Large Vessel Atherosclerosis Research Articles

Fibrosis-related biomarkers and large and small vessel disease: The Cardiovascular Health Study

ObjectiveFibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels. MethodsWe evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-β and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998. ResultsAfter adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-β was associated with incident PAD (hazard ratio [HR] = 1.36 per doubling of TGF-β, 95% confidence interval [CI] = 1.04, 1.78) and retinal venular diameter (1.63 μm per doubling of TGF-β, CI = 0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102 mm per doubling of PIIINP, CI = 0.029, 0.174) and impaired brachial artery reactivity (−0.20% change per doubling of PIIINP, CI = −0.39, −0.02). Neither TGF-β nor PIIINP were associated with retinal arteriolar diameter or retinopathy. ConclusionsSerum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults.

Abstract T P137: Cerebral Ischemic Events In Patients With Therapeutic Warfarin Treatment

Background: Patients on long term warfarin treatment can have cerebral ischemic events despite therapeutic levels. We sought to determine unique patient attributes that result in ischemic events on therapeutic warfarin treatment. Methods: We reviewed the medical records and imaging data of consecutive patients with cerebral ischemic events who were on long term warfarin treatment over a 4 year period. We stratified the patients based on international normalized ratio (2.0-3.0 versus <2.0) and compared the demographic and clinical characteristics between the two groups of patients. Results: A total of 163 patients (mean age±SD; 77.3 ± 11.2) on long term warfarin treatment were admitted with cerebral ischemic events (97 ischemic strokes and 40 transient ischemic attacks). The mean age was not different between patients who were sub therapeutic and therapeutic on warfarin (78.2 ±11.6 versus 77.5±10.5, p=0.7). The proportion of patients with hypertension (87.2% versus 84.0%, p=0.6), diabetes mellitus (44.2% versus 50.0 %, p=0.5), and cigarette smoking (7.0% versus 6.0%, p=0.8), was similar between the two groups. Patients who were therapeutic on warfarin were more likely to have large vessel atherosclerosis (8.0% versus 2.3 %, p=0.1) and small vessel disease (2.0% versus 1.2 %, p=0.6) and less likely to have atrial fibrillation (66.0% versus 77.5%, p=0.2) as the underlying etiologies for ischemic events. IV alteplase was used in 5 and none of patients who were sub therapeutic and therapeutic on warfarin, respectively. Conclusions: Patients who have concurrent predisposing factors appear to be at risk for cerebral ischemic events despite therapeutic warfarin treatment and concomitant preventive strategies should be evaluated.

Abstract T MP58: Incidence and Etiology of Punctate Infarcts in Ischemic Stroke Patients

Background/Objective: Punctate infarcts (PI) are increasingly seen on DWI of patients with intracerebral hemorrhage (ICH) due to small vessel disease (SVD). We aimed to determine their incidence and potential causes in a large ischemic stroke (IS) cohort that had thorough etiologic workup. Methods: Consecutive patients with MRI-confirmed IS within 72 hours of onset were enrolled. Subjects had either a single high-risk embolic source (cardioembolic or large vessel disease) or no embolic source. PIs were classified by their relationship to the primary infarct as within or outside the same vascular territory. White matter disease burden (WMDB) and microbleed counts were obtained to be used as markers of severity of SVD. Multivariable regression models were constructed to assess the association between PIs and potential etiologies (embolism vs SVD). Results: We analyzed 946 IS patients, mean age 69 +/- 15 years, 46% female. We detected PI (≤5mm) in 269 (28%) subjects, 190 (71%) within the vascular territory of the primary infarct. Large-vessel atherosclerosis (p<0.001), cardioembolic source (p<0.001), higher WMDB (p=0.032) and lower systolic blood pressure (SBP, p=0.024) were independently associated with the presence of PI. While lower SBP was associated with PI in any location (p<0.05), WMDB was only associated with PI outside the vascular territory of the primary infarct (p=0.033); and large vessel atherosclerosis was only associated with PI within the vascular territory of the primary infarct (p=0.004). Conclusions: PIs occurring within the vascular territory of a larger infarct are more likely to have a proximal embolic source, but those occurring outside are more likely related to SVD. Their relatively high incidence and diverse etiologic associations in a cohort of IS patients emphasize the importance of research into their mechanisms.

Ischemic Strokes in Pakistan: Observations from the National Acute Ischemic Stroke Database

The objective of this study was to establish a multicenter ischemic stroke registry, first of its kind in Pakistan, to provide insight into the epidemiology, subtypes, and risk factors of ischemic strokes in this country. Four academic centers (3 urban and 1 rural) participated in this project. The inclusion criteria for subjects included adults (>14 years) with acute neurologic deficit, consistent with clinical diagnosis of ischemic stroke and supported by neuroimaging. Data were available for 874 subjects. Mean age of the subjects was 59.7 years, 60.5% were males, and 18% were young. Large vessel strokes were the most common subtype found in 31.7% subjects, followed by small vessel disease (25.7%) and cardioembolic strokes (10.4%). Almost 32% subjects had ill-defined etiology for their ischemic stroke. Dyslipidemia was a most common risk factor present in 83% patients. Data related to in-hospital complications were available for 808 subjects, of which 233 complications were recorded. Pneumonia was the most common of these seen in 105 (13%) subjects, followed by urinary tract infection (7.2%). Outcome at discharge was recorded for 697 subjects. Ninety-two had died during their hospital stay (13.2%). Only 36% subjects had a favorable outcome at discharge defined as a modified Rankin Scale (mRS) score of 2 or less. A total of 446 of 697 subjects had poor outcome at discharge (defined as an mRS score≥3). Hypertension and dyslipidemia were the most common risk factors and large vessel atherosclerosis was the most common stroke etiology. Elderly patients were significantly more likely to have in-hospital complications, die during their hospital stay, and have a higher mRS score at discharge.

Clinical Associations and Causes of Convexity Subarachnoid Hemorrhage

It has been previously found noted that ≈15% to 20% of subarachnoid hemorrhage (SAH) is nonaneurysmal. Nontraumatic convexity SAH (cSAH) is increasingly recognized. Data concerning incidence and associations are scant. We identified all SAH-coded cases from South Australian public hospitals between January 2005 and July 2011. Electronic discharge summaries were reviewed, and cases of cSAH were ascertained. Clinical and radiological features were recorded, and pathogenesis was assigned. Of 742 cases with SAH, 41 (6%) cases were cSAH, giving a minimum population annual incidence of 5.1 per million (95% confidence interval, 3.7-7.0). Median age was 70 years (interquartile range, 48-79). Commonest causes were cerebral amyloid angiopathy (39%), reversible cerebral vasoconstriction syndrome (17%), cerebral venous sinus thrombosis (10%), large-vessel stenotic atherosclerosis (10%), and posterior reversible encephalopathy syndrome (5%). No cause was identified in 20% (mostly elderly patients with incomplete evaluation). Most (63%) presented with transient neurological symptoms. Many (49%) were misdiagnosed as transient ischemic attacks and treated inappropriately with antithrombotics. cSAH comprises a significant proportion of SAH. Commonest causes are cerebral amyloid angiopathy in the elderly and reversible cerebral vasoconstriction syndrome in the young, but differential diagnosis is broad. Misdiagnosis is common and leads to potentially harmful treatments.

Abstract T P31: Microembolus (MES) Detection by TCD in Acute Stroke Service

Background and purpose: One of the main applications of TCD in acute stroke is microembolic signal (MES) detection. Both Spectral display and M-mode can be used to detect MES using validated criteria published previously. MES is reported to be an independent risk factor for stroke. Our study’s aim is to evaluate the yield of TCD MES in an acute stroke service and if this correlate with stroke’s mechanism and recurrence of stroke. Methods: We did analysis of all stroke and TIA patients who were evaluated in the University of Alberta Hospital between jan2006- July 2013. The clinical information was collected from charts and TCD studies for MES detection were reviewed by Neurologists certified by American Society of Neuroimaging using validated criteria. All cases had bilateral TCD monitoring of MCA /ACA or PCA vessels. The positive emboli on spectrogram was defined based on the consensus criteria and the M mode one based on our previous published criteria. Positive MES TCD monitoring was defined by the presence of ≥1 MES on either hemisphere. RESULTS: 49 /455 patients(10.7%) were MES positive. Mean age was 54.7(StD ±20), Gender: 33/49( 67.3%)were male, Median duration of monitoring was 50minutes( interquartile range 27.5-60), the indication was TIA in 16/49( 32.7%) acute ischemic stroke in 32/49(65.3%) subarachnoid hemorrhage in 1/49(2%), 36/49( 73.5%) presented with motor weakness 4/49( 8.2%) with isolated vision disturbances, 45/49(91.9%) patients had anterior circulation related symptoms, whereas 4/49(8.2%) had posterior circulation related symptoms,17/49(34.7%) showed acute infarct on imaging 6/49(12.2%) showed both acute and chronic infarcts and 3/49(6.1%) showed chronic infarcts only, 12/49(24.5%) showed infarcts in multiple vessels territories, TOAST: 20/49(40.8%) had large vessel atherosclerosis(LVA), 14/49(28.6%)had cardioembolic(CE) cause, 8/49(16.3%) had other determined etiology and 7/49(14.3%) had cryptogenic stroke, 7/49(14.3%) had recurrent stroke and 1/49(2%) had recurrent TIA. Total no of MES in anterior circulation were 324. CONCLUSION: Our study showed that 1 out of every 10 patients with acute ischemic stroke or TIA showed positive micro embolic signal on TCD monitoring. The high yield was mainly seen in LVA and CE stroke.

Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans

BackgroundRecently, plasma miRNAs have been reported as biomarkers for various diseases. However, the knowledge on the association of plasma miRNAs with ischemic stroke is still lacking. In this study, we investigated whether plasma concentrations of miR-30a, miR-126 and let-7b may be biomarkers for ischemic stroke in humans.MethodsOne hundred ninety seven patients with ischemic stroke were recruited and their blood samples were collected at 24 h, 1 week, 4 weeks, 24 weeks and 48 weeks after symptoms onset, and fifty healthy volunteers were selected as control. Levels of miRNA were quantified by quantitative real-time PCR. Relative expression level of miRNA was calculated using 2-ΔΔct method. The ability to distinguish the ischemic stroke group from control group was characterized by receiver operating characteristic (ROC) curve, and the area under ROC curve (AUC) was calculated.ResultsCirculating miR-30a and miR-126 levels were markedly down-regulated in all patients with ischemic stroke until 24 weeks. However, circulating let-7b was lower in patients with large-vessel atherosclerosis than healthy volunteers, whereas circulating let-7b had higher level in patients with other kinds of ischemic stroke until 24 weeks. Among all patients, circulating miRNAs levels returned to normal 48 weeks after symptom onset. Receiver operating characteristic (ROC) curve analysis showed that the areas under the curve (AUC) of plasma miR-30a were 0.91, 0.91, 0.92 and 0.93, the miR-126 were 0.92, 0.94, 0.93 and 0.92, and let-7b were 0.93, 0.92, 0.92 and 0.91 at 24 h, 1 w, 4 w and 24 w, respectively.ConclusionsThese data suggest that miR-30a, miR-126 and let-7b might be useful biomarkers for ischemic stroke in humans.

Fragmented QRS and Cardio Ankle Vascular Index in Asymptomatic Hypertensive Patients

PP-023 Patients with hypertension are predisposed to atherosclerosis of large vessels and are at increased risk of target organ damage and related clinical sequelae. Cardio-ankle vascular index (CAVI) is a novel parameter of arterial stiffness and surrogate marker of subclinical atherosclerosis.

The heart-brain connection: mechanistic insights and models

While both cardiac dysfunction and progressive loss of cognitive function are prominent features of an ageing population, surprisingly few studies have addressed the link between the function of the heart and brain. Recent literature indicates that autoregulation of cerebral flow is not able to protect the brain from hypoperfusion when cardiac output is reduced or atherosclerosis is prominent. This suggests a close link between cardiac function and large vessel atherosclerosis on the one hand and brain perfusion and cognitive functioning on the other. Mechanistically, the presence of vascular pathology leads to chronic cerebral hypoperfusion, blood brain barrier breakdown and inflammation that most likely precede neuronal death and neurodegeneration. Animal models to study the effects of chronic cerebral hypoperfusion are available, but they have not yet been combined with cardiovascular models.

Glycosaminoglycans as Key Molecules in Atherosclerosis: The Role of Versican and Hyaluronan

Cardiovascular disease is the largest cause of death in Western societies and it primarily results from atherosclerosis of large and medium-sized vessels. Atherosclerosis leads to myocardial infarction, when it occurs in the coronary arteries, or stroke, when it occurs in the cerebral arteries. Pathological processes involved in macrovascular disease include the accumulation of lipids which are retained by extracellular matrix (ECM) molecules, especially by the chondroitin sulfate/dermatan sulfate (CS/DS) proteoglycans (CS/DSPGs), such as versican, biglycan and decorin. The sulfation pattern of CS is a key player in protein interactions causing atherosclerosis. Several studies have shown that lipoproteins bind CSPGs via their glycosaminoglycan chains. Galactosaminoglycans, such as CS and DS, bind low density lipoproteins (LDL), affecting the role of these molecules in the arterial wall. In this article, the role of CS and versican in atherosclerosis and hyaluronan in atherogenesis as well as the up to date known mechanisms that provoke this pathological condition are presented and discussed.

Carotid Artery Stenosis as a Cause of Stroke

Background: Population-based studies have estimated that about 15% of ischemic strokes are caused by large-vessel cerebrovascular disease. We determined the types of large-vessel atherosclerosis responsible for ischemic strokes in a population-based stroke study. Methods: Patients with first-ever or recurrent ischemic stroke in the Greater Cincinnati area were identified during 2005 at all local hospitals. Study physicians assigned ischemic stroke subtypes. Overall event rates and incidence rates for first-ever events were calculated, and age-, race- and sex-adjusted to the 2000 US population. Results: There were 2,204 ischemic strokes, including 365 strokes of large-vessel subtype (16.6% of all ischemic strokes). Extracranial internal carotid artery (ICA) stenosis was associated with 8.0% of all ischemic strokes, while extracranial ICA occlusion and intracranial atherosclerosis were each associated with 3.5% of strokes. The annual rate of first-ever and recurrent stroke attributed to extracranial ICA was 13.4 (11.4–15.4) per 100,000 persons. We conservatively estimate that about 41,000 strokes may be attributed to extracranial ICA stenosis annually in the United States. Conclusions: Large-vessel atherosclerosis is an important cause of stroke, with extracranial ICA stenosis being significantly more common than extracranial ICA occlusion or intracranial atherosclerotic disease.

Should all patients with mild ischemic stroke be excluded from therapeutic stroke trials?

We aimed to investigate stroke etiology in our cohort of patients with mild ischemic stroke (MIS) and to study the effect of stroke etiology on patient outcome. We also studied the effect of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in this cohort. We analyzed patients with MIS who were eligible for IV rt-PA presenting within 3hours of symptom onset with a National Institutes of Health Stroke Scale (NIHSS) score ⩽5 admitted from March 2006 through June 2009. Stroke etiology was determined using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Primary outcome was the discharge NIHSS score. We identified 110 patients with MIS with a male-to-female ratio of: 1.4:1 and a mean age of 69±13years. The mean admission NIHSS score was 2±3. The stroke risk factors were identified as: hypertension, 82 patients (75%); previous stroke/transient ischemic attack, 36 patients (33%); and atrial fibrillation, 28 patients (26%). Stroke etiology was identified as: large vessel atherosclerosis (31 patients, 28%), cardioembolism (29, 26%), small vessel occlusion (seven, 6%) and those with other or undetermined conditions (43, 39%). IV rt-PA was administered to 25 patients (23%). Despite the use of IV rt-PA in only one patient with small vessel occlusion, patients in our study with this stroke etiology tended to have better outcomes compared to those with other stroke subtypes, although the difference was not statistically significant. The discharge NIHSS score did not show any statistically significant difference between the treated and untreated patients with MIS. Our study shows that MIS may be caused by non small vessel occlusion in more patients than previously reported and this subgroup of patients with MIS should not be excluded from trials of intravenous and endovascular therapies.

Aortic distensibility and its relationship to coronary and thoracic atherosclerosis plaque and morphology by MDCT: Insights from the ROMICAT Trial

BackgroundMulti-detector cardiac computed tomography (CT) allows for simultaneous assessment of aortic distensibility (AD), coronary atherosclerosis, and thoracic aortic atherosclerosis. ObjectivesWe sought to determine the relationship of AD to the presence and morphological features in coronary and thoracic atherosclerosis. MethodsIn 293 patients (53±12years, 63% male), retrospectively-gated MDCT were performed. We measured intraluminal aortic areas across 10 phases of the cardiac cycle (multiphase reformation 10% increments) at pre-defined locations to calculate the ascending, descending, and local AD (at locations of thoracic plaque). AD was calculated as maximum change in area/(minimum area×pulse pressure). Coronary and thoracic plaques were categorized as calcified, mixed, or non-calcified. ResultsAscending and descending AD were lower in patients with any coronary plaque, calcified or mixed plaque than those without (all p<0.0001) but not with non-calcified coronary plaque (p≥0.46). Per 1mm Hg−1 10−3 increase in ascending and descending AD, there was an 18–29% adjusted risk reduction for having any coronary, calcified plaque, or mixed coronary plaque (ascending AD only) (all p≤0.04). AD was not associated with non-calcified coronary plaque or when age was added to the models (all p>0.39). Local AD was lower at locations of calcified and mixed thoracic plaque when compared to non-calcified thoracic atherosclerosis (p<0.04). ConclusionsA stiffer, less distensible aorta is associated with coronary and thoracic atherosclerosis, particularly in the presence of calcified and mixed plaques, suggesting that the mechanism of atherosclerosis in small and large vessels is similar and influenced by advancing age.

Stroke in Patients with HIV Infection: Is It Different? (P01.246)

Objective: To describe epidemiological and clinical characteristics of stroke in HIV patients. Background Incidence of stroke in HIV population in United States is increasing over the last 2 decades. Antiretroviral therapy, metabolic syndrome, vasculopathy, and coagulopathy are thought to be factors causing premature strokes in HIV infected individuals. Design/Methods: Retrospective chart review of patients with a primary diagnosis of stroke and concurrent diagnosis of HIV or AIDS admitted to a comprehensive stroke center between 2005 and 2011 was performed. Results: Out of 1679 admissions with acute stroke we identified 43 patients (32 males and 11 females) with concurrent diagnosis of HIV. Mean age was 53 years old. All 43 patients had ischemic strokes confirmed by imaging. Eighteen patients (42%) were on HAART prior to stroke onset. Large vessel atherosclerosis was found in 20 patients (46.5%), small vessel occlusion in 18 (41.8%), cardioembolism in 3 (6.9%), 2 were cryptogenic (4.7%). Ten patients (23%) had recurrent strokes in the same or different vascular territories. CD4 count was available in 37 patients; 19 had CD4 >200 and 18 had CD4 Conclusions: Risk factors and morphological characteristics of stroke in patients with HIV tend to be similar to those in general population, yet they develop stroke at younger age. Immune status might not be a determining factor. Small sample size and retrospective nature of the study are major limiting factors in our analysis. Further prospective study would be aimed to identify specific biomarkers for stroke risk in HIV patients. Disclosure: Dr. Shah has nothing to disclose. Dr. Walker has nothing to disclose. Dr. Nigo has nothing to disclose. Dr. Skliut has nothing to disclose.

Identifying coronary artery disease in men with type 2 diabetes

In patients with type 2 diabetes, high serum levels of osteoprotegerin (OPG) have been associated with a greater risk of cardiovascular events. However, it remains unclear how well OPG performs when compared with traditional biomarkers of cardiovascular risk such as high-sensitivity C-reactive protein (hsCRP). Furthermore, OPG levels are also high in the presence of diabetes-related microvascular disease, and it is unclear whether OPG can distinguish microvascular disease from large-vessel atherosclerosis. The first aim of this study was to compare OPG levels against other biomarkers of cardiovascular risk in the identification of patients with documented multivessel coronary artery disease (CAD). The second aim was to compare OPG levels in patients with microvascular complications (microalbuminuria) against those with established CAD. Three groups of male patients with type 2 diabetes were recruited: patients without microvascular complications or large-vessel atherosclerosis (n = 24), patients with microalbuminuria only (n = 23), and patients with microalbuminuria and documented multivessel CAD (n = 25). OPG, hsCRP, interleukin 6, urate, and pulse wave velocity were measured. Serum OPG levels were significantly higher in patients with a combination of microalbuminuria and CAD than in those with microalbuminuria alone. There were no significant differences in any of the other biomarkers between the groups. OPG was found to be superior to the other biomarkers studied in identifying patients with documented CAD. The presence of CAD was a greater determinant of serum OPG levels than microalbuminuria in our population. These findings support the use of OPG as a biomarker of cardiovascular risk.

Hypervolemia rather than arterial calcification and extracoronary atherosclerosis is the main determinant of pulse pressure in hemodialysis patients

Pulse pressure (PP) has been reported as an independent predictor of cardiovascular mortality in hemodialysis patients. In this study, we aimed to investigate association of PP with echocardiographic and vascular structural changes such as atherosclerosis and arterial calcifications in HD patients. In this cross-sectional study, 108 chronic hemodialysis patients (49 male, 59 female, mean age: 46 ± 13 years) were included. Biochemical analyses, echocardiographic and high-resolution carotid Doppler examinations were done. Aortic wall and coronary artery calcifications were measured with electron beam computed tomography. The degree of carotid artery stenosis was measured at four different sites (communis, bulbus, interna and externa) in both carotid arteries. PP was strongly correlated with systolic (r: 0.82) and diastolic (r: 0.33) blood pressure, left ventricular mass index (r: 0.58), left ventricle end diastolic diameter (r: 0.38) and weakly correlated with aortic wall calcification score (r: 0.26) and carotid plaque score (r: 0.27), but not with coronary artery calcification score. Patients with carotid plaque had higher PP than patients without plaque (50 ± 16 mmHg versus 44 ± 14 mmHg, P = 0.05). Patients were divided into three groups according to aortic wall calcification score. PP was significantly higher in patients with higher aortic wall calcification (54 ± 16 mmHg) than patients with lower aortic wall calcification (44 ± 15 mmHg, P = 0.04). However, on multivariate linear regression analysis for predicting PP, the only significant factor retained was left ventricle end diastolic diameter. PP was weakly associated with large vessel calcification and atherosclerosis in hemodialysis patients. The bulk of the effect on PP seems to be due to hypervolemia.

Lowering blood pressure with β-blockers in peripheral artery disease: the importance of comorbidity

Lowering blood pressure with β-blockers in peripheral artery disease: the importance of comorbidity

Etiologic investigation of ischemic stroke in young adults

We attempted to classify causes of ischemic stroke in young adults using a progressive diagnostic algorithm and the ASCO (atherosclerosis, small-vessel disease, cardiac source, other cause) classification system. Patients aged 16-54 years consecutively treated for acute ischemic stroke in a tertiary stroke unit were included in this retrospective analysis. Causes of stroke were classified using the ASCO system, which assigns a graded level of likelihood to each potential cause in individual patients. The initial etiologic workup included brain imaging, magnetic resonance or CT angiography of cerebral and cervical vessels, EKG, and routine blood studies. Patients without a definite cause of ischemic stroke after initial evaluation underwent transesophageal echocardiography. We included 318 patients (195 men and 123 women); 131 patients were aged 16-44 years, and 187 were aged 45-54 years. A definite cause of stroke (ASCO grade 1) could be identified in 145 patients (45.5%). An uncertain cause of stroke (ASCO grade 2) was found in 59 (18.5%) further patients. Most (130 of 145) definite causes were identified by initial evaluation. The 2 major definite or uncertain causes of stroke were patent foramen ovale associated with atrial septal aneurysm (PFO-ASA) (20 of 131 [15.3%]) and dissection of the cervical or cerebral artery (19 of 131 [14.5%]) in patients aged 16-44 years and large-vessel atherosclerosis (37 of 187 [19.8%]) and PFO-ASA (23 of 187 [12.3%]) in patients aged 45-54 years. Our findings suggest that PFO-ASA may be a major cause of ischemic stroke in young adults.

RNA Expression Profiles From Blood for the Diagnosis of Stroke and Its Causes

A blood test to detect stroke and its causes would be particularly useful in babies, young children, and patients in intensive care units and for emergencies when imaging is difficult to obtain or is unavailable. Whole genome microarrays were used to show specific gene expression profiles in rats 24 hours after ischemic and hemorrhagic stroke, hypoxia, and hypoglycemia. These proof-of-principle studies revealed that groups of genes (called gene profiles) can distinguish ischemic stroke patients from controls within 3 to 24 hours after the strokes. In addition, gene expression profiles have been developed that distinguish stroke due to large-vessel atherosclerosis from cardioembolic stroke. These profiles will be useful for predicting the causes of cryptogenic stroke. The results in adults suggest that similar diagnostic tools could be developed for children.

Evidence-based review of primary and secondary ischemic stroke prevention in adults: a neurosurgical perspective

In this paper, the authors' aim is to provide an evidence-based review of primary and secondary ischemic stroke prevention guidelines covering most of the common risk factors and stroke etiologies for the practicing neurosurgeon. The key to stroke prevention is in the identification and treatment of the major risk factors for stroke. These include hypertension, heart disease, diabetes mellitus, dyslipidemia, and tobacco smoking. An updated approach to secondary prevention of stroke in the setting of intracranial and extracranial large vessel atherosclerosis and cardioembolism is provided along with a brief overview of pertinent clinical trials. Novel pharmacological options for prevention of cardioembolic strokes, such as new alternatives to warfarin, are addressed with recommendations for interruption of therapy for elective surgical procedures. In addition, the authors have reviewed the anticoagulation guidelines and the risk of thromboembolic complications of such therapies in the perioperative period, which is an invaluable piece of information for neurosurgeons. Less common etiologies such as arterial dissections and patent foramen ovale are also briefly discussed. Finally, the authors have outlined the quality measures in the Medicare Physician Quality Reporting System and essential guidelines for Primary Stroke Center certification, which have implications for day-to-day neurosurgical practice.