Elevated Risk Of Stroke Research Articles

Left atrial appendage closure for stroke prevention in atrial fibrillation : An update

Atrial fibrillation (AF) is one of the most frequent causes of ischemic stroke. Without treatment the annual risk of ischemic stroke is on average approximately 5-6%/year in patients with atrial fibrillation, depending on the overall cardiovascular risk profile. Oral anticoagulation with new oral anticoagulants (NOAC) or vitamin K antagonists (VKA) is recommended for patients with AF and an elevated risk for stroke (CHA2DS2-VASc score ≥1); however, severe bleeding complications are potential reasons for discontinuation of this treatment. Overall, up to 30 % of the patients with AF remain without effective thromboembolism prophylaxis. Left atrial appendage (LAA) closure represents an alternative to pharmaceutical stroke prevention. Catheter-based and surgical LAA closure techniques are available. For catheter-based procedures with closure systems, high implantation success rates and relatively low periprocedural complication rates have been observed in recent registry studies. The reason for the restrained recommendation in the European guidelines is the as yet limited experience from large randomized studies.

Cooking with biomass fuel and cardiovascular disease: a cross-sectional study among rural villagers in Phitsanulok, Thailand.

Background: Burning biomass fuel is a major source of indoor air pollution; about 40% of Thai people still use biomass for cooking. There is increasing evidence of the association between biomass smoke exposure and serious health effects including cardiovascular disease. The object of this cross-sectional study was to investigate the association between biomass use for household cooking and cardiovascular outcome, including coronary heart disease, hypertension, high cholesterol, diabetes mellitus, and stroke among rural villagers in Phitsanulok, Thailand. Methods: Data from 1078 households were collected using a face-to-face interview questionnaire. Results: After being adjusted for gender, age, cigarette smoke, secondhand smoke, and exposure to other sources of air pollution, it was found that the family members of cooks using biomass fuel were at risk of coronary heart disease (CHD; OR=4.35; 95%CI 0.10-18.97), high blood pressure (HBP; OR=1.61; 95%CI 1.10-2.35), high cholesterol (HC; OR=2.74; 95%CI 1.66-4.53), and diabetes (OR= 1.88; 95%CI 1.03-3.46). Compared to LPG use, using wood was associated with stroke (OR=7.64; 95%CI 1.18-49.61), and using charcoal was associated with HC (OR=1.52; 95%CI 1.04-2.24). Compared to never user, household cooks who sometimes use charcoal had an increased risk of HBP (OR=2.04; 95%CI 1.32-3.15), HC (OR=2.61; 95%CI 1.63-4.18), and diabetes (OR=2.09; 95%CI 1.17-3.73); and cooks who often use charcoal had an elevated risk of stroke (OR=3.17; 95%CI 1.04-9.71), and HC (OR=1.52; 95%CI 1.02-2.27) to their family members. Conclusions: The study results were consistent with those found in studies from other parts of the world, and supports that exposure to biomass smoke increase cardiovascular diseases. The issue should receive more attention, and promotion of clean fuel use is a prominent action.

Loss of mitochondrial ClpP, Lonp1, and Tfam triggers transcriptional induction of Rnf213, a susceptibility factor for moyamoya disease

Human RNF213, which encodes the protein mysterin, is a known susceptibility gene for moyamoya disease (MMD), a cerebrovascular condition with occlusive lesions and compensatory angiogenesis. Mysterin mutations, together with exposure to environmental trigger factors, lead to an elevated stroke risk since childhood. Mysterin is induced during cell stress, to function as cytosolic AAA+ ATPase and ubiquitylation enzyme. Little knowledge exists, in which context mysterin is needed. Here, we found that genetic ablation of several mitochondrial matrix factors, such as the peptidase ClpP, the transcription factor Tfam, as well as the peptidase and AAA+ ATPase Lonp1, potently induces Rnf213 transcript expression in various organs, in parallel with other components of the innate immune system. Mostly in mouse fibroblasts and human endothelial cells, the Rnf213 levels showed prominent upregulation upon Poly(I:C)-triggered TLR3-mediated responses to dsRNA toxicity, as well as upon interferon gamma treatment. Only partial suppression of Rnf213 induction was achieved by C16 as an antagonist of PKR (dsRNA-dependent protein kinase). Since dysfunctional mitochondria were recently reported to release immune-stimulatory dsRNA into the cytosol, our results suggest that mysterin becomes relevant when mitochondrial dysfunction or infections have triggered RNA-dependent inflammation. Thus, MMD has similarities with vasculopathies that involve altered nucleotide processing, such as Aicardi-Goutières syndrome or systemic lupus erythematosus. Furthermore, in MMD, the low penetrance of RNF213 mutations might be modified by dysfunctions in mitochondria or the TLR3 pathway.

Migraine and Ischemic Stroke in Women. A Narrative Review

Migraine is associated with ischemic stroke. Women are 3-fold as likely as men to have migraine, and high estrogen states increase the risk of migraine with aura (MWA), venous thromboembolism (VTE), and of stroke.We review the epidemiological and mechanistic evidence of the migraine-stroke relationship and its risk factors, with a focus on women and conditions that exclusively or predominantly affect them. METHODS: We performeda search of MEDLINE/PubMed database, then a narrativereview ofthe epidemiological evidence of the migraine-stroke relationship as well as the evidence forarterial, thrombophilic, and cardiac mechanisms to explain this connection. We examinethe implications of this evidencefor thediagnostic evaluation and treatmentof MWA. MWA is associated with multiple stroke risk factors, such as hypertension, hyperlipidemia, diabetes mellitus, cigarette smoking, atrial fibrillation, and patent foramen ovale. In women, MWA is also associated with biomarkers of endothelial activation, hormonal contraceptive use, pregnancy, and VTE. This suggests that a subset of auras may be secondary, that is, induced by ischemia related to microemboli or in situ thrombosis. MWA-associated ischemic stroke is more common in young (<45years old) women with high frequency of migraine attacks, hormonal contraception use, and with pregnancy and preeclampsia. There is increasing evidence that cardioembolism, often in conjunction with thrombophilia, plays a prominent role in MWA-associated cerebral infarction. The commonality of factors associated with MWA and with MWA-associated stroke suggest that persons with secondary, ischemia-induced aura may be at elevated risk of stroke. Although further research is needed, we recommend consideration of a diagnostic evaluation of MWA that mirrors the evaluation of transient ischemic attack, given that prophylactic treatment targeting the ischemic origin of secondary aura may prevent migraine as well as stroke.

The Effect of Chemotherapy on Stroke Risk in Cancer Patients.

Chemotherapy may be a cause of cancer-associated stroke, but whether it increases stroke risk remains uncertain. We investigated how chemotherapy affects stroke risk in cancer patients. Of 27,932 patients in a hospital-based cancer registry (which contains clinical data on all patients treated for cancer at Osaka University Hospital) screened between 2007 and 2015, medical records of 19,006 patients with complete data were investigated. A validated algorithm was used to identify stroke events within 2 years of cancer diagnosis. Patients were divided based on whether their initial treatment plan included chemotherapy. The association between chemotherapy and stroke was analyzed using the Kaplan-Meier method and stratified Cox regression. Of 19,006 patients, 5,887 (31%) were in the chemotherapy group. Stroke occurred in 44 (0.75%) and 51 (0.39%) patients in the chemotherapy and nonchemotherapy group, respectively. Kaplan-Meier curve analysis showed that patients in the chemotherapy group had a higher stroke risk than those in the nonchemotherapy group (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23-2.75). However, this difference was insignificant after adjustment for cancer status using inverse probability of treatment weighting with propensity scores (HR 1.20; 95% CI 0.76-1.91). Similarly, in the stratified Cox regression model, chemotherapy was not associated with stroke after adjustment for cancer status (HR 1.26; 95% CI 0.78-2.03). In our study, the elevated stroke risk in cancer patients who received chemotherapy was presumably due to advanced cancer stage; chemotherapy was not associated with the increased risk of stroke.

A life-time of hazardous drinking and harm to health among older adults: findings from the Whitehall II prospective cohort study.

AimsTo investigate associations of life‐time hazardous and binge drinking with biomarkers of cardiometabolic health, liver function, cardiovascular disease (CVD) and mortality.DesignProspective cohort study with median follow‐up time to CVD incidence of 4.5 years.SettingLondon, UK: civil servants within the Whitehall II Study.ParticipantsA total of 4820 drinkers aged 59–83 years with biological measurements during the 2011–12 survey.MeasurementsHazardous drinking was defined as having an AUDIT‐C score ≥ 5 calculated at each decade of life, forming the following groups: never hazardous drinker, former early (stopping before age 50), former later (stopping after age 50), current hazardous drinker and consistent hazardous drinker (hazardous drinker at each decade of life).FindingsMore than half the sample had been hazardous drinkers at some point during their life‐time, comprising former early (< age 50) (19%), former later (≥ age 50) (11%), current (21%) and consistent hazardous drinker (AUDIT‐C ≥ 5 across life (5%). After adjusting for covariates, waist circumference was larger with more persistent hazardous drinking (e.g. compared with never hazardous drinkers, former early had increased waist circumference by 1.17 cm [95% confidence interval (CI) = 0.25‐2.08]; former later by 1.88 cm (CI = 0.77–2.98); current by 2.44 cm (CI = 1.50–3.34) and consistent hazardous drinker by 3.85 cm (CI = 2.23–5.47). Current hazardous drinkers had higher systolic blood pressure (2.44 mmHg, CI = 1.19–3.68) and fatty liver index scores (4.05 mmHg, CI = 2.92–5.18) than never hazardous drinkers. Current hazardous drinkers [hazard ratio (HR) = 2.75, CI = 1.44–5.22) had an elevated risk of stroke, and former later hazardous drinkers had an elevated risk of non‐CVD mortality (HR = 1.93, CI = 1.19–3.14) than never hazardous drinkers. Life‐time binge drinking was associated with larger waist circumferences and poorer liver function compared with never binge drinkers.ConclusionHazardous drinking may increase cardiometabolic risk factors; this is made worse by persistent hazardous drinking throughout life, particularly in relation to weight gain, suggesting benefits of early intervention.

Increased Mean Platelet Volume is Associated with Decreased Survival in Patients Supported with Impella

Increased mean platelet volume (MPV) has been associated with elevated risk of stroke and myocardial infarction in the general population and stroke/pump thrombosis in Heartmate II recipients. It has been proposed that contact with foreign surfaces and centrifugation promote prothrombotic states with platelet activation and increased MPV. An association between MPV and outcomes of patients treated with percutaneous short-term circulatory devices has not been investigated. This was a retrospective study of 67 patients who received percutaneously inserted ventricular assist device (pVAD) support for high risk percutaneous coronary interventions. Mean platelet volume (MPV) was measured by impedance technology with Sysmex XN-10 hematological analyzer and expressed in femtoliters (fL). Average MPV (aMPV) and percentage change from admission (∆MPV%) were calculated. All patients experienced rise in MPV during the hospital stay (10.7+/-0.9 pre-pVAD, 10.8+/-0.8 in 24hrs post pVAD, and 11.1+/-1 fL at 7d, p<0.0001). However, MPV increase was more pronounced in the 24 patients (34.5%) who expired in the hospital (Figure A) and the ∆MPV% was significantly higher in expired patients (7.7+/-7.8 vs. 4.6+/-4.9% in survivors, p=0.026). When adjusted for clinical variables (age, gender, and histories of atrial fibrillation, hypertension, coronary artery disease, and congestive heart failure), every 1% increase in ∆MPV% was associated with 11% increased odds of dying in patients undergoing high risk PCI with pVAD support (OR 1.111, 95%CI 1.015-1.216, p=0.022). This pilot study indicates that rise in MPV is associated with increased mortality in PCI patients treated with pVAD. Simple and widely available MPV measurements may be useful in identifying high risk patients and estimating prognosis, which may aid in proper resource allocation. More studies on this subject are necessary.

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation

Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Radiotherapy Is Associated with an Accelerated Risk of Ischemic Stroke in Oral Cavity Cancer Survivors after Primary Surgery.

The number of oral cavity carcinoma (OCC) survivors continues to increase due to advances in definitive surgery and radiation therapy (RT), however the risk of ischemic stroke is unclear in long-term survivors. In this study, survivors are defined as those who survived for >5 years after a diagnosis of OCC. They were matched at a 1:5 ratio with normal controls. Those who received surgery alone versus surgery+RT were also matched at a 1:1 ratio. From 2000 to 2005, 5172 OCC survivors who received surgery alone (n = 3205) or surgery+RT (n = 1967), and 25,860 matched normal controls were analyzed using stratified Cox regression models. Adjusted HRs (aHR) revealed that the surgery+RT group (aHR = 1.68, p < 0.001) had an elevated risk of stroke, but this was not seen in the surgery alone group (aHR = 0.99, p = 0.953). Furthermore, the age at stroke onset was at least 10 years earlier in the surgery+RT group than in the controls. In conclusion, radiotherapy increased the risk of ischemic stroke by 68% and also accelerated the onset of stroke in long-term OCC survivors after primary surgery compared with matched normal controls. Secondary prevention should include stroke as a late complication in OCC survivorship programs.

Abstract P114: Association of Atrial Fibrillation With Incidence of Extracranial Systemic Embolic Events (SEE) in the Atherosclerosis Risk in Communities (ARIC) Study

Objectives: Embolic stroke is a major complication of atrial fibrillation (AF). Mechanisms that lead to elevated stroke risk in AF are also likely to increase risk of extracranial systemic embolic events (SEE). However, little is known about the magnitude of the association of AF with SEE, needed to fully characterize the impact of AF on cardiovascular outcomes. We evaluated the association of AF with SEE and the prediction of SEE among persons with AF in a community-based cohort. Methods: We included 14,941 participants of the ARIC study (mean age, 54 ± 6, 55% women, 74% white) without AF at baseline (1987-89) and followed through 2017. AF was identified from study electrocardiograms, hospital discharges, and death certificates. SEE was defined as the presence of hospitalization discharge codes ICD-9-CM 444.xx or ICD-10-CM I74.x (Arterial embolism and thrombosis) in any position. CHA2DS2-VASc score, a predictor of stroke risk in AF, was calculated at the time of AF diagnosis. Cox models adjusting for fixed and time-varying covariates were used to estimate associations of incident AF with SEE risk and between CHA2DS2-VASc score and SEE risk in those with incident AF. Results: Among eligible participants, 3,114 developed AF and 270 had a SEE event. Incident AF was associated with increased risk of SEE [hazard ratio (HR) = 3.6, 95% confidence interval (CI) 2.6 - 5.0], after adjusting for baseline and time-dependent covariates (Table). The association of incident AF with SEE was stronger in women (HR 5.3, 95% CI 3.3 - 8.4) than in men (HR 2.7, 95% CI 1.7 - 4.3) (p for interaction = 0.002). In participants with incident AF, we identified 59 SEE events. Higher CHA 2 DS 2 -VASc score was associated with increased SEE risk (HR per 1-point increase = 1.2, 95% CI 1.1 - 1.5). Conclusions: AF is associated with more than a tripling of the risk of SEE, with a stronger association in women than in men. CHA 2 DS 2 -VASc is associated with SEE risk in AF patients, highlighting the value of the score to predict outcomes and guide treatments in persons with AF.

Association between methylene tetrahydrofolate reductase polymorphisms and risk of ischemic stroke

Background: The methylene tetrahydrofolate reductase (MTHFR) is a folate-dependent enzyme which catalyzes the conversion of homocysteine to methionine. Two single nucleotide polymorphisms (SNPs) within this gene namely rs1801133 (C677T) and rs1801131 (A1298C) have been associated with elevated risk of ischemic stroke and total serum homocysteine in some populations.Aim: To assess associations between MTHFR SNPs and risk of ischemic stroke in Iranian population.Methods: In the current case-control study, we genotyped rs1801133 and rs1801131 SNPs in 318 Iranian patients with history of ischemic stroke and 400 age- and sex-matched controls using tetra-primer amplification refractory mutation system-polymerase chain reaction method.Results: The rs1801133 was significantly associated with risk of stroke in recessive model (OR (95% CI) = 1.89 (1.12–3.20), p = 0.03). The CT haplotype (rs1801131 and rs1801133, respectively) was significantly over-represented in patients compared with controls (OR (95% CI) = 1.71 (0.25–2.32), p = 0.002).Conclusion: Consequently, our data demonstrate contribution of MTHFR variants in risk of ischemic stroke in Iranian population.

Clinical burden of autosomal dominant polycystic kidney disease.

There are no specific therapies for autosomal dominant polycystic kidney disease (ADPKD), and clinical data evaluating the effects of non-specific therapies on ADPKD patients are scarce. We therefore evaluated those effects using data from a longitudinal health insurance database collected from 2000-2010. We individually selected patients with and without ADPKD from inpatient data files as well as from the catastrophic illness registry in Taiwan based on 1:5 frequency matching for sex, age, and index year. The hazard ratios (HR) of all-cause mortality, ischemic stroke, hemorrhagic stroke and end-stage renal disease (ESRD) in ADPKD inpatients were elevated as compared to the controls. Similarly, ADPKD patients from the catastrophic illness registry had an increased risk of hemorrhagic stroke and ESRD. Allopurinol users also had an increased risk of all-cause mortality. The HR for developing ESRD after medication exposure was 0.47-fold for statin and 1.93-fold for pentoxifylline. These results reveal that patients with ADPKD (either inpatient or from the catastrophic illness registry) are at elevated risk for hemorrhagic stroke and ESRD, and suggest that allopurinol and pentoxifylline should not be prescribed to ADPKD patients due to possible adverse effects.

Plasma Estradiol and Testosterone Levels and Ischemic Stroke in Postmenopausal Women.

Background and Purpose- Although exogenous hormone therapy (HT) use has been associated with increased risk of ischemic stroke in postmenopausal women, it remains unknown whether sex hormone levels contribute to ischemic stroke risk. We aimed to estimate associations between plasma sex hormone levels and ischemic stroke risk, by HT status, in a nested case-control study of postmenopausal women from the NHS (Nurses' Health Study). Methods- Women with confirmed incident ischemic stroke (n=419) were matched with controls (n=419) by age, HT use, and other factors. Plasma estradiol and testosterone levels were measured using liquid chromatography tandem mass spectrometry; SHBG (sex hormone-binding globulin) was assayed by electrochemiluminescence immunoassay. Associations of total and free estradiol and testosterone, the estradiol/testosterone ratio, and SHBG with ischemic stroke were estimated using conditional logistic regressions stratified by HT status with adjustment for matching and cardiovascular risk factors. Results- Current HT users had different hormone profiles from never/past users. No clear linear trends were observed between estradiol (total or free) levels or the estradiol/testosterone ratio and ischemic stroke risk among either current users (Ptrend>0.1) or never/past users (Ptrend>0.6). For both current and never/past users, the associations between some of the sex hormones and ischemic stroke differed by body mass index categories (Pinteraction≤0.04). For women with a body mass index <25 kg/m2, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (Ptrend=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (Ptrend≤0.04). Testosterone and SHBG were not associated with ischemic stroke in either current or never/past users. Conclusions- Our findings do not support a role of sex hormone levels in mediating ischemic stroke risk among postmenopausal women. Replications in additional larger studies are required.

Physical Activity, Hormone Therapy Use, and Stroke Risk among Women in the California Teachers Study Cohort

Background: Postmenopausal hormone therapy (HT) increases the risk of stroke. Here we evaluate whether leisure time physical activity (LTPA) can change stroke risk in women using HT, leveraging data from the California Teachers Study. Methods: Female California educators without a prior history of stroke (n = 118,294) were followed from 1995 through 2015 for stroke end points. Based on statewide hospitalization data, 4,437 women had ischemic (n = 3,162; International Classification of Diseases [ICD]-9 433, 434, 436) or hemorrhagic (n = 1,275; ICD-9 430–432, excluding 432.1) stroke. LTPA and HT use were evaluated at 2 time points (baseline [1995–1996] and 10-year follow-up [2005–2006]). LTPA was assessed using American Heart Association (AHA) recommendations (>150 min/week moderate or >75 min/week strenuous physical activity). Using multivariable Cox proportional hazards models, we estimated the hazard ratios (HRs) and 95% CIs for the associations between HT use and concurrent LTPA with incident stroke. Results: Compared to women who never used HT, stroke risk was highest among women who were current HT users and did not meet AHA recommendations for LTPA at the time of their HT use: HR_baseline 1.28 (95% CI 1.13–1.44); HR_{10-year follow-up} 1.17 (95% CI 0.91–1.50). Based on the baseline questionnaire, current HT users who met AHA recommendations for LTPA in 1995–1996 still had elevated stroke risk in the 20-year follow-up (HR 1.22, 95% CI 1.08–1.37). However, among current HT users who met AHA recommendations for LTPA at the 2005–2006 follow-up questionnaire, stroke risk was not elevated (HR 1.01, 95% CI 0.80–1.29). Evaluation of the 2 time points in concert further demonstrated that meeting AHA recommendations for LTPA at the most recent follow-up time point was required to reduce HT-related stroke risk. Conclusion: Concurrent physical activity may attenuate the short-term increase in risk of stroke risk associated with HT use.

SUPPORT-AF II: Supporting Use of Anticoagulants Through Provider Profiling of Oral Anticoagulant Therapy for Atrial Fibrillation

Previous provider-directed electronic messaging interventions have not by themselves improved anticoagulation use in patients with atrial fibrillation. Direct engagement with providers using academic detailing coupled with electronic messaging may overcome the limitations of the prior interventions. We randomized outpatient providers affiliated with our health system in a 2.5:1 ratio to our electronic profiling/messaging combined with academic detailing intervention. In the intervention, we emailed providers monthly reports of their anticoagulation percentage relative to peers for atrial fibrillation patients with elevated stroke risk (CHA2DS2-VASc ≥2). We also sent electronic medical record-based messages shortly before an appointment with an anticoagulation-eligible but untreated atrial fibrillation patient. Providers had the option to send responses with explanations for prescribing decisions. We also offered to meet with intervention providers using an academic detailing approach developed based on knowledge gaps discussed in provider focus groups. To assess feasibility, we tracked provider review of our messages. To assess effectiveness, we measured the change in anticoagulation for patients of intervention providers relative to controls. We identified 85 intervention and 34 control providers taking care of 3591 and 1908 patients, respectively; 33 intervention providers participated in academic detailing. More than 80% of intervention providers read our emails, and 98% of the time a provider reviewed our in-basket messages. Replies to messages identified patient refusal as the most common reason for patients not being on anticoagulation (11.2%). For the group of patients not on anticoagulation at baseline assigned to an intervention versus control provider, the adjusted percent increase in the use of anticoagulation over 6 months was 5.2% versus 7.4%, respectively (P=0.21). Our electronic messaging and academic detailing intervention was feasible but did not increase anticoagulation use. Patient-directed interventions or provider interventions targeting patients declining anticoagulation may be necessary to raise the rate of anticoagulation. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03583008.

Abstract TP209: Effect of Chemotherapy on Stroke Risk in Cancer Patients

Introduction: Chemotherapy may be a cause of cancer-associated stroke, but whether it increases stroke risk remains uncertain. We aimed to clarify the impact of chemotherapy on stroke risk in cancer patients. Methods: We investigated 27,932 patients enrolled in a hospital-based cancer registry at Osaka University Hospital between 2007 and 2015. The registry collects clinical data, including cancer status (site and stage), on all patients treated for cancer. Of them, 19,006 patients with complete data were included. A validated algorithm was used to identify stroke events within 2 years of cancer diagnosis. Patients were divided based on whether their initial treatment plan included chemotherapy. The association between chemotherapy and stroke was analyzed using the Kaplan-Meier method and stratified Cox regression. Results: Of the 19,006 patients, 5,887 (31%) patients were in the chemotherapy group. Non-targeted chemotherapy was used in 5,371 patients. Stroke occurred in 44 patients (0.75%) in the chemotherapy group and 51 patients (0.39%) in the no-chemotherapy group. Kaplan-Meier curve analysis showed that patients in the chemotherapy group had a higher stroke risk than patients in the no-chemotherapy group (HR 1.84; 95% CI 1.23-2.75; Figure [A]). However, this difference was insignificant after adjustment for cancer status using inverse probability of treatment weighting with propensity scores (HR 1.20; 95% CI 0.76-1.91; Figure [B]). Similarly, in the stratified Cox regression model, chemotherapy was not associated with stroke after adjustment for cancer status (HR 1.26; 95% CI 0.78-2.03). These findings were consistent with analysis wherein the effect of chemotherapy was treated as a time-dependent covariate (HR 1.02; 95% CI 0.55-1.88). Conclusions: In this population, the elevated stroke risk in cancer patients who received chemotherapy was presumably due to advanced cancer stage; chemotherapy was not associated with the increased risk of stroke.

Black and Asian Patients Face Elevated Risk of Recurrent Hemorrhagic Stroke

Black and Asian Patients Face Elevated Risk of Recurrent Hemorrhagic Stroke

Endodontic therapy and incident cardiovascular disease: The Atherosclerosis Risk in Communities (ARIC) study.

Previous studies on a potential association between endodontic infection (EI) and cardiovascular disease (CVD) produced mixed results. Endodontic treatment (ET) may also be linked to cardiovascular risk, as a marker for prior chronic dental infection and subclinical EI in other teeth. We tested the hypothesis that ET is associated with elevated risk of coronary heart disease (CHD), ischemic stroke (IS), heart failure (HF), or venous thromboembolism (VTE). ARIC participants who completed the dental ancillary study exam 4 (1996-1998; n = 6,638) were included in the analyses. Participants were followed through 2013 for CHD, stroke, and HF and 2011 for VTE. Cox-proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for CHD, IS, HF, and VTE across ET classifications adjusting for age, sex, race/center, education, income, smoking, alcohol consumption, BMI, statin use, family history of CHD, physical activity, diet quality, insurance status, last dental visit, dental visit frequency, having a current dentist, and tooth loss due to gum disease. Among participants, 21.0% reported a single ET, while 28.5% reported multiple ETs. Over a median of 15.8 years of follow-up, there were 506 incident CHD events, 311 IS events, 739 HF events, and 219 VTE events. There were no significant associations between self-reported history of ET and any of our outcomes (HR (95%CI): CHD = 1.16 (0.87,1.44), IS = 0.77 (0.55,1.09), HF = 1.00 (0.81,1.24), VTE = 0.98 (0.67,1.43)) after adjustment. Our results do not support an independent association between ET and development of CHD, IS, HF, or VTE.

Stroke Avoidance for Children in República Dominicana (SACRED):a Prospective Trial to Reduce Stroke in Children with Sickle Cell Anemia

Introduction. The burden of sickle cell anemia (SCA) is high across the Caribbean, including the Dominican Republic where the morbidity of SCA is substantial due to limited resources. Approximately 10% of affected children will develop primary stroke, with serious medical and neurocognitive sequelae. In the US, transcranial Doppler (TCD) ultrasonography is an effective screening tool to identify children at risk for primary stroke, which then allows preventive therapy with either hydroxyurea or blood transfusions. To date, however, no routine TCD screening and treatment program for stroke prevention has been established in the Dominican Republic. We designed a prospective screening and treatment study (SACRED, NCT02769845) for prevention of primary stroke in children with SCA using open-label hydroxyurea at maximum tolerated dose (MTD). Methods. Children with SCA between age 3-15 years and receiving medical care at Robert Reid Cabral Children's Hospital in Santo Domingo, Dominican Republic were recruited over a 12-month period. Treatment depended on the baseline TCD examination: children with abnormal time-averaged mean velocities (≥200 cm/sec, high stroke risk) were recommended to receive monthly transfusions for primary stroke prevention, as per standard treatment preferences at the Robert Reid Hospital; those with conditional velocities (170-199 cm/sec, moderate stroke risk) were offered hydroxyurea study treatment unless they were currently receiving chronic transfusions for other clinical indications. Oral open-label hydroxyurea using 500mg capsules was prescribed at fixed-dose (20 mg/kg/day) for 6 months, followed by dose escalation to MTD. TCD examinations were repeated every 6 months, with the main study endpoints being changes in laboratory parameters and TCD velocities after 18 months of study treatment. Results. A total of 283 children were enrolled with the following baseline TCD velocities: 200 (70.7%) normal, 63 (22.3%) conditional, 11 (3.9%) abnormal, and 9 (3.1%) inadequate velocities. Among 50 children eligible for hydroxyurea study treatment, the average age was 6.8 ± 2.8 years and included 27 males/23 females with evidence of substantial SCA-related morbidity (88% with previous transfusions, 60% with &gt;5 hospitalizations). A total of 48 children initiated hydroxyurea at 20.2 ± 1.2 mg/kg/day, which was maintained for 6 months followed by dose escalation, reaching MTD at 24.1 ± 6.0 mg/kg/day. Laboratory changes from baseline to Month 18 included significant increases in hemoglobin (7.5 ± 0.9 to 8.9 ± 1.3 g/dL, P&lt;0.0001) and fetal hemoglobin (16.4 ± 7.4 to 30.9 ± 13.6%, P&lt;0.0001). Serial TCD examinations revealed a significant decline over the treatment period, with the average TCD velocity decreasing from 180 ± 8 cm/sec at baseline to 159 ± 21 cm/sec at Month 18, P&lt;0.0001. At Month 18, 68% of the originally conditional TCD examinations had reverted to a normal velocity, while only 4% had converted to abnormal velocity. No clinical strokes occurred in the hydroxyurea treatment cohort. Conclusion. Conditional TCD velocities are common (&gt;20%) in the Dominican Republic, which documents an elevated stroke risk for children with SCA. The SACRED trial established a local TCD screening program and provided open-label hydroxyurea treatment for children with conditional TCD velocities. Hydroxyurea treatment at MTD led to improved hematological parameters, lower TCD velocities, and decreased stroke risk. SACRED represents an important international partnership and prospective collaborative research trial providing capacity building and valuable epidemiological data regarding TCD screening, stroke risk, and hydroxyurea effects for children with SCA. Hydroxyurea at MTD is a suitable treatment to reduce primary stroke risk for children with SCA living in the Dominican Republic or other low-resource settings. Disclosures Jeste: Jannsen: Employment. Ware:Novartis: Other: DSMB; Nova Laboratories: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Other: Research Drug Donation; Addmedica: Other: Research Drug Donation; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees.

Transcranial Doppler Velocities Conversion Rate Based on Increasing Hemoglobin Concentration: Analysies from the SCCRIP Cohort Study

Transcranial Doppler Velocities Conversion Rate Based on Increasing Hemoglobin Concentration: Analysies from the SCCRIP Cohort Study