Risk Of Stroke Research Articles

Sex differences in outcomes of percutaneous left atrial appendage closure

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia in adults and is associated with an increased risk of embolic stroke. In a previous survey, 91% of nonrheumatic AF-related left atrial thrombi was originated in the left atrial appendage (LAA). Percutaneous left atrial appendage closure (LAAC) with the Watchman device has been shown to be noninferior to anticoagulation therapy in clinical trials for stroke prevention in nonrheumatic AF. It has been used in Japan since September 2019 only for patients who are at the high risk of bleeding events. The WATCHMAN family is the only left atrial appendage closure (LAAC) device in Japan. Since long time ago, sex differences have been attracting attention in the cardiology. Due to the cardiovascular protective effects of endogenous estrogens, premenopausal women are thought to be less likely to develop cardiovascular disease. Whereas, in area of AF, Female with AF have higher stroke risk and female with AF have severe after effect. However, there are few studies on sex differences in LAAC implantation outcomes. Purpose We aimed to identify the sex differences of outcomes of LAAC in Japanese patients. Methods A total of 118 consecutive patients who underwent LAAC at our hospital from January 2020 to August 2023 were prospectively analyzed. Various patient characteristics, comorbidities, and outcomes were identified and compared between male and female. Results Results are shown in Table. Female were older (79 vs. 73 years, p = 0.0009), thinner (Body mass index 22 vs. 24 kg/m2, p = 0.0326), and less likely to have had diabetes (19 vs. 40%, p = 0.0340). Pulmonary embolism was significantly more common in female after LAAC. If anticoagulants are discontinued after LAAC, women’s susceptibility to coagulation may become apparent. Conclusions LAAC was feasible and safe for Japanese patients of both genders. However, these results could have a relevant impact on the antithrombotic management of patients who are at the high risk of embolic considering sex difference. Especially, we should pay great attention when discontinuing anticoagulants after LAAC in female.

Extracranial systemic embolic events in patients with atrial fibrillation: an individual patient-level meta-analysis of 71 683 patients randomized to NOAC vs warfarin from the COMBINE-AF study

Abstract Background Atrial Fibrillation (AF) poses a significant risk for both ischemic stroke and systemic embolic events (SEE). While the effectiveness of NOAC in preventing ischemic stroke is well-established, there is a lack of detailed analyses specifically characterizing SEE, which constitutes 5- 10% of all embolic events. Purpose To study the clinical characteristics, procedural management, and outcomes by randomized treatment (NOAC vs warfarin) of patients with SEE. Methods Using the COMBINE AF dataset, we conducted an individual patient level meta-analysis of 4 global RCTs (RE-LY, ROCKET AF, ARISTOTLE, ENGAGE AF-TIMI 48) of warfarin vs. NOAC in AF to assess risks of SEE. Outcomes were analyzed as time-to-first-event using a Cox proportional hazards model. Two authors independently reviewed deaths within 30 days after SEE to identify fatal SEE. Moreover, we independently assessed post SEE procedures to determined relatedness to SEE. Results There were 188 total SEEs, 9 patients (5%) had SEE then developed ischemic stroke; 16 patients (9%) had ischemic stroke then developed SEE; 1 patient had SEE and ischemic stroke simultaneously. Among the 171 patients with SEEs as first event, the median (IQR) age was 75 (68-80) years, 49.7% were female, median (IQR) of BMI was 27.5 (23.5-30.7) kg/m2, mean (SD) of CHADS2-VASC score was 4.7 (1.5). As compared with ischemic stroke (n=1789), SEE patients were more likely to have, PAD (16.5% vs. 5.4%, p <0.001), prior MI (24% vs. 17%, p = 0.02), be Vitamin K Antagonist experienced (57% vs 46%; p=0.007), have worse renal function (median CrCl mL/min; 58 vs 62, p = 0.02) and less likely to have paroxysmal AF (14% vs. 20%, p = 0.05). Of the total of 188 SEEs, 33 (18%) were fatal, 62 (31%) patients underwent surgical or percutaneous intervention (Fig). Standard dose (SD) NOAC significantly reduced the risk of SEE by 29% (95% CI 1-49%, p=0.04) compared with warfarin, However, no significant difference in the risk of SEE was observed between low dose (LD) NOAC and warfarin (Fig). Conclusion Standard dose NOAC was superior to warfarin in preventing SEE in AF patients. This benefit trends to be more pronounced for fatal cases. While SEE were about 1/10th as frequent as ischemic stroke in patients with AF, they were associated with significant morbidity and mortality and often required surgical or percutaneous intervention to restore blood flow.

Comparative efficacy of colchicine and intensive LDL-C lowering in patients with ASCVD receiving statins: a network meta-analysis of randomised controlled trials

Abstract Background Adding intensive low-density lipoprotein cholesterol (LDL-C) lowering treatments or colchicine to statins resulted in additional cardiovascular benefits. However, the relative efficacy and priority of these agents are unclear. Purpose We aimed to compare the effects of these supplementary agents on cardiovascular outcomes in patients with atherosclerotic cardiovascular diseases (ASCVD) receiving statins. Methods We performed a systematic review and frequentist network meta-analysis on randomized controlled trials. The primary efficacy endpoint was the main adverse cardiovascular event (MACE), and the secondary efficacy endpoints were myocardial infarct, stroke, coronary revascularization, cardiovascular death and all-cause mortality. The safety endpoints were treatment discontinuation and non-cardiovascular death. Colchicine was used as reference treatment. Random-effects model was used in case of high heterogeneity, the fixed-effects model was preferred otherwise. We ranked the comparative effects of all drugs with surface under the cumulative ranking (SUCRA) probabilities. Results 17 trials totaling 85823 participants treated with colchicine, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, Niemann-Pick C1-like 1 protein (NPC1L1) inhibitor and ATP citrate lyase (ACL) inhibitor were included. Compared with colchicine, NPC1L1 inhibitor was associated with increased risk of MACE (risk ratio [RR]: 1.39, 1.21-1.59), stroke (RR: 1.81, 1.09-3.00) and coronary revascularization (RR: 1.36, 1.11-1.68), and PCSK9 inhibitor was associated with increased risk of MACE (RR: 1.27, 1.10-1.46). However, NPC1L1 inhibitor (RR: 0.68, 0.48-0.96) and PCSK9 inhibitor (RR: 0.64, 0.44-0.93) were associated with reduced risk of non-cardiovascular death in comparison to colchicine. PCSK9 inhibitors had a lower risk of MACE (RR: 0.91, 95% CI: 0.85-0.98) and coronary revascularization (RR: 0.89, 95% CI: 0.81-0.97) compared with NPC1L1 inhibitor. Although no regimen prolonged survival, colchicine had the lowest rank at non-cardiovascular death and the worse performance on all-cause mortality. Conclusions In patients with ASCVD receiving statins, inflammation-inhibiting with colchicine seems to be superior to intensive LDL-C lowering therapy with PCSK9 inhibitor or NPC1L1 inhibitor in cardiovascular prevention. However, using colchicine as an alternative to intensive lipid-lowering therapy may need to be weighed against the greater cardiovascular benefits and the potential harms of higher non-cardiovascular death. Given the worse performance of colchicine on survival based on current evidence, colchicine may be more appropriate for patients who have been treated with intensive LDL-C-lowering agents but still have recurrent cardiovascular events.Forest plots of included agentsRadar plot of treatments based on SUCRA

The relationship between retinal vascular parameters measured by artificial intelligence and the risk of new-onset cardiovascular disease in a Chinese community-based population

Abstract Background Studies on the association between retinal vascular diameter and tortuosity and the risk of new-onset cardiovascular disease (CVD) are controversial. The predictive value of retinal vascular parameters, measured through artificial intelligence (AI), for incident CVD risk in the community population, remains to be explored. Objectives Our study aims to investigate the association between retinal vascular parameters (diameter and tortuosity) measured through AI, and the risk of new-onset CVD in the Chinese community-based population. Methods We conducted a prospective cohort study on subjects from a Beijing community in China who were free of prevalent stroke or myocardial infarction and underwent retinal photography at baseline. By deep-learning algorithm, quantitative retinal vascular parameters were measured 0.5 to 1 disc diameter from the optic disc margin, including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar-to-venular ratio (AVR), curvature tortuosity arteriole (cTORTa), and curvature tortuosity venule (cTORTv). The primary endpoint was a new-onset major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, first non-fatal stroke, and first non-fatal acute myocardial infarction (AMI). The secondary endpoints included cardiovascular death, first stroke, and first AMI. Cox proportional-hazards regression analyses were performed. Results A total of 3,585 participants were included. The mean age was 56.49 ± 8.94 years, and 2,335 (65.1%) were female. Prevalence of prior hypertension and diabetes was 1594 (44.5%) and 676 (18.9%), respectively. During the follow-up (median, 7.53 years), there were 293 cases of new-onset MACE (8.2%), 44 cardiovascular deaths (1.2%), 226 strokes (6.3%), and 57 AMIs (1.6%). The Kaplan–Meier curves showed significant differences in cumulative hazards of new-onset MACE among tertiles of CRAE, CRVE, AVR, and cTORTa, but not for cTORTv (Figure 1). In Cox proportional-hazards models (Figure 2) adjusting for covariates, CRAE was negatively associated with the risk of new-onset MACE (per 10 μm increase, hazard ratio [HR]=0.95, 95% confidence interval [CI]: 0.92-0.99, P=0.009) and the risk of new-onset stroke (per 10 μm increase, HR=0.96, 95%CI: 0.92-1.00, P=0.04). Similarly, AVR was negatively associated with new-onset MACE risk (per 0.1 increase, HR=0.82, 95%CI: 0.72-0.94, P<0.001) and new-onset stroke risk (per 0.1 increase, HR=0.84, 95%CI: 0.73-0.98, P=0.022). No significant associations were observed between CAVE, cTORTa, and cTORTv with any of the primary or secondary endpoints. Conclusions CRAE and AVR, measured through AI, are associated with the risk of new-onset MACE in the Chinese population. These findings suggest the potential for AI-measured parameters in retinal vasculature to aid in stratifying CVD risk in the general population.

Temporal trends in initiation of oral anticoagulants and stroke-free survival among elderly and very elderly patients with new onset atrial fibrillation - a 20-year perspective.

Abstract Background Oral anticoagulants (OACs) significantly reduce the risk of ischemic stroke in patients with atrial fibrillation (AF). However, evidence regarding efficacy of OACs are lacking in the very elderly patients. Aim To examine temporal trends in initiation of OACs and five-year stroke-free survival in the very elderly patients with new onset AF over a time span of 20 years. Methods From the Danish nationwide registries, we identified patients ≥ 65 years of age with new onset AF from 1999 to 2018. The index date was defined as the day of AF diagnosis for outpatients and as the day of discharge for inpatients. Patients with a prescription of OAC, history of bleeding events, or history of stroke/transient ischemic attack prior to index were excluded. Patients were divided into two age groups based on their age at index: 1) 65-84 years (elderly); and 2) ≥ 85 years (very elderly). Patients were further divided into four calendar year groups from 1999-2018, based on the year of inclusion. We investigated the initiation of OACs and calculated the absolute five-year probability of stroke-free survival in both age groups. Results We included 167,122 patients with new-onset AF between January 1st, 1999, and December 31st, 2018. Among the patients, 23.1 % were aged 85 years or older, 48 % were male and 80.5 % had a CHA2DS2-VASc score equivalent to 2 or higher for men and 3 or higher for women. Initiation of OACs increased in both age groups after the guideline implementation of DOACs in 2010 (Figure 1). In the elderly age group, the proportion of patients receiving OACs increased from 50% in 2010 to almost 90% in 2018. In the very elderly age group, the proportion increased from 25% in 2010 to almost 90% in 2018. The probability of the five-year stroke-free survival improved by approximately 15% from 1999 to 2018 in the elderly age group, with no significant changes in the very elderly age group. Conclusion The proportion of elderly AF patients receiving OAC has increased markedly in the last 20 years. Even so, stroke-free survival remains the same among the very elderly patients.Five-year stroke-free survival

The long-term usage of statin prevents adverse events in patients with atrial fibrillation

Abstract Background The effectiveness of statins in preventing adverse cardiovascular events in individuals with atrial fibrillation (AF) has remained uncertain. This study aimed to assess whether statin use could lead to better outcomes among individuals with AF. Purpose Our study aimed to investigate the relationship between statin use and cardiovascular outcomes in patients with newly-diagnosed AF. Methods This study used the National Health Insurance Research Database (NHIRD) in Taiwan. We enrolled 397,787 patients with AF from January 1st, 2012, to December 31st, 2020. Patients with AF were divided into 2 groups (statin user and statin non-user), and the risks of composite outcomes (ischemic stroke, hemorrhagic stroke and transient ischemic attack [TIA]), all-cause death and major adverse cardiovascular events (MACEs, which encompassed cardiovascular death, non-fatal myocardial infarction and heart failure hospitalization) were analyzed. Propensity score matching with time-dependent analysis was examined. Results We analyzed 288,958 patients with newly diagnosed AF (mean age, 73 years; 44% women; mean CHA2DS2-VASc score, 3.5). Compared with patients without statin use, statin user had a lower risk of composite endpoint, which included ischemic stroke, hemorrhagic stroke and TIA. (adjusted hazard ratio, 0.92; 95% confidence interval, 0.88-0.95; p < 0.01) after adjusting for patients’ age, gender, CHA2DS2-VASc score, cardiovascular medications, and comorbidities. In regard to all-cause mortality, statin users exhibited a 62% risk reduction compared to statin non-users (hazard ratio, 0.38; 95% confidence interval, 0.37-0.39; p < 0.01). Statin use was also associated with reduced incidence of MACEs (hazard ratio, 0.70, 95% confidence interval, 0.68-0.71; p < 0.01). In the subgroups stratified by CHA2DS2 VASc score, statin therapy was particularly effective for patients with CHA2DS2-VASc scores 0-3 for composite endpoints but consistently reduced all-cause mortality and MACEs across all score categories. Conclusions Among patients with newly diagnosed AF, statin use was associated with a lower risk of ischemic stroke, hemorrhagic stroke, TIA, all-cause mortality and MACEs.

Independent association between radial secondary access and stroke in patients undergoing transcatheter aortic valve implantation

Abstract Background Radial access has become the primary approach for invasive coronary angiography due to its lower complication rate than femoral access. Transcatheter aortic valve implantation (TAVI) frequently requires a secondary access, which has traditionally been femoral access. However, radial access for TAVI is feasible and gaining popularity, but data on its safety and complication rates is still limited. Purpose To evaluate the occurrence of stroke rate in patients undergoing a TAVI procedure with femoral or radial secondary access. Methods A prospective single-center TAVI registry of 2327 patients who received a TAVI procedure between 2019 and 2022 was conducted. All procedures had the primary access over the femoral route. 337 (14.5%) patients had a secondary access over the radial route, whereas 1990 (85.5%) received a femoral secondary access. The primary endpoint was the occurrence of stroke within the hospital stay. Both groups were compared using the t-test or the Mann-Whitney U test according to the distribution of the data. In a second step, a multivariable model was created in which parameters were included that were associated with the endpoint in the previous analysis, as well as parameters that are known to be associated with stroke. Results: Patients were 81.1 ± 6.3 years old, with a Euroscore II of 5.3 ± 6. A total of 610 (26.2%) patients received a balloon-expandable valve. The primary endpoint (stroke within 30 days of the TAVI procedure) was met by 94 (4%) of all patients. Stroke occurred more often in the group with radial secondary access (6.6% (22) vs. 3.6%(72), p = 0.012). Other significant differences between the two groups included (radial vs. femoral access): burden of atrial fibrillation (36.8% vs. 44.6%, p = 0.007), arterial hypertension (87.4% vs. 92%, p = 0.007), Euroscore II (4.6 vs. 5.5, p = 0.006), and frailty (25.2% vs. 40%, p < 0.001). There were no significant differences between the two groups in terms of secondary diagnosis of diabetes or coronary artery disease, age, occurrence of NYHA class III/IV, gender, or cerebral artery disease. In the multivariate analysis including Age, Euroscore II, NYHA class, gender, secondary diagnosis of arterial Hypertension, diabetes or cerebral artery disease, arterial fibrillation, Frailty and radial secondary access, only radial secondary access was independently associated with in-hospital stroke (p = 0.01). Conclusion Radial secondary access was significantly associated with an increased risk of in-hospital stroke following transcatheter aortic valve implantation (TAVI) in our study population. Intense manipulation of the guidewire and catheter to reach the ascending aorta at the beginning of the procedure and to reach the descending aorta for the final angiogram of the primary access vessel may be causative and should be minimized.

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

Troponin T as a risk marker for recurrent cardiovascular events in the post-discharge setting one month after acute coronary syndrome: a TRACER substudy

Abstract Background Troponin T (TnT) is a protein found in cardiac myocytes that is released during myocardial injury, such as myocardial infarction (MI). TnT levels rapidly rise during an MI, remain elevated for several days, and are a key criterion for diagnosing MI. Additionally, circulating TnT levels may offer prognostic information later, particularly during the rehabilitation phase after an acute coronary syndrome (ACS). Purpose To examine the relationship between circulating TnT at one month after hospitalisation for ACS and subsequent cardiovascular (CV) events. Methods The TRACER trial randomly assigned 12,944 patients diagnosed with non-ST-segment elevation ACS (NSTE-ACS) to receive either vorapaxar or placebo. Plasma samples were obtained after one month, and high-sensitivity (hs)-TnT was measured among 5,313 patients using the Elecsys electrochemiluminescence immunoassays. In this sub-study, the primary composite endpoint was the one-year risk of CV mortality, MI, or ischaemic stroke. Associations with outcomes were evaluated using Cox regression models, both unadjusted and adjusted for clinical baseline characteristics. Results The median concentration of hs-TnT was 11 ng/L one month after hospitalisation for ACS. Higher levels of hs-TnT at one month were associated with older age, coronary artery bypass surgery during the index ACS, male sex, a history of heart failure, renal disease, and diabetes mellitus. The composite outcome of CV mortality, MI, or ischaemic stroke occurred in 381 patients (incidence rate 5.4 per 100 person-years). Hs-TnT at one month after ACS was independently associated with the risk of the composite CV endpoint (relative hazard ratio with 95% confidence interval comparing the third vs. the first sample quartile: 2.40 [1.80 – 3.20]) (see Figure 2). Similarly, hs-TnT, when added to a model including established risk factors, increased the concordance index of the multivariable model from 0.711 to 0.740 (p<0.001). The results were consistent across the different components of the composite endpoint. Conclusions The level of hs-TnT provides useful information on the risk of future CV events in patients when measured one month after an ACS. This information might be useful for optimising secondary preventive treatment following an ACS.Figure.Hs-TnT and composite CV outcome

Impact of atrial fibrillation on cardiac autonomic function in elderly patients

Abstract Introduction Cardiac autonomic dysfunction has been linked to an increased risk of mortality (1), stroke and silent brain lesions (2) and cognitive impairment (3) in patients with atrial fibrillation (AF). However, the impact of AF on cardiac autonomic function is poorly understood. Purpose We aimed to explore the impact of AF on cardiac autonomic function by comparing AF patients with a matched control cohort without AF. Methods We enrolled patients with and without AF from two ongoing, prospective, multicenter cohort studies (Swiss-AF Cohort and Swiss-AF Control) if they had a high-resolution 16-lead resting ECG recording in sinus rhythm for a duration of 5 minutes at baseline visit. Cardiac autonomic function was quantified by periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity. PRD was quantified by means of wavelet analysis, as validated previously (4). Cardiac autonomic dysfunction was defined present if PRD exceeded the established cut-off of 10.0 deg2 (5). We built multivariable adjusted linear and logistic regression models to explore the association of AF with PRD and cardiac autonomic dysfunction. Results We included 2077 patients, 1113 (54%) from the AF cohort and 964 (46%) from the matched non-AF cohort. Baseline characteristics were well balanced between the groups (mean age 71 vs. 73 years in patients with and without AF, mean CHA2DS2-VASc score 3.0 vs. 3.5, female sex 31.3% vs. 36.6%). The median PRD was 18.2 deg2 (IQR 9.9-25.4) in patients with AF and 15.8 deg2 (IQR 8.1 -23.0) in patients without AF (p<0.001, Figure). 832 (75%) of the AF patients suffered from cardiac autonomic dysfunction, vs. 656 (68%) of the non-AF patients (p<0.001). Multivariable adjusted linear regression analysis revealed an independent association of AF with continuous levels of PRD (beta-coefficient -1.57, 95% CI -2.64 - -0.488, p=0.004). Further, AF was independently associated with the presence of cardiac autonomic dysfunction (Odds Ratio 1.48, 95% CI 1.18-1.87, p<0.001, Table). Conclusion In this cross-sectional analysis of a patient population with and without AF, AF was independently associated with increased PRD values, reflecting sympathetic predominance, and with the presence of cardiac autonomic dysfunction. These findings implicate a relevant role of AF in the development of cardiac autonomic dysfunction in elderly patients.Figure

Exploring the association between hypertension and atherosclerotic cardiovascular disease in adults with familial hypercholesterolemia: insights from the HELLAS-FH registry

Abstract Aim While the link between hypertension and atherosclerotic cardiovascular disease (ASCVD) is well-established, its impact on patients with familial hypercholesterolemia (FH) remains less explored. This study aims to assess the association between hypertension and ASCVD in adult FH patients. Material-Methods: Participants from the HELLAS-FH registry were divided into two groups based on the presence or absence of hypertension. We compared demographic information, lipid profile and history of ASCVD between the two groups. Results The study included 2367 FH patients, of whom 602 (25.4%) had a diagnosis of hypertension. Hypertensive patients were generally older and exhibited higher rates of ASCVD risk factors such as increased body mass index (28.6 vs 26.3 kg/m2), waist circumference (98 cm in men and 97 cm in women compared with 95 cm and 88 cm in non-hypertensive counterparts), and more prevalent history of smoking (44.2% vs 35.8%) (p<0.01 for all comparisons). Patients with hypertension had higher triglyceride levels (148 vs 123 mg/dL; p<0.05), lower high-density lipoprotein cholesterol (HDL-C) levels (48 vs 53 mg/dL; p<0.05) while total cholesterol and non-HDL-C levels were not significantly different. When adjusted for age, sex, and major ASCVD risk factors, hypertension was significantly associated with prevalent coronary artery disease (CAD) (adjusted odds ratio [OR] 3.10; 95% CI 2.29-4.19; p<0.001), ischemic stroke (OR 1.89; 95% CI 1.02-3.49; p=0.04), and peripheral arterial disease (PAD) (OR 3.15; 95% CI 1.62-6.13; p<0.001). Conclusions Hypertension is frequent and is independently associated with an increased risk of CAD, stroke, and PAD in patients with FH.

Efficacy of lipid lowering therapy beyond statins to prevent cardiovascular events

Abstract Background Lipid lowering therapy is a key cornerstone in secondary prevention of patients with coronary artery disease. However, only a minority of patients with statin therapy reach LDL thresholds as suggested by the ESC. Ezetimibe, bempedoic acic, and proprotein convertase subtilisin/kexin type 9 (PCSK-9) (synthase-) inhibitors allow for the reduction in LDL-cholesterol in addition to statin therapy. Purpose We aimed to perform a meta-analysis of existing trials, evaluating how lipid lowering therapy beyond statins impacts cardiovascular outcome. In specific, we evaluated the potential influence of duration of follow-up on the association with mortality endpoints. Methods We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, evaluating the impact of an intensified lipid lowering therapy via ezetimibe, bempedoic acid, Bococizumab, Alirocumab, Evolocumab, Inclisiran in addition to statin therapy compared to statin therapy alone. Manuscript and congress presentations, published until 1st of August 2023, were included. We made our search specific and sensitive using Medical Subject Headings terms and free text and considered studies published in English language. Search terms used were : "Bempedoic Acid" or "Bococizumab" or "Alirocumab" or "Evolocumab" or "Ezetimibe" or "Inclisiran" and "statin" and "cardiovascular events". Results A total of 123,785 patients from 15 randomized controlled trials (IMPROVE-IT, FOURIER, ODYSSEY Outcomes, ODYSSEY LONG TERM, EWTOPIA 75, PACMAN-AMI, RACING, SIPRE I, SPIRE II, OSLER-1 and OSLER-2, CLEAR HARMONY, CLEAR OUTCOMES, CLEAR SERENITY, CLEAR WISDOM) were included. Treatment with ezetimibe or a PCSK-9 inhibitor was associated with a 19% risk reduction in cardiovascular events (OR [95%CI]: 0.81 [0.75; 0.86]). Effect sizes were similar for myocardial infarction (0.81 [0.74; 0.89]) and even more pronounced for ischemic stroke (0.77 [0.70; 0.84]). In contrast, all-cause mortality was not improved by the intensified lipid lowering therapy (0.99 [0.93; 1.04]). Stratifying by follow-up duration of < vs. ≥ 3 years, no improvement in all-cause mortality was observed in both groups (<3 years: 1.04 [0.93; 1.17]; ≥3 years: 0.97 (0.88; 1.06). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown). Conclusion Intensified LDL-lowering therapy with ezetimibe, bempedoic acic or PCSK-9 inhibitors, in addition to statins, reduces the risk of myocardial infarction and stroke, however, does not impact overall mortality. A potential survival benefit was also not observed in studies with follow-up duration of ≥ 3 years.

Outcome and life expectancy associated with novel subgroups of atrial fibrillation: a data-driven cluster analysis

Abstract Background/Introduction Atrial fibrillation (AF) presents a significant global health burden, affecting millions and associated with elevated risks of mortality, heart failure, and stroke despite current treatment strategies. The current diagnosis of AF relies on episode characteristics, yet its heterogeneity calls for personalized assessment incorporating clinical features, biomarkers, and substrate determination for improved classification and management. Purpose This study aimed to develop a refined classification of AF according to comprehensive risk factors to identify patients at high-risk for poor prognosis and their life expectancy, aiming to facilitate personalized interventions. Methods A total of 7,391 participants aged 40-69 with AF at baseline, from UK Biobank, were recruited in the main analyses. Firstly, LASSO regression with Cox model and factor analysis were adopted for identification and integration of principal risk factors. Second, Consensus clustering analysis was employed to estimate the optimal cluster number and group all 7,391 participants. Difference in the risk of death and major complications, as well as reductions in life expectancy, among clusters were estimated. Replication was done in 2,399 participants with newly diagnosed AF within two years after baseline. Results Risk factors for AF were categorized into seven aspects (metabolic factors, respiratory factors, cardiovascular factors, renal and immunity diseases, mental health, acute illness, age), based on the correlation between them. Five distinct AF clusters were identified according to these seven characteristics: acute illness-related (Cluster 1), mental health-related (Cluster 2), cardiovascular disease-related (Cluster 3), immune-and-renal disease-related (Cluster 4), and respiratory-and-metabolism disease-related AF (Cluster 5). Patients with respiratory-and-metabolism disease-related AF had the highest risk of death, acute myocardial infarction, heart failure, and cerebral ischemic stroke, while those with acute illness-related AF had the lowest corresponding risk. In addition, compared with individuals with acute illness-related AF, those with respiratory-and-metabolism disease-related and mental health-related AF had the top 2 greatest loss of life expectancy. Furthermore, genetic variants for AF had different effect among the five clusters. Replication analysis confirmed the result stability. Conclusion A novel AF classification was developed, which provided insights into varying life expectancy and risks of death and complications among AF subgroups with distinct characteristics. It offers a practical approach for identifying high-risk patients, which may help to tailor precise interventions for AF management.Graphic abstractCluster features

Oral anticoagulants or antiplatelets for cryptogenic stroke: a systematic review and meta-analysis

Abstract Background Cryptogenic strokes comprise 20 to 30% of ischemic strokes and include a substantial proportion classified as embolic stroke of undetermined source (ESUS). However, the optimal antithrombotic strategy for cryptogenic stroke remains contentious. Purpose We conducted a systematic review and meta-analysis to compare the efficacy and safety of oral anticoagulants (OAC) versus antiplatelets in patients with cryptogenic stroke. Methods Six electronic databases of PubMed, Embase, Web of Science, the Cochrane Library, Google Scholar and ClinicalTrials.gov were searched from inception to Feb 15, 2024 to identify relevant randomized controlled trials (RCTs) comparing stroke recurrence and major bleeding rates between OAC and antiplatelets in cryptogenic stroke patients. We included trials adhering to a stringent diagnostic work-up for cryptogenic stroke, defined as cerebral infarction not attributed to definite sources of cardioembolism, large artery atherosclerosis, or small artery disease despite undergoing comprehensive investigations. The primary outcome was recurrent ischemic stroke, and the secondary outcome was major bleeding based on International Society of Thrombosis and Hemostasis criteria. Subgroup analysis was conducted for ESUS patients with an increased risk of cardiac emboli, such as patent foramen ovale (PFO) and atrial cardiopathy, defined as lead V1 terminal P-wave > 5000 μV × ms in electrocardiogram, serum N-terminal pro-B-type natriuretic peptide level > 250 pg/mL, and left atrial diameter (LAE) > 4 cm, or LAE index ≥ 3 cm/m2 on echocardiogram. Hazard ratio (HR) with 95% confidence (CI) was used as a measure of the effect estimates for aforementioned outcomes. Random-effects meta-analysis was performed using a restricted maximum likelihood model given between-study variance is inevitable. Results Our meta-analysis included 9 RCTs with a total of 15,139 patients (OAC = 7,343; antiplatelets = 7,796). ARCADIA, RE-SPECT ESUS, and NAVIGATE ESUS Trial investigated apixaban, dabigatran, and rivaroxaban, respectively, while warfarin was primarily used as OAC in the remaining six trials. Aspirin was predominantly utilized for antiplatelet therapy. There was no significant difference in recurrent ischemic stroke between OAC and antiplatelets (HR, 0.90; 95% CI, 0.78 to 1.04; I2 = 0%). However, OAC use was associated with a significantly higher risk of major bleeding (HR, 1.66; 95% CI, 1.07 to 2.56; I2 = 36%). Subgroup analysis in ESUS patients revealed comparable rates of recurrent ischemic stroke in those with atrial cardiopathy (HR, 0.91; 95% CI, 0.65 to 1.29; I2 = 0%) and PFO (HR, 0.72; 95% CI, 0.49 to 1.07; I2 = 0%). Conclusions Our meta-analysis suggests that OAC use does not decrease the risk of recurrent ischemic stroke compared with antiplatelet use but is associated with a significantly higher risk of major bleeding in patients with cryptogenic stroke.Primary (A) and secondary (B) outcomesSubgroup analysis for recurrent stroke

Adherence to the ABC pathway improves prognosis in patients with AF: preliminary findings from an updated meta-analysis of 360,000 patients

Abstract Background With the increasing complexity of patients with Atrial Fibrillation (AF), the ‘Atrial Fibrillation Better Care’ (ABC) pathway was proposed to streamline a holistic approach for the comprehensive management of patients with AF. The ABC pathway is based on three main pillars: ‘A’ Avoid stroke (through optimal anticoagulant use); ‘B’ Better symptom control; and ‘C’ Cardiovascular and Comorbidity management optimization. Such a holistic and integrated approach is currently recommended by international guidelines, including the ones from the European Society of Cardiology (ESC); a previous meta-analysis showed sub-optimal adherence to such approach in real-world cohorts, with an overall reduction in the risk of major outcomes in patients treated according to the ABC pathway. We hereby performed an updated systematic review and meta-analysis of the current evidence on the implementation of the ABC pathway in patients with AF. Methods We performed a systematic review and meta-analysis according to PRISMA Guidelines. MEDLINE and EMBASE were searched for all studies reporting data on the prevalence of ABC pathway adherent management in patients with AF, and/or the association between ABC pathway management and the incidence of major outcomes, including all-cause death, cardiovascular death, thromboembolism, and major bleeding. Data on the prevalence of ABC pathway management were pooled using a generalized linear mixed model; number of events and total number of patients were pooled using a random-effect model. Pooled estimates were reported as odds ratios (OR) and 95% Confidence Intervals (95%CI); heterogeneity was estimated using the restricted maximum-likelihood estimator, and the Inconsistency index (I2) was also reported. Results 4,059 articles were retrieved from the literature search; after duplicates removal, title and abstract screening and full-text evaluation, 16 studies were included, for a total of more than 360,000 patients. Pooled prevalence of adherence to the ABC pathway was 28.5% (95%CI: 21.1-37.3%, I2=100%; Figure 1). Adherence to the ABC pathway was associated with a significant lower risk of all-cause death (pooled OR: 0.47, 95%CI: 0.40-0.56, I2=97%), cardiovascular death (pooled OR: 0.43, 95%CI: 0.33-0.56, I2=95%) and stroke (pooled OR: 0.61, 95%CI: 0.47-0.79, I2=91%; Figure 1). Patients treated adherent to the ABC pathway also showed a lower risk of major bleeding (pooled OR: 0.77, 95%CI: 0.66-0.90, I2=85%). Conclusions In this updated systematic review and meta-analysis, adherence to the ABC pathway was found in less than one-third of patients with AF. Implementation of the ABC pathway was associated with lower risk of all major adverse events in patients with AF, including all-cause death, and thromboembolic and bleeding events. These data further reinforce the need for routine implementation of the ABC pathway for the management of AF in clinical practice.Figure 1

The clinical characteristics and prognosis of patients with acute non-ST-segment elevation myocardial infarction complicated with impaired activity daily living

Abstract Background Impaired activities of daily living (ADL) have been identified as an independent risk factor for cardiovascular diseases. This study aims to describe the clinical characteristics, treatment modalities, and prognosis of acute non-ST-segment elevation myocardial infarction (NSTEMI) patients with impaired ADL. Methods The data for this study were derived from a Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. The inclusion criteria encompassed patients with a discharge diagnosis of NSTEMI.ADL prior to NSTEMI was evaluated using the Barthel index(BI),a widely used assessment tool for evaluating ADL.The patients' BI were obtained from patients’ resident health records, and patients were categorized into two groups: ADL normal and ADL impaired group. A comparative analysis was conducted between the two groups regarding clinical characteristics, treatment regimens, and prognosis. Results The study included 28,227 NSTEMI patients with normal ADL and 1,576 NSTEMI patients with impaired ADL. Baseline data revealed that the ADL impaired group had a higher proportion of females (49.4% vs. 43.2%, p < 0.001), older age (77.0 [69.0, 83.0] vs. 71.0 [66.0, 78.0], p < 0.001), and a higher proportion of patients with KILLIP III and above (25.86% vs. 17.44%, p < 0.001). Additionally, the ADL impaired group had a greater number of pre-existing comorbidities. Regarding treatment, the proportion of patients undergoing percutaneous coronary intervention (PCI) was significantly lower in the ADL impaired group (16.5% vs. 65.3%, p < 0.001). Moreover, the ADL impaired group showed lower utilization rates of antiplatelet agents, ACEI/ARBs, beta-blockers, ARNI, statins, and nitrates, while the utilization rates of diuretics and cardiac glycosides were higher. In terms of prognosis, the ADL impaired group exhibited a higher in-hospital mortality rate (6.03% vs. 3.35%, p < 0.001). During a median follow-up period of 876 days, the ADL impaired group had significantly higher rates of all-cause mortality (61.2% vs. 35.9%, p < 0.001) and cardiovascular mortality (41.8% vs. 24.8%, p < 0.001), while the rate of revascularization (6.69% vs. 9.20%, p = 0.008) was lower. There were no significant differences in the risks of recurrent non-fatal myocardial infarction (10.7% vs. 10.8%, p = 0.935), recurrent stroke (10.90% vs. 9.48%, p = 0.08), and hemorrhagic stroke (0.82% vs. 0.74%, p = 0.806). Following adjustment for age, gender, KILLIP classification, medical history, and treatment strategies in a multivariable Cox regression analysis, impaired ADL remained an independent risk factor for increased all-cause mortality (aHR 1.167, 95%CI: 1.091-1.249, p < 0.001). Conclusions The decline in ADL is significantly associated with adverse clinical outcomes among NSTEMI patients.Baseline characteristics of patientsMedications of patients

Weekend compensatory sleep is associated with reduced risk of heart disease: a prospective UK Biobank-based cohort study

Abstract Background and Aims Influenced by the demands of school or work, people often fall out of sync with their circadian rhythms, which leads to sleeping in on days off. Despite this phenomenon, there is a lack of research examining whether compensatory weekend sleep has positive effects on heart health. Methods and results Our prospective cohort study utilized data from the UK Biobank (UKB) and encompassed 90,903 participants. To evaluate the relationship between compensated weekend sleep and heart disease. The sleep data was recorded by Axivity AX3 accelerometer from UKB and grouped by quartiles. Hospitalization records and cause of death registry information were used to diagnose various cardiac diseases including IHD, HF, AF, and stroke. Then multivariate Cox proportional hazard modeling was used to examine the potential impact of compensated sleep on the risk of heart disease. At a median follow-up time of up to 13.8 years, we found that participants in the compensatory sleep group(Q4) had a lower risk of having heart disease in the fully adjusted model (HR: 0.809, 95%CI: 0.766,0.854), which was not influenced by the effect of genetic risk for IHD, HF, or AF. These relationships were even more pronounced in the subgroup with daily sleep deprivation (HR:0.801, 95%CI: 0.718,0.894). Conclusion Sufficient compensatory sleep on weekends is linked to a low risk of heart disease, including IHD, AF, HF, and stroke, which is independent of genetic risk. And the association becomes even more pronounced among individuals who regularly experience inadequate sleep on weekdays.Visual abstract

Choosing the most effective and safest P2Y12 Inhibitor for use in >70-year-old acute coronary syndrome patients: a network meta-analysis

Abstract Background Acute coronary syndrome (ACS) represents a significant health burden, especially in elderly patients. Antiplatelet therapy forms the cornerstone of medical treatment for ACS, prasugrel and ticagrelor are preferred for their rapid action and proven efficacy. Despite their benefits, the comparative effectiveness and safety of prasugrel, ticagrelor, and clopidogrel, especially in elderly ACS patients, represents a true gap of knowledge. Aim This study aims to compare the efficacy and safety of prasugrel, ticagrelor, and clopidogrel in elderly patients with ACS, focusing on outcomes such as major adverse cardiovascular events (MACE), stroke, major or moderate bleeding, myocardial infarction (MI), all-cause mortality, cardiac mortality, revascularization, and stent thrombosis. Methods We conducted a comprehensive literature search across PubMed, Web of Science, Cochrane, Scopus, and ClinicalTrials.gov. Thirty-seven studies were included in our network meta-analysis (NMA), with data extracted on various outcomes. Data reported as relative risks (RRs) with 95% confidence intervals. Results Our NWM revealed that there is no significant difference in the incidence of MACE between prasugrel and ticagrelor or clopidogrel (RR 0.91 [0.67, 1.25] and RR 0.86 [0.64, 1.15], respectively). Stroke outcomes also showed no significant difference (RR 0.88 [0.60, 1.28] for prasugrel vs. ticagrelor; RR 0.73 [0.52, 1.02] for prasugrel vs. clopidogrel). Ticagrelor compared to clopidogrel significantly increased the risk of major or moderate bleeding (RR 1.23 [1.08, 1.39]). Significantly decreased risks of cardiac mortality were found for prasugrel and ticagrelor compared to clopidogrel (RR 0.88 [0.78, 0.98] and OR 0.81 [0.73, 0.90], respectively). Prasugrel significantly reduced the risk of revascularization compared to ticagrelor and clopidogrel (RR 0.57 [0.42, 0.78] and RR 0.75 [0.64, 0.88], respectively). For stent thrombosis, prasugrel and ticagrelor both showed significantly decreased risks compared to clopidogrel (RR 0.71 [0.55, 0.92] and RR 0.76 [0.62, 0.93], respectively). for MI, no significant difference was observed between prasugrel and ticagrelor (RR 0.88 [CI 0.64-1.20]), prasugrel and clopidogrel (RR 0.81 [0.60-1.09]), or ticagrelor and clopidogrel (RR 0.92 [CI 0.73-1.16]). Similarly, all-cause mortality rates did not significantly differ, with an RR of 0.93 [0.68-1.27] for prasugrel vs. ticagrelor, and an RR of 0.80 [0.61-1.06] for prasugrel vs. clopidogrel. Conclusion Our NMA suggests that while there are no significant differences among prasugrel, ticagrelor, and clopidogrel in reducing the risk of MACE, stroke, MI, and all-cause mortality in elderly ACS patients, ticagrelor may increase the risk of bleeding. Prasugrel and ticagrelor offer advantages in reducing cardiac mortality, revascularization, and stent thrombosis.

Integrated care using the ABC-stroke pathway improves cardiovascular outcomes and survival in patients with recent ischaemic stroke: a population-based cohort study

Abstract Background A recent European Society of Cardiology (ESC) Council on Stroke position paper proposed the ABC-stroke pathway, a holistic and integrated care approach to optimise the post-stroke management for patients with recent stroke, and associated heart disease. The ABC-stroke pathway is based on 3 pillars: "A" Appropriate Antithrombotic therapy; "B" Better functional and psychological status; and "C" Cardiovascular risk factors and Comorbidity optimisation (including lifestyle changes). There are limited data on the impact of adherence to the ABC-stroke pathway on post-stroke patient outcomes. Purpose We aimed to investigate the potential impact of ABC-stroke pathway adherence in the Clinical Data Analysis and Reporting System (CDARS) database in Hong Kong. Methods The analysis included patients with new-onset ischaemic stroke recorded in CDARS between 1st June 2006 and 31st May 2022. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between adherence to the ABC-stroke pathway and the primary outcome. The primary endpoint was a composite outcome of recurrent ischaemic stroke, transient ischaemic attack, haemorrhagic stroke, myocardial infarction, heart failure and all-cause death. Secondary outcomes were the individual components of the composite outcome, and cardiovascular death. Results Of the 9,669 included patients with ischaemic stroke (mean age 69.6 ± 13.4 years; 42.5% female), 58.1% were adherent to all 3 main ABC-stroke pillars. After 1 year of follow-up, adherence to the ABC-stroke pathway was associated with a lower risk of the primary composite endpoint (HR: 0.80; 95% CI: 0.72–0.88). Risk reductions increased progressively with a higher number of ABC-stroke criteria obtained (Figure 1). On multivariate analyses of the secondary outcomes, ABC-stroke pathway-adherent care was associated with a reduced risk of all-cause mortality (HR: 0.72; 95% CI: 0.62–0.85), cardiovascular death (SHR: 0.64; 95% CI: 0.45–0.90), haemorrhagic stroke (SHR: 0.50; 95% CI: 0.38–0.67) and heart failure (SHR: 0.771; 95% CI: 0.596-0.998) (Table 1). Conclusion In a large cohort of patients with ischaemic stroke, adherence to the ABC-stroke pathway was associated with a reduction of the risk of adverse outcomes.

How much does elective cardioversion increase the risk of ischaemic stroke compared to the baseline risk in atrial fibrillation? A nationwide study

Abstract Background Patients with atrial fibrillation (AF) undergoing cardioversion (CV) are exposed to an increased risk for stroke during the post-cardioversion period, but the exact magnitude of this risk after elective CV with preceding appropriate oral anticoagulant (OAC) therapy is unknown. Purpose We explored the rate of ischaemic stroke (IS) after elective CV and compared the IS rate during the post-cardioversion period with the long-term stroke rate in patients with AF using guideline-recommended OAC therapy. Methods This is a nationwide register-based study, including all AF patients undergoing their first-ever elective CV between 2012-18 in Finland. Data were collected from the Finnish health care registers covering uniquely all levels of care. Visual assessment of the survival curve identified a cut-off point in IS rate at 1 week after CV. Therefore, the follow-up time was split into two intervals, the 1-week post-cardioversion period and the subsequent period up to 360 days. Stroke rates were calculated separately for these periods. Unadjusted and adjusted incidence rate ratios were estimated with Poisson regression. Moreover, interaction between the two follow-up periods and conventional IS risk factors as well as OAC treatment was assessed. Results A total of 9625 AF patients undergoing their first elective CV were identified (mean age 67.7±9.9 years, 61.2% men, mean CHA2DS2-VASc score 2.6±1.6). Warfarin was used in 6 245 (64.9%) and non-vitamin K oral anticoagulants in 3 380 (35.1%) patients. Overall, 92 (1.0%) patients suffered an IS during the year after CV. The survival plot displayed a higher incidence of IS within the first week after CV, stabilizing thereafter to a consistent level (Figure). In the adjusted regression analyses, IS rate within the first week after elective CV was 13.6-fold (95% confidence interval [CI]: 8.6-21.5) compared the subsequent rate of IS (Table). We observed no significant interaction between any of the conventional IS risk factors or OAC treatment and the two follow-up time periods, indicating that their association with IS rate did not differ during the post-cardioversion period compared to the subsequent time period. Conclusions In this nationwide study, the rate of IS was roughly 14 times higher during the first week after elective CV compared to the subsequent follow-up time.Cumulative risk of IS after elective CVIncidence rates of IS after elective CV