Ischemic Stroke Hazard Ratio Research Articles

Blood pressure during long-term cilostazol-based dual antiplatelet therapy after stroke: a post hoc analysis of the CSPS.com trial

We determined the associations of follow-up blood pressure (BP) after stroke as a time-dependent covariate with the risk of subsequent ischemic stroke, as well as those of BP levels with the difference in the impact of long-term clopidogrel or aspirin monotherapy versus additional cilostazol medication on secondary stroke prevention. In a sub-analysis of a randomized controlled trial (CSPS.com), patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone, or a combination of cilostazol with aspirin or clopidogrel. The percent changes, differences, and raw values of follow-up BP were examined. The primary efficacy outcome was the first recurrence of ischemic stroke. In a total of 1657 patients (69.5 ± 9.3 years, female 29.1%) with median 1.5-year follow-up, ischemic stroke recurred in 74 patients. The adjusted hazard ratio for ischemic stroke of a 10% systolic BP (SBP) increase from baseline was 1.19 (95% CI 1.03–1.36), that of a 10 mmHg SBP increase was 1.14 (1.03–1.28), and that of SBP as the raw value with the baseline SBP as a fixed (time-independent) covariate was 1.14 (1.00–1.31). Such significant associations were not observed in diastolic BP-derived variables. The estimated adjusted hazard ratio curves for the outcome showed the benefit of dual therapy over a wide SBP range between ≈120 and ≈165 mmHg uniformly. Lower long-term SBP levels after ischemic stroke were associated with a lower risk of subsequent ischemic events. The efficacy of dual antiplatelet therapy including cilostazol for secondary stroke prevention was evident over a wide SBP range.

Potential interactions between medications for rate control and direct oral anticoagulants: Population-based cohort and case-crossover study

BackgroundDirect oral anticoagulants (DOACs) are commonly co-prescribed with amiodarone/diltiazem/verapamil, but whether there is a drug interaction between these drugs is unclear. ObjectiveThe purpose of this study was to investigate the risk of clinical outcomes associated with concomitant use of DOACs and amiodarone/diltiazem/verapamil. MethodsWe identified DOAC users in the Clinical Practice Research Datalink Aurum from January 1, 2011, to December 31, 2019. We used a cohort design to estimate hazard ratios for ischemic stroke, myocardial infarction, venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, other bleeding, cardiovascular mortality, and all-cause mortality, comparing DOACs + amiodarone/diltiazem/verapamil users and DOACs + beta-blocker users. A case-crossover design comparing odds of exposure to different drug initiation patterns for all outcomes in hazard window vs referent window within an individual also was conducted. ResultsOf 397,459 DOAC users, we included 9075 co-prescribed amiodarone, 9612 co-prescribed diltiazem, and 2907 co-prescribed verapamil. There was no difference in risk of any outcomes between DOACs + amiodarone/diltiazem/verapamil users vs DOACs + beta-blocker users in the cohort design. However, in the case-crossover design, we observed an odds ratio (OR) of 2.09 (99% confidence interval [CI] 1.37–3.18) for all-cause mortality associated with initiation of a DOAC while taking amiodarone, which was greater than that observed for DOAC monotherapy (OR 1.30; 99% CI 1.25–1.35). Similar findings were observed for cardiovascular mortality and all-cause mortality respectively with diltiazem. ConclusionOur study showed no evidence of higher bleeding or cardiovascular risk associated with co-prescribed DOACs and amiodarone, diltiazem, or verapamil. Elevated risks of cardiovascular and all-cause mortality were only observed during DOAC initiation when diltiazem/amiodarone were being taken.

Prognosis and antithrombotic practice patterns in patients with recurrent and transient atrial fibrillation following acute coronary syndrome: A nationwide study

BackgroundFirst-time detected atrial fibrillation (AF) is associated with aggravated prognosis in patients admitted with acute coronary syndrome (ACS). Yet, among patients surviving beyond one year after ACS, it remains unclear how the recurrence of AF within the initial year after ACS affects the risk of stroke. MethodsWith Danish nationwide data from 2000 to 2021, we identified all patients with first-time ACS who were alive one year after discharge (index date). Patients were categorized into: i) no AF; ii) first-time detected AF during ACS admission without a recurrent hospital contact with AF (transient AF); and iii) first-time detected AF during ACS admission with a subsequent recurrent hospital contact with AF (recurrent AF). From index date, two-year rates of ischemic stroke were compared using multivariable adjusted Cox regression analysis. Treatment with antithrombotic therapy was assessed as filled prescriptions between 12 and 15 months following ACS discharge. ResultsWe included 139,137 patients surviving one year post ACS discharge: 132,944 (95.6%) without AF, 3920 (2.8%) with transient AF, and 2273 (1.6%) with recurrent AF. Compared to those without AF, the adjusted two-year hazard ratios of ischemic stroke were 1.45 (95% CI, 1.22–1.71) for patients with transient AF and 1.47 (95% CI: 1.17–1.85) for patients with recurrent AF. Prescription rates of oral anticoagulation increased over calendar time, reaching 68.3% and 78.7% for transient and recurrent AF, respectively, from 2019 to 2021. ConclusionIn patients surviving one year after ACS with first-time detected AF, recurrent and transient AF were associated with a similarly increased long-term rate of ischemic stroke.

Abstract 54: Circulating Biomarkers and Anticoagulation Breakthrough Stroke Risk in Atrial Fibrillation: The REGARDS Study

Introduction: Anticoagulation reduces ischemic stroke risk in atrial fibrillation (AF), but “breakthrough” stroke occurs. Blood biomarkers might help identify patients at risk for anticoagulation breakthrough stroke, but existing studies are limited by examining few biomarkers in select populations. Hypotheses: Established biomarkers of ischemic stroke risk will also be associated with ischemic stroke risk in people with AF on anticoagulation sampled from the general population. Methods: REGARDS is a prospective cohort of 30,239 Black or White adults aged ≥45 on enrollment in 2003-7 monitored for stroke. Nine established blood biomarkers of ischemic stroke risk were measured at baseline in participants with AF and with no prior stroke who were taking oral anticoagulation at baseline. Hazard ratios of ischemic stroke were estimated by Cox models adjusted for demographics and stroke risk factors. Results: Among 713 participants with AF on anticoagulation (median age 76, 36% female, 17% Black, all taking vitamin K antagonists), 67 (9%) developed a first-time ischemic stroke over 12 years. In models adjusted for demographics, there were positive associations of all biomarkers with stroke risk except for galectin-3, lipoprotein(a), and cystatin C which had inverse or null associations (Figure). Adjustment for risk factors minimally impacted interpretation of results. The greatest associations were with higher N-terminal pro-B type natriuretic peptide, factor VIII, D-dimer, and growth differentiation factor 15; associations for D-dimer and growth differentiation factor 15 were not statistically significant. Hazards for galectin-3, gamma glutamyl transferase, interleukin 6, and lipoprotein (a) were modest and not statistically significant. Conclusion: Biomarkers of cardiac strain (specifically atriopathy), coagulation, and inflammation were associated with higher ischemic stroke risk in people with AF on anticoagulation at baseline. Findings highlight new avenues for reducing stroke risk in AF.

Evaluating the risk of ischemic stroke at a young age in patients with autoimmune inflammatory rheumatic diseases: a population-based cohort study in Taiwan.

Recent studies have demonstrated an increased incidence of ischemic stroke among patients with certain autoimmune inflammatory rheumatic diseases (AIIRDs). However, the associations between young stroke and AIIRDs have not been fully investigated. This study aimed to evaluate the risk of ischemic stroke among young patients with AIIRDs. The National Health Insurance Research Database in Taiwan was utilized to establish cohorts of patients with AIIRDs diagnosed between 2004 and 2015, who were compared with 1,000,000 control participants. Cox proportional hazards regression models were used to calculate the hazard ratio of ischemic stroke and young ischemic stroke for individual AIIRDs after adjustment for relative risk factors. During the study period, a total of 64,120 patients with AIIRDss and 1,000,000 control patients were identified. The overall mean follow-up time was 5.33 years. There were 223 (0.8%) and 1,923 (0.3%) young ischemic stroke-related hospitalizations among patients with AIIRDs and controls, respectively. The incidence rate of young ischemic stroke was 0.08 in patients with rheumatoid arthritis, 0.08 in patients with Sjögren's syndrome, 0.26 in patients with systemic lupus erythematosus, 0.17 in patients with idiopathic inflammatory myositis, 0.24 in patients with systemic sclerosis, 0.05 in patients with Behçet's disease, and 0.44 in patients with systemic vasculitis, versus 0.05 per 100 person-years in the general population. The adjusted hazard ratios for young ischemic stroke were 1.07 (95% CI 0.70-1.43) for rheumatoid arthritis, 1.39 (95% CI 0.94-2.06) for Sjögren's syndrome, 5.79 (95% CI 4.68-7.17) for systemic lupus erythematosus, 2.07 for idiopathic inflammatory myositis (95% CI 0.98-4.38), 2.79 for systemic sclerosis (95% CI 1.38-5.63), 0.82 for Behçet's disease (95% CI 0.26-2.55), and 4.15 (95% CI 1.96-8.82) for systemic vasculitis. Patients younger than 50 years with systemic lupus erythematosus, systemic sclerosis, or systemic vasculitis have a significantly elevated risk of developing ischemic stroke. Further research is needed to elucidate the pathogenesis of accelerated atherosclerosis in these AIIRDs.

Physical activity and the risk of ischemic stroke: A population-based longitudinal follow-up study in Taiwan (KCIS no. 43)

Lack of exercise is a leading risk factor for stroke, and it has been demonstrated that increasing physical activity (PA) can prevent ischemic stroke. However, there has been limited research on the relationship between ischemic stroke and PA, especially among Asian populations. This study therefore investigates whether the level of PA in the Taiwanese population affects its risk of first-ever ischemic stroke, utilizing screening data on 58,857 individuals collected by the Keelung Health Bureau between 2005 and 2012. These subjects were divided into three groups based on their weekly exercise frequency and duration, i.e., 1) a no PA (NPA) group, 2) a low PA (LPA) group (less than 90 min of exercise per week), and 3) a high PA (HPA) group (90 min or more of exercise per week). The results showed that, as compared to the NPA group, the adjusted hazard ratio for ischemic stroke in the LPA group was 0.86 (95 % CI, 0.78–0.95, p < 0.0001); and that in the HPA group, it was also 0.86 (95 % CI, 0.79–0.94, p < 0.0001). In other words, even engaging in PA for less than 90 min per week may lower the risk of first-ever ischemic stroke. Importantly, LPA is more accessible, more sustainable, and easier to promote for the general population than the 150 min per week recommended by the World Health Organization.

Association Between Premature Menopause and Cardiovascular Diseases and All-Cause Mortality in Korean Women.

Background Mortality from cardiovascular diseases in Asian populations is considerable. Menopause is a risk-enhancing factor for cardiovascular disease, but it is unclear whether menopause is an independent risk factor for cardiovascular disease and mortality in Asian women. Methods and Results A total of 1 159 405 postmenopausal women, who had participated in the health examinations of the Korean National Health Insurance Service in 2009, were analyzed, and their reproductive histories were taken. A multivariable Cox proportional hazard model assessed the hazard ratios (HRs) of myocardial infarction (MI), ischemic stroke, and all-cause mortality, according to the history of premature menopause and age at menopause. After an average 10-year follow-up, there were 31 606, 45 052, and 77 680 new cases of MI, ischemic stroke, and all-cause mortality, respectively. The women with premature menopause exhibited increased risks of MI (HR, 1.40 [95% CI, 1.31-1.50]), ischemic stroke (HR, 1.24 [95% CI, 1.17-1.31]), and all-cause mortality (HR, 1.19 [95% CI, 1.14-1.24]) when compared with women with menopause aged ≥50 years. The highest risk was evident with menopause between the ages of 30 and 34 years (HR for MI, 1.52 [95% CI, 1.30-1.78]; HR for ischemic stroke, 1.29 [95% CI, 1.12-1.48]; HR for all-cause mortality, 1.33 [95% CI, 1.20-1.47]) when compared with women with menopause aged ≥50 years. Conclusions Earlier age at menopause was associated with increased risks for MI, ischemic stroke, and all-cause mortality. Future guidelines and risk assessment tools should consider menopause as an independent risk factor of cardiovascular disease in Korean women.

Abstract 11396: Circulating Biomarkers Improve ChA 2 DS 2 -VASC Risk Prediction in Atrial Fibrillation: The CHA 2 DS 2 -VASc-Biomarkers Model

Introduction: Anticoagulation reduces stroke risk in atrial fibrillation (AF) but increases bleeding. Risk calculators are used to inform decision making for anticoagulation in AF. Yet, existing tools have substantial limitations and improvement efforts failed to change practice. Hypotheses: Biomarkers of ischemic stroke risk for general populations are associated with stroke risk in AF and improve performance of a recommended risk score (CHA 2 DS 2 -VASc). Methods: REGARDS is a prospective cohort of 30,239 Black or White adults aged ≥45 monitored for stroke. Nine blood biomarkers were measured at baseline in participants with AF, no prior stroke, and not taking anticoagulation at baseline. Hazard ratios of ischemic stroke were estimated by Cox models adjusted for demographics and stroke risk factors. Models with CHA 2 DS 2 -VASc alone and with biomarkers (CHA 2 DS 2 -VASc-B) were compared using tests of fit (likelihood ratio test and Aikake information criterion [AIC]) and predictive ability (continuous net reclassification index [NRI]). Results: Among 2,411 participants with baseline AF (median age 69, 55% female, 36% Black), 163 (7%) developed stroke over 13 years. After adjustments, higher cystatin C, growth differentiation factor 15 (GDF-15), interleukin 6, lipoprotein (a), and N-terminal pro-B type natriuretic peptide (NTproBNP) were associated with higher stroke risk (Figure A). Including all biomarkers substantially improved CHA 2 DS 2 -VASc model fit (Figure B; p &lt;0.001; ΔAIC -12.6; &lt;-10 indicates marked improvement) and predictive ability (Figure C; 5-year NRI 0.42). Adding only GDF-15 and NTproBNP resulted in the best model fit and a similar NRI, compared to all biomarkers. Conclusions: Higher levels of five blood biomarkers were associated with ischemic stroke risk in a large general population cohort with AF. Moreover, the CHA 2 DS 2 -VASc-B model was superior to CHA 2 DS 2 -VASc. Findings suggest we can better tailor anticoagulation to reduce stroke in AF.

Time trends in atrial fibrillation-related stroke during 2001-2020 in Sweden: a nationwide, observational study.

Great efforts have been made to improve stroke prevention in atrial fibrillation (AF) patients. Meanwhile, incidence of AF is increasing, which may affect the share of AF-related stroke on all strokes. We aimed to examine the temporal trends in the incidence of AF-related ischemic stroke between 2001 and 2020, if it varied by use of novel oral anticoagulant drugs (NOAC), and if the relative risk of ischemic stroke associated with AF changed over time. Data from the total Swedish population aged ≥70 years during the period 2001-2020 were used. Annual incidence rate (IR) was calculated for overall and AF-related ischemic stroke which was defined as first-ever ischemic stroke with AF diagnosed up to 5 years before, on the same day, or within 2 months after the stroke event. Cox regression models were performed to examine if the hazard ratio (HR) between AF and stroke changed over time. While IR of ischemic strokes declined during 2001-2020, IR of AF-related ischemic stroke remained stable between 2001 and 2010 but showed a consistent decline between 2010 and 2020. The HR of ischemic stroke within 3 years from an AF diagnosis came down from 2.39 (95% confidence interval: 2.31-2.48) to 1.54 (1.48-1.61) over the study period, which was largely explained by a substantial increase in the use of NOAC among AF patients after 2012. Yet, by the end of 2020, 24% of all ischemic strokes had a preceding or concurrent AF diagnosis, which is slightly higher than in2001. Even though both the absolute and relative risk of AF-related ischemic stroke declined over the past 20 years, every fourth ischemic stroke in 2020 still had a preceding or concurrent AF diagnosis. This represents a great potential for future gains in stroke prevention among AF patients. Swedish Research Council and Loo and Hans Osterman Foundation for Medical Research.

Prevalence and incidence of cardiovascular and renal diseases in type 1 compared with type 2 diabetes: A nationwide French observational study of hospitalized patients

BackgroundType 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) increase risks of cardiovascular (CV) and renal disease compared with diabetes-free populations. There are only a few studies comparing T1DM and T2DM for the relative risk of these clinical events. MethodsAll adult patients hospitalized in French hospitals in 2013 with at least 5 years of follow-up were identified and categorized by their diabetes status. A total of 50,623 patients with T1DM (age 61.4 ± 18.6, 53% male) and 425,207 patients with T2DM (age 68.6 ± 14.3, 55% male) were followed over a median period of 5.3 years (interquartile range: 2.8 - 5.8 years). Prevalence and event rates of myocardial infarction (MI), heart failure (HF), ischemic stroke, chronic kidney disease (CKD), all-cause death and CV death were assessed with age stratification of 10-year intervals. For clinical events during follow-up, we report hazard ratios (HRs) in T1DM relative to T2DM. ResultsThe age and sex-adjusted prevalence of CV diseases was higher in T2DM for ages above 40 years whereas the prevalence of CKD was more common in T1DM between ages 18 and 70 years. During 2,033,239 person-years of follow-up, age and sex-adjusted HR event rates comparing T1DM, versus T2DM as reference, showed that MI and HF relative risks were increased above 60 years (1.2 and 1.4 -fold). HR of ischemic stroke did not markedly differ between T1DM and T2DM. Risk of incident CKD was 2.4-fold higher in T1DM above 60 years. All-cause death HR risk was 1.1-fold higher in T1DM after 60 years and the CV death risk was 1.15-fold higher in T1DM between 60 and 69 years compared to T2DM. ConclusionsAlthough the crude prevalent burden of CV diseases may be lower in T1DM than in T2DM, patients with T1DM may have a higher risk of incident MI, HF, all-cause death and CV death above 60 years of age, highlighting the need for improved prevention in this population.

Abstract 84: Impact Of Gastrointestinal Surgery On Efficacy Of Oral Anticoagulants In Patients With Nonvalvular Atrial Fibrillation: A Nationwide Population-based Study

Introduction: Alteration of the gastrointestinal (GI) tract by resection or bypass surgery might affect the absorption of both warfarin and direct oral anticoagulants (DOACs). The clinical trials of DOACs excluded individuals with altered GI tract, hence there are limited pharmacokinetic data for them. Only several cases have been reported suggesting atrial fibrillation-related stroke due to reduced absorption of DOACs after GI surgery. We aimed to investigate the efficacy of warfarin and DOACs who underwent GI surgery using nationwide population-based data. Methods: This was a retrospective cohort study using claim-based national data from 2013 to 2020 from Korean Health Insurance Review and Assessment Service (HIRA). Patients with nonvalvular AF (NVAF) taking oral anticoagulants (OACs) were included. The patients taking OACs due to other indications than NVAF were excluded. Cox proportional hazard models with time-varying covariates were used to investigate the impact of GI surgery in patients taking warfarin and DOACs. Results: Of the 311,782 patients (mean age 72, male 56.7%) with NVAF, 3,807 underwent GI surgery. Warfarin and DOACs were prescribed in 14.3% and 85.7% of the patients, respectively. Overall, warfarin was associated with a higher risk of ischemic stroke compared with DOACs (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.44-1.59). In the GI surgery group, the hazard ratio for ischemic stroke for warfarin compared with DOACs was 2.70 (95% CI, 1.63-4.45, Figure). In the no GI surgery group, warfarin also had a higher risk of ischemic stroke compared with DOACs (HR 1.51, 95% CI 1.44-1.59). Among DOAC-treated patients, GI surgery was not associated with a risk of ischemic stroke (HR 0.87, 95% CI 0.67-1.12). Conclusions: DOACs were more effective for stroke prevention than warfarin in patients with NVAF whose GI tracts were altered due to previous surgery. GI surgery did not affect the risk of stroke in patients with NVAF taking DOAC.

Small Dense Low-Density Lipoprotein Cholesterol and Ischemic Stroke.

For decades, it has been suggested that small dense low-density lipoprotein (sdLDL) may be particularly atherogenic. High levels of sdLDL are associated with an increased risk of ischemic heart disease; however, the association of sdLDL with ischemic stroke has not been explored in a large prospective study on the general population. We tested the hypothesis that high sdLDL cholesterol levels are associated with an increased risk of ischemic stroke. This prospective study included 38,319 individuals from the Copenhagen General Population Study with fresh sample measurements of sdLDL cholesterol. Median follow-up time was 3.1 years. We observed 302 and 74 ischemic and hemorrhagic strokes from baseline in 2013 to 2017 to the end of follow-up in 2018. For comparison, we included estimates for large buoyant LDL cholesterol and total LDL cholesterol. Higher levels of sdLDL cholesterol were log-linearly associated with increased risk of ischemic stroke. Compared with individuals with sdLDL cholesterol in the lowest tertile (≤0.60 mmol/l; ≤23 mg/dl) the multivariable adjusted hazard ratio for ischemic stroke was 1.79 (95% confidence interval=1.31-2.43) for the highest tertile (≥0.86 mmol/l; ≥33 mg/dl). Multivariable adjusted hazard ratios for ischemic stroke per 1 mmol/l (38.7mg/dl) higher levels were 1.69 (1.28-2.22) for sdLDL cholesterol, 0.95 (0.78-1.16) for large buoyant LDL cholesterol, and 1.08 (0.93-1.25) for total LDL cholesterol. Hazard ratios were similar when further adjusting for body mass index (BMI) and diabetes mellitus in the biological pathway in combination with related lipids and lipoproteins. Higher sdLDL cholesterol levels were robustly associated with increased risk of ischemic stroke. ANN NEUROL 2023;93:952-964.

Association between ischemic stroke and pyogenic spondylitis in Korea: Nationwide longitudinal cohort study.

The purpose of this nationwide age- and sex- matched longitudinal study was to determine the pyogenic spondylitis (PS) increases the incidence of ischemic stroke (IS) in Korea. From the National Health Insurance Service (NHIS), we collected the patient data for the period from January 1, 2004 to December 31, 2015. PS was classified according to the International Classification of Disease codes M46.2-M46.8, M49.2, and M49.3. By using a 1:5 age- and sex- stratified matching, a total of 628 patients and 3140 control subjects were included in the study. The IS incidence rates in PS and control group was calculated by using the Kaplan-Meier method. The outcome of hazard ratio of IS was estimated by Cox proportional hazards regression analyses. This study did not exclude PS as a result of postoperative complications. According to the study, 51 patients (8.12%) in the PS group and 201 patients (6.4%) in the control group experienced IS. The adjusted hazard ratio of IS in the PS group was 3.419 (95% CI: 2.473-4.729) after adjusting individual medical condition and demographics. Following the results of subgroup analysis, the risk ratio of IS was greater in most of the subgroup categories (male, female, age <65, age >65, non-diabetic, hypertensive, non-hypertensive, dyslipidemic and non-dyslipidemic subgroup). However, the risk of IS did not differ significantly in diabetic subgroup (95% CI: 0.953-4.360). The risk rate of IS increased in patient with pyogenic spondylitis.

Ischemic stroke in patients with congenital heart disease and atrial fibrillation

Abstract Background Atrial fibrillation (AF) is one of the most common arrhythmias in patients with congenital heart disease (CHD). The risk of developing AF is more than 20 times higher in patients with CHD compared with non-CHD controls. However, while it is known that young non-CHD patients with AF have a low risk for ischemic stroke (IS), little is known about the risk for IS young CHD patients with AF. Purpose To investigate the risk of developing IS in younger patients with CHD and AF compared to non-CHD control patients with AF. Method Using data from the National Swedish Patient Register and Cause of Death register, all CHD and born in Sweden between 1970 and 2017 with history of AF were identified. The Swedish total population register was used to identify age and sex matched controls. Among the matched controls, non-CHD patients AF were identified and used as reference group. CHD and non-CHD patients were followed from onset of AF until index IS, death or end of study (31st December 2017). Cox proportional hazard regression model with hazard ratio (HR) and 95% confidence interval (CI) was used to estimate the risk of IS in CHD patients with AF compared with non-CHD controls with AF. Results A total of 951 CHD with AF and 606 non-CHD controls with AF were identified. With ages ranging from 0 to 47 years, the median age was 25.6 and 30.7 years for CHD and non-CHD respectively. In patients with CHD and AF, 2.9% of patients (n=28) developed IS during follow up (mean follow up 34 years, SD ± 11.2), compared 0.5% (n=3) in non-CHD controls with AF (mean follow up 37 years, SD ± 9.5 years). The unadjusted HR for IS in CHD patients with AF compared with non-CHD controls with AF was 4.61 (95% CI1.39–15.25). When adjusted for age, sex, hypertension and heart failure, the risk of IS was more than five times higher (HR 5.16, 95% CI 1.52–17.46) in CHD patients compared with non-CHD patients. The adjusted HR for developing IS in non-complex CHD with AF compared with matched controls was 4.56 (95% CI 1.00–20.79). For patients born 1970–1989 the HR of IS was 7.35 (95% CI 1.70–31.75). Conclusion In this nationwide, register-based cohort study, the absolute number of IS among younger CHD patients with AF was relatively low. However, the risk for developing IS was more than 5 times higher compared to non-CHD patients with AF; highlighting the need of stroke score models in younger population, particularly to CHD patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish state under an agreement between the Swedish government and city Councils

Stroke Risk in Patients with Gout: A Nationwide Retrospective Cohort Study in Taiwan.

Objectives: To estimate stroke risk in Taiwanese patients with gout. Methods: We enrolled patients from the Taiwan National Health Insurance Database, with gout diagnosed from 2000 to 2008, and followed them up until December 2018. This cohort was propensity score-matched according to birth year, sex, the date of diagnosis of gout, comorbidities, and co-medications with individuals without gout (controls) (n = 310,820 in each group). Stroke was defined as the primary diagnosis at discharge after the index date. To evaluate ischemic and hemorrhagic stroke risks, we calculated their incidence, hazard ratio (HR), and two-year moving average incidence rate. Results: The incidence (95% CI) and HR of ischemic stroke were lower in the gout group than in the control group in the first 3 years (incidence: 4.74 [4.60–4.88] vs. 5.17 [5.03–5.32] per 1000 person-years; HR: 0.92 [0.88–0.96]), then became significantly higher than in the control group after 3 years (incidence: 4.10 [4.04–4.16] vs. 3.81 [3.75–3.87] per 1000 person-years; HR: 1.08 [1.05–1.10]). Similarly, the incidence (95% CI) and HR of hemorrhagic stroke was lower in the gout group than in the control group in the first 3 years (incidence: 1.51 [1.43–1.59] vs. 1.70 [1.62–1.79] per 1000 person-years; HR: 0.88 [0.82–0.92]), then became significantly higher than in controls after 3 years (incidence: 1.43 [1.39–1.46] vs. 1.26 [1.22–1.29] per 1000 person-years; HR: 1.14 [1.10–1.18]). Conclusions: In Taiwan, patients with gout had higher risks of ischemic and hemorrhagic stroke after 3 years.

Long-Term Efficacy and Anticoagulation Strategy of Left Atrial Appendage Occlusion During Total Thoracoscopic Ablation of Atrial Fibrillation to Prevent Ischemic Stroke.

ObjectivesAtrial fibrillation (AF) is associated with an increased ischemic stroke, and the left atrial appendage (LAA) represents the main source of thrombus formation. We evaluated the long-term efficacy of surgical thoracoscopic LAA occlusion during total thoracoscopic ablation of AF to prevent the stroke and anticoagulation strategy after surgery.MethodsPatients who underwent total thoracoscopic ablation for AF, from February 2012 to May 2020, were included; Patients who did not receive LAA occlusion were excluded. We evaluated the development of thromboembolism in these patients.ResultsThe total number of 460 patients [mean age, 57.1 ± 9.2 years; 400 (87.0%) males] were included in the study. The mean follow-up duration was 44.8 months. The mean CHA2DS2-VASc score was 1.9 ± 1.6. Median OAC duration was 109.5 days after the surgery, and the final number of patients who discontinued OAC were 411 (89.3%) in total. Anticoagulation discontinuation rate according to CHA2DS2-VASc score are as follows; (i) 0 = 99.0%; (ii) 1 = 98.2%; and (iii) ≥2 = 81.3%. The annualized incidence rate of ischemic stroke was 0.78%/year, showing a 73% risk reduction compared with the CHA2DS2-VASc predicted rate without anticoagulation. The hazard ratio for ischemic stroke according to previous stroke history was 1.5 [95% confidential interval (CI) 0.3–7.3, p = 0.62], and that of remnant LAA was 5.1 (1.2–20.9, p = 0.02).ConclusionsThoracoscopic LAA occlusion during total thoracoscopic ablation of AF was effective to prevent ischemic stroke. Most patients could discontinue OAC therapy after the procedure. Patients who had a residual trabeculated LAA, or peri-occluder pouch in follow-up CT need to maintain OAC therapy even after LAA occlusion.

Abstract 13230: Bone Morphogenetic Protein 10 - A Novel Biomarker of Ischemic Stroke in Patients With Atrial Fibrillation

Background: Biomarkers specifically related to the atrial tissue might increase the understanding of the pathophysiology and improve risk prediction in atrial fibrillation (AF). Bone morphogenetic protein 10 (BMP10) is a novel biomarker expressed in atrial myocardium. We evaluated the association between BMP10 and the risk of stroke, bleeding, and death in patients with AF not treated with oral anticoagulation. Methods: BMP10 was measured in 2,974 plasma samples collected at randomisation in patients with AF randomized to aspirin in two cohorts, the ACTIVE-A (n=951) and AVERROES (n=2023) trials, median follow-up of 3.8 and 1.2 years, respectively. BMP10 was analysed with a prototype Elecsys electrochemiluminescence immunoassay. Associations between BMP10 and outcomes were evaluated by Cox-regression analyses adjusted for clinical characteristics, kidney function, and NT-proBNP. Results: Median age was 71 years, 58.1% were men. The median concentration of BMP10 was 2.46 (25 th -75 th percentiles, 2.09 - 2.94) ng/L. The variables most strongly associated with higher BMP10 levels were: heart rhythm (AF vs sinus), older age, female sex, lower BMI, and kidney dysfunction. BMP10 was the baseline variable most strongly associated with ischemic stroke during follow-up (Figure). After adjustments, the hazard ratio for ischemic stroke (BMP10 3rd vs 1st quartile) was 1.57 [95%CI 1.08-2.28], p=0.025), and the discriminatory value (c-index) was 0.643 (vs 0.634 of CHA 2 DS 2 -VASc score) and improved the full model from 0.737 to 0.746. BMP10 was not associated with bleeding or death. The results were consistent across both cohorts and irrespective of cardiac rhythm at blood sampling. Conclusions: In patients with AF, circulating plasma levels of BMP10 are independently associated with the risk of ischemic stroke but not with bleeding or death. BMP10 has an incremental discriminatory value for the risk of ischemic stroke, and may be a novel specific biomarker in patients with AF.

Association of Parkinson's disease with ischemic stroke in Korea: A nationwide longitudinal cohort study in Korea.

ObjectiveThe aim of this nationwide age- and sex- matched longitudinal follow up study is to determine the risk of Parkinson’s disease (PD) associated with ischemic stroke in Korea.MethodsPatient data were collected from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). PD was identified using the International Classification of Diseases (ICD) 10-CM code G 20. In total, 6,475 patients were enrolled in the PD group from the NHISS. After subtracting 1,039 patients who underwent hospitalization less than once or those who visited an outpatient clinic less than two times, 5,259 patients who were diagnosed after January 1, 2004 ultimately participated in this study. After case-control match was done through 1:5 age- and sex- stratified matching, 26,295 individuals were chosen as control. Kaplan-Meier method and Cox proportional hazard regression analysis were performed to evaluate the risk of ischemic stroke in PD.ResultsThe hazard ratio of ischemic stroke in the PD group was 3.848 (95% confidence interval (confidence interval [CI]): 3.14-4.70) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in PD group was 3.885 (95% CI: 3.17-4.75) after adjusting for comorbidities. According to subgroup analysis, in male and female and non-diabetes and diabetes and non-hypertension and hypertension and dyslipidemia and non-dyslipidemia subgroups, ischemic stroke incidence rates were significantly higher in the PD group than those in the control group.ConclusionsThis nationwide longitudinal study suggests an increased risk of ischemic stroke in PD patients.

Hypertensive Retinopathy and the Risk of Stroke Among Hypertensive Adults in China.

PurposeThis study aimed to investigate the association between hypertensive retinopathy and the risk of first stroke, examine possible effect modifiers in hypertensive patients, and test the appropriateness of the Keith-Wagener-Barker (KWB) classification for predicting stroke risk.MethodsIn total, 9793 hypertensive participants (3727 males and 6066 females) without stroke history from the China Stroke Primary Prevention Trial were included in this study. The primary outcome was first stroke.ResultsOver a median follow-up of 4.4 years, 592 participants experienced their first stroke (509 ischemic, 77 hemorrhagic, and six unclassifiable strokes). In total, 5590 participants were diagnosed with grade 1 retinopathy (57.08%), 1466 with grade 2 retinopathy (14.97%), 231 with grade 3 retinopathy (2.36%), and three with grade 4 retinopathy (0.03%). Grades 1 and 2 were merged and classified as mild retinopathy, and grades 3 and 4 were merged and classified as severe retinopathy. There was a significant positive association between hypertensive retinopathy and the risk of first stroke and first ischemic stroke, and no effect modifiers were found. The hazard ratios (HRs) for first stroke were as follows: mild versus no retinopathy, 1.26 (95% confidence interval [CI], 1.01–1.58, P = 0.040), and severe versus no retinopathy, 2.40 (95% CI, 1.49–3.84, P < 0.001). The HRs for ischemic stroke were as follows: severe versus no retinopathy, 2.35 (95% CI, 1.41–3.90, P = 0.001), and nonsignificantly increased HRs for mild versus no retinopathy, 1.26 (95% CI, 0.99–1.60, P = 0.057).ConclusionsThere was a significant positive association between hypertensive retinopathy and the risk of first stroke in patients with hypertension, indicating that hypertensive retinopathy may be a predictor of the risk of stroke. A simplified two-grade classification system based on the KWB classification is recommended for predicting stroke risk.

June 2021 Stroke Highlights

June 2021 <i>Stroke</i> Highlights