Incidence Of Stroke Research Articles

The effect of metformin use on the risk of atrial fibrillation in patients with type 2 diabetes: data from the UK biobank

Abstract Objective The present study aims to investigate the protective role of metformin against atrial fibrillation (AF) and stroke in type 2 diabetes (T2DM) patients treated with other antidiabetic medications. Methods We included 10,011 participants with T2DM from the UK biobank database, with a follow-up for new diagnoses of AF and stroke recorded until 2023. We employed logistic regression analysis and competing risk models to assess the association between metformin use and the incidence of AF or stroke. Results The cross-sectional analysis revealed that, compared with the use of other antidiabetics, metformin was associated with a lower prevalence of AF (odds ratio [OR] 0.71, 95% CI: 0.57–0.89) and stroke (OR 0.70, 95% CI: 0.56–0.86). In the competing risk model, compared to other antidiabetics, metformin may reduce the risk of AF (sub-hazard ratio [SHR] 0.86, 95% CI: 0.75–0.98) and stroke (SHR 0.62, 95% CI: 0.44–0.86) (Figure 1). Subgroup analysis indicated a significantly lower incidence of AF or stroke in patients under 65 years of age (SHRs were 0.80, 95% CI:0.67-0.96 for AF and 0.52, 95% CI: 0.34-0.81 for stroke) and in female patients (SHRs were 0.65, 95% CI:0.52-0.81 for AF and 0.53, 95% CI: 0.30-0.91 for stroke). Notably, metformin significantly reduced the incidence of AF in non-insulin users (SHR 0.80, 95% CI: 0.66-0.97) and the incidence of stroke in insulin users (SHR 0.55, 95% CI: 0.35-0.87) (Figure 2). Conclusion Our findings suggest that metformin use, in comparison to other antidiabetic medications, is associated with a reduced risk of AF and stroke, especially in non-insulin users for AF and insulin users for stroke.

Racial and ethnic disparities in the incidence of stroke and mortality in atrial fibrillation: a US nationwide study

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia globally and is associated with increased risks of cardiovascular mortality and ischemic stroke. Prior research has demonstrated racial/ethnic disparities in AF outcomes yet this work has been limited to small cohorts and did not adjust for anticoagulant therapy. Purpose We compared incidence of ischemic stroke and death by race/ethnicity for patients with AF in the Veterans Health Administration (VA), the largest integrated, low-cost, national healthcare system in the US. Methods In this retrospective cohort study we identified those with an outpatient diagnosis of AF and a confirmatory diagnosis ≦ 180 days of their index AF diagnosis enrolled in VA from January 1, 2014 to December 31, 2021, with follow-up for outcomes from the index AF diagnosis date until May 31, 2022. To create a cohort of incident AF cases, we excluded patients with an AF diagnosis or anticoagulant therapy in the 2 years prior to their index AF diagnosis. We also excluded patients with pre-existing valvular heart disease, prior stroke, receiving hospice care or who died within 180 days of index AF diagnosis. We categorized our independent variable as race (i.e., non-Hispanic American Indian / Alaska Native [AI/AN], Asian, Black, or White [reference group]), and ethnicity (i.e., Hispanic). Our primary outcomes were incidence of stroke or death at any point within the study follow-up period. To compare these outcomes by race/ethnicity we conducted a survival analysis, adjusting for anticoagulant use as a time-varying covariate along with sociodemographic factors (age, sex, region, area deprivation index), clinical factors (CHADS2VA2Sc stroke risk and HAS-BLED bleeding risk), and facility type. Results There were 187,080 patients in the final cohort including 0.5% AI/AN, 1% Asian, 9% Black, 4% Hispanic, 85% White; mean age was 73 years. Over a mean study follow-up period of 4.43 years, 65,375 (34.9%) patients died and 24,910 (13.3%) developed stroke. The adjusted hazard ratio [95% CI] for death was lower for Hispanic (0.84 [0.78, 0.91]) and Black (0.94 [0.91, 0.97]) patients than White patients. In contrast, the adjusted hazard ratio for stroke incidence was higher for Black (1.21 [1.16, 1.27]) and Hispanic (1.10 [1.03, 1.17]) patients than White patients. There was no difference observed between AI/AN or Asian and White patients in either outcome. Conclusions In a national cohort of patients with incident AF, we identified significantly higher rates of stroke in Black and Hispanic than White patients even controlling for myriad factors including anticoagulant use. Conversely, racial/ethnic disparities in mortality appear to be eliminated in VA, counter to prior data. Understanding the factors, beyond anticoagulation, driving disparities in stroke outcomes and identifying factors reducing mortality among minority groups is critical to improving overall AF care in the largest integrated US health system.Adjusted Hazard Ratios of Study Outcomes

Deprivation and stroke incidence, treatment and mortality in Germany

Abstract Background Previous research suggests that regional deprivation significantly influences the risk of stroke. However, little is known about regional differences in stroke incidence and mortality within Germany. Methods We utilized data from the Diagnosis Related Groups statistics (2016-2019) and the German Federal Register of Physicians (2019). We used negative binomial regression analysis to investigate the relationship between the German Index of Multiple Deprivation 2015, covering 401 districts and district-free cities in Germany, and stroke incidence, treatment, and mortality. Results The adjusted rate ratios of stroke incidence and mortality with the highest deprivation level compared with the least deprived area were 1.16 (95% CI [1.14, 1.17]) and 1.19 (95% CI [1.14, 1.23]), respectively. Furthermore, this study showed that the density of physicians was higher in district-free cities than in districts. Conclusions The findings document a relationship between regional deprivation and stroke incidence and mortality, and call for a more targeted approach to stroke prevention in deprived regions. Key messages • Regional deprivation in Germany linked to increased stroke incidence and mortality rates. • Policy action needed for effective prevention measures.

Paracetamol and adverse cardiovascular outcomes in patients with heart failure

Abstract Background Paracetamol is the most widely used pain killer worldwide, yet its potential influence on cardiovascular events among patients with heart failure (HF) remains unclear. Thus, this study aims to investigate both the short-term and long-term effects of paracetamol use on all-cause mortality and cardiovascular events in HF patients. Methods Using the previously validated territory-wide clinical information registry, paracetamol use was identified among all eligible patients with HF (N = 211,409) from 2000 to 2020. A case-crossover design was used to investigate the associations between short-term use of paracetamols and all-cause mortality and cardiovascular outcomes. Defined daily dose (DDD) was used to evaluate the dose-response relationship. Additionally, the marginal structural design was applied to model paracetamol use as a time-varying exposure and evaluate its long-term effects during the follow-up period. Results Of all eligible subjects, the mean age was 73.2±12.3 years, and 43.6% was male. Over a median follow-up of 10.5 years (interquartile range: 5.7-15.8), 113,258 (53.6%) patients were re-hospitalised for HF, HF-related death occurred in 11,892 (5.6%) patients, incident myocardial infarction (MI) in 28223 (13.3%) patients, incident stroke in 26458 (12.5%) patients, cardiovascular death (CVD) in 72,175 (34.1%) patients and all-cause death in 123,505 (58.4%) patients. Associating HF rehospitalisation to previous paracetamol exposure using the case-crossover design displayed an elevated risk (OR 3.62, 95% CI 3.53-3.71). Associations were similar for MI (OR 5.77, 95% CI 5.50-6.05), stroke (OR 2.37, 95% CI 2.25-2.49), HF-related death (OR 1.86, 95% CI 1.75-1.98), CVD (OR 3.64, 95% CI 3.55-3.73), and all-cause mortality (OR 3.32, 95% CI 3.26-3.39). Moreover, compared with paracetamol users taking the reference dose, users of low, medium and high doses of paracetamol had 16%, 17% and 52% higher risk of HF rehospitalisation. During the long-term follow-up, the average weighted hazard ratio (HR) for HF rehospitalisation in paracetamol users was 2.48 (95% CI 2.46–2.50) as compared with paracetamol non-users after accounting for all-cause mortality as a competing risk. Similarly, the average weighted HR for incident MI or stroke was 2.71 (2.62-2.81) and 3.45 (3.34-3.57), respectively. However, neutral results were shown for HF-related death, CVD and all-cause mortality. Conclusion The use of paracetamol among patients with HF is common. Paracetamol was associated with adverse cardiovascular outcomes both in short-term and long-term follow-up with a dose-response relationship, while its impact on long-term mortality remained neutral. Future randomized controlled trials or experimental studies are warranted to gain a comprehensive understanding of the underlying mechanisms driving such associations between paracetamol and adverse cardiovascular outcomes.

Subgroup analysis of diabetes in COVID-positive revascularized patients: implications for clinical management

Abstract Background The management of revascularized patients with COVID-19, particularly in the presence of diabetes mellitus (DM), presents significant challenges. Understanding the clinical outcomes in this subgroup is essential for optimizing patient care during the pandemic. Purpose This study aimed to investigate the clinical outcomes of revascularized COVID-positive patients with and without DM, focusing on revascularization methods, hospitalization rates, mechanical ventilation requirement, mortality, stroke incidence, and presentation of acute coronary syndrome (ACS) subtypes. Methods A retrospective analysis was conducted on the cohort of 620 COVID-positive revascularized patients. Among them, 267 patients had diabetes mellitus (DM), while 353 patients did not. Data on revascularization methods, hospitalization rates, mechanical ventilation requirement, mortality, stroke incidence, and ACS presentation were collected and compared between the two groups. Statistical analysis was performed to assess the significance of differences observed. Results Among the 620 COVID-positive revascularized patients, 267 (43.1%) had diabetes mellitus, while 353 (56.9%) did not. Demographic analysis revealed that 299 (84.7%) of the COVID-positive patients with diabetes mellitus were male, compared to 181 (67.8%) of those without diabetes mellitus. This difference in gender distribution between the two groups was statistically significant (p < 0.001). Additionally, smoking was more prevalent among COVID-positive patients without diabetes mellitus (38.8%) compared to those with diabetes mellitus (22.5%), with a significant difference observed (p < 0.001) (Table 1). Among the revascularized patients, a higher proportion of patients with diabetes mellitus underwent coronary artery bypass grafting (CABG) compared to those without DM (32.6% vs. 24.1%, p = 0.019). Patients with diabetes exhibited significantly higher hospitalization rates (27.0% vs. 15.6%, p = 0.001) and a trend towards increased mechanical ventilation requirement (11.1% vs. 3.6%, p = 0.121). However, mortality rates, stroke incidence, and ACS presentation did not significantly differ between the two groups (Table2). Conclusion This study underscores the heightened vulnerability of revascularized COVID-positive patients with DM, as evidenced by higher hospitalization rates and a trend towards increased mechanical ventilation requirement. These findings emphasize the importance of tailored management strategies for this high-risk subgroup to optimize patient outcomes during the ongoing COVID-19 pandemic.Table 1Table 2

Is the incidence of cerebral embolic events underestimated in Takotsubo cardiomyopathy?

Abstract Introduction Although initially considered a benign cause of transient left ventricular dysfunction, Takotsubo cardiomyopathy (TCM or stress cardiomyopathy) has become an increasingly recognized cause of cerebral embolic events. Prior case series have suggested a 0.9% to 3% risk of ischemic stroke following the diagnosis of TCM. With the growing number of cases of stress cardiomyopathy reported since the COVID pandemic, we want to evaluate if the risk of stroke in the literature has been underestimated. Purpose In our study, we want to evaluate the risk of ischemic stroke one year following the diagnosis of Takotsubo cardiomyopathy in our university health centre. We also want to evaluate the time interval between the incidence of stroke and the initial diagnosis of TCM. Methods In this retrospective single-centre observational study, we collected data from 267 consecutive patients hospitalized for a diagnosis of Takotsubo cardiomyopathy (confirmed by echocardiography and cardiac catheterization) between May 2008 and December 2017 at our medical centre in Sherbrooke. All patients were followed for a minimum of one year. We excluded 14 patients with a prior history of stroke or a diagnosis of atrial fibrillation in the year following the diagnosis of TCM. We used a descriptive statistical analysis to evaluate the rate and time to event up to 1 year after the diagnosis. Results 253 patients were included in the study. The cohort was composed of 220 females (88% of the population), and the mean age was 69 years (SD: 11.8 years). Among this population, we identified 15 patients presenting with a stroke within a year after the diagnosis of stress cardiomyopathy, with a crude incidence of 5.9%. The median time interval between the incidence of stroke and the initial diagnosis of TCM was 17 days (2 to 298 days; an inter-quartile range of 3 to 105 days). The proportion of patients that reached the primary endpoint in the first 30 days was 67%. Conclusion According to our study, the risk of stroke in the year following the diagnosis of TCM is significantly higher than what is currently described in the literature. The fact that 10 of the 15 events occurred in the first 30 days may suggest a therappy design to lower the risk during that critical period could be explored. However, further studies are needed to address this issue.

Impact of protruding and ulcerated aortic atheroma on periprocedural ischemic stroke in patients undergoing transcatheter aortic valve replacement: a comprehensive analysis

Abstract Backgrounds Aortic atherosclerosis has the potential to impact both the strategy and outcomes of transcatheter aortic valve replacement (TAVR). Past research has established a correlation between the thickness and volume of aortic atheroma with periprocedural ischemic stroke and long-term mortality. However, there is limited investigation into the relationship between the morphology of aortic atheroma and outcomes following TAVR. Purpose The study aimed to assess the influence of protruding and ulcerated aortic atheroma on the occurrence of periprocedural ischemic stroke following TAVR. Methods A total of 979 patients who underwent TAVR between February 2012 and May 2019, and had retrospectively available data from contrast-enhanced computed tomography, were included in this analysis. The presence of protruding or ulcerated atheroma was evaluated across four aortic segments: ascending aorta, aortic arch, descending aorta, and abdominal aorta. Protruding aortic atheroma was defined as atheroma with a thickness exceeding 3 mm and protruding components. Ulcerated aortic atheroma was defined as atheroma presenting with ulcer-like disruption of the intima. The primary endpoint assessed was periprocedural ischemic stroke occurring within 48 hours following TAVR. Results The frequencies of protruding and ulcerated aortic atheroma were as follows: 0.2% in the ascending aorta, 6.5% in the aortic arch, 11.1% in the descending aorta, 15.7% in the abdominal aorta, and 24.2% in the entire aorta (Figure 1). Among the 979 patients analyzed, 25 (2.6%) experienced periprocedural ischemic stroke. Patients with protruding or ulcerated aortic atheroma exhibited a significantly higher incidence of periprocedural ischemic stroke compared to those without (5.5% vs. 1.6%, p=0.0010). Multivariate logistic analysis revealed that protruding or ulcerated aortic atheroma, particularly in the aortic arch, independently increased the risk of periprocedural ischemic stroke. (Table 1). Among the subset of patients (309, 34%) undergoing transfemoral TAVR (TF-TAVR) with a self-expandable valve, those with protruding or ulcerated aortic atheroma had a notably higher incidence of periprocedural ischemic stroke compared to those without (9.6% vs. 1.6%, p=0.0083). Conversely, among patients (587, 66%) undergoing TF-TAVR with a balloon-expandable valve, there was no statistically significant difference in the incidence of periprocedural ischemic stroke between those with and without protruding or ulcerated aortic atheroma (4.2% vs. 1.8%, p=0.102). Conclusions Protruding and ulcerated aortic atheroma, particularly in the aortic arch, were linked to a higher risk of periprocedural ischemic stroke post-TAVR. Consequently, careful selection of TAVR strategy, including valve type and procedural approach, is essential for patients with such aortic lesions.Figure 1Table 1

Modifying effect of obesity status on the association between low-density lipoprotein cholesterol with incident hemorrhagic stroke: evidence from a community-based longitudinal cohort study in China

Abstract Background Previous results on the association between lipids and hemorrhagic stroke were controversial. Modifying effect of obesity on the association between low-density lipoprotein cholesterol (LDL-C) and hemorrhagic stroke risk in the Chinese community-based population remains unclear. Objectives We aimed to investigate the association between LDL-C and hemorrhagic stroke risk in the Chinese community-based population. In addition, we aimed to explore the potential modifying effect of obesity status, particularly abdominal obesity, on this relationship. Methods A total of 7899 eligible subjects, without history of stroke and myocardial infarction, and any use of lipid-lowering medication at baseline, were enrolled in this study. Levels of LDL-C, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were assessed at baseline. The primary endpoint was the hemorrhagic stroke. Abdominal obesity was defined as waist circumference > 90 cm in men and > 85 cm in women. Results Of all participants, the mean age was 56.13 ± 8.87 years, 2848 (36.1%) were male. During a mean 9.71-year follow-up, 66 hemorrhagic strokes occurred. After multivariable adjustment (Figure 1), compared to participants with LDL-C levels 2.6 – 3.4 mmol/L, those with LDL-C levels < 1.8 mmol/L had 3.32 times the risk (hazard ratio [HR]: 3.32; 95% confidence interval [CI]: 1.24, 8.84) of incident hemorrhagic stroke. Compared with participants with TC levels 3.1 – 5.2 mmol/L, HR (95% CI) was 7.82 (2.36, 25.90) for hemorrhagic stroke in those with TC < 3.1 mmol/L. We observed no significant associations between TG or HDL-C levels and hemorrhagic stroke risk. Interaction effects were found between obesity and LDL-C for incident hemorrhagic stroke. Accordingly, significant associations between low LDL-C level (< 1.8 mmol/L) and the risk of incident hemorrhagic stroke were found only among abdominal obesity participants (HR: 3.76; 95% CI: 1.01, 13.97), or those with body mass index (BMI) > = 24 kg/m2 (HR: 3.74; 95% CI: 1.24, 11.34) (Figure 2). Conclusions LDL-C levels < 1.8mmol/L and TC levels < 3.1mmol/L were associated with increased risk of hemorrhagic stroke. Modifying effect of obesity status on the association between low LDL-C level and hemorrhagic stroke was observed in our study.

Lipid lowering therapy in patients aged 90 years or older with acute myocardial infarction:a multicenter cohort study

Abstract Background Lipid-lowing therapy significantly reduce adverse cardiovascular events in patients with acute myocardial infarction (AMI). However, evidence regarding the efficacy of lipid-lowing therapy in extremely elderly patients with AMI is limited. Purpose This study aims to evaluate major adverse cardiovascular events (MACCE) at 1 year in relation to taking lipid-lowing therapy (statins) among patients aged 90 years or older. Methods The data for this study were derived from a retrospective cohort comprising patients admitted to secondary or tertiary hospitals from 2010 to 2023. Patients were grouped by lipid-lowing therapy: statins group (n=549) and not taking statins group (n=811). The primary endpoint was MACCE, a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, at 1 year. Secondary endpoints included cardiac death (CD), stroke, and recurrence of myocardial infarction at 1 year. Inverse probability treatment weighting (IPTW) based on propensity scores was performed to balance baseline characteristics. A multivariate adjusted Cox proportional hazard model evaluated the association between lipid-lowing therapy and clinical endpoints. Results Of the 1,360 patients, 77.2% were men, and the median age was 92 years. During 1 year follow up, 35.3% of patients experienced MACCE, and 28.7% died due to CD. After IPTW, the incidence of MACCE was lower in the statins group compared to the non-statins group (33.3% vs. 42.6%, p=0.036), as was 1- year mortality due to CD (26.2% vs.35.9%, p=0.021). However, there were no differences in the incidence of stroke (2.8% vs. 4.5%, p＞0.274) or recurrence of myocardial infarction (4.7% vs. 5.1%, p=0,855) at 1 year. Kaplan-Meier analysis showed a lower probability of 1-year MACCE and CD in the statins group (log-rank test, p<0.001). Multivariate Cox regression analysis demonstrated that statin therapy reduced the incidence of MACCE (aHR 0.67; 95%CI, 0.40–0.91; p=0.009) and 1-year CD (aHR 0.63; 95%CI, 0.45–0.87; p=0.005). Conclusions Lipid-lowering therapy with statins was associated with a significantly lower risk of 1-year MACEE and cardiac death in elderly patients aged over 90 years with AMI. These findings support the use of lipid-lowing therapy in elderly individuals.

Maintenance of sinus rhythm is associated with lower incidence of stroke in patients with drug-refractory atrial fibrillation

Abstract Introduction Recent studies have demonstrated that early rhythm control for first-line treatment of atrial fibrillation (AF) improved cardiovascular outcomes. However, there is limited data regarding the long-term outcome of patients who failed antiarrhythmic drugs and who refuse radiofrequency catheter ablation (RFCA). Methods Patients with AF who were refractory to antiarrhythmic drugs and had refused further rhythm control attempts via RFCA were retrospectively identified and propensity-score matched with who had been treated with RFCA. The primary outcome of interest was all-cause mortality or ischemic stroke. Results A total of 169 patients who refused rhythm control with RFCA and propensity-score matched 169 patients who had been treated with RFCA were included for analysis. During a mean follow-up of 4.3[2.3;6.9] years, maintenance of sinus rhythm was more achieved in RFCA group (7 [4.1%] in Refuse group vs. 133 [78.7%] in RFCA group, p<0.001). the incidence of ischemic stroke was significantly higher in patients who refused RFCA compared with patients who underwent RFCA (24 [14.2%] vs. 6 [3.5%], log-rank p<0.001), but all-cause mortality was not significantly different (log-rank p=0.8). Refusal of attempted rhythm control via RFCA was an independent risk factor for ischemic stroke on multivariate Cox analysis (hazard ratio 3.2; 95% confidence interval 1.2 to 8.53, p=0.02). The risk of major adverse cardiovascular events (MACE) were also significantly higher in Refuse group (31 [18.3%] vs. 12 [7.1%], HR 3.83, 95% CI 1.57-9.37, p=0.003). Conclusion In patients with antiarrhythmic drug-refractory AF, maintenance of sinus rhythm was significantly different dependent on rhythm control via RFCA, therefore the risk of stroke was significantly higher in patients who refused rhythm control via RFCA compared with that of those treated with RFCA.

Impact of blood pressure control on the risk of stroke and mortality in patients with atrial fibrillation across different ages: a nationwide population-based study

Abstract Background High blood pressure in patients with atrial fibrillation (AF) is strongly associated with adverse outcomes, including stroke and death. The impact of blood pressure (BP) control on stroke and mortality rates among different age groups in patients with AF has not been extensively studied. Purpose To examine the impact of blood pressure on stroke and death in AF patients by age group. Methods Based on data from the Korean National Health Insurance Service database, we enrolled 194,302 patients newly diagnosed with AF between January 2009 and December 2016, who underwent health check-ups within two years. We divided patients into four groups based on age: 40-49 years, 50-59 years, 60-69 years, and 70 years and above, to analyze the primary outcome based on the level of BP control within each group. BP control was categorized into five levels. Patients with systolic BP (SBP)<120 mmHg and diastolic BP (DBP)<80 mmHg (Level 1), 120≤SBP<130 mmHg and DBP<80 mmHg (level 2), 130≤SBP<140 mmHg and 80≤DBP<90 mmHg (Level 3), 140≤SBP<160 mmHg and 90≤DBP<100 mmHg (Level 4), and patients with SBP≥160 mmHg and DBP ≥100 mmHg (Level 5). We also divided patients into five groups based according to their SBP levels. We analyzed the occurrence of stroke and death based on the level of BP control within each age group. Results Among a total of 194,302 patients, 55,142 (28%) were included in Level 1, 24,925 (13 %) in Level 2, 88,020 (46%) in Level 3, 23,179 (12%) in Level 4, and 3,036 (1%) in Level 5, categorized by blood pressure. During a median follow-up of 5.2±2.4 years, 14,409 patients had an incident stroke (incidence rate, 14.2 per 1000 person-years), and 27,230 patients died (incidence rate, 25.8 per 1000 person-years). The lowest incidence of stroke was in the group with 120≤SBP<130 mmHg and DBP<80 mmHg (Level 2) across most age groups (Figure). Stroke risk significantly increased with BP levels above 160/100 mmHg, and BP≥140/90 mmHg was associated with stroke occurrence from the age of 50 onwards. Higher SBP (160 mmHg) was consistently associated with a higher incidence of stroke across all ages (HR 1.32, 95% confidence interval (CI) 1.22-1.43 compared to SBP<100 mmHg). Mortality incidence was also lowest in Level 2, and a trend of gradually increasing mortality was observed as BP levels rise above this level. (Figure). Especially when SBP exceeded 160 mmHg, the probability of death also significantly increased across all age groups below 70 years old. Conclusion Uncontrolled hypertension (especially SBP>160 mmHg) was associated with higher risks of stroke and mortality in patients with AF. This association is notably more significant in the middle-aged group, specifically those between 40 and 59 years old, compared to older age groups. Therefore, particularly in middle-aged groups, it is crucial to emphasize adequate blood pressure control in patients with AF.Figure_DeathFigure_Stroke

Clinical impact of transcatheter aortic valve implantation (TAVI) in frail patients: a single-center prospective study

Abstract Introduction Transcatheter aortic valve implantation (TAVI) stands as an effective treatment option for symptomatic severe aortic stenosis, applicable across all surgical risk spectrum. Registries show that up to 60% of these patients exhibit at least one marker of frailty. Frailty has been associated with higher 1-year mortality rates and heightened susceptibility to complications. Conservative treatment, however, has a poor prognosis, with mortality ranging from 30-60% within a year after diagnosis. Objective The primary objective was to assess the clinical impact of TAVI implantation in the frail population. A secondary objective was to assess the occurrence of in-hospital and short-term (30 days) complications. Methods Observational, prospective, single-center study that included all patients with TAVI implantation in our unit in 2023. Frailty was assessed by an interventional cardiologist according to the Rockwood Clinical Frailty Scale (CFS) or Frailty Scale, assigning a score from 1 to 9, with patients being classified as high CFS if they scored ≥5 points or low CFS if <5 points. Results Out of the 298 patients included, 45 (15%) had high CFS vs 253 (85%) with low CFS. Significant differences were found in age (83.3±5.3 years for high CFS vs 79.4±5.8 years for low CFS;p<0.01), gender (60% of females for high CFS vs 43.9% for low CFS;p=0.046) and baseline haemoglobin (12.2±1.5 g/dL for high CFS vs 12.9±1.8 g/dL for low CFS;p=0.008). Other baseline characteristics remained comparable. Patients with high CFS had greater baseline dyspnoea according to the YHA scale (NYHA III-IV 71.1% for high CFS vs 37.9% for low CFS;p<0.001) with greater diuretic use (71.1% for high CFS vs 51% for low CFS;p=0.013). Patients with high CFS had a greater need for a preferential/urgent procedure (p=0.044). There were no differences in the occurrence of complications: stroke (p=0.463), bleeding (p=0.667), vascular complications (p=0.234); except for a higher occurrence of complete AV block (22.3% for high CFS vs 8.7% for low CFS;p=0.024). In-hospital mortality rates showed no differences (0% for high CFS vs 1.6% for low CFS;p=0.396). At 1-month follow-up, there was a significant reduction in NYHA dyspnoea grade within the high CFS group (71.1% NYHA III-IV pre-TAVI vs 2.3% post-TAVI; p<0.001). There was no difference in the incidence of stroke (p=0.375), heart failure readmissions (p=0.734), and vascular complications (p=0.66). There was no difference in all-cause mortality (4.4% for high CFS vs 3.2% for low CFS;p=0.675). Conclusions Highly frail patients undergoing TAVI experience a significant enhancement in functional class compared to their less frail counterparts. While short-term complications parallel those observed in less frail individuals, there is a slightly elevated incidence of pacemaker requirements in this group.NYHA Frail pre and post TAVIComplications

Depression and its impact on stroke risk and mortality in post-percutaneous coronary intervention patients: a nationwide retrospective cohort study

Abstract Background/Introduction Cardiovascular disease (CVD) remains a leading cause of global mortality, with percutaneous coronary intervention (PCI) being a common therapeutic procedure for managing CVD. While depression is recognized as a risk factor for adverse cardiovascular outcomes post-PCI, its association with stroke risk in this patient group has been less explored. Purpose This study aims to evaluate the association between pre-existing depression and the incidence of stroke, alongside other cardiovascular outcomes and mortality, in patients undergoing PCI. Methods Utilizing the Korean National Health Insurance Service database, a population-based retrospective cohort study was conducted, encompassing individuals who underwent PCI between 2010 and 2017, with a follow-up until 2019. Depression was identified through ICD-10 codes prior to PCI. The primary outcome was acute stroke incidence, with all-cause mortality and revascularization as secondary outcomes. Adjustments were made for sociodemographic, lifestyle factors, and comorbidities. Results Among 164,198 individuals, those with pre-existing depression (17.4% of the cohort) exhibited a 27% increased risk of acute stroke (aHR 1.27, 95% CI 1.20-1.35) and a 25% higher risk of all-cause mortality (aHR 1.25, 95% CI 1.21-1.29) compared to those without. The association was stronger in individuals under 65 years and varied by sex, with males showing a higher risk of mortality. Conclusion(s) Pre-existing depression in patients undergoing PCI is associated with a significantly increased risk of stroke and all-cause mortality, particularly in younger patients. These findings highlight the importance of depression management as part of comprehensive care in post-PCI patients, suggesting potential benefits in reducing stroke risk and improving survival outcomes. Further research is warranted to explore the mechanisms and intervention strategies that could mitigate these risks.Study FlowchartRisk of stroke and all-cause death

Effect of catheter ablation in atrial fibrillation patients irrespective of their baseline heart failure: An updated meta-analysis

Abstract Introduction Patients with atrial fibrillation (AF) are associated with higher morbidity and mortality. Catheter ablation (CA) is supposed to improve outcomes in these patients. We aimed to update the evidence regarding CA in AF patients irrespective of their baseline heart failure. Methods We searched PubMed, Scopus, WOS, and Cochrane until February 2024 for relevant studies assessing the impact of CA compared to medical regimens in AF patients with and without heart failure. Outcomes of interest were all-cause mortality, cardiovascular mortality, hospitalization for HF, hospitalization for other cardiovascular causes, and stroke. Results 13 studies were included with a total of 18370 patients. In HF patients, irrespective to their ejection fraction, CA was associated with a significant reduction in all-cause mortality (RR 0.40, 95%CI [0.37 to 0.44], cardiovascular mortality (RR 0.36, 95%CI [0.32 to 0.42]), hospitalization from HF (RR 0.65, 95%CI [0.51 to 0.82]), hospitalization from other cardiovascular causes (RR 0.71, 95%CI [0.57 to 0.89]), and the incidence of stroke (RR 0.55, 95%CI [0.50 to 0.62]). Also, six studies with a total of 2015 patients compared CA to medical treatment in AF patients with HFrEF and HFpEF. CA showed a significant reduction in all-cause mortality in HFpEF patients compared to HFrEF (RR 0.46, 95%CI [0.25 to 0.85]) with no significant differences in terms of other studied outcomes. Moreover, six studies compared CA to medical treatment in HF vs no HF with a total of 2931 patients. Patients with AF and no HF had a significant reduction in all-cause mortality (RR .041, 95%CI [0.20 to 0.80]), with no significant differences in stroke or AF recurrence. Conclusion Current evidence supports the use of catheter ablation in atrial fibrillation patients, irrespective of their baseline heart failure, to achieve lower mortality and hospitalization rates.all-cause mortalitycardiovascular mortality

Proteomic and genomic evaluation of plasma protein biomarkers for atrial fibrillation

Abstract Background Atrial fibrillation (AF) is a common arrhythmia and an important cause of ischemic stroke. Several plasma proteins have been suggested as biomarkers for the risk of AF and subsequent stroke in previous studies, but validation in independent cohorts is needed. Large-scale integration of proteomics with genetic and clinical data holds potential for refinement of disease prediction and risk stratification. Purpose This study aimed to evaluate previously suggested plasma protein biomarkers of AF and ischemic stroke using plasma protein measurements in a large cohort. Methods Ten tentative protein biomarkers previously associated with AF or ischemic stroke in AF patients, were evaluated in a nested case-control study comprising 49,757 individuals from the UK biobank (UKB). Plasma proteins were measured by normalized protein expression on the Olink platform. Outcomes were incident AF and ischemic stroke. The proteins were evaluated in Cox regression models adjusted for sex, age, and clinical risk factors. To assess whether the proteins were independent predictors, they were evaluated in sensitivity analyses with additional adjustment for NT-proBNP levels. Polygenic risk scores were calculated for plasma protein concentrations using the PRS-CS-auto algorithm and tested for association with AF or ischemic stroke in an independent subset of the UKB cohort without plasma protein measurements (n=379,392). Results All ten plasma proteins were associated with incident AF in the primary model, and eight were associated with incident ischemic stroke (P-values < 0.0025 for all). Adjusted for NT-proBNP levels, the proteins interleukin-6, GDF15, angiopoietin 2, and Troponin-I remained independently associated with AF, and the proteins GDF15, Cystatin-C, interleukin-6, ADAMTS13, and FGF23 remained independently associated with ischemic stroke. Polygenic risk scores for NT-proBNP and angiopoietin 2 were associated with increased rates of AF. No polygenic scores were significantly associated with ischemic stroke. Conclusion Large-scale proteomic evaluation validated ten plasma proteins associated AF and found eight to be associated with ischemic stroke. Seven proteins were associated with AF or ischemic stroke independently of NT-proBNP levels. Additional genomic evaluation provided evidence of associations between incident AF and genetically predicted plasma levels of angiopoietin 2 and NT-proBNP. As proteomic analyses of the plasma proteome become cheaper and more readily available, these findings could contribute to future risk stratification and selection of individuals for AF screening programs.Proteins associated with AFProteins associated with ischemic stroke

LE8 score in relation to cardiovascular disease and mortality in individuals with diabetes

Abstract Background Evidence regarding the potential health effects of Life’s Essential 8 (LE8) score among individuals with type 2 diabetes (T2D) is limited. Purpose We aimed to examine the associations of LE8 score with risk of cardiovascular disease (CVD) and mortality, among individuals with T2D. Methods We prospectively followed 19,915 Chinese participants with T2D at baseline or diagnosed during follow-up (Kailuan Study: 2006-2020), who were free of CVD at diagnosis of diabetes. Diet, lifestyle, and health conditions were repeatedly assessed every 2 years. The LE8 score (range, 0-100), was calculated based on 8 components: diet quality, physical activity, smoking status, sleep health, BMI, blood lipids, blood glucose, and blood pressure. We used time-varying cox models to model the associations. Results During a median follow-up of 11.5 years in participants with T2D, there were 3,295 incident CVD cases and 3,123 deaths. Higher LE8 score was associated with lower risk of CVD incidence and total mortality among participants with diabetes. The multivariate-adjusted hazard ratios and 95%CIs for the highest quintile of LE8 score compared with the lowest quintile were 0.56 (0.53, 0.59) for CVD incidence, 0.57 (0.53, 0.62) for heart disease incidence, 0.53 (0.49, 0.57) for stroke incidence, and 0.73 (0.69, 0.78) for total mortality (all p trend<0.001). Furthermore, compared with participants with stable or decreased LE8 score after diabetes diagnosis, those with increased LE8 score had 17%-42% lower risk of CVD incidence, heart disease incidence, stroke incidence, and total mortality. These associations persisted in subgroup analysis stratified by age, sex, BMI, smoking status, alcohol intake, family history of diabetes and CVD, and follow-up time. Conclusions Higher LE8 score was associated with a substantially lower risk of CVD incidence and total mortality among adults with T2D. These findings further support the tremendous benefit of adhering to a high CVH, defined as the LE8 in reducing the subsequent burden of cardiovascular complications and improving overall health in individuals with T2D.Main TableMain Figure

Independent associations of educational attainment and its joint associations with LE8 score for risk of cardiovascular disease incidence and mortality among Chinese people

Abstract Background/Introduction Educational attainment is a social determinant of health. Quantifying its associations with risk of cardiovascular disease (CVD) incidence and mortality has public health importance. Recently, the American Heart Association introduced the Life’s Essential 8 (LE8) score to evaluate CVD risk. However, it remains unclear how educational attainment and the LE8 score interact in their joint associations with CVD and mortality. Purpose To examine the associations of educational level with the incidence of CVD, including coronary heart disease (CHD) and stroke, and total mortality. Also, we examined the joint associations of educational level and the LE8 score with CVD incidence and total mortality. Methods We prospectively followed 91,744 Chinese adults from the Kailuan Study (2006-2021), who were free of CVD at baseline. Information on educational level, diet, lifestyle, and health conditions was collected every 2 years. LE8 score was calculated based on eight components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. We used time-dependent Cox models to assess the associations of educational level with the outcomes as well as the joint associations of educational level and LE8 score, with adjustments for demographics, dietary and lifestyle factors, and medical history. Results During a mean follow-up of 13.1 years, there were 12,916 incident CVD cases and 13,090 deaths. Compared with the participants who only received illiteracy or elementary education, those who received high school education and above had a lower risk of CVD incidence (HR = 0.82, 95% CI = 0.76, 0.88), stroke incidence (0.72, (0.66, 0.79)), and total mortality (0.73, (0.68, 0.77)). Educational level was not associated with risk of CHD. Furthermore, significant additive interactions between educational attainment and LE8 score on the risk of CVD and mortality were observed (all p values for additive interactions <0.01). Compared with the participants who only received illiteracy or elementary education and had a low LE8 score, those who only received illiteracy or elementary education but had a high LE8 score still had a 27%-47% lower risk of CVD and total mortality, while those who received high school education and above and had a high LE8 score had a 51%-74% lower risk of CVD and total mortality. Conclusions Higher educational level was associated with a lower risk of CVD and mortality. These inverse associations were most apparent among participants with both a high educational level and a high LE8 score, while the participants with a low educational level but with a high LE8 score still had a significantly lower risk. These findings highlight the importance of improvement in educational attainment in preventing CVD events and deaths, and suggest that CVD events and deaths attributable to lower levels of education may be reduced by improving LE8 score.

The incidence of atrial fibrillation in patients with interatrial shunt: is it reduced after surgical or transcatheter closure of the shunt?

Abstract Background Atrial fibrillation (AF) is a prevalent diagnosis among individuals with interatrial shunts, and the prevalence increases with age (1). Since the 1990s, interventionists have introduced transcatheter techniques, to close interatrial shunts, while surgical procedures reserved in cases of technical complexity (2). Despite the potential reduction in AF incidence post interatrial shunt closure, discernible modifications in the cardiac conduction system may persist (3). Notwithstanding, reports indicate an incidence of new-onset AF in approximately 10-25% of patients after interatrial shunt closure, with a pronounced prevalence among elderly (4). This study aims to delineate the incidence of AF subsequent to interatrial shunt, surgical och transcatheter, closure within a national cohort in Sweden. Methods The study includes all patients diagnosed with an interatrial shunt, atrial septal defect and patent foramen ovale, classified using the International Classification of Diseases, 10th edition (ICD-10), as documented in the Swedish National Patient Register, along with data sourced from the Cause of Death Register. Patients with multiple diagnoses of other congenital heart diseases are excluded, and interventions performed between 1997 and 2017 are identified using the NOMESCO surgical classification. Comorbidities such as chronic ischemic heart disease, myocardial infarction, heart failure, hypertension, and diabetes are considered, with the primary endpoint being the incidence of AF post-intervention. Results A total of 3,426 patients with interatrial shunts underwent intervention between 1997 and 2017, with a mean follow-up duration of 6.2 years. Among these, 49% (n=1,725) underwent transcatheter closure, while 41 patients underwent both transcatheter and surgical procedures. The mean age was 36 years, with 9% presenting with heart failure at baseline. Before the intervention, 14% (n=483) had AF, increasing to 22% (n=755) post-intervention. Of those developing AF post-intervention, 16% (n=119) experienced the AF event within 60 days, evenly distributed between transcatheter and surgical procedures. Over 40% of patients with post-intervention AF had an average age of 62. The incidence of AF post-intervention was 1.6 per 100 patient-years (see Figure). Stroke incidence was 3.6 per 100 patient-years and the mortality rate was 7% (n=257) during follow up (see Table). Conclusions Patients with interatrial shunts exhibit a high incidence of AF, which further escalates following closure of the interatrial shunt, not only within the first few days post-intervention, particularly among the elderly population. This can relate to high incidence of ischemic stroke.Figure

Machine learning identification of risk factors for ischaemic stroke in patients with heart failure with reduced ejection fraction but without atrial fibrillation: A report from WARCEF trial

Abstract Background The prediction of ischaemic stroke in patients with heart failure with reduced ejection fraction (HFrEF) but without atrial fibrillation (AF) remains challenging and risk stratification based clinical factors alone has limited discrimination. Our aim was to evaluate the performance of machine learning (ML) to identify risk factors for ischaemic stroke in such HFrEF patients. Methods We performed a post-hoc analysis of the WARCEF trial, only including patients without prior history of AF, and censoring those who developed incident AF during follow-up. We evaluated the performance of 9 ML models to identify risk factors for incident stroke, using metrics including area under the curve (AUC), precision, specificity, and decision curve analysis. The importance of each feature in constructing the model was quantified using SHapley Additive exPlanations (SHAP) values. Results We included 2,213 patients with HFrEF but without AF (mean age 59±12 years; 79% male). Of these, 74 (3.3%) had an ischaemic stroke during mean follow-up of 3.5±1.8 years. Out of the 29 patient-demographics variables, 12 were selected for the ML training. All ML models demonstrated high AUC values, outperforming the CHA2DS2-VASc score (Figure 1). The logistic regression model exhibited a slight deviation from this trend. The XGBoost model achieved an AUC of 0.86 (95% confidence interval [CI]: 0.72-0.99), while the Random Forest model showed an AUC of 0.85 (95% CI: 0.74-0.96). Similarly, the Support Vector Machine and Light Gradient Boosting Machine models recorded AUCs of 0.85 (95% CI: 0.72-0.97) and 0.83 (95% CI: 0.70-0.96), respectively. Each of these models attained precision and specificity scores of 1.0, indicating high performance. These models consistently provided significant net clinical benefits. Key risk factors for stroke identified across these models were creatinine clearance and blood urea nitrogen. The use of warfarin appears to be protective. Conclusions Machine-learning models can identify risk factors for ischaemic stroke in patients with HFrEF but without AF. Worsening renal failure was predictive of an incident stroke, while warfarin use was protective against stroke (Figure 2).Figure 1Figure 2

Social determinants of health, blood pressure classification, and incident stroke in community-dwelling adults: a prospective cohort study

Abstract Objective To determine whether the association of blood pressure (BP) categories, defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline, with stroke differ among Chinese adults with low or high burden of unfavorable social determinants of health (SDOH). Design and Methods: Analyses were conducted in the prospective sub-cohort of the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project, started in 1, July 2017 and followed stroke events until 31, June 2023. Participants were divided into groups with low and high burden of unfavorable SDOH, which consisted of educational attainment, economic stability, health care access, social support, and neighborhood relationship. Within each group, participants were categorized as having normal BP (systolic BP [SBP] <120 mm Hg and diastolic BP [DBP] <80 mm Hg), elevated BP (SBP 120-129 mm Hg and DBP <80 mm Hg), stage 1 hypertension (SBP 130-139 mm Hg or DBP 80-89 mm Hg), and stage 2 hypertension (SBP ≥140 mm Hg or DBP ≥90mm Hg). The association between BP categories and stroke risk were examined within each SDOH group, separately, using multivariable-adjusted Cox proportional hazards models. Results Of the 96,686 adults included in this study (mean [SD] age, 53.8 [10.1] years; 59,080 [61.1%] women), 64,823 (67.0%) were categorized as having high burden of unfavorable SDOH. Over a median follow-up of 5.0 years, 4,673 (4.8%) incident stroke events occurred. In the group of low burden of SDOH, hazard ratios (95% CI) for stroke events for elevated BP, stage 1 hypertension, and stage 2 hypertension vs normal BP were 1.09 (0.86-1.37), 1.14 (0.94-1.37), and 1.59 (1.33-1.90), respectively. In the group of high burden of SDOH, hazard ratios for stroke events for elevated BP, stage 1 hypertension, and stage 2 hypertension vs normal BP were 1.20 (1.04-1.38), 1.45 (1.29-1.62), and 1.71 (1.53-1.91), respectively. Results were similar after excluding those taking antihypertensive medications. Conclusion Lower BP categories were closely associated with increased risk of stroke in the context of high burden of SDOH. Early counseling and surveillance of high BP should be emphasized within socioeconomically disadvantaged populations.