Plasma myeloperoxidase levels in acute brain ischaemia and high grade carotid stenosis.

BACKGROUND AND PURPOSE: Myeloperoxidase (MPO) is an important oxidative enzyme participating in different stages of cardiovascular disease and predicts prognosis. Little is known about its role in acute cerebrovascular events and carotid plaque vulnerability. In this study, the aim was to assess plasma MPO levels in acute stroke patients and their correlation to stroke severity and stroke outcome. METHODS: Plasma MPO levels were assessed in patients presenting with acute brain ischaemia within 36 h of symptom onset (n = 144, mean age 64.7 ± 11.6 years, 67% men) and in patients with moderate-to-severe carotid stenosis undergoing carotid artery stenting (n = 51, mean age 66.3 ± 8.4 years, 75% men). Patients presenting with acute brain ischaemia were assessed serially for stroke severity and disability. RESULTS: Plasma MPO concentrations (ng/ml) were associated with interleukin-6 (r = 0.38, P < 0.0001) and gender (median interquartile range) of 68.6 (49.8-107.0) vs. 59.7 (42.7-85.5) in women vs. men (P = 0.02). In acute brain ischaemia, MPO concentrations were associated with non-lacunar subtype (bottom, middle and top tertiles 37.5%, 71.7% and 71.7% respectively; P = 0.001), with stroke severity (baseline National Institutes of Health Stroke Scale score > 10, bottom, middle and top tertiles 6.3%, vs. 41.7% and 31.3%, respectively; P < 0.006) as well as with stroke severity at days 1-2, days 4-5 and at discharge (P < 0.05 for all), but less with disability at discharge (modified Rankin Scale score ≥ 2, 41.7% vs. 60.4% and 58.7% for the bottom, middle and top tertiles, respectively; P = 0.096). CONCLUSIONS: Amongst patients with acute brain ischaemia, plasma MPO concentrations were associated with stroke severity and non-lacunar subtype, but not with long-term functional disability.

Cerebral artery calcification in patients with acute cerebrovascular diseases: determinants and long-term clinical outcome.

BACKGROUND AND PURPOSE: Coronary artery calcium is an independent predictor of all-cause mortality. We sought to examine the determinants of intracranial cerebral artery calcification (CAC) and its association with long-term outcome in a large prospective cohort of stroke patients. METHODS: Consecutive patients hospitalized because of acute stroke (ischaemic and intracerebral hemorrhage) or TIA throughout a large medical center were systematically assessed and followed up for 1 year. Intracranial CAC was assessed from baseline brain CT blinded to clinical data. Patients were categorized to no, mild, and severe CAC according to their total CAC score. Determinants of CAC were studied with logistic regression analysis. Risk of death, Barthel Index ≤ 60 or death and living in a nursing facility or death were assessed. RESULTS: Amongst 1049 patients (mean age: 70 ± 13 years, 59% males) CAC was present in 727 (69%) patients. The main determinants of CAC were increasing age (OR 1.4, 95% CI 1.3-1.6, per 5 years), diabetes (OR: 2.1, 1.4-3.0), smoking (1.4, 1.0-2.2), hypertension (1.4, 1.0-2.1), and prior coronary heart disease (1.9, 1.3-2.9). CAC was associated with mortality and poor outcome amongst patients with ischaemic stroke; however, after adjusting for age and stroke severity, no significant association was observed. In patients with intracerebral hemorrhage, outcomes were not related to CAC. CONCLUSIONS: Intracranial CAC is highly prevalent in patients with acute stroke and its main determinants are older age, diabetes, smoking, hypertension, and prior coronary heart disease. Associations between CAC and mortality or poor functional outcome in the first year after ischaemic stroke are mainly age- and stroke severity-driven.

Cerebral leukoaraiosis in patients with stroke or TIA: clinical correlates and 1-year outcome.

BACKGROUND AND PURPOSE: Cerebral leukoaraiosis is frequently observed in patients with acute stroke, but its clinical consequences on functional recovery remain incompletely defined. We evaluated the clinical correlates of leukoaraiosis, and its association with stroke-outcome in a cohort of consecutively hospitalized patients. METHODS: One-thousand twenty-four consecutive patients with acute stroke or transient ischemic attack (TIA) undergoing brain CT were included in this single-center study. Patients were systematically evaluated at hospitalization and followed-up for 1 year. Mortality, functional outcome, quality of life (QoL), psychological distress, community integration, and patient perception of recovery were evaluated by leukoaraiosis severity. Adjusted ORs (95%CI) were calculated. RESULTS: Moderate/severe leukoaraiosis was diagnosed in 177 patients (17.3%) and mild leukoaraiosis in 362 patients (35.3%). After 1 year, adjusted ORs for moderate/severe leukoaraiosis compared with no leukoaraiosis were 2.0 (95%CI 1.1-4.0) for Barthel Index

Interleukin-6 and soluble intercellular adhesion molecule-1 in acute brain ischaemia.

Inflammation plays a critical role in the pathogenesis of atherothrombosis. Our aim was to examine the association between plasma concentrations of inflammatory biomarkers and severity and outcome of acute brain ischaemia. Plasma samples were collected within 36 h of symptom onset in patients with acute brain ischaemia, and assessed by conventional ELISA kits for concentration of interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1). Patients were assessed serially for stroke severity (National Institute of Health stroke scale) and outcome during follow-up (modified Rankin Scale, mRS; and Stroke Impact Scale-16, SIS). Patients (n = 113, 65% men, mean age 64 +/- 12 years) had a mean IL-6 concentrations of 5.1 +/- 5.0 pg/ml and sICAM-1 of 377 +/- 145 ng/ml. IL-6, but not sICAM-1, concentrations were strongly associated with stroke severity (P < 0.01 at all serial assessments). Ln-transformed IL-6 levels (per 1 SD) were associated with disability (mRS > or = 2, OR = 1.7; 95% CI 1.1-3.0) and poor physical function (SIS < or = 85, OR = 1.7; 95% CI 1.0-2.8). Further adjustment for baseline stroke severity, however, eliminated these associations. Our results suggest that high plasma concentrations of the inflammatory biomarker IL-6 but not sICAM-1 are associated with stroke severity and poorer functional outcome. IL-6 does not add, however, additional prognostic information for stroke outcome beyond that conveyed by the stroke severity.

Aspirin responsiveness in acute brain ischaemia: association with stroke severity and clinical outcome.

PURPOSE: Platelets play a critical role in the pathogenesis of acute brain ischaemia. We studied the association between the degree of inhibition of platelet function by aspirin (ASA) and the severity and outcome of acute brain ischaemia. METHODS: Platelet responsiveness to ASA was assessed in patients with acute brain ischaemia, treated with ASA since hospital admission. The degree of ASA responsiveness was assessed by optical aggregometry and categorized into patients with good response, partial response and complete unresponsiveness to ASA (good responders, partial responders and non-responders, respectively). An additional evaluation of responsiveness to ASA was performed by Impact-R (cone and platelet analyzer). Patients underwent serial clinical assessment during hospitalization, at discharge and during follow-up. RESULTS: Among 105 patients (mean age 63 +/- 12 years; 66% men), impaired ASA responsiveness at baseline as assessed by aggregometry was associated with increased stroke severity at baseline, unfavourable clinical course, and poor functional outcome during follow-up (p < 0.05 for all). Age-adjusted odds ratios in non-responders compared to good responders were 9.8 for severe stroke on admission (95% CI 2.8-34.9), 3.1 for lack of early clinical improvement (95% CI 1.1-8.8) and 8.6 for poor functional outcome during follow-up (95% CI 2.4-30.4). Less robust trends were observed with the Impact-R. CONCLUSIONS: Impaired responsiveness to ASA in acute brain ischaemia is common and is associated with worse neurological deficits at stroke onset, early clinical deterioration and poorer functional outcome. The clinical significance of these findings requires further evaluation in larger longitudinal studies.

Patients with valvular heart disease presenting with sustained ventricular tachyarrhythmias or syncope: results of programmed ventricular stimulation and long-term follow-up.

BACKGROUND: Programmed ventricular stimulation is commonly used to guide therapy in post-myocardial infarction patients with sustained monomorphic ventricular tachycardia (VT) or ventricular fibrillation (VF). In patients with valvular heart disease presenting with spontaneous VT, VF, or syncope, the usefulness of this technique is still unclear. The aim of the study was to analyze whether programmed ventricular stimulation was helpful in guiding therapy and determining prognosis in 97 patients with valvular heart disease presenting with VT (60%), VF (18%), or syncope (22%). METHODS AND RESULTS: Patients were classified as having either predominant ventricular pressure or volume overload or no significant pressure or volume overload. Overall, sustained VT or VF was inducible in 38 (39%) and 19 (20%) patients, respectively. Forty-six (47%) patients were discharged on antiarrhythmic drugs, 29 (30%) received an implantable cardioverter-defibrillator, and 22 (23%) remained without therapy. With serial drug testing, inducibility was completely or partially suppressed in 18 (19%) and 9 (9%) patients, respectively. During a mean follow-up of 51 months (n=97), 17 patients (18%) died (sudden death, n=7; heart failure, n=4; noncardiac causes, n=6). One-, 2- and 3-year event-free survival for sudden death, sustained VT, or VF was 77%, 68%, and 61%, respectively. Only inducibility of VT during baseline study (P<.0003) and left ventricular volume overload (P<.008) were significant predictors of arrhythmic events. Recurrence of arrhythmic events occurred in 56% and 56% of patients with complete or partial suppression of inducibility during serial drug testing as well as in 10 of 19 (53%) patients without a change in inducibility. CONCLUSIONS: Although programmed ventricular stimulation seems to predict adverse outcome, serial drug testing is unreliable in guiding therapy. The type of workload imposed on the ventricles influences outcome, being worse in patients with left ventricular volume overload. Therefore, implantation of a cardioverter-defibrillator should be considered early for the management of these patients.