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BACKGROUND: Stroke remains more common in the “buckle” of the stroke belt, and disproportionately impacts African Americans. The reasons for this racial disparity are poorly understood and are not entirely explained by traditional stroke risk factors. The PeRiodontal treatment to Eliminate Minority InEquality and Rural disparities in Stroke (PREMIERS) study will evaluate the effect of periodontal treatment on recurrent vascular events and stroke risk factors among ischemic stroke and transient ischemic attack patients. DESIGN: Eligibility for the trial includes a non-disabling stroke confirmed by neuroimaging or Transient Ischemic Attack (TIA), being at least 18 years of age, having ≥ 5 natural teeth with ≥ 2 interproximal sites with ≥ 4 mm of clinical attachment loss and at least 2 sites with probing depth of ≥ 5 mm, and who are able to provide written informed consent. Within 90 days of the index event, patients are randomly assigned to intensive or initial standard cycle of supragingival mechanical scaling, polishing, and oral health instruction and followed for 1 year. The primary outcome is a composite of death, myocardial infarction and stroke or TIA. Secondary outcomes include A1C, fasting lipid profile, triglycerides, high sensitivity C-reactive protein, carotid intimal medial thickness, and blood pressure. A five year enrollment period followed by an addition one year of follow-up is planned.

Background and Purpose— Periodontal disease is independently associated with cardiovascular disease. Identification of periodontal disease as a risk factor for incident ischemic stroke raises the possibility that regular dental care utilization may reduce the stroke risk. Methods— In the ARIC (Atherosclerosis Risk in Communities) study, pattern of dental visits were classified as regular or episodic dental care users. In the ancillary dental ARIC study, selected subjects from ARIC underwent fullmouth periodontal measurements collected at 6 sites per tooth and classified into 7 periodontal profile classes (PPCs). Results— In the ARIC study 10 362 stroke-free participants, 584 participants had incident ischemic strokes over a 15-year period. In the dental ARIC study, 6736 dentate subjects were assessed for periodontal disease status using PPC with a total of 299 incident ischemic strokes over the 15-year period. The 7 levels of PPC showed a trend toward an increased stroke risk (χ 2 trend P Conclusions— We confirm an independent association between periodontal disease and incident stroke risk, particularly cardioembolic and thrombotic stroke subtype. Further, we report that regular dental care utilization may lower this risk for stroke.

Background Periodontal disease (PD) is associated with recurrent vascular event in stroke or transient ischemic attack (TIA). In this study, we investigated whether PD is independently associated with aortic arch atheroma (AA). We also explored the relationship PD has with AA plaque thickness and other characteristics associated with atheroembolic risk among patients with stroke or TIA. Finally, we confirmed the association between AA and recurrent vascular event in patients with stroke or TIA. Methods In this prospective longitudinal hospital-based cohort study, PD was assessed in patients with stroke and TIA. Patients with confirmed stroke and TIA (n = 106) were assessed by calibrated dental examiners to determine periodontal status and were followed over a median of 24 months for recurrent vascular events (stroke, myocardial infarction, and death). The extent of AA and other plaque characteristics was assessed by transesophageal echocardiography. Results Within our patient cohort, 27 of the 106 participants had recurrent vascular events (including 16 with stroke or TIA) over the median of 24-month follow-up. Severe PD was associated with increased AA plaque thickness and calcification. The results suggest that PD may be a risk factor for AA. In this cohort, we confirm the association of severe AA with recurrent vascular events. Conclusions In patients with stroke or TIA, severe PD is associated with increased AA plaque thickness, a risk factor for recurrent events. Further studies are needed to confirm this finding and to determine whether treatment of PD can reduce the rate of AA plaque progression and recurrent vascular events.

Introduction: Craniocervical artery dissection (CeAD) is a leading cause of stroke in the young patient population. Recent studies reported a low rate of major adverse cardiac events (MACEs) in patients with CeAD, with no significant difference between patients randomized to anticoagulation or antiplatelet therapy. Objective: To compare the effectiveness of anticoagulation and antiplatelet therapy in patients with CeAD. Methods: All CeAD patients from 2015 to 2017 were consecutively identified by an electronic medical record-based application and enrolled in this prospective longitudinal registry. CeAD was confirmed by imaging and graded using the Denver scale for blunt cerebrovascular injury. Patients were followed for 12 months for MACE defined as stroke, transient ischemic attack (TIA), or death. Results: The cohort included 111 CeAD patients (age 53 ± 15.9 years, 56% Caucasian, 50% female). CeAD was detected by magnetic resonance (5%), computed tomography (88%), or catheter angiography (7%). CeAD was noted in the carotid (59%), vertebral (39%), and basilar (2%) arteries, 82% of which were extracranial dissections. CeAD was classified as grade I, II, III, and IV in 16, 33, 19, and 32%, respectively. A total of 40% of dissections were due to known trauma. A predisposing factor was noted in the majority (78%) of patients, including violent sneezing (21%), carrying a heavy load (19%), sports/recreational activity (11%), chiropractic manipulation (9%), abrupt/prolonged rotation of head (9%), and prolonged phone use (9%). At presentation, 41% had a stroke, 5% had TIA, 39% had headache, and 36% were asymptomatic. Favorable outcome defined as a modified Rankin Scale score of 0–2 was noted in 68% at 3 months and 71% at 12 months. The rate of MACEs at 3 and 12 months was 11 and 14%, respectively, with more events observed in patients who were not receiving anticoagulation/antiplatelet therapy due to contraindications (p = 0.008). Conclusions: We report diagnostic characteristics, as well as short- and long-term outcomes of CeAD. A high MACE rate was observed within the first 2 weeks of CeAD diagnosis, notably in patients not initiated on anticoagulation or antiplatelet therapy.

Introduction and Hypothesis: Approximately a third of stroke/TIA events occur in patients taking daily Aspirin. We studied the comparative effectiveness of FDA approved antiplatelet agents (Aspirin, Clopidogrel, and Aspirin-dipyridamole or ASA+DP) in prevention of recurrent vascular events in stroke/TIA patients on Aspirin. Methods: Consecutive patients identified as having stroke or TIA were screened and enrolled into this prospective longitudinal registry. Patients on dual antiplatelet therapy or oral anticoagulants were excluded. Patient’s etiological stroke subtype, medication history, medication compliance and Aspirin Platelet Function Test were assessed at baseline. Changes in antiplatelet regimen including Aspirin dose, Clopidogrel, ASA+DP, changes in statin therapy were recorded. Follow up 6 and 12 month phone visits were conducted to assess primary outcomes (stroke/TIA, MI, death), adjudicated by chart review. Results: A total of 183 subjects (mean age 68+12, 58% males, 50% white, 44% African-American) were enrolled over a 24 month period on Aspirin. Majority (63%) had ischemic stroke (NIHSS: 0-21) and remaining (37%) had TIA (ABCD 2 : 2-7). Ischemic strokes were attributed to penetrating artery disease (41%), large artery atherosclerosis (35%), other/undetermined (18%), and cardiogenic (6%). After 12-months, 4.9% of participants on Clopidogrel, 15.1% of participants on aspirin and 35.3% of participants on ASA+DP had a primary outcome (p=0.006), depicted in the Kaplan-Meier curve. Changes in Aspirin dose from 81mg to 325mg or statin therapy regimen did not appear to impact primary outcome. Conclusions: This study shows a significant difference in secondary vascular event within 12 months of stroke/TIA on Aspirin, with effectiveness recorded in the order: Clopidogrel>Aspirin>ASA+DP. A larger randomized pragmatic trial may help ascertain this finding and clarify if specific subtype benefit from specific antiplatelet agent. Figure

Goal: Significant proportions of stroke/transient ischemic attack events occur in patients taking daily aspirin. We studied the comparative effectiveness of Food and Drug Administration approved antiplatelet agents (aspirin, clopidogrel, and aspirin-dipyridamole combination) in prevention of recurrent vascular events in stroke/transient ischemic attack patients on aspirin.Materials and Methods: Consecutive patients having stroke or transient ischemic attack were screened and enrolled into this registry. Patients on long-term dual antiplatelet therapy or oral anticoagulants were excluded. Patient’s etiological stroke subtype, medication history, medication compliance, and Aspirin Platelet Function Test were assessed at baseline. Changes in antiplatelet regimen and statin therapy were also recorded. Follow up 6 and 12-month phone visits were conducted to assess primary outcomes of major adverse cardiovascular events that included a composite of death, myocardial infarction and stroke or transient ischemic attack.Result: One-hundred-eighty subjects (mean age ± SD= 68 ± 12 years, 59% male, 51% white, 49% African-American) were enrolled over 24-months. Majority (64%) had ischemic stroke (NIHSS: 0-21) and remaining (36%) had transient ischemic attack (ABCD2: 2-7). Within 12-months of the index cerebrovascular event, 3 (5.9%) participants on clopidogrel, 21 (18.8%) participants on aspirin and 7 (41.2%) participants on aspirin-dipyridamole combination had a composite vascular event (Log rank p=0.0011).Conclusion: This study shows a significant difference in major adverse cardiovascular event within 12 months of stroke/ transient ischemic attack on Aspirin, with effectiveness recorded in the order: clopidogrel>aspirin> aspirin-dipyridamole combination. A larger randomized pragmatic trial may help ascertain this finding and clarify if specific stroke subtypes benefit from specific antiplatelet agents.

Introduction: Prior epidemiological studies have shown that periodontal disease (PD), also referred to as gum disease, is an independent risk factor for ischemic stroke. We assessed the hypothesis that users of regular dental care may have a lower risk for incident ischemic stroke and specific stroke subtype when compared with users of episodic dental care. Methods: In this prospective, longitudinal community-based cohort study, participants without prior stroke were assessed for dental care utilization represented by patient-reported responses to questionnaires. The pattern of dental care utilization was classified as regular use (every year), episodic use (as needed), or no use (never). Episodic visits, or visits as needed, are considered signs of inadequate utilization of dental care. These participants were followed for incident ischemic strokes. Ischemic stroke diagnoses were defined as sudden onset of neurological deficit(s) lasting ≥24 hours along with neuroimaging confirmation. Strokes were further classified according to etiologic subtype as thrombotic, lacunar, or cardioembolic stroke subtype according to criteria adopted from the National Survey of Stroke. Results: Of 11,242 participants (mean age±SD=62.8±5.6, 56% female, 78% white and 22% African-American) assessed for dental care utilization at the fourth ARIC visit (1996-1998). Over a 15-year follow-up period a total of 583 participants had incident ischemic stroke events, of who 19% were lacunar, 29% were cardioembolic and 45% were of the thrombotic stroke subtype. After adjustment for confounders (race/center, age, gender, BMI, hypertension, diabetes, LDL level, smoking, and education), regular dental care utilization was associated with lower risk for ischemic stroke overall compared with episodic dental users (adjusted HR 0.77, 95% CI 0.63-0.94). Regular dental care specifically lowered the risk of thrombotic stroke subtype (adjusted HR 0.75, 95% CI 0.56-0.99). Conclusions: Results from this prospective cohort study demonstrates an independent association between regular dental care utilization with a lower ischemic stroke risk. Further, we report the highest impact of regular dental care in lowering risk of the thrombotic stroke subtype.

Introduction: Stroke is a leading cause of adult disability that has long-term impact on outcome of patients. The current outcome measures are felt to be inadequate in measuring the impact of stroke in young patients (≤65) in midst of managing education, career, and family. Methods: This study assessed the reliability and discriminate validity of the young stroke questionnaire (YSQ). The development framework of the YSQ involved a two-step process. Initial feedback from stroke survivors and healthcare providers via multiple focus groups helped identify questions used to measure impact of stroke on 4 patient-centered domains: work and leisure, relationships, wellbeing, and healthcare resources. A subsequent focus group prioritized and refined items on the final YSQ. To determine the reliability and discriminate validity of YSQ, 25 young stroke survivors were consented at the Neurology Clinic. Standardized clinical assessments completed included the modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and the Stroke Impact Scale (SIS). Additionally, all patients were asked to complete the patient-centered questionnaire, YSQ. Results: Of 48 ischemic stroke patients screened, 25 (Mean age ± SD = 51 ± 9.2, 36% Males, 40% African-American, 56% White) patients qualified for enrollment into the young stroke questionnaire validation study. Using Levene’s test for equality of variance to compare YSQ and standardized clinical assessments, the YSQ was more likely to detect patient-centered disabilities post stroke in the following domains: relationships (α = 0.035) and healthcare resources (α = 0.027). Reliability of the summary measure was assessed using Cronbach’s alpha and found to be high (α = 0.903), indicating that the index created by summing the 4 dimensions is internally consistent and reproducible. Conclusions: Standardized clinical assessments are not sensitive to disabilities in young stroke survivors. When compared to standardized clinical assessments, the young stroke questionnaire is significantly capable of differentiating the young survivor perspective of the impact of stroke, specifically in area of relationships and healthcare resources.

Introduction: Epidemiological studies have shown that serum inflammatory markers are independently associated with ischemic stroke. We assessed the hypothesis that specific inflammatory mediator is associated with specific ischemic stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. Methods: In the ARIC study, serum inflammatory mediators were assessed in a cohort of subjects without prior stroke. They included high sensitivity C-reactive protein (hs-CRP), interleukin 1ra (IL-1ra), and Intercellular Adhesion Molecule 1(sICAM1) and were followed for all vascular events. All stroke events were adjudicated and classified into stroke subtypes by standard definitions. Multivariable Cox proportional hazards models were used to study the relationship between elevated inflammatory markers (upper quartile compared with lower three quartiles) and ischemic stroke, as well as stroke subtypes (cardioembolic, lacunar or thrombotic). Results: At the fourth ARIC study visit, serum inflammatory mediators were assessed in a cohort of 5663 subjects (mean age±SD=62.3±5.6, 55% female, 83% white and 17% African-American). Over a 15-year follow-up, 237 (4.2%) subjects had incident ischemic stroke of which 47% were thrombotic, 26% were cardioembolic, and 20% were of the lacunar stroke subtype. After adjustment for Race/Center, Age, Gender, BMI, Hypertension, Diabetes, LDL Level, Smoking (3-levels), Pack Years, Education (3-levels), hs-CRP (adjusted HR 1.45, 95% CI 1.08-1.96), IL-1ra (adjusted HR 1.90, 95% CI 1.09-3.28) and sICAM1(adjusted HR 1.33, 95% CI 1.0-1.78) were associated with overall ischemic stroke. This was driven by associations between hs-CRP and thrombotic stroke (adjusted HR 1.73, 95% CI 1.14-2.61), IL-1ra and cardioembolic stroke (adjusted HR 3.42, 95% CI 1.23-9.53), and sICAM-1 and lacunar stroke (adjusted HR 1.92, 95% CI 1.05-3.50). Conclusions: Results from this prospective show an independent association between serum inflammatory mediators and incident ischemic stroke. These associations appear to be attributed to the association between specific inflammatory mediator and individual stroke subtype. These results shed light to the mechanism by which inflammatory mediators contribute to stroke risk.

Introduction: Gum, or periodontal disease (PD) is a risk factor for cardiovascular disease. We assessed the graded association of PD levels with incident ischemic stroke as well as the etiological stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. Methods: PD was assessed by full-mouth periodontal measurements from 6 sites per tooth, in subjects without prior stroke and categorized into periodontal profile class (PPC). A Latent Class Analysis was used to identify 7 distinct PPCs using the entire cohort that included tooth level periodontal measurements and tooth loss. Stroke diagnoses were based on computer derived diagnosis medical record review and imaging confirmation. Classification required evidence of sudden onset of neurological deficit(s) lasting ≥24 hours. Strokes were classified according to etiology as thrombotic, lacunar, and cardioembolic subtypes. Results: At the fourth ARIC visit (1996-1998), a cohort of 6711 subjects (mean age±SD=62.3±5.6, 55% female, 81% white and 19% African-American) were assessed for PD. A total of 299 incident ischemic strokes (47% thrombotic, 26% cardioembolic and 20% lacunar) occurred over a 15-year period. The seven levels of PPC showed a graded association with incident ischemic stroke as noted in the figure. Participants with mild PD (adjusted HR 1.9 95% CI 1.2-3.0), moderate PD group (adjusted HR 2.1 95% CI 1.2-3.5) and severe PD (adjusted HR 2.2 95% CI 1.3-3.8) had an increased risk of incident ischemic stroke, compared with participants without PD after adjustment for confounders (age, race, gender, BMI, hypertension, diabetes, LDL cholesterol, smoking and education). There were class specific associations noted between PD with cardioembolic and thrombotic stroke subtypes. Conclusions: A graded association was noted between incident ischemic stroke and increasing levels of PPC. Further, we report class specific associations between PD with cardioembolic and thrombotic stroke subtypes.

Stroke has been defined as symptoms of neurological deficits due to decreased blood flow to the brain. The average age of stroke patients is 48.4 years, whereas the average age for stroke patients with human immunodeficiency virus (HIV) is 42.9 years old. Worldwide, there are an estimated 36.7 million people living with HIV though this number is likely conservative, given the lack of census data from many rural areas (WHO). It is clear that many of these people are at an increased risk for suffering from stroke and the morbidities and mortality associated with strokes.

Objective: To investigate the effect of dietary factors such as calorie intake and dietary fats on the progression of aortic arch atheroma (AA). Background: In stroke/TIA patients, progression of AA is associated with recurrent vascular events. Design/Methods: Consecutive patients with measurable (>1 mm) AA atheroma on baseline transesophageal echocardiogram (TEE) evaluation consented to a protocol mandated follow-up TEE at 12 months. Patients that had adequate paired AA images were assessed for progression, defined as Δ ≥ 1 grade worsening (based on plaque thickness over 12 months). Stroke risk factors and fasting lipid profile were assessed at baseline. The patient’s nutritional intake was measured at baseline using the Gladys Block Food Frequency Questionnaire. Results: One-hundred-nine patients (70 strokes, 33 TIAs) had sequential TEEs, of whom 27% (N=30) progressed and 73% (N=79) did not. Patients with progression had higher daily calorie (1778 ± 623 vs. 1378 ± 406 Calories, p=0.008), fat (76 ± 33 vs. 52 ± 23 grams, p=0.0002), carbohydrate (208 ± 78 vs. 169 ± 57 grams, p=0.01) and protein (73 ± 26 vs. 57 ± 21 grams, p=0.005) intake. On Further analysis among different fats showed a higher consumption of saturated fats (25 ± 12 vs. 17 ±8 grams, p=0.00051) as well as unsaturated fats (44 ± 20 vs. 30 ± 13 grams, p=0.002). These differences remained significant after we adjusted for the medication use. However the significance of these differences was attenuated after adjusting for the calorie intake. Cholesterol consumption did not differ between the progression and no-progression group (262 ± 125 vs. 213 ± 149 mg, p=0.2). Conclusions/Relevance: Calorie intake plays a significant role in the progression of AA. Further studies are needed to confirm these findings and determine the specific dietary modifications that may prevent AA progression and associated recurrent vascular events.

Periodontal disease is an infectious disease causes my microorganisms resulting in the corrosion of tissues around the tooth surface and soft tissue lining the mouth, loss of connective tissue attachment, breakdown of bone that holds the teeth, and tooth loss. The symptoms are bleeding gum (gingivitis), gingival pockets and bone loss (periodontal disease) leading to tooth mobility and eventually tooth loss. In the United States, periodontal disease is very prevalent and becomes more prevalent in aging populations. According to a recent survey in the United States, approximately half of adults have some level of periodontal disease and almost 10% of those have severe disease.

Objective: To investigate the association among migraine, ischemic stroke, and stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. Methods: In this ongoing, prospective, longitudinal community-based cohort study, participants were given an interview ascertaining migraine history in 1993–1995, and were followed for all vascular events, including stroke. All stroke events over the subsequent 20 years were adjudicated and classified into stroke subtypes by standard definitions. Cox proportional hazards models adjusted for stroke risk factors were used to study the relationship between migraine and ischemic stroke, overall, as well as stroke subtypes (cardioembolic, lacunar, or thrombotic). Results: We identified 1,622 migraineurs among 12,758 participants. Mean age of the study population at the 3rd clinical visit was 59 years. When compared to nonheadache participants, there was a significant association between migraine with visual aura and ischemic stroke (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.2–2.6, p = 0.008). Migraine without visual aura was not significantly associated with ischemic stroke (HR 1.2, CI 1.0–1.8, p = 0.28) when compared to nonheadache participants. Among the 3 subtypes of ischemic stroke evaluated, migraine with visual aura was significantly associated only with cardioembolic stroke (HR 3.7, 95% CI 1.6–8.7, p = 0.003). Conclusion: In participants with migraine with visual aura in late middle age, increased risk of cardioembolic stroke was observed. Migraine with visual aura was linked to increased stroke risk, while migraine without visual aura was not, over the period of 20 years. These results are specific to older migraineurs.