Secular Trends in Ischemic Stroke Subtypes

Background: With an aging population and an increasing prevalence of therapy for atherosclerosis, it might be expected that stroke subtypes would be changing over time. Limited information exists on the ischemic stroke subtypes in adults in Canada. Methods: Patients referred to the Urgent TIA Clinic, in London, Ontario, between 2002-2012 were included. Secular trends were analyzed using Poisson regression with spline trend function. Ischemic stroke subtype classification was validated. Results: 3,445 consecutive patients (mean age + SD 64.8 + 14.9) were included. Cardioembolic strokes/TIAs increased from 21% in 2002 to 56% in 2012, whereas all other ischemic stroke subtypes decreased (p\u3c0.05). Separate analysis in men and women showed similar results. Conclusions: The decrease in atherosclerotic risk factors resulted in fewer strokes/TIAs caused by large artery atherosclerosis. On the contrary, cardioembolic strokes/TIAs have increased. This has important implications for more intensive investigation and treatment to reduce the risk of recurrent embolic stroke/TIA

Ezetimibe and regression of carotid atherosclerosis: Importance of measuring plaque burden

Background and Purpose-There has been recent controversy over failure of ezetimibe to reduce carotid intima-media thickness. Much of this is based on failure to understand important differences among ultrasound phenotypes of atherosclerosis. Methods-We analyzed the effect of adding ezetimibe to the regimen of patients being followed in vascular prevention clinics where measurement of carotid plaque burden (total plaque area) is used to guide therapy. Results-There were complete data in 231 patients with total plaque area for 2 years before and 2 years after initiation of ezetimibe. In the 2 years before and after initiation of ezetimibe, total cholesterol decreased significantly before (P\u3c0.0001) and after initiation of ezetimibe (P\u3c0.0001); low-density lipoprotein cholesterol declined significantly before (P\u3c0.0001) and after (P=0.003) initiation of ezetimibe. Triglycerides declined significantly before ezetimibe (P\u3c0.0001) but did not change after addition of ezetimibe (P=0.48). High-density lipoprotein cholesterol did not change significantly before (P=0.87) but declined significantly after ezetimibe (P=0.03). Despite the decline in low-density lipoprotein cholesterol before addition of ezetimibe, there was a significant mean increase in within-individual total plaque area in the 2 years before addition of ezetimibe by 6.89±39.57 mm 2 (SD); after addition of ezetimibe, despite the decline in high-density lipoprotein, plaque area decreased by-3.05±SD 38.18 mm 2 SD (P\u3c0.01). Conclusions-Ezetimibe appears to regress carotid plaque burden. To assess effects of antiatherosclerotic therapies, it is important to measure plaque burden. These findings should be tested in a clinical trial. © 2012 2012 American Heart Association, Inc

Risk of stroke at the time of carotid occlusion

IMPORTANCE: Many patients with asymptomatic carotid stenosis are offered carotid stenting for the prevention of carotid occlusion. However, this treatment may be inappropriate if the risk of stroke is low at the time of occlusion and with intensive medical therapy. OBJECTIVES: To determine the risk resulting from progression to occlusion among patients with asymptomatic carotid stenosis and to assess the role of severity of carotid stenosis or the presence of contralateral occlusion as factors that may predict the risk of stroke or death after occlusion of a previously asymptomatic carotid stenosis. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective analysis of data collected from patients at the Stroke Prevention Clinic of Victoria Hospital from January 1, 1990 (when annual surveillance with carotid ultrasonography first began), through December 31, 1995, or the Stroke Prevention at University Hospital from January 1, 1995, through December 31, 2012. The last date of follow-up was August 26, 2014. EXPOSURES: A new carotid occlusion during annual monitoring with carotid duplex ultrasonography (index occlusion). MAIN OUTCOMES AND MEASURES: Ipsilateral stroke or transient ischemic attack, death from ipsilateral stroke, or death from unknown cause. RESULTS Among 3681 patients in our clinic database with data on sequential annual carotid ultrasonographic examinations during the study period, 316 (8.6%) were asymptomatic before an index occlusion that occurred during observation. Most of the new occlusions (254 of 316 [80.4%]) occurred before 2002, when medical therapy was less intensive; the frequency decreased by quartile of years (P \u3c.001, χ2 test). Only 1 patient (0.3%) had a stroke at the time of the occlusion, and only 3 patients (0.9%) had an ipsilateral stroke during follow-up (all before 2005). In Kaplan-Meier survival analyses, neither severity of stenosis (P =.80, log-rank test) nor contralateral occlusion (P =.73) predicted the risk of ipsilateral stroke or transient ischemic attack, death from stroke, or death from unknown cause at a mean (SD) follow-up of 2.56 (3.64) years. In Cox proportional hazards regression analyses, only age (P =.02), sex (P =.01), and carotid plaque burden (P =.006) significantly predicted risk of those events. CONCLUSIONS AND RELEVANCE: The risk of progression to carotid occlusion is well below the risk of carotid stenting or endarterectomy and has decreased markedly with more intensive medical therapy. Preventing carotid occlusion may not be a valid indication for stenting

Stroke Prevention: Little-Known and Neglected Aspects

Combining available therapies has the potential to reduce the risk of stroke by 80% or more. A comprehensive review of all aspects of stroke prevention would be very lengthy; in this narrative review, we focus on some aspects of stroke prevention that are little-known and/or neglected. These include the following: (1) implementation of a Mediterranean diet; (2) B vitamins to lower homocysteine; (3) coordinated approaches to smoking cessation; (4) intensive lipid-lowering therapy; (5) lipid lowering in the elderly; (6) physiologically individualized therapy for hypertension based on renin/aldosterone phenotyping; (7) avoiding excessive blood pressure reduction in patients with stiff arteries; (8) treatment of insulin resistance with pioglitazone in stroke patients with prediabetes and diabetes; (9) impaired activation of clopidogrel in patients with variants of CYP2C19; (10) aspirin pseudoresistance due to enteric coating; (11) rationale for anticoagulation in patients with embolic stroke of unknown source; (12) pharmacologic properties of direct-acting oral anticoagulants that should be considered when choosing among them; (13) the identification of which patients with asymptomatic carotid stenosis are at a high enough risk to benefit from carotid endarterectomy or stenting; and (14) the importance of age in choosing between endarterectomy and stenting. Stroke prevention could be improved by better recognition of these issues and by implementation of the principles derived from them

Effects of eplerenone on resistance to antihypertensive medication in patients with primary or secondary hyperaldosteronism

Background and Objectives: Resistant hypertension is an important problem; nearly half of diagnosed hypertensives are not controlled to target blood pressure levels, and approximately 90% of strokes occur among patients with resistant hypertension. Primary aldosteronism accounts for approximately 20% of resistant hypertension, but the role of secondary hyperaldosteronism in resistant hypertension is seldom considered. We assessed the effects of eplerenone in patients with hypertension and either primary or secondary hyperaldosteronism. Methods: Patients with a history of resistant hypertension and a supine plasma aldosterone level ≥ 360 pmol/L were randomized to eplerenone versus placebo in a fully blinded study for one year. A medication intensity score was developed to assess the resistance of hypertension to medication (blood pressure × medication intensity). We assessed the effects of eplerenone on blood pressure and on resistance to concomitant medication. Results: Final results were available in 37 patients (19 on eplerenone and 18 on placebo). Resistance to medication, as assessed by the intensity of concomitant medication required to maintain blood pressure control, was markedly reduced by eplerenone: medication intensity scores declined by −0.50 ± 1.04 (SD) on placebo versus −2.11 ± 1.45 with eplerenone (P = 0.0001), the Systolic Resistance Score declined by −80.00 ± 122.93 on placebo versus −334.05 ± 21.73 on eplerenone (P = 0.0001), and the Diastolic Resistance Score increased by 1.28 ± 31.65 on placebo and declined by −40.74 ± 57.08 on eplerenone (P = 0.009). Conclusions: Eplerenone significantly reduced resistance to concomitant antihypertensive medication in both primary and secondary hyperaldosteronism

SPARKLE (Subtypes of ischaemic stroke classification system), Incorporating measurement of carotid plaque burden: A new validated tool for the classification of ischemic stroke subtypes

Background: Previous classification systems of acute ischemic stroke (Causative Classification System, CCS, of acute ischemic stroke, Trial of Org 10172 in Acute Stroke Treatment, TOAST) established the diagnosis of large artery disease (LAD) based on the presence or absence of carotid stenosis. However, carotid plaque burden is a stronger predictor of cardiovascular risk than stenosis. Our objective was to update definitions of ischemic stroke subtypes to improve the detection of LAD and to assess the validity and reliability of a new classification system: SPARKLE (Subtypes of Ischaemic Stroke Classification System). Methods: In a retrospective review of clinical research data, we compared three stroke subtype classifications: CCS, TOAST and SPARKLE. We analyzed a random sample of 275 patients presenting with minor stroke or transient ischemic attack (TIA) in an Urgent TIA Clinic in London, Ont., Canada, between 2002 and 2012. Results: There was substantial overall agreement between SPARKLE and CCS (κ = 0.75), with significant differences in the rate of detection of LAD, cardioembolic and undetermined causes of stroke or TIA. The inter-rater reliability of SPARKLE was substantial (κ = 0.76) and the intra-rater reliability was excellent (κ = 0.91). Conclusion: SPARKLE is a valid and reliable classification system, providing advantages compared to CCS and TOAST. The incorporation of plaque burden into the classification of LAD increases the proportion of cases attributable to LAD and reduces the proportion classified as being of \u27undetermined\u27 etiology. © 2014 S. Karger AG, Basel

Association of homocysteine and smoking with cerebral microemboli in patients with mechanical heart valves: A transcranial Doppler study

Objectives Microembolic signals (MES) on transcranial Doppler (TCD) predict stroke and cognitive decline. Plasma levels of total homocysteine (tHcy), a prothrombotic factor, are higher in patients with microemboli in carotid stenosis and in patients with paradoxical embolism. In this study we assessed the association between the level of tHcy and the number of MES in patients with mechanical heart valves (MHVs). Methods TCD monitoring was performed to detect MES before and after breathing 100% oxygen and repeated every 2-4 weeks up to six times. Results Twenty-five patients with MHVs (mean age: 63.60±10.15 years) participated in this study; 15 were men (66.47±7.25 years) and 10 were women (59.30±12.60 years). In total, there were 126 study visits. In multiple regression, higher tHcy was associated with more MES in both preoxygenation (OR 1.34 (95% CI 1.07 to 1.68, P=0.009)) and postoxygenation (OR 1.40 (95% CI 1.07 to 1.83, P=0.01)) phases. Current smoking and the length of time between the operation and monitoring also correlated with a higher number of MES before and after breathing oxygen, particularly in women. Conclusions Higher tHcy and smoking were associated with a higher MES count in both preoxygenation and postoxygenation phases. Because smoking can be stopped and hyperhomocysteinaemia is treatable, these are clinically important findings

Vitamin B12 Deficiency and Hyperhomocysteinemia in Outpatients with Stroke or Transient Ischemic Attack: a cohort study at an academic medical centre

Objective We sought to assess the current magnitude of the opportunity for secondary stroke prevention with B vitamins. Design A cohort study. Setting The Urgent TIA (Transient Ischaemic Attack) Clinic at an academic medical centre. Main outcome measures We assessed the prevalence of biochemical vitamin B 12 deficiency (B 12 Def, serum B 12 \u3c156 pmol/L), hyperhomocysteinaemia (HHcy; plasma total homocysteine [tHcy] \u3e14 μmol/L) and metabolic B 12 deficiency (MetB 12 Def, serum B 12 \u3c258 pmol/L and HHcy) between 2002 and 2017, by age group and by stroke subtype. Results Data were available in 4055 patients. B 12 Def was present in 8.2% of patients overall; it declined from 10.9% of patients referred before 2009 to 5.4% thereafter (p=0.0001). MetB 12 Def was present in 10.6% of patients, and HHcy was present in 19.1% of patients. Among the patients aged ≥80 years, MetB 12 Def was present in 18.1% and HHcy in 35%. Among the 3410 patients whose stroke subtype was determined, HHcy was present in 18.4% of patients: 23.3% of large artery atherosclerosis, 18.1% of cardioembolic, 16.3% of small vessel disease, 10.8% of other unusual aetiologies and 13.6% of undetermined subtypes (p=0.0001). Conclusions Despite a decline in our referral area since 2009, B 12 Def, MetB 12 Def and HHcy remain common in patients with stroke/TIA. Because these conditions are easily treated and have serious consequences, all patients with stroke/TIA should have their serum B 12 and tHcy measured

Reliability, Reproducibility, and Advantages of Measuring Carotid Total Plaque Area

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