.19-1.41, p<0.001) and LVH according to the Cornell voltage-duration product criteria (RR 4.95, 95% CI 1.09-22.37, p<0.05). CONCLUSIONS LVH according to the Cornell voltage-duration product criteria appears to be associated with more severe stroke and with higher in-hospital mortality in patients with acute ischemic stroke.

Treatment with Mannitol is Associated with Increased Risk for In-Hospital Mortality in Patients with Acute Ischemic Stroke and Cerebral Edema

BackgroundCurrent guidelines state that osmotic therapy is reasonable in patients with clinical deterioration from cerebral infarction-related cerebral edema. However, there are limited data on the safety and efficacy of this therapy. We aimed to evaluate the effect of mannitol on the outcome of ischemic stroke-related cerebral edema.Methods and ResultsWe prospectively studied 922 consecutive patients admitted with acute ischemic stroke. Patients who showed space-occupying brain edema with tissue shifts compressing the midline structures received mannitol. The outcome was assessed with dependency rates at discharge (modified Rankin Scale grade 2–5) and in-hospital mortality. Rates of dependency were higher in patients treated with mannitol (n = 86) than in those who were not (97.7 and 58.5%, respectively; p < 0.001). Independent predictors of dependency were age, history of ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) score at admission. Rates of mortality were higher in patients treated with mannitol than in those who were not (46.5 and 5.6%, respectively; p < 0.001). Independent predictors of in-hospital mortality were diastolic blood pressure [relative risk (RR) 1.05, 95% confidence interval (CI) 1.02–1.08, p < 0.001], NIHSS score at admission (RR 1.19, 95% CI 1.14–1.23, p < 0.001) and treatment with mannitol (RR 3.45, 95% CI 1.55–7.69, p < 0.005).ConclusionsAdministration of mannitol to patients with ischemic stroke-related cerebral edema does not appear to affect the functional outcome and might increase mortality, independently of stroke severity.

Impaired kidney function evaluated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is associated with more severe acute ischemic stroke

Impaired kidney function (IKF), defined as glomerular filtration rate (GFR)<60 mL/min/1.73 m2, affects 23–41% of elderly individuals and patients with cardiovascular disease.1 IKF is independently associated with increased risk for cardiovascular events,2 including stroke.3 However, it is unclear whether IKF affects stroke severity and outcome.4–7 Moreover, most studies that evaluated this association used the Modification of Diet in Renal Disease equation (MDRD) to estimate GFR4,6,7 and only one applied the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI),5 which appears to evaluate GFR more accurately.8 To assess the effects of IKF on stroke severity and outcome, we prospectively studied all patients admitted in our department with acute ischemic stroke between September 2010 and March 2016 (n=922). GFR was calculated using creatinine measured at the first day after admission. Stroke severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Severe stroke was defined as NIHSS≥5. The outcome was assessed with dependency at discharge (modified Rankin scale (mRS) 2–5) and in-hospital mortality. Differences in categorical and continuous variables were assessed with the chi-squared test and independent samples t-test, respectively. Binary logistic regression analysis was used to identify independent predictors of severe stroke, dependency and mortality, including characteristics significant in univariate analysis. Two separate models were built, one with IKF defined according to MDRD and one with IKF defined according to CKD-EPI. When risk of other significant variables is presented, the effect size estimates are based on the model including IKF defined according to CKD-EPI. Patients’ characteristics at admission are shown in Table 1. NIHSS did not correlate with GFR estimated with MDRD (r=−0.043, p=NS) but correlated with GFR estimated with CKD-EPI (r=−0.071, p<0.05). At admission, 55.2% of patients had severe stroke and a higher prevalence of IKF than patients with non-severe stroke when GFR was estimated with MDRD (38.8 vs 29.9%, respectively; p<0.05) or CKD-EPI (47.9 vs 36.6%, respectively; p<0.005). Independent predictors of severe stroke were age (relative risk (RR) 1.04, 95% confidence interval (CI) 1.02–1.06, p<0.001), atrial fibrillation (RR 1.95, 95% CI 1.44–2.64, p<0.001) and IKF according to CKD-EPI (RR 1.37, 95% CI 1.02–1.85, p<0.05). At discharge, 60.8% of patients were dependent on others for performing usual activities. The prevalence of IKF according to CKD-EPI was higher in dependent than in independent patients (46.5 vs 37.2%, respectively; p<0.05) but the prevalence of IKF according to MDRD was similar (37.6 vs 31.9%, respectively; p=NS). Independent predictors of dependency were age (RR 1.08, 95% CI 1.04–1.12, p<0.001), history of ischemic stroke (RR 1.89, 95% CI 1.22–2.94, p<0.005) and NIHSS (RR 1.49, 95% CI 1.39– 1.62, p<0.001). During hospitalization, 9.4% of patients died. The prevalence of IKF did not differ between patients who died and Impaired kidney function evaluated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is associated with more severe acute ischemic stroke

Effect of antihypertensive treatment on the long-term outcome of patients discharged after acute ischemic stroke

ABSTRACT We aimed to evaluate the effects of the five main classes of antihypertensive agents on the long-term outcome of 313 consecutive patients discharged after acute ischemic stroke (36.4% males, age 78.5 ± 6.3 years). One year after discharge, the functional status [evaluated with the modified Rankin scale (mRS)], the occurrence of cardiovascular events, and vital status were recorded. Patients prescribed angiotensin receptor blockers (ARBs) had lower mRS than patients not prescribed ARBs (1.7 ± 2.0 vs. 2.9 ± 2.5, respectively; p = 0.006). The rates of adverse outcome (mRS 2-6) and cardiovascular events did not differ between patients prescribed each one of the major classes of antihypertensive agents and those not prescribed the respective class. Patients who were prescribed ARBs had lower risk of death during follow-up than patients who did not receive ARBs (9.4 and 26.9%, respectively; p < 0.05). In binary logistic regression analysis, the only independent predictor of all-cause mortality during follow-up was the mRS at discharge (relative risk 1.69, 95% confidence interval 1.25–2.28; p < 0.001). In conclusion, in patients discharged after acute ischemic stroke, administration of ARBs appears to have a more beneficial effect on long-term functional outcome and all-cause mortality than treatment with other classes of antihypertensive agents.