Lower Risk Of Ischemic Stroke Research Articles

Association between physical activity changes and risk of incident ischemic stroke following cancer diagnosis: A nationwide retrospective cohort study.

Physical inactivity is prevalent after cancer treatment, which could increase ischemic stroke risk in cancer survivors. This study investigated the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. Using data from the Korean National Health Insurance Service database, 269,943 cancer survivors (mean [SD] age, 56.3 [12.1] years; 45.7% male) with no history of cardiovascular disease were evaluated based on changes in physical activity from pre- to post-diagnosis. Using the Fine-Gray model, subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. After cancer diagnosis, 62.0% remained inactive, 10.1% remained active, 16.6% became active, and 11.4% became inactive. During a mean (SD) follow-up of 4.1 (2.0) years, being active both pre- and post-diagnosis was associated with a 15% decreased risk of ischemic stroke (sHR, 0.85; 95% CI, 0.75-0.96), compared with those who remained inactive. Cancer survivors who became active and inactive post-diagnosis showed a 16% and 11% lower ischemic stroke risk (sHR, 0.84; 95% CI, 0.75-0.93; sHR, 0.89; 95% CI, 0.79-0.99), respectively, than those who remained inactive. Analysis by the primary cancer site did not substantially differ from the main findings. Physical activity is associated with reduced ischemic stroke risk among cancer survivors. The potential benefits of physical activity are not limited to individuals who were physically active before cancer diagnosis, thus preventive strategies against ischemic stroke should emphasize physical activity throughout the cancer journey.

Risk of Ischemic Stroke in Relation to Helicobacter pylori Infection and Eradication Status: A Large-Scale Prospective Observational Cohort Study.

: A few studies have suggested the association between Helicobacter pylori (HP) infection and ischemic stroke. However, the impact of HP eradication on stroke risk has not been well evaluated. This study aimed to assess the influence of HP eradication on the incidence of ischemic stroke, considering the potential effect of sex. : This prospective observational cohort study was conducted at Seoul National University Bundang Hospital, from May 2003 to February 2023, and involved gastroscopy-based HP testing. Propensity score (PS) matching was employed to ensure balanced groups by matching patients in the HP eradicated group (n=2,803) in a 3:1 ratio with patients in the HP non-eradicated group (n=960). Cox proportional hazard regression analysis was used to evaluate the risk of ischemic stroke. : Among 6,664 patients, multivariate analysis after PS matching indicated that HP eradication did not significantly alter the risk of ischemic stroke (hazard ratio, 0.531; 95% confidence interval, 0.221 to 1.270; p=0.157). Sex-specific subgroup analyses, both univariate and multivariate, did not yield statistically significant differences. However, Kaplan-Meier analysis revealed a potential trend: the females in the HP eradicated group exhibited a lower incidence of ischemic stroke than those in the HP non-eradicated group, although this did not reach statistical significance (p=0.057). : This finding suggests that HP eradication might not impact the risk of ischemic stroke. However, there was a trend showing that females potentially had a lower risk of ischemic stroke following HP eradication, though further investigation is required to establish definitive evidence.

Outcomes of non-vitamin K oral anticoagulants for secondary prevention in ischemic stroke with atrial fibrillation

Previous studies have rarely investigated the role of non-vitamin K oral anticoagulants (NOAC) and warfarin in the secondary prevention of ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). In this study, we compared the effectiveness and safety of NOAC and warfarin for secondary prevention in Korean ischemic stroke patients with NVAF. Based on the Korean National Health Insurance Service Database, this study included 21,064 oral anticoagulants-naïve acute ischemic stroke patients with NVAF between July 2015 and June 2019. The main study outcomes included ischemic stroke, systemic embolism, major bleeding, and death. During the observational periods, NOAC users had a significantly decreased risk of ischemic stroke + systemic embolism (adjusted hazard ratio [aHR] 0.86; 95% confidence interval [CI] 0.78–0.95), ischemic stroke (aHR 0.89; 95% CI 0.81–0.99), major bleeding (aHR 0.78; 95% CI 0.68–0.89), and all-cause death (aHR 0.87; 95% CI 0.81–0.93). Standard-dose NOAC users had a lower risk of ischemic stroke, systemic embolism, and major bleeding events than warfarin users. In contrast, low-dose NOAC users did not differ in risk from warfarin users for all outcomes. In conclusion, NOACs were associated with a lower risk of secondary thromboembolic events and bleeding complications in Korean ischemic stroke patients with NVAF than warfarin.

Genetically predicted high serum sex hormone-binding globulin levels are associated with lower ischemic stroke risk: A sex-stratified Mendelian randomization study

ObjectiveCross-sectional and cohort studies have found insufficient evidence of a causal relationship between sex hormone-binding globulin and ischemic stroke, only associations. Here, we performed a sex-stratified, bidirectional, two-sample Mendelian randomization analysis to evaluate whether a causal relationship exists between sex hormone-binding globulin and ischemic stroke. MethodsSingle-nucleotide polymorphisms associated with sex hormone-binding globulin and ischemic stroke were screened from genome-wide association studies summary data as instrumental variables to enable a bidirectional, two-sample Mendelian randomization study design. Inverse-variance weighted analysis was used as the main method to evaluate potential causality, and additional methods, including the weighted median and MR-Egger tests, were used to validate the Mendelian randomization results. Cochran's Q statistic, MR-Egger intercept test, and Mendelian Randomization-Pleiotropy Residual Sum and Outlier global test were used as sensitivity analysis techniques to assure the reliability of the results. Multivariable analysis was used to show the robustness of the results with key theorized confounders. ResultsInverse-variance weighted analysis showed that genetically predicted higher serum sex hormone-binding globulin levels were associated with significantly decreased risk of ischemic stroke in males (odds radio = 0.934, 95 % confidence interval = 0.885-0.985, P = 0.012) and females (odds radio = 0.924, 95 % confidence interval = 0.868-0.983, P = 0.013). In an analysis of ischemic stroke subtypes, genetically predicted higher serum sex hormone-binding globulin levels were also associated with significantly decreased risk of small-vessel occlusion in both males (odds radio = 0.849, 95 % confidence interval = 0.759-0.949, P = 0.004) and females (odds radio = 0.829, 95 % confidence interval = 0.724-0.949, P = 0.006). The association remained in sensitivity analyses and multivariable analyses. The reverse analysis suggested an association between genetically predicted risk of cardioembolism and increased serum sex hormone-binding globulin in females (Beta = 0.029 nmol/L, Standard Error = 0.010, P = 0.003). ConclusionOur findings provide new insight into the etiology of ischemic stroke and suggest that modulating serum sex hormone-binding globulin may be a therapeutic strategy to protect against ischemic stroke.

Abstract 6291: Changes in physical activity and ischemic stroke risk after cancer diagnosis: A nationwide cohort study

Abstract Background: Physical inactivity is prevalent after cancer treatment, which may pose a greater risk of ischemic stroke in cancer survivors. Objective: To investigate the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. Methods: Cancer survivors without prior history of cardiovascular disease were identified. Pre- and Post-adherence to physical activity was determined within two years from cancer diagnosis. The primary outcome was incident ischemic stroke. Using the Fine-Gray model, sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. Results: Among 269,943 cancer survivors (mean [SD] age 56.3 [12.1] years, 45.7% male), 10.1% remained active, 11.4% became inactive, and 16.6% became active post-diagnosis. During 1,109,566.68 person-years[YMP1] , remaining active both pre- and post-diagnosis was associated with 15% decreased risk of ischemic stroke (sHR 0.85, 95% CI 0.75-0.96), compared to those who remained inactive. Cancer survivors who became active, and inactive post-diagnosis showed a 16%, and 11% lower risk of ischemic stroke (sHR 0.84, 95% CI 0.75-0.93; sHR 0.89, 95% CI 0.79-0.99) than those who remained inactive. Conclusions: Our findings suggest that staying physically active is associated with a reduced risk of ischemic stroke among cancer survivors. Notably, these advantages are not limited to individuals who were physically active before their diagnosis, and it is not too late to start post-diagnosis. Preventive strategies against ischemic stroke in cancer survivors should emphasize the incorporation of regular physical activity at any stage of their cancer journey. Citation Format: Dong Wook Shin, Wonyoung Jung, In Young Cho, Jinhyung Jung, Mihee Cho, Hye Yeon Koo, Be-Long Cho, Jin Ho Park, Hyuk Tae Kwon, Kyungdo Han, Yong-Moon Mark Park. Changes in physical activity and ischemic stroke risk after cancer diagnosis: A nationwide cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6291.

Combination of early rhythm control and healthy lifestyle on the risk of stroke in elderly patients with new-onset atrial fibrillation: a nationwide population-based cohort study.

The impact of early rhythm control (ERC) combined with healthy lifestyle (HLS) on the risk of ischemic stroke in elderly patients with atrial fibrillation (AF) remains unaddressed. To evaluate the impact of combined ERC and HLS on the risk of stroke in elderly patients with new-onset AF. Using the Korean National Health Insurance Service database, we included patients aged ≥75 years with new-onset AF from January 2009 to December 2016 (n = 41,315). Patients who received rhythm control therapy within 2 years of AF diagnosis were defined as the ERC group. Non-smoking, non-to-mild alcohol consumption (<105 g/week), and regular exercise were defined as HLS. Subjects were categorized into four groups: group 1 (without ERC and HLS, n = 25,093), 2 (HLS alone, n = 8,351), 3 (ERC alone, n = 5,565), and 4 (both ERC and HLS, n = 2,306). We assessed the incidence of ischemic stroke as the primary outcome, along with admissions for heart failure, all-cause death, and the composite of ischemic stroke, admission for heart failure, and all-cause death. Median follow-up duration of the study cohort was 3.4 years. After adjusting for multiple variables, groups 2 and 3 were associated with a lower stroke risk (adjusted hazard ratio [aHR]: 95% confidence interval [CI]: 0.867, 0.794-0.948 and 0.713, 0.637-0.798, respectively) than that of group 1. Compared to Group 1, group 4 showed the lowest stroke risk (aHR: 0.694, 95% CI: 0.586-0.822) among all groups, followed by group 3 (0.713, 0.637-0.798) and group 2 (0.857, 0.794-0.948), respectively. Group 4 was associated with the lowest risk of all-cause death (aHR: 0.680, 95% CI: 0.613-0.754) and the composite outcome (aHR: 0.708, 95% CI: 0.649-0.772). ERC and HLS were associated with a lower risk of ischemic stroke in elderly patients with new-onset AF. Concurrently implementing ERC and maintaining HLS was associated with the lowest risk of death and the composite outcome, with a modest synergistic effect on stroke prevention.

Polymorphism in Genes Encoding Adaptor Proteins ST13 and STIP1 and the Risk of Ischemic Stroke: a Pilot Study.

Adaptor proteins stress induced phosphoprotein 1 (STIP1) and ST13 Hsp70 interacting protein (ST13) may play a crucial role in the pathophysiology of ischemic stroke through controlling protein folding, neuronal survival, and regulation of HSP70/HSP90. The present pilot study investigated whether tagSNPs in genes encoding ST13 (rs138335, rs138344, rs7290793, and rs138344) and STIP1 (rs4980524) are associated with ischemic stroke. DNA samples from 721 ischemic stroke patients and 471 healthy controls were genotyped using the MassArray-4. Our research revealed a relationship between rs138344 ST13 and the risk of ischemic stroke, which was seen only in females (risk allele G; OR=1.34, 95%CI=1.07-1.69; p=0.01). The haplotype rs138335G-rs138344C-rs7290793C ST13 was linked with lower risk of ischemic stroke in females: OR=0.42; 95%CI=0.26-0.68; p=0.0005. Thus, ST13 represents a novel genetic marker for ischemic stroke.

Omega-3 Fatty Acids and Markers of Thrombosis in Patients with Atrial Fibrillation.

Omega-3 fatty acids (n-3 FAs) are associated with a lower risk of ischemic stroke in patients with atrial fibrillation (AF). Antithrombotic mechanisms may in part explain this observation. Therefore, we examined the association of n-3 FAs with D-dimer and beta-thromboglobulin (BTG), markers for activated coagulation and platelets, respectively. The n-3 FAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA) were determined via gas chromatography in the whole blood of 2373 patients with AF from the Swiss Atrial Fibrillation cohort study (ClinicalTrials.gov Identifier: NCT02105844). In a cross-sectional analysis, we examined the association of total n-3 FAs (EPA + DHA + DPA + ALA) and the association of individual fatty acids with D-dimer in patients with detectable D-dimer values (n = 1096) as well as with BTG (n = 2371) using multiple linear regression models adjusted for confounders. Median D-dimer and BTG levels were 0.340 ug/mL and 448 ng/mL, respectively. Higher total n-3 FAs correlated with lower D-dimer levels (coefficient 0.94, 95% confidence interval (Cl) 0.90-0.98, p = 0.004) and lower BTG levels (coefficient 0.97, Cl 0.95-0.99, p = 0.003). Likewise, the individual n-3 FAs EPA, DHA, DPA and ALA showed an inverse association with D-dimer. Higher levels of DHA, DPA and ALA correlated with lower BTG levels, whereas EPA showed a positive association with BTG. In patients with AF, higher levels of n-3 FAs were associated with lower levels of D-dimer and BTG, markers for activated coagulation and platelets, respectively. These findings suggest that n-3 FAs may exert antithrombotic properties in patients with AF.

Moderate alcohol consumption on the risk of stroke in the Million Veteran Program

BackgroundThere is inconsistent evidence on the association of moderate alcohol consumption and stroke risk in the general population and is not well studied among U.S. Veterans. Furthermore, it is unclear whether primarily drinking beer, wine, or liquor is associated with a difference in stroke risk.MethodsThe study included 185,323 Million Veteran Program participants who self-reported alcohol consumption on the Lifestyle Survey. Moderate consumption was defined as 1–2 drinks/day and beverage preference of beer, wine or liquor was defined if ≥ 50% of total drinks consumed were from a single type of beverage. Strokes were defined using ICD-9 and ICD-10 codes from the participants’ electronic health record.ResultsThe mean (sd) age of the sample was 64 (13) years and 11% were women. We observed 4,339 (94% ischemic; 6% hemorrhagic) strokes over a median follow-up of 5.2 years. In Cox models adjusted for age, sex, race, education, income, body mass index, smoking, exercise, diet, cholesterol, prevalent diabetes, prevalent hypertension, lipid-lowering medication, antihypertensive medication, and diabetes medication, moderate alcohol consumption (1–2 drinks/day) was associated with a 22% lower risk of total stroke compared with never drinking [Hazards ratio (HR) 95% confidence interval (CI): 0.78 (0.67, 0.92)]. When stratifying by stroke type, we observed a similar protective association with moderate consumption and ischemic stroke [HR (95% CI): 0.76 (0.65, 0.90)], but a non-statistically significant higher risk of hemorrhagic stroke [HR (95% CI): 1.29 (0.64, 2.61)]. We did not observe a difference in ischemic or hemorrhagic stroke risk among those who preferred beer, liquor or wine vs. no beverage preference. When stratifying by prior number of hospital visits (≤ 15, 16–33, 34–64, ≥ 65) as a proxy for health status, we observed attenuation of the protective association with greater number of visits [HR (95% CI): 0.87 (0.63, 1.19) for ≥ 65 visits vs. 0.80 (0.59, 1.08) for ≤ 15 visits].ConclusionsWe observed a lower risk of ischemic stroke, but not hemorrhagic stroke with moderate alcohol consumption and did not observe substantial differences in risk by beverage preference among a sample of U.S. Veterans. Healthy user bias of moderate alcohol consumption may be driving some of the observed protective association.

Once-weekly glucagon-like peptide-1 receptor agonists vs dipeptidyl peptidase-4 inhibitors: cardiovascular effects in people with diabetes and cardiovascular disease

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1 RAs), which have proven cardiovascular benefits, are recommended in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). However, there is limited real-world evidence comparing the effects of once-weekly (OW) GLP-1 RAs and dipeptidyl peptidase-4 inhibitors (DPP-4is). This observational cohort study (1/1/2017–9/30/2021) used data from the Optum Clinformatics® Data Mart to compare time to incident clinical cardiovascular outcomes, health care resource utilization (HCRU), and medical costs in new adult users of OW GLP-1 RAs and DPP-4is with T2D and ASCVD.MethodsTime to occurrence of ischemic stroke, myocardial infarction (MI), or their composite and ASCVD-related and all-cause HCRU and medical costs were investigated. Baseline characteristics were balanced using inverse probability of treatment weighting. Survival analyses were conducted to compare risks during exposure.ResultsOW GLP-1 RA users (weighted N = 25,287) had 26%, 22%, and 24% lower risk of ischemic stroke, MI, and their composite, respectively, compared with DPP-4i users (weighted N = 39,684; all P < 0.01). Compared with DPP-4i users, OW GLP-1 RA users had 25% and 26% lower ASCVD-related and all-cause hospitalization costs, 19% and 23% lower ASCVD-related and all-cause medical costs, 23% and 27% fewer ASCVD-related and all-cause hospitalizations, 13% and 8% fewer ASCVD-related and all-cause outpatient visits, and 8% fewer all-cause ER visits (all P < 0.01).ConclusionsIn adults with T2D and ASCVD, OW GLP-1 RAs are associated with reduced stroke and MI risks and ASCVD-related and all-cause HCRU and costs vs DPP-4is.

Early rhythm control on diabetes-related complications and mortality in patients with type 2 diabetes mellitus and atrial fibrillation

AimsWe evaluated the impact of early rhythm control (ERC) on diabetes-related complications and mortality in subjects with type 2 diabetes mellitus (T2DM) and atrial fibrillation (AF). MethodsThis observational cohort study based on the Korean National Health Insurance Service claims database from 2009 to 2016, divided newly diagnosed AF patients with T2DM into ERC or usual care groups based on receiving rhythm control treatment within 1 year of AF diagnosis. The primary outcome was ischemic stroke, and the secondary outcomes were macro/microvascular complications, and all-cause death. ResultsAmong 47,509 subjects (mean age 66.7 ± 10.5 years; 61.8 % men; mean CHA2DS2-VASc score 4.6 ± 1.8; mean follow-up 4.3 ± 2.3 years; mean DM duration 5.6 ± 4.7 years), 23.1 % received ERC, and 76.9 % did not (usual care group). ERC was associated with lower risks of ischemic stroke, macrovascular and microvascular complications, and all-cause death compared to usual care (adjusted hazard ratios [95 % confidence interval]: 0.77 [0.70–0.85], 0.79 [0.73–0.86], 0.86 [0.82–0.90], and 0.92 [0.87–0.98], p < 0.001, <0.001, <0.001, and 0.012, respectively). ConclusionsEarly rhythm control was associated with reduced risks of diabetes-related complications and mortality in subjects with T2DM and AF. Rhythm control within 1 year of AF diagnosis with proper anticoagulation should be considered to prevent adverse outcomes.

Risk of incident atrial fibrillation and subsequent use of oral anticoagulants in patients with dementia

Abstract Background Dementia and atrial fibrillation (AF) have many shared risk factors, and the presence of AF is associated with a higher risk of incident dementia. Although patients with dementia have higher risk of adverse cardiovascular events, there are limited data on the risks of incident AF, and the associated AF-related clinical outcomes. Patients with dementia are under-represented in randomised trials, and even if AF is present, oral anticoagulants (OAC) are not prescribed frequently. We aimed to report the incidence of newly-diagnosed AF in dementia patients, and the impact on stroke and bleeding outcomes with vitamin K antagonist (VKA, eg warfarin) and non-VKA OAC (NOACs). Methods Nationwide cohort study of 544,074 patients with dementia, compared to 554,074 age- and sex-matched patients without dementia. Results Rates of newly-diagnosed AF were higher in patients with dementia compared to those without history of dementia (1.89 per 100 person-years vs 1.78 per 100 person-years, respectively); adjusted risk of incident AF was greater in all types of dementia, pre-senile/senile dementia and vascular dementia (Figure 1). When compared to non-OAC users, warfarin use was associated with higher risk of ischaemic stroke (aHR, 1.290; 95% CI, 1.156 - 1.440), intracranial hemorrhage (ICH) risk (aHR, 1.678; 95% CI, 1.346 - 2.09) and major bleeding (aHR, 1.192; 95% CI, 1.073 - 1.323). NOAC use was associated with lower risk of ischaemic stroke (aHR, 0.42; 95% CI, 0.352 - 0.501) and major bleeding (aHR; 0.504, 95% CI, 0.433 - 0.587), when compared to non-OAC use (Figure 2). Conclusions In this large nationwide cohort of dementia patients, the incidence rate of newly-diagnosed or incident AF was higher in patients with dementia compared to patients without dementia. Compared to non-OAC users, NOAC use was associated with a lower risk of ischaemic stroke and major bleeding. Patients with dementia require a holistic approach to their care and management, including the use of NOACs to reduce their risks of clinical events.

Atrial fibrillation burden and timing of anticoagulation therapy in patients with screen-detected and clinically-diagnosed AF

Abstract Purpose We evaluated the impact of atrial fibrillation (AF) burden and timing of oral anticoagulation (OAC) therapy initiation on stroke risk in patients with screen-detected and clinically-diagnosed AF. Methods Consecutive patients aged ≥65 years attending medical outpatient clinics with or without known AF were prospectively enrolled for AF-screening using handheld single-lead ECG (AliveCor) from 12/2014 to 12/2017 (NCT02409654). Repeated screening was performed in patients with &amp;gt;1 visit during this period. Patients who participated in repeat screening were included in final analysis. Patients with previously known AF who were in AF in the initial screening and those with repeat screen-positivity were considered probably persistent AF, otherwise paroxysmal AF (single screen-positivity) or no AF (never screen-positive). Time from AF detection to initiation of OAC (Dx-to-Rx) was divided into two exposure levels, Dx-to-Rx ≤ 1 and &amp;gt;1 month. Ischemic stroke risk was estimated using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk, adjusting for components of CHA2DS2VASC score and chronic renal disease, with no AF as reference and stratified according to AF burden and Dx-to-Rx. Results Of 11,972 patients enrolled, 3,853(32.2%) received repeated screening (mean age 76.7±7.3, female 47.5%), of which 3.7% (n=144) had screened-detected AF, 25.2% (n=972) previously known AF, 5.9% (n=226) clinically-diagnosed AF during follow-up, and 65.2% (n=2,511) no AF. Persistent AF was identified in 16.7% (n=644/3,853). Of patients with all AF categories, 55.1% (n=739/1,342) initiated OAC within 1 month after AF diagnosis. During a median follow-up period of 7.2(IQR: 6.1-7.5) years, compared to no AF, patients with paroxysmal AF and Dx-to-Rx ≤ 1m (aSHR=1.40, 95%CI:0.80-2.47) had similar low risk of ischemic stroke, while aSHR was highest for persistent AF and Dx-to-Rx &amp;gt;1m (aSHR=2.42, 95%CI:1.38-4.26), followed by persistent AF with Dx-to-Rx≤ 1m (aSHR=2.19,95%:1.47-3.28), and paroxysmal AF with Dx-to-Rx &amp;gt;1m (aSHR=2.00,95%CI:1.32-3.02) (Figure). Subgroup analysis revealed the effect of early initiation of OAC (P for interaction=0.936) and higher AF burden (P for interaction=0. 863) were consistent across screen-detected and clinically-diagnosed AF. Conclusion Among patients with screen-detected AF or clinically-diagnosed AF, lower AF burden and immediate initiation of OAC therapy were associated with reduction in risk of ischemic stroke. Early detection of AF by screening facilitating early OAC prophylaxis might improve clinical outcomes.Cumulative risk of ischemic stroke

Comparison of early rhythm control strategies in patients with atrial fibrillation: a nationwide population-based cohort study

Abstract Background Early rhythm control within 1-year after atrial fibrillation (AF) diagnosis is associated with a lower risk of major adverse cardiovascular event (MACE). Recently, AF catheter ablation (AFCA) using cryoballoon ablation as initial therapy has been demonstrated to be superior to drug therapy for the prevention of AF recurrence in patients with paroxysmal AF. However, there is still lack of evidence whether AFCA for the method of early rhythm control is superior to medical rhythm control therapy for the reduction of MACE risk. Purpose To evaluate the association between rhythm control treatment and the risk of MACE for early rhythm control in AF patients Methods Using a Korean nationwide claims database, patients with AF who received rhythm control therapy including antiarrhythmic agents (AAD), direct current cardioversion (DCC), and AF catheter ablation (AFCA, radiofrequency ablation or cryoballoon ablation) within 1-year after AF onset between 2011 and 2020 were included. According to rhythm control treatment, patients were categorized two groups as follow: (1) medical rhythm control group who prescribed AAD or underwent DCC, and (2) AFCA group who underwent radiofrequency or cryoballoon ablation. The primary outcome was MACE, the composite of ischemic stroke, admission for heart failure (HF), and myocardial infarction (MI). For the safety outcome, the composite of cardiac tamponade, syncope, sick sinus syndrome, atrioventricular block, pacemaker implantation, and sudden cardiac arrest was evaluated. Multivariable Cox regression analysis were performed. Results A total of 229,056 pateints were included (mean age 67.3±13.6 and 59.4% of men). Mean duration from new AF diagnosis to rhythm control treatment was 29.1±69.2 days. Among total, 221,952 patients received medical rhythm control and 7104 patients received AFCA. Compared to medical rhythm control group, AFCA group was associated with lower risks of ischemic stroke, admission for HF, and MI (adjusted hazard ratio [95% confidence interval]: 0.342 [0.287-0.408], p&amp;lt;0.001 for ischemic stroke, 0.356 [0.282-0.451], p&amp;lt;0.001 for admission for HF, and 0.640 [0.452-0.906], p=0.011 for MI) (Figure A). AFCA for early rhythm control showed a significantly lower risk of MACE than medical early rhythm control (0.328 [0.283-0.380], p&amp;lt;0.001, Figure A). Compared to medical rhythm control, AFCA showed a similar risk for safety outcome (1.197 [0.920-1.556], p=0.180). Among AFCA group, cryoballoon ablation showed comparable risks of ischemic stroke (0.465 [0.113-1.922], p=0.290), admission for HF (0.262 [0.035-1.936], p=0.189), MI (0.823 [0.100-6.767], p=0.856), and MACE (0.449 [0.164-1.228], p=0.118) with radiofrequency ablation (Figure B). Conclusion Regarding on the method of early rhythm control for AF, catheter ablation of AF might reduce the risk of MACE without a significant increase of safety outcome to medical rhythm control. Further results from randomized clinical trials are needed.

The inflammatory proteome and risk of atrial fibrillation: genetic insights into causal relevance

Abstract Background Cardiac and systemic inflammation have been associated with a higher risk of atrial fibrillation (AF) in both animal models and human studies. Causality, however, has been questioned due to inconsistent efficacy of anti-inflammatory treatments in preventing incident or recurrent AF, and potentially confounding associations with AF risk factors such as ischaemic heart disease. Inflammatory processes are highly complex and involve a large number of proteins, but the individual relevance and causal role of these for AF remains unclear. Purpose To explore the nature of the relationship between the inflammatory proteome and risk of AF. Methods Associations between 26 inflammatory proteins and AF were assessed in a two-sample Mendelian randomization (MR) framework, with primary MR causal estimates with AF estimated among 339,214 White British UK Biobank (UKB) participants (AF cases=30,630). MR analyses for each inflammatory protein included independent variants previously associated with the relevant protein at genome-wide significance (p&amp;lt;5x10-8) across the genome (trans-protein quantitative trait loci [pQTLs]), or restricted to at least 50kb from the closest upstream gene and 50 kb downstream from the target gene (cis-pQTLs). Sensitivity analyses to assess potential pleiotropy were conducted (MR-Egger, weighted median, and weighted mode). Associations passing multiple testing threshold (p&amp;lt;0.002) in UKB were further validated in meta-analyses with independent datasets including over 50,000 AF cases (FinnGen and AFGen). Research undertaken using UKB application 14568. Results This inflammatory protein-wide study identified three proteins that have support for causal associations with AF. Genetically-predicted levels of IL6R, CD40, and Chitinase-3-like protein 1 (YKL40) each showed a negative association with risk of AF, with up to a 5% lower AF risk per standard deviation higher genetically-predicted levels of these proteins (Figure 1). These findings were further confirmed in meta-analysis with data from AFGen and FinnGen. No evidence of pleiotropy was identified, and results were also confirmed in cis-pQTL analyses, which were fully consistent with the trans-pQTL analyses (Table 1). Analyses stratified by various baseline characteristics highlighted stronger causal estimates in those with higher levels of C-reactive protein (with interaction p-values &amp;lt;0.001). Conclusions Genetic approaches support the relevance of lifelong differences in the inflammatory proteome for AF, and causal relationships between specific inflammatory markers and risk of AF. Greater soluble IL6R and CD40 as measured in proteomic analyses are both associated with lower levels of inflammation. As previous work indicates that genetically upregulated CD40 and IL6R are similarly associated with a lower risk of ischemic stroke, the risk-benefit of directly targeting these pathways needs further consideration.Figure 1Table 1

Abstract 13089: Plasma Proteomics and Risk of Incident Ischemic Stroke: Meta-Analysis of the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS)

Background: Proteomic profiling can screen large numbers of proteins to discover novel biomarkers related to ischemic stroke. However, prior studies have used a targeted approach or assessed a limited number of proteins (&lt;1300). Using data from the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), we examined the prospective association between 4954 plasma protein targets and incident ischemic stroke. Methods: Participants free of prevalent stroke at the time of proteomic profiling were included. Proteomics data were obtained from the 1990-92 exam in ARIC and the 1992-93 exam in CHS. Plasma proteins were quantified using the aptamer-based SOMAScan platform. Ischemic stroke events were ascertained and adjudicated through 2019 in ARIC and June 30, 2015 in CHS. Cox proportional hazards models adjusting for demographics, ischemic stroke risk factors, and estimated glomerular filtration rate were used. ARIC and CHS results were combined using fixed-effects meta-analysis. A Bonferroni-corrected p&lt;1.01e-5 was considered significant. Results: Median follow-up time in ARIC and CHS were 25 and 12 years, respectively. Among 10,856 ARIC participants (mean age 57 years, 56% female, 23% Black), 890 had an incident ischemic stroke. Among 3,283 CHS participants (mean age 74 years, 62% female, 18% Black), 507 had an incident ischemic stroke. In the meta-analysis, 44 proteins were significantly associated with incident ischemic stroke, of which 32 have not been previously reported ( Figure ). Of the 32, amyloid-like protein and kit ligand were the most strongly associated with ischemic stroke; each SD increment in log 2 (amyloid-like protein) and log 2 (kit ligand) were associated with 20% and 19% lower risk of ischemic stroke. Conclusion: In a meta-analysis of two community-based cohorts, we identified 32 novel protein associations with incident ischemic stroke. Further research is needed to determine causal associations.

Risk of Incident Atrial Fibrillation and Subsequent Use of Oral Anticoagulants in Patients with Dementia.

Dementia and atrial fibrillation (AF) have many shared risk factors. Besides, patients with dementia are under-represented in randomized trials, and even if AF is present, oral anticoagulants (OACs) are not prescribed frequently. This study aimed to report the incidence of newly diagnosed AF in dementia patients, and the impacts of use of vitamin K antagonist (VKA; e.g., warfarin) and non-VKA OAC (NOACs) on stroke and bleeding outcomes. Our study utilized the Taiwan National Health Insurance Research Database. A total of 554,074 patients with dementia were compared with 554,074 age- and sex-matched patients without dementia regarding the risk of incident AF. Among patients with dementia who experienced incident AF, the risks of clinical events of patients treated with warfarin or NOACs were compared with those without OACs (reference group). The risk of incident AF was greater for patients with dementia compared with those without (adjusted hazard ratio [aHR]: 1.054; 95% confidence interval [CI]: 1.040-1.068 for all types of dementia, aHR: 1.035; 95% CI: 1.020-1.051 for presenile/senile dementia, and aHR: 1.125; 95% CI: 1.091-1.159 for vascular dementia). Among patients with dementia and experienced incident AF, warfarin use was associated with a higher risk of ischemic stroke (aHR: 1.290; 95% CI: 1.156-1.440), intracranial hemorrhage (ICH; aHR: 1.678; 95% CI: 1.346-2.090), and major bleeding (aHR: 1.192; 95% CI: 1.073-1.323) compared with non-OACs. NOAC use was associated with a lower risk of ischemic stroke (aHR: 0.421; 95% CI: 0.352-0.503) and composite risk of ischemic stroke or major bleeding (aHR: 0.544; 95% CI: 0.487-0.608) compared with non-OACs. These results were consistent among the patients after the propensity matching. In this large nationwide cohort, the risk of newly diagnosed AF was higher in patients with dementia (all dementia, presenile/senile dementia, and vascular dementia) compared with those without dementia. For patients with dementia who experienced incident AF, NOAC use was associated with a better clinical outcome compared with non-OAC. Patients with dementia require a holistic approach to their care and management, including the use of NOACs to reduce the risks of clinical events.

Dietary amino acids and risk of stroke subtypes: a prospective analysis of 356,000 participants in seven European countries

PurposePreviously reported associations of protein-rich foods with stroke subtypes have prompted interest in the assessment of individual amino acids. We examined the associations of dietary amino acids with risks of ischaemic and haemorrhagic stroke in the EPIC study.MethodsWe analysed data from 356,142 participants from seven European countries. Dietary intakes of 19 individual amino acids were assessed using validated country-specific dietary questionnaires, calibrated using additional 24-h dietary recalls. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic and haemorrhagic stroke in relation to the intake of each amino acid. The role of blood pressure as a potential mechanism was assessed in 267,642 (75%) participants.ResultsAfter a median follow-up of 12.9 years, 4295 participants had an ischaemic stroke and 1375 participants had a haemorrhagic stroke. After correction for multiple testing, a higher intake of proline (as a percent of total protein) was associated with a 12% lower risk of ischaemic stroke (HR per 1 SD higher intake 0.88; 95% CI 0.82, 0.94). The association persisted after mutual adjustment for all other amino acids, systolic and diastolic blood pressure. The inverse associations of isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, glutamic acid, serine and tyrosine with ischaemic stroke were each attenuated with adjustment for proline intake. For haemorrhagic stroke, no statistically significant associations were observed in the continuous analyses after correcting for multiple testing.ConclusionHigher proline intake may be associated with a lower risk of ischaemic stroke, independent of other dietary amino acids and blood pressure.

THU338 Risks Of Stroke, Its Subtypes And Atrial Fibrillation Associated With Glucagon-like Peptide 1 Receptor Agonists Versus Sodium-glucose Cotransporter 2 Inhibitors: A Real-world Population-based Study In Hong Kong

Abstract Disclosure: D. Lui: None. E. Tang: None. T. Wu: None. I. Au: None. C. Lee: None. Y. Woo: None. K.C. Tan: None. C. Wong: None. Objectives: There are limited data on head-to-head comparative risk of stroke between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). Such a comparison may provide further insights in the selection of appropriate anti-diabetic agents. We compared risk of stroke with its subtypes and incident atrial fibrillation (AF) between them in a population-based cohort. Methods: A population-based cohort of adult patients (aged 18 years or above) with type 2 diabetes between 2008 and 2020 were identified from the electronic health records of Hong Kong Hospital Authority. Patients who received SGLT2i or GLP-1RA were matched pairwise by propensity score. The index date of each patient was set at the date of SGLT2i or GLP-1RA initiation. Patients with end-stage kidney disease or co-initiation of SGLT2i and GLP-1RA at the index date were excluded. The primary outcome was all events of stroke, consisting of hemorrhagic and ischemic stroke. Secondary outcomes included hemorrhagic stroke, ischemic stroke, incident AF, and cardioembolic stroke. Each patient was observed from the index date until the occurrence of events, death, treatment cross-over, or end-of-study (31 December 2020), whichever was earlier. Risks of stroke and AF were evaluated by hazard ratios (HRs) from the Cox proportional hazard regression models. Results: A total of 5,840 patients (2,920 SGLT2i users; 2,920 GLP-1RA users) were included (mean age 55.5 years, 56.1% men, mean HbA1c 8.9% and duration of diabetes 13.7 years). Upon median follow-up of 17 months (IQR: 8-34), there were 111 events of stroke. SGLT2i users had comparable risk of all stroke as GLP-1RA users (HR=1.46, 95%CI 0.99-2.17, p=0.058). SGLT2i users had higher risk of ischemic stroke (HR=1.53, 95%CI 1.01-2.33, p=0.044) but similar risk of hemorrhagic stroke (HR=1.29, 95%CI: 0.53-3.14, p=0.582) compared to GLP-1RA users. Although SGLT2i was associated with lower risk of incident AF (HR=0.43, 95%CI 0.23-0.79, p=0.006), risk of cardioembolic stroke was similar (HR=1.40, 95%CI: 0.62-3.17, p=0.414). Subgroup analyses showed no significant interaction between subgroups by age, sex, glycemic control and history of AF. However, patients with history of stroke appeared to benefit more from GLP-1RA use (p for interaction=0.043) than those without history of stroke. Patients with shorter duration of diabetes (&amp;lt;10 years) also appeared to benefit more from GLP-1RA use than those with longer duration of diabetes (p for interaction=0.017). Conclusions: Our real-world study demonstrated that GLP-1RA use was associated with lower risk of ischemic stroke, despite the association between SGLT2i use and lower risk of incident AF. There was no significant difference in hemorrhagic stroke risk. GLP-1RA may be the preferred agent for patients with type 2 diabetes at risk of ischemic stroke. Presentation: Thursday, June 15, 2023

Higher Habitual Dietary Intakes of Flavanols and Anthocyanins Differentially Associate with Lower Incidence of Ischemic Stroke Subtypes—A Follow-Up Analysis

BackgroundWe previously reported that habitual consumption of dietary flavanol oligomers + polymers and anthocyanins is associated with a lower risk of ischemic stroke. However, no studies have investigated their relationship with ischemic stroke subtypes. ObjectivesIn this follow-up analysis, we aimed to examine the association of flavanol oligomers + polymers and anthocyanin intake with ischemic stroke subtypes, including the following: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) other determined etiology, and 5) undetermined etiology. MethodsParticipants (n = 55,094) from the Danish Diet, Cancer, and Health Study were followed up for <16 y for first-time ischemic stroke events, which were classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Intakes of flavanol oligomers + polymers and anthocyanins were calculated from food frequency questionnaires using the Phenol-Explorer database, and their relationships with ischemic stroke subtypes were investigated using restricted cubic splines within Cox proportional hazards models. After multivariable adjustment, higher habitual intakes (quintile 5 compared with quintile 1) of flavanol oligomers + polymers and anthocyanins were associated with a lower risk of specific ischemic stroke subtypes, including large-artery atherosclerosis [flavanol oligomers + polymers, hazard ratio {HR} (95% confidence interval {CI}): 0.64 (0.47, 0.87)], cardioembolism [anthocyanins, HR (95% CI): 0.45 (0.25, 0.82)], and small-vessel occlusion [flavanol oligomers + polymers, HR (95% CI): 0.65 (0.54, 0.80); anthocyanins, HR (95% CI): 0.79 (0.64, 0.97)], but not stroke of other determined or undetermined etiology. ConclusionsHigher habitual intakes of flavanols and anthocyanins are differentially associated with a lower risk of ischemic stroke from atherosclerosis and/or cardioembolism but not with other subtypes.