Yvonne Schwammenthal

Chronic Kidney Disease and Clinical Outcome in Patients With Acute Stroke

Background and Purpose— Chronic kidney disease (CKD) is increasingly recognized as an independent risk factor for cardiovascular disease and stroke. Our aim was to examine the association between estimated glomerular filtration rate (GFR) and stroke outcome and to assess whether CKD and its severity affect stroke outcome in a large cohort of unselected patients with acute stroke. Methods— We examined the association between baseline estimated GFR and CKD and 1-year outcomes in 821 consecutive patients with acute stroke (ischemic or hemorrhagic). GFR was estimated by 2 methods: the Modification of Diet in Renal Disease and the Mayo Clinic quadratic equation. An estimated GFR rate ≤60 mL/min/1.73 m2 defined CKD. Results— Odds ratios (95% CI) for death across levels of estimated GFR based on both equations were estimated. CKD was present in 36% (n=291) of patients based on the Modification of Diet in Renal Disease equation and 18% (n=147) based on the Mayo Clinic equation. The adjusted ORs for mortality after 1-year based on the Modification of Diet in Renal Disease equation were 0.7 (95% CI, 0.4 to 1.2) associated with GFR 45 to 60 and 3.2 (1.7 to 6.4) associated with GFR 15 to 44 as compared with GFR >60 mL/min/1.73 m2, whereas those based on the Mayo Clinic equation were 2.3 (1.1 to 4.7) and 3.3 (1.6 to 7.1), respectively. The adjusted ORs for Barthel Index ≤75 or death after 1 year were 0.8 (0.5 to 1.5) and 2.1 (0.9 to 4.8) by the Modification of Diet in Renal Disease equation and 1.9 (0.8 to 4.4) and 3.9 (1.5 to 11.0) by the Mayo Clinic equation, respectively. Conclusions— CKD is a strong independent predictor of mortality and poor outcome in patients with acute stroke. The estimation of the prevalence of CKD and of the GFR cutoffs associated with poor outcome depend on the equation used to estimate GFR.

Chronic Kidney Disease in Patients with Acute Intracerebral Hemorrhage: Association with Large Hematoma Volume and Poor Outcome

Background: Chronic kidney disease (CKD) is associated with both a risk of adverse vascular outcome and a risk of bleeding. We have tested the hypothesis that in the setting of an acute intracerebral hemorrhage (ICH), CKD is associated with poor outcome and with larger hematoma volume. Methods: We examined the association between CKD and ICH characteristics and outcome within a prospective cohort study of consecutive patients hospitalized with an acute stroke and followed for 1 year. CKD was categorized by the estimated baseline glomerular filtration rate into moderate/severe impairment (<45), mild impairment (45–60) and no impairment (>60 ml/min/1.73 m2). Results: Among 128 patients with an ICH (mean age = 71.7 ± 12.3 years, 41.4% women) 46.1% had CKD (23.4% mild and 22.7% moderate/severe). Patients with moderate/severe impairment had >4-fold adjusted hazard ratio for mortality over 1 year (4.29; 95% CI = 1.69–10.90) compared to patients with no impairment. The hematoma volumes [median (25–75%)] were 15.3 ml (5.4–37.5) in patients with no impairment, 16.6 (6.8–36.9) in mild impairment and 50.2 (10.4–109.1) in moderate/severe impairment (p = 0.009). The location of the hematoma was lobar in 12% with no impairment, 17% with mild impairment and 39% with moderate/severe impairment (p = 0.02). Patients with moderate/severe impairment exhibited a 2.3-fold higher hematoma volume (p = 0.04) and a >6-fold higher odds of lobar location (95% CI = 1.59–24.02) as compared to no impairment. Further adjustment for antiplatelet use and for presence of leukoaraiosis attenuated the association with hematoma volume (p = 0.15), while moderate/severe impairment was associated with an adjusted OR of 5.35 (95% CI = 1.18–24.14) for lobar location. Conclusions: Presence of moderate/severe CKD among patients with ICH is associated with larger, lobar hematomas and with poor outcome.

Anemia status, hemoglobin concentration and outcome after acute stroke: a cohort study

BackgroundIn the setting of an acute stroke, anemia has the potential to worsen brain ischemia, however, the relationship between the entire range of hemoglobin to long-term outcome is not well understood.MethodsWe examined the association between World Health Organization-defined admission anemia status (hemoglobin<13 in males, <12 g/dl in women) and hemoglobin concentration and 1-year outcome among 859 consecutive patients with acute stroke (ischemic or intracerebral hemorrhage).ResultsThe mean baseline hemoglobin concentration was 13.8 ± 1.7 g/dl (range 8.1 - 18.7). WHO-defined anemia was present in 19% of patients among both women and men. After adjustment for differences in baseline characteristics, patients with admission anemia had an adjusted OR for all-cause death at 1-month of 1.90 (95% CI, 1.05 to 3.43) and at 1-year of 1.72 (95% CI, 1.00 to 2.93) and for the combined end-point of disability, nursing facility care or death of 2.09 (95% CI, 1.13 to 3.84) and 1.83 (95% CI, 1.02 to 3.27) respectively. The relationship between hemoglobin quartiles and all-cause death revealed a non-linear association with increased risk at extremes of both low and high concentrations. In logistic regression models developed to estimate the linear and quadratic relation between hemoglobin and outcomes of interest, each unit increment in hemoglobin squared was associated with increased adjusted odds of all-cause death [at 1-month 1.06 (1.01 to 1.12; p = 0.03); at 1-year 1.09 (1.04 to 1.15; p < 0.01)], confirming that extremes of both low and high levels of hemoglobin were associated with increased mortality.ConclusionsWHO-defined anemia was common in both men and women among patients with acute stroke and predicted poor outcome. Moreover, the association between admission hemoglobin and mortality was not linear; risk for death increased at both extremes of hemoglobin.

Transcutaneous detection of aortic arch atheromas by suprasternal harmonic imaging

OBJECTIVES The goal of the present study was to examine whether suprasternal harmonic imaging (SHI) (i.e., harmonic imaging from the suprasternal windows) can visualize protruding arch atheromas (PAAs) and reliably predict the presence or absence of significant lesions. BACKGROUND Protruding arch atheromas are a major source of cerebral and peripheral embolism and probably the most frequent cause of stroke during cardiac catheterization and open-heart surgery. Preprocedural screening by transesophageal echocardiography (TEE) would be desirable but is limited by the nature of the examination. METHODS Of 354 patients who underwent a TEE study in our laboratory during the study period, 106 were referred for detection of a source of embolism. Findings were classified based on the French Aortic Plaque study criteria as: 1) no or minimal atherosclerotic changes; 2) PAAs < 4 mm; 3) PAAs > or =4 mm or presence of a mobile component. RESULTS Adequate transcutaneous image quality could be achieved in 89 patients (84%). Protruding arch atheromas were present in 42 patients (47%) and absent in 47 (53%). Positive and negative predictive values for large PAAs on TEE were 91% and 98%, respectively. In one case, SHI detected a complex PAA inaccessible for TEE due to interposition of the left bronchus as demonstrated by dual helical computed tomography. Inter-observer agreement for SHI was 91%. CONCLUSIONS Suprasternal harmonic imaging reliably predicted or excluded the presence of PAAs in a sizable, consecutive group of patients referred to TEE for detection of a source of embolism. It represents an excellent screening test and provides complimentary views of regions, which may be blind spots for TEE.

Homocysteine, B-vitamin supplementation, and stroke prevention: from observational to interventional trials

BACKGROUND Homocysteine is an amino acid, the metabolism of which is linked to that of several vitamins-especially folic acid, B6, and B12. A high concentration of homocysteine in the plasma is linked to vascular disease, including stroke. Concentrations of homocysteine can be inexpensively and safely lowered by treatment with a combination of folate, vitamin B12, and vitamin B6. However, whether the association between high plasma concentrations of homocysteine and vascular disease is causal is unclear. RECENT DEVELOPMENTS Two studies have assessed the relation between dietary or supplementary B vitamin intake on the risk of stroke. In a prospective observational study of 43?732 healthy men, there was an inverse relation between dietary folate intake and the risk of ischaemic stroke. The Vitamin Intervention for Stroke Prevention study (VISP) was the first large-scale randomised interventional study that investigated the lowering of homocysteine concentrations with B vitamins in patients with ischaemic stroke. There was an association between baseline homocysteine concentrations and vascular risk in this trial. Plasma concentrations of homocysteine were only modestly reduced by high-dose versus low-dose formulation, and there was no treatment effect on recurrent stroke, coronary events, or deaths. Limitations of VISP included that only patients with mild increases in baseline homocysteine concentrations were studied, only modest reductions of homocysteine concentrations were achieved, and follow up was short. In addition, fortification of food with folate and treatment of low vitamin-B12 concentrations may have masked the effect of treatment on stroke risk. WHAT NEXT?: When exposure can be safely assigned at random, as in the case of B-vitamin therapy, randomised trials should be the standard proof to determine the effect of therapy. The results of the first randomised clinical trial of B vitamins for secondary prevention of stroke were neutral. Larger trials with longer follow-up, selection of patients with higher plasma concentrations of homocysteine, and systematic assessment of cognitive functions and dementia are needed. In the meantime, homocysteine-lowering treatment that is cheap and well-tolerated should be considered a rational approach in patients at high risk of stroke and high concentrations of homocysteine.

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.

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.

An outbreak of Phialemonium infective endocarditis linked to intracavernous penile injections for the treatment of impotence.

BACKGROUND In March 2002, a patient in Tel Aviv, Israel, died of endocarditis caused by Phialemonium curvatum. As part of his therapy for erectile dysfunction, the patient had been trained to self-inject a compound of vasoactive drugs provided by an impotence clinic into his penile corpus cavernosous. METHODS We identified the used prefilled syringes as the source of his infection. Similar cases were investigated as a putative outbreak of P. curvatum invasive disease among customers of this impotence clinic. P. curvatum isolates, cultured from samples obtained from the patients and from prefilled syringes, were compared by DNA sequencing of the nuclear ribosomal internal transcribed spacer. RESULTS We identified 2 additional customers at the impotence clinic who had P. curvatum endocarditis. In addition, cultures of unused, prefilled syringes and bottles provided by the same clinic to 5 asymptomatic customers tested positive for pathogenic molds (P. curvatum in 4 cases and Paecilomyces lilacinus in 1). All P. curvatum isolates were of a single genetic type that is known only from this outbreak but is closely related to 3 other P. curvatum genotypes associated with pathogenicity in humans. CONCLUSIONS P. curvatum is an emerging pathogen that can be readily isolated from blood. We identified an outbreak of P. curvatum endocarditis among men who had erectile dysfunction treated by intracavernous penile injections from contaminated prefilled syringes.

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 ≥2, OR = 1.7; 95% CI 1.1–3.0) and poor physical function (SIS ≤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.

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.