Incidence Of Stroke Research Articles

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.

Unleashing the potential: early evaluation of blood pressure control with novel measurements in patients with hypertension

Abstract Objective To assess the prognostic value of two novel blood pressure measurements——short-term cumulative systolic blood pressure (SBP) load and Time in Target Rang (TTR) in major adverse cardiovascular outcomes and all-cause mortality. Method This is a post-hoc analysis of the SPIRNT (Systolic Blood Pressure Intervention Trial). Participants with complete record of BP values and no adverse events occurred in the initial 90-days follow-up were enrolled. Short-term cumulative SBP load and TTR were calculated by the 3-month SBP values in the follow-up period (Fig 1). The primary outcome was major adverse cardiovascular events (MACEs), defined as the composite of myocardial infarction, stroke, heart failure and cardiovascular death. Secondary outcomes were the components of the primary outcomes and all-cause mortality. Results The study population included 8639 adults (median [IQR]or mean (%) baseline age, 67 [61,76] years; 2940 women (35.1%); Median follow-up time 3.8[3.3-4.4] years). 559 MACEs were occurred. Participants categorized by tertiles of cumulative SBP Load (T1: [0,0.1572]; T2: (0.1572 ,3.5946]; T3: (3.5946 ,30.2949]) showed a significant increase hierarchical trend (P for trend <0.05) in the incidence of MACEs and stroke. For Participants grouped by SBP TTR (T1: [0,21.2657]; T2: (21.2657 ,71.1462]; T3: (71.1462 ,100]), it indicated a decrease hierarchical trend (P for trend <0.05) in the incidence of MACEs and MI (Fig2 and Fig3). Both short-term cumulative SBP Load (HR: 1.117(1.033-1.208)) and TTR (HR: 0.861(0.785-0.945)) were correlated with MACEs independently(tabal1). According to C-statistics and Net Reclassification Indexes (NRI), short-term cumulative SBP Load and TTR both outperformed mean SBP and SBP standard derivation (SD) on the prognosis value of MACEs. Moreover, our results showed that the coefficient of cumulative SBP Load under penalty decreased to 0 with the largest log(lambda),which indicted a major role across 4 different measures in models. (Fig 4). Conclusions Both short-term cumulative SBP load and TTR had an independent prognosis value for MACEs superior to mean SBP and SBP SD in hypertension patients without diabetes. This study provided the evidence of novel BP measurements for early assessment of BP levels after antihypertensive treatment.

Adverse cardiovascular outcomes due to potential drug-drug interactions in statin therapy: a population-based study

Abstract Background Statins have been proven to reduce morbidity and mortality in patients with known atherosclerotic cardiovascular disease (ASCVD) and in primary prevention. Given their unique role in ASCVD, concomitant use of statins and other medications are inevitable. Our clinicians’ duty is to identify clinically important drug-drug interactions (DDI) with statins and to minimize potential life-threatening adverse drug reactions. Purpose To understand the clinical relevance of statin related DDI, we aimed to analyse the prevalence and level of severity of potential statin DDI in a real-world territory-wide population-based study. Methods We retrospectively analysed 95278 patients (mean age 64.3±11.4, female 45.0%) prescribed simvastatin (N=56111, 59%), atorvastatin (N=33902, 36%), or rosuvastatin (N=5265, 5%) from 2013-2022 among 16 public hospitals. Covariates were balanced with 1:1 propensity score matching for patients with and without potential DDI, resulting in 35907 patients in each arm. A composite 4-point MACE (major adverse cardiovascular events) was used as the primary outcome, which included coronary revascularisation, stroke, myocardial infarction (MI), and cardiovascular-related death (CV death). Cox proportional-hazard model with competing risk regression was performed to estimate adjusted hazards ratio (aHR) with corresponding 95% confidence intervals (CI). Secondary analyses would be focusing on adverse drug reactions in these three different statin subgroups. Results At 1-year follow up, subjects with potential statin related DDI have higher propensities of deranged liver function (ALT>=3x ULN, 4.9% vs 3.4%; p<0.001), elevated creatine kinase (CK>=5x ULN, 0.9% vs 0.5%, p<0.001) and deranged renal function (creatinine level >=2X ULN, 0.3% vs 0.2%, p<0.001) than non-DDI group. At 5-year follow up, the statin DDI group had higher incidences of MI (2.9% vs 1.9%, p<0.01), stroke (4.0% vs 2.3%, p<0.001) and CV death (1.7 % vs 1.5%, p=0.038). Potential DDI had most significant effect seen on simvastatin compared to other statins. Simvastatin DDI cohort had strong association with subsequent coronary vascularization (aHR 1.41, 95% CI 1.21–1.64, p<0.005), MI (aHR 1.66, 95% CI 1.46–1.88, p<0.005), stroke (aHR 1.95, 95% CI 1.76–2.16, p<0.005), and CV-related death (aHR 1.18, 95% 1.00–1.38, p=0.05) as compared to control. Atorvastatin DDI cohort was associated with higher rates of MI (aHR 1.81, 95% CI 1.54–2.12, p<0.005) and stroke (aHR 1.64, 95% CI 0.39–1.94, p<0.005) than control. Rosuvastatin DDI cohort was weakly associated with higher rates of MI (aHR 1.75, 95% CI 1.02–3.01, p=0.04). Conclusion Potential statin related drug-drug interactions are prevalent and were associated with major adverse cardiovascular events. Our real-world data demonstrated that simvastatin related drug-drug interaction pose a significant threat to our patients with association with CV death, myocardial infarction, stroke and future coronary revascularization.4-point MACE

Transcatheter versus surgical aortic valve replacement in aortic stenosis patients requiring mechanical circulation support: a nationwide Japanese study

Abstract Introduction Transcatheter aortic valve replacement (TAVR) has demonstrated comparable clinical outcomes to surgical aortic valve replacement (SAVR) in patients with aortic stenosis (AS). However, previous trials excluded patients who had required mechanical circulatory support (MCS) for cardiogenic shock. Thus, the clinical feature of aortic valve replacement requiring MCS and the efficacy of TAVR compared to SAVR has not been fully exhibited in AS patients. Purpose This study investigated the demography and clinical outcomes comparing TAVR and SAVR for AS demanding MCS. Methods The current study was an observational retrospective study using Japanese nationwide data from the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC). Between April 1, 2012, and March 31, 2022, AS patients undergoing TAVR or SAVR who required MCS were evaluated. The primary outcome was 30-day mortality. In addition, we assessed ischemic stroke, hemorrhagic stroke during hospitalization. Result During the period, 80,752 patients (TAVR=36,546 and SAVR=44,206) were identified. The frequency of MCS (intra-aortic balloon pumping and/or extracorporeal membrane oxygenation) was 3.0% (1,097 patients) of the TAVR group and 4.8% (2,133 patients) of the SAVR group. In the TAVR group, 78% of patients were implanted balloon-expandable valve and 7.1% of patients were transapical apical approach. TAVR was performed in older (median age: 85 years vs. 76 years, p<0.001), lower body mass index (BMI) (median BMI: 21.5 kg/m2 vs. 22.7 kg/m2, p<0.001), and more female patients (42% vs. 27%, p<0.001) than SAVR. The 30-day mortality was lower in TAVR than SAVR (12% in TAVR and 19% in SAVR, p<0.001) (Figure). After adjusting age, gender, TAVR was significantly associated with decreased 30-day mortality compared to SAVR (adjusted HR 0.52 (0.41–0.67), p<0.001). In contrast, the incidence of ischemic stroke and hemorrhagic stroke were comparable in 2 groups (ischemic stroke; 4.2% in TAVR vs. 4.1% in SAVR, p=0.93 and hemorrhagic stroke; 0.3% vs. 0.3%, respectively). Conclusion According to nationwide real-world clinical data on aortic valve replacement for AS, the frequency of patients requiring MCS due to cardiogenic shock was 3.0% in the TAVR group and 4.8% in the SAVR group. Our findings demonstrated short-term outcomes following TAVR for patients requiring MCS for cardiogenic shock was better than those following SAVR.

Cardiovascular prevention with GLP1 agonists in high or very-high cardiovascular risk irrespective of diabetes

Abstract Introduction Patients with established cardiovascular disease have an increased risk of stroke and myocardial infarction, even in the absence of atrial fibrillation. Several trials have analyzed the effect of glucagon-like peptide-1 receptor (GLP1) agonists in patients with high cardiovascular risk and lately this effect has been studied even in the absence of diabetes. Methods A meta-analysis of randomized clinical trials (RCT) comparing GLP1 agonists with placebo was performed. The primary objective of the study was to analyze the composite endpoint of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke (MACE). As secondary objectives, cardiovascular death, non-fatal myocardial infarction and non-fatal stroke have been studied separately. The meta-analysis was performed using the inverse variance method, using the fixed effects model when there was no heterogeneity and the random effects model when heterogeneity is significant. In the case of significant heterogeneity in the primary objective, a stratified analysis with exposure time have been performed to explain this outcome. Results A sum of 9 randomized controlled trials were included where a GLP1 agonist such as albiglutide, dulaglutide, exenatide, liraglutide, lixinatide or semaglutide was compared with placebo. 77684 patients were incorporated, while 39497 were treated with a GLP1 agonist. The mean age was of 63.7 years (SD ± 1.97 years), 60080 (77.3%) suffered from diabetes and 60552 (77.9%) from cardiovascular disease. As showed in figure 1, the GLP1 agonists showed a reduction of 13% of the MACE (RR: 0.87, 95% CI 0.81-0.92; p<0.001). Heterogeneity could be explained by exposure time and concentration in the blood, considering that it disappears within each group when applying this condition. Treatment with GLP1 agonist also reduced cardiovascular death by 12% (RR: 0.88, 95% CI 0.82-0.94; p<0.001), non-fatal strokes by 14% (RR: 0.86, 95%CI 0.79-0.95; p<0.001) and non-fatal miocardial infarction by 13% (RR: 0.87, 95% CI 0.78-0.97; p<0.001). Conclusion Treatment with a GLP1 agonist reduced the incidence of the MACE by 13% and cardiovascular death by 12%, as well as it decreased the incidence of nonfatal stroke by 14% and of nonfatal myocardial infarction by 13% in different RCTs involving patients with high or very-high cardiovascular risk with or without diabetes.

Clinical outcome based on functional complete revascularization in patients with three-vessel coronary artery disease: The FAME 3 Trial

Abstract Background Anatomic complete revascularization after angiography-guided percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. The impact of functional complete revascularization (PCI of all fractional flow reserve (FFR) positive lesions) in patients with 3-vessel coronary artery disease (3VD) amenable to PCI or coronary artery bypass grafting (CABG) is unknown. Purpose To investigate the clinical impact of functional complete revascularization after FFR-guided PCI in the FAME 3 trial Methods The FAME 3 trial is a multicenter, international, randomized study comparing FFR-guided PCI with CABG in patients with angiographic 3VD. This pre-specified sub-study evaluated the impact of functional complete revascularization after PCI on the primary endpoint of death, myocardial infarction (MI), or stroke at 3 years. The degree of functional complete revascularization was quantified by calculating the residual functional SYNTAX score (rFSS), defined as the residual anatomic SYNTAX score based on post-PCI angiography minus any FFR-negative deferred lesions. Results Of the 757 patients treated with FFR-guided PCI, the rFSS could be calculated by the core laboratory in 81% (n=601). Among the angiographically significant lesions, PCI was deferred based on FFR in 17% (51 % of patients had deferral of at least one lesion). The patients were divided into two groups according to acceptable functional complete revascularization: rFSS 0-8 (63%) and functional incomplete revascularization: rFSS>8 (37%). The cumulative incidence of death, MI, or stroke at 3 years was significantly lower in patients with rFSS 0-8 (9% vs. 17%, Hazard ratio[HR]:0.5, 95% confidence interval[CI]:0.3-0.8, p=0.006) compared with rFSS>8. In comparison with the CABG arm, the patients with rFSS 0-8 had similar outcome (HR:0.97, 95%CI:0.6-1.5, p=0.87), while in those with rFSS >8 outcome was worse (HR:1.9, 95%CI: 1.3-2.8, p=0.002) (Figure). There was no difference in death, MI or stroke in CABG patients with or without anatomic complete revascularization. In a multivariate-adjusted model, rFSS>8 showed a significant association with death, MI or stroke at three years (adjusted HR: 1.83, 95% CI: 1.09-3.09, p=0.02). Conclusions Acceptable functional complete revascularization with FFR-guided PCI in patients with 3VD is an independent predictor of death, MI or stroke at three years and can be achieved in 63% of patients resulting in similar outcomes compared with CABG.

Inappropriate dosing of direct oral anticoagulants in patients with atrial fibrillation undergoing percutaneous coronary intervention

Abstract Background Underdose (inappropriate low-dose) of direct oral anticoagulants (DOAC) is sometimes prescribed due to concerns of bleeding risk in patients with atrial fibrillation (AF). In AF patients with coronary artery disease requiring percutaneous coronary intervention (PCI), careful treatment is required to prevent bleeding events because of intensive antithrombotic therapy with a combination of oral anticoagulants and antiplatelet agents. Purpose The purpose of this study was to investigate the prevalence of underdose of DOAC and its impact on clinical outcomes in AF patients with coronary artery disease undergoing PCI. Methods This multicenter observational cohort study enrolled patients with AF on DOAC undergoing PCI between January 2015 and March 2021 at 15 institutions. Appropriateness of DOAC dose was determined according to the manufacturer's labeling recommendations in Japan. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE), all-cause mortality, ischemic stroke, and major bleeding events, were evaluated. Results Of 630 patients enrolled, 168 patients (26.7%) received underdose, 227 (36.0%) received appropriate low-dose, 213 (33.8%) received appropriate standard-dose, and 22 (3.5%) received overdose. Because of the extremely small number of patients in the overdose group, the primary analysis of the present study was a comparison between the underdose group (n=168) and the appropriate dose group (appropriate low-dose and standard-dose groups) (n=440). Although the incidence of MACE, all-cause mortality, and major bleeding events was not significantly different between the 2 groups (log-rank p=0.872, p=0.170, and p=0.725), ischemic stroke more frequently occurred in the underdose group compared with the appropriate dose group (log-rank p=0.010) (Figure 1). The multivariable Cox regression analysis determined underdose of DOAC as an independent predictor for ischemic stroke (adjusted HR 3.288, 95% CI: 1.189-9.088, p=0.022). Conclusions Compared with appropriate dose of DOAC, underdose was associated with a higher incidence of ischemic stroke, despite no significant difference in MACE, all-cause mortality, and major bleeding events, in AF patients undergoing PCI.Figure 1

Silent cerebral microvascular disease and longitudinal risk of cognitive decline in atrial fibrillation

Abstract Background A relationship between silent stroke and cognitive disorder has recently been suggested in patients with nonvalvular atrial fibrillation (NVAF). This research is an exploratory research study to investigate the occurrence of asymptomatic cerebrovascular disorders with NVAF. Methods The SKAF (Silent cerebral microvascular disease and longitudinal risK of cognitive decline in Atrial Fibrillation) study is a prospective, investigator-initiated, multicenter, observational study of Japanese patients with NVAF aged 60 years or older. We had planned to enroll two hundred NVAF patients with no history of symptomatic stroke or dementia, and an anticoagulant therapy with edoxaban is being performed or an anticoagulant therapy is not being performed, and one hundred patients with sinus rhythm, for comparison. We collected patient characteristics, clinical course, the data of head MRI test and cognitive function test (Montreal Cognitive Assessment (MoCA)) at the baseline and the 24 months follow-up. The primary endpoint was the composite of silent ischemic stroke and micro-bleeding over a 24-month follow-up period. The secondary endpoint was cognitive decline over a 24-month follow-up period. Results The study was started in October 2016, with a planned 2-year recruitment period. As of January 31, 2018, a total of 326 patients were enrolled. Of those, 99 patients with sinus rhythm (SR group) and 214 patients with NVAF (NVAF group) were analyzed (male, 193 (62%) patients; age, 72.2±6.5 years). 156 of 195 (80%) patients with NVAF received the anticoagulant therapy with edoxaban. There was no significant difference of the primary composite for the endpoints between two groups (17.4% versus 17.4%; p=1.00). The incidences of silent ischemic stroke and micro-bleeding in SR and NVAF groups over a 24-month follow-up period were 9.3% and 10.8% (p= 0.833), and 8.1% and 9.2% (p=1.00), respectively. The NVAF group exhibited a significantly larger decline in cognition changes in MoCA score than SR group (-0.830 versus 0,000; p=0.0131). Notably, NVAF was found to be associated with cognitive decline. Conclusion The SKAF registry provided an equivalent risk of silent cerebral microvascular disease in patients with SR and NVAF. Clinically, NVAF had an impact on cognitive decline.

Trimetazidine reduces stroke risk in ischemic atrial fibrillation: a territory-wide, propensity-matched study

Abstract Introduction Trimetazidine ameliorates myocardial ischemia via potentiating glucose oxidation. Whether such metabolic reprogramming protects against stroke risk in atrial fibrillation (AF) with ischemic heart disease (IHD) was unknown. Purpose To investigate the therapeutic impact of trimetazidine dihydrochloride on ischemic stroke in AF associated with IHD. Methods We collected data from a territory-wide clinical data registry (January 1999 to December 2020) with a coverage of 7.5 million population. 200,563 patients with IHD were identified. Amongst them, 13,092 (6.5%) had baseline AF (mean [SD] age: 79.7 [10.3] years, 44.8% female), and were identified as trimetazidine users (n=1,488) versus non-users (long-acting nitrates as control, n=11,604). Propensity matching at 1:1 was performed. Multivariable Cox regression was used to derive hazard ratios (HRs) for new-onset ischemic stroke. Result Over mean follow-up over 53.5 +/- 50.4 months, trimetazidine use was associated with a lower incidence of ischemic stroke (3.4% vs 7.6%, P<.001). Kaplan-Meier analyses showed trimetazidine use was associated with increased stroke-free survival period (Mean survival: 227.9 [4.9] versus 217.5 [3.6] months, Chi-square=39.0 P<.001). After adjusting for confounding factors, trimetazidine use remained an independent predictor of reduced ischemic stroke risk (adjusted HRs, 0.54, 95% CI, 0.37-0.78, P<.001). Conclusion Trimetazidine may reduce the risk of ischemic stroke in ischemic AF. These findings will need to be confirmed by randomized controlled trials.

Transcatheter Aortic-Valve Replacement for Asymptomatic Severe Aortic Stenosis.

For patients with asymptomatic severe aortic stenosis and preserved left ventricular ejection fraction, current guidelines recommend routine clinical surveillance every 6 to 12 months. Data from randomized trials examining whether early intervention with transcatheter aortic-valve replacement (TAVR) will improve outcomes in these patients are lacking. At 75 centers in the United States and Canada, we randomly assigned, in a 1:1 ratio, patients with asymptomatic severe aortic stenosis to undergo early TAVR with transfemoral placement of a balloon-expandable valve or clinical surveillance. The primary end point was a composite of death, stroke, or unplanned hospitalization for cardiovascular causes. Superiority testing was performed in the intention-to-treat population. A total of 901 patients underwent randomization; 455 patients were assigned to TAVR and 446 to clinical surveillance. The mean age of the patients was 75.8 years, the mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 1.8% (on a scale from 0 to 100%, with higher scores indicating a greater risk of death within 30 days after surgery), and 83.6% of patients were at low surgical risk. A primary end-point event occurred in 122 patients (26.8%) in the TAVR group and in 202 patients (45.3%) in the clinical surveillance group (hazard ratio, 0.50; 95% confidence interval, 0.40 to 0.63; P<0.001). Death occurred in 8.4% of the patients assigned to TAVR and in 9.2% of the patients assigned to clinical surveillance, stroke occurred in 4.2% and 6.7%, respectively, and unplanned hospitalization for cardiovascular causes occurred in 20.9% and 41.7%. During a median follow-up of 3.8 years, 87.0% of patients in the clinical surveillance group underwent aortic-valve replacement. There were no apparent differences in procedure-related adverse events between patients in the TAVR group and those in the clinical surveillance group who underwent aortic-valve replacement. Among patients with asymptomatic severe aortic stenosis, a strategy of early TAVR was superior to clinical surveillance in reducing the incidence of death, stroke, or unplanned hospitalization for cardiovascular causes. (Funded by Edwards Lifesciences; EARLY TAVR ClinicalTrials.gov number, NCT03042104.).

Drug-coated balloon versus drug-eluting stent for de novo culprit lesion in acute coronary syndromes: a report from nationwide registry in japan

Abstract Background Randomized trials have demonstrated the non-inferiority of DCB strategy compared to DES strategy for ACS [1-3]. However, generalizability in clinical settings remains unclear. Purpose This study aims to compare the outcomes between drug-coated balloon (DCB) and drug-eluting stent (DES) strategies in percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) within a nationwide procedure-based registry. Methods This is a retrospective analysis of a cohort study from a prospective, nationwide registry from January 2017 to December 2020 in Japan, focusing on ACS patients who underwent DCB or DES strategy for a single de novo lesion. One-year incidence of all-cause death, cardiovascular death, non-cardiovascular death, non-fatal ACS, stroke, and major bleeding events were compared. Subgroup analysis included lesion-based and ST-elevation myocardial infarction/non-ST-elevation ACS stratification. Results Among 5,212 propensity-matched ACS patients, DCB and DES strategies showed no significant differences in one-year incidence of all-cause death (4.5% vs. 4.6%, hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.72-1.19), cardiovascular death (2.5% vs. 2.5%, HR: 0.90, 95% CI: 0.64-1.26), non-cardiovascular death (2.0% vs. 2.1%, HR: 0.96, 95% CI: 0.65-1.42), and non-fatal ACS (1.7% vs. 2.0%, HR: 1.04, 95% CI: 0.70-1.54). DCB showed higher stroke occurrence (0.8% vs. 0.3%, HR: 2.33, 95% CI: 1.06-5.08) but lower major bleeding events (1.4% vs. 2.3%, HR: 0.65, 95% CI: 0.43-0.99) (Figure 1). Subgroup analyses did not reproduce these findings (Figure 2). Conclusions ACS patients using the DCB strategy demonstrated clinical outcomes equivalent to those undergoing the DES strategy at one year. Further investigation with an extended follow-up is necessary to confirm these findings.

Exploring the effects of reduced alcohol consumption on major adverse cardiovascular and cerebrovascular events in chronic heavy drinkers: a nationwide population-based cohort study

Abstract Background/Introduction Chronic heavy alcohol consumption is a well-established risk factor for cardiovascular disease (CVD), and the potential cardiovascular benefits of mild to moderate alcohol consumption need validation, particularly in the context of behavioral change from heavy drinking. Currently, there is a lack of research examining the potential benefits of reduced alcohol consumption in chronic heavy drinkers, specifically in relation to different subtypes of CVD. We hypothesized that habitual changes in alcohol consumption among chronic heavy drinkers would have a long-term prognostic effect on future CVD outcomes. Purpose We investigated the association between reduced alcohol consumption and the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in chronic heavy drinkers. Methods From the Korean National Health Insurance Service-Health Screening database, we included a cohort of chronic heavy drinkers who underwent serial health examinations over two consecutive time-periods (first period: 2005–2008; second period: 2009–2012). Heavy drinking was defined according to the National Institute on Alcohol Abuse and Alcoholism criteria as &amp;gt;56 g/day or &amp;gt;196 g/week for men, and &amp;gt;42 g/day or &amp;gt;98 g/week for women. Overall, 13,854 heavy drinkers at baseline (mean age 55.84 ± 5.98 years; 91.6 % men) were categorized into two groups based on the alcohol consumption changes in the second period: sustained heavy drinking (n=9,403; 67.9%) or reduced drinking (n=4,451; 32.5%). The primary outcome was MACCE, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death during follow-up. Results In this nationwide population-based cohort study, during a total follow-up of 107,102 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACCE than the reduced drinking group (incidence rate, 825 vs. 655 per 100,000 person-years; log-rank p=0.004). Reduced alcohol consumption was associated with a 28% lower risk of MACCE compared to sustained heavy drinking (adjusted-hazard ratio [HR]: 0.780, 95% confidence interval [CI] 0.656–0.928). These benefits were mostly driven by a significant reduction in the incidence of angina (adjusted-HR: 0.631, 95% CI 0.425–0.926) and ischemic stroke (adjusted-HR: 0.657, 95% CI 0.472–0.914). The preventive effects of reduced alcohol intake were consistently observed across various subgroups of heavy drinkers, except for smoking status (p-interaction=0.015) and even after including abstainers in the sensitivity analysis. Conclusion Reduced alcohol consumption in heavy drinkers could lower the future risk of CVD, with the most pronounced benefits expected for stable/unstable angina and ischemic stroke. Further research is warranted to explore the optimal strategies for promoting sustained reductions in alcohol intake.Cumulative MACCE incidence curves

Levosimendan improves the early prognosis of patients with Non ST-segment elevation myocardial infarction and Killip class &amp;gt; II

Abstract Background Levosimendan is an inotropic agent known for its calcium-sensitizing myofilament effect and ATP-dependent potassium channel opening mechanism, which enhances myocardial contractility without increasing oxygen consumption. Despite its potential benefits, the impact of levosimendan on the prognosis of patients with myocardial infarction remains uncertain and requires further investigation through larger-scale studies. Purpose This study aimed to investigate the effect of levosimendan on the short-term prognosis of patients with Non-ST-segment elevation myocardial infarction (NSTEMI) and Killip&amp;gt; II. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals in the City from 2010 to 2023. A total of 12472 patients with NSTEMI and Killip &amp;gt; II were included. Patients were divided into the levosimendan group and the non-leosimendan group based on whether levosimendan was used during hospitalization. Propensity score matching (PSM) was employed to balance covariates between the two groups. Multivariate Cox regression was used to evaluate the relationship between levosimendan and clinical outcomes. Covariates adjusted in PSM included age, sex, Killip class, early PCI, previous PCI, previous medical conditions (diabetes, hypertension, ischemic stroke, and chronic kidney disease), and medications during hospitalization (aspirin, clopidogrel, indobufen, ticagrelor, statins, cedilanid, recombinant human brain natriuretic peptide [rhBNP], milrinone, dopamine, dobutamine, and angiotensin converting enzyme inhibitor/angiotensin receptor blockers [ACEI/ARB]). The primary endpoint was major cardiovascular and cerebrovascular adverse events (MACCE), defined as the composite endpoint of cardiac death, myocardial infarction, and ischemic stroke within 3 months. Results The levosimendan group comprised 782 patients, while the non-leosimendan group included 11690 patients. After PSM, the covariates were balanced, resulting in 756 well-matched pairs. In PSM patients, the levosimendan group exhibited a significantly lower incidence of MACCE (aHR, 0.573; 95%CI, 0.466–0.704; p &amp;lt; 0.001) and cardiac death (aHR, 0.500; 95%CI, 0.399-0.626; p &amp;lt; 0.001). However, there was no significant difference in the incidence of myocardial infarction and ischemic stroke. Conclusions Levosimendan was associated with a lower incidence of MACCE within 3 months in patients with NSTEMI and Killip&amp;gt; II, mainly driven by lower incidence of cardiac death. However, these findings are based on observational data and require confirmation through adequately powered, randomized, controlled trials.

A multi-center retrospective cohort analysis of age and racial disparities in patients undergoing repeat ablation for recurrent atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, and its prevalence has been increasing worldwide. Current data shows that AF is more common in white males compared to blacks despite blacks having multiple cardiovascular comorbidities. There is paucity of data showing the recurrence of AF re-ablation after index ablation specifically as it pertains to race, gender, and age. We sought to explore the rates of recurrent AF re-ablation in this retrospective cohort analysis. Methods Using a multi-center database, we examined 23,558 encounters and 10,530 had readmission records i.e. readmitted within 3 years. The encounters included adults (18+) who had an ablation procedure for atrial fibrillation between 1/1/2018-06/30/2020. We used binary logistic regression models and Tukey-Kramer procedure to analyze pairwise comparisons among different subgroups of race, sex, and age group. The primary endpoint was recurrence of repeat ablation. Secondary endpoints included non-fatal stroke and myocardial infarction. Results Our sample size was 23,558 patients, 20,276 were white patients (86%) and 3,282 were non-white patients (14%). The average age was 66.29 years (SD 10.43) and average age at the time of repeat ablation was 65.97 years. The average BMI was 21.55. Out of the 23,558 patients, 14.30% (N= 3368) had re-ablation within 3 years of the index ablation. The odds ratio of re-ablation for patients in their 50s is 1.4229 (95% CI [1.1172, 1.8122]) compared to patients in their 80s. Similarly, the odds ratio is 1.4330 (95% CI [1.1466, 1.7909]) for the 60-69 group, 1.3075 (95%CI [1.0458, 1.6346]) for the 70-79 group and 1.3443 (95% CI [1.0088, 1.7914]) for patients below 50 compared to over 80 group. The LR for re-ablation was 0.8438 (p=0.3583) in females. The incidence of non-fatal stroke and MI were 0.27% (N= 63) and 0.19% (N= 45). Average length of time to re-ablation was 415.5 days. Discussion When controlling for age group and sex, race was not significantly associated with an increased likelihood of repeat ablation. When controlling for race and age group, sex was not significantly associated with an increased likelihood of repeat ablation. When controlling for race only, females were not at a higher risk of re-ablation. However, when controlling for race and sex, patients in their 50s are 42.3% more likely to have re-ablation when compared to patients in their 80s. In contrast, the age of patients at their first ablation increased, there appeared to be a rising trend indicating a higher chance of AF recurrence within 3 years when controlling for race and sex. Conclusion The incidence of repeat AF ablation is not higher in racial minorities when compared to whites. Interestingly, there appears to be an decreasing rate of AF re-ablation in older patients despite a higher rate of AF recurrence as age increases possibly owing to more conservative therapeutic approach such as medical management.

The influence of concomitant antiplatelet therapy in venous thromboembolism patients treated with anticoagulants in the DOAC era: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction The mainstay of treatment and second prevention of venous thromboembolism (VTE) is anticoagulation therapy, and recently direct oral anticoagulant (DOAC) for VTE have prevailed all over the world as oral anticoagulation therapy. Although concomitant antiplatelet therapy in addition to oral anticoagulation therapy could have an influence on both recurrent VTE and bleeding events, there have been still limited real-world data on the issue in the DOAC era. Purpose We aimed to investigate long-term clinical outcomes in VTE patients treated with concomitant antiplatelet therapy in the DOAC era. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. After excluding 407 patients without oral anticoagulation therapy, the current study population was consisted of 4790 VTE patients with oral anticoagulation therapy, who were divided into 374 patients (7.8%) treated with concomitant antiplatelet therapy and 4416 patients (92.2%) treated with only oral anticoagulation therapy. Results Patients with concomitant antiplatelet therapy were older (Concomitant antiplatelet therapy: 74.1 vs. Only oral anticoagulation therapy: 67.3 years, P&amp;lt;0.001), were less often women (52% vs 59%, P=0.005) and more frequently had history of major bleeding (9.8% vs 6.0%, P=0.003), myocardial infarction (16% vs 0.9%, P&amp;lt;0.001) and stroke (33% vs 6.8%, P&amp;lt;0.001). The cumulative incidences of recurrent VTE were not significantly different between the 2 groups (5.9% vs 9.6% at 5-year, Log rank P=0.06). Similarly, the cumulative incidences of major bleeding (14.6% vs 13.3% at 5-year, Log rank P=0.11) and stroke (8.3% vs 6.0% at 5-year, Log rank P=0.12) were not significantly different between 2 groups. However, the cumulative incidences of clinically relevant all bleeding (29.0% and 23.0% at 5-year, Log rank P=0.007) were significantly higher in concomitant antiplatelet therapy group, which was statistically significant even after adjusting confounders. Conclusion In the current large VTE registry in the DOAC era, concomitant antiplatelet therapy in addition to oral anticoagulation therapy for patients with VTE was not significantly associated with the risks recurrent VTE, major bleeding or stroke, but was associated with an increased risk of clinically relevant all bleeding.Study Flow ChartMain results

Severe aortic stenosis is associated with left atrial prothrombotic flow changes that persists despite successful aortic valve replacement

Abstract Background Severe aortic stenosis (AS) is associated with ischaemic stroke independently of atrial fibrillation (AF) or other causes. Even after aortic valve replacement (AVR), patients remain affected by up to 15% five-year rate of incident ischaemic strokes independently of AVR-related complications and with knowledge gaps in the underlying pathophysiology. Purpose To assess whether severe AS leads to prothrombotic left atrial (LA) flow changes with reduction of LA velocities and vorticity which do not normalise after AVR. Methods Seventy-seven participants without history of AF were recruited in this study: N=40 with severe AS (60% male; age 73 ±10 years, BMI 28 ±5 Kg/m2, median CHA2DS2VASc = 3) and N=37 controls with similar clinical risk profile (51% male; age 71 ±6 years, BMI 28 ±5 Kg/m2, median CHA2DS2VASc = 3). All participants underwent a cardiovascular magnetic resonance (CMR) scan to quantify left ventricular (LV) volumes, mass, and ejection fraction (LVEF), LV global longitudinal strain (GLS) as a sensitive marker of longitudinal dysfunction, LA maximum volume and emptying fraction (LAEF), LA blood flow peak velocity and vorticity by 4-dimensional flow CMR. Out of the 40 patients with severe AS, N=23 (58%) underwent a successful AVR and were followed-up with a repeat CMR scan at approximately 6 months after surgery. Results When compared to matched controls, patients with severe AS displayed significantly higher LV mass, smaller LA and LV volumes (i.e. concentric LV hypertrophy), significantly reduced GLS but higher (more hyperdynamic) LVEF (all p&amp;lt;0.05), as expected. LAEF (i.e. global LA function) was not significantly different from controls but despite this, severe AS was associated with slightly lower LA peak flow velocity (mean 0.25 vs. 0.28 m/sec respectively) and lower LA flow vorticity (mean 16.6 vs. 21.1 radians) compared to controls (both p&amp;lt;0.05). Successful AVR led to complete regression of LV hypertrophy (p&amp;lt;0.05) with LV mass that was no longer different from controls (p&amp;gt;0.05). Nevertheless, post-AVR patients displayed a persistent adverse morpho-functional phenotype characterised by persistently smaller LA and LV volumes, persistently hyperdynamic LV function with reduced GLS (all p&amp;lt;0.05), as well as adverse LA flow changes with significantly lower velocity (mean 0.24 vs 0.28 m/sec, p=0.003) and vorticity when compared to controls (17.1 vs 21.1 radians, p&amp;lt;0.001). Conclusions Patients with severe AS display adverse LA physiology and structure (prothrombotic LA flow characteristics in smaller LA size) and LV changes (smaller size with reduced longitudinal function and hyperdynamic function), which persist after successful AVR despite normalisation of the LV hypertrophy.Figure 1

Pathogenic cardiomyopathy gene variants inform prognosis in atrial fibrillation: results from exome sequencing in over 17,000 patients in TIMI trials

Abstract Background Rare genetic variants in cardiomyopathy genes are associated with risk of atrial fibrillation (AF), even in the absence of overt ventricular dysfunction. Data on clinical outcomes for rare genetic variant carriers among patients with AF remain sparse. Purpose We aimed to study the prognostic implication of rare pathogenic/likely pathogenic (PLP) variants for dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) in patients with AF from large, well-phenotyped randomized clinical trials. Methods and results Rare variants were called using exome sequencing data in 5 large clinical trials from the TIMI study group (ENGAGE-AF, FOURIER, SAVOR, PEGASUS, DECLARE). PLP variants for cardiomyopathy were identified using phenotype- and gene-specific curation of protein-truncating variants and high-confidence variant classifications from the ClinVar database. In 17,190 patients with a history of AF, we identified 421 (2.4%) PLP variant carriers (age 67±10, 35% women) and 16,769 (97.6%) pts without PLP variants (age 70±9, 36% women). Among these individuals, we identified 265 DCM carriers (1.5%), 106 (0.6%) HCM carriers and 54 (0.3%) ARVC carriers. In this cohort, 9,275 (54%) had a history of heart failure (HF) and 2,991 (17.4%) prior ischemic stroke. Over 2.5 years median follow-up, 1,365 pts (7.9%) were hospitalized for HF, 599 (3.5%) had an ischemic stroke, and 1147 (6.7%) died of cardiovascular causes. In logistic regression analyses adjusting for age, sex, trial, and principal components of ancestry, PLP variants were significantly associated with a history of HF (OR 1.66, p&amp;lt;0.0001), most notably for DCM variants (OR 1.97, 1.48-2.62, p&amp;lt;0.0001). PLP variants were independently associated with incident HF admissions (adj HR 1.75, 1.39-2.29, p&amp;lt;0.0001), most notably for HCM (adj HR 2.59, 1.68-3.99, p&amp;lt;0.0001) and ARVC variants (adj HR 2.50, 1.34-4.66, p=0.004). The increased risk of HF admissions remained consistent in patients with (adj HR 1.49, 1.11-2.00, p=0.009) and those without (adj HR 1.88, 1.00-3.54, p=0.049) a history of HF. PLP variants were also associated with higher risk of cardiovascular death (adj HR 1.46, 1.06-2.02, p=0.02), most notably for DCM variants (adj HR 1.77, 1.21-2.58, p=0.003). In contrast, PLP variants were not associated with history of ischemic stroke at baseline (adj OR 0.99, p=0.96) nor with incident ischemic stroke (adj HR 0.95, p=0.84). Conclusion In patients with AF, rare cardiomyopathy gene variants are associated with increased risks of HF and of cardiovascular death, but not stroke. These results, collected from large well-phenotyped randomized clinical trials, demonstrate an important prognostic implication for rare genetic variants for CMP in pts with AF.

Red cell distribution width as a predictor of cardiovascular events in high-risk patients with statin intolerance: post-hoc analysis of the CLEAR Outcomes trial

Abstract Background Despite optimal lipid-lowering therapy there is up to 70% residual risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events, motivating further testing of alternative risk factors and disease pathways. Red cell distribution width (RDW) is a simple and reproducible marker of heterogeneity of cell size in the peripheral blood. High RDW is associated with an increased risk of ASCVD and death, independent of established risk factors. Recent data suggest no significant impact of PCSK9 inhibitors on hsCRP or RDW. In CLEAR Outcomes, baseline hsCRP predicted risk for future cardiovascular (CV) events and death more strongly than elevated LDL-C. It has been shown that bempedoic acid (BA) reduces hsCRP, but its effects on RDW are unknown. Purpose To analyze the effect of BA on a 4-component composite of incident myocardial infarction, stroke, coronary revascularization, or cardiovascular death (MACE-4) and for CV death by baseline RDW, and to confirm the association of increased RDW with elevated risk of MACE. Methods A total of 13,970 individuals with statin intolerance, with or at high risk for ASCVD, were randomized in the multinational CLEAR Outcomes trial with a median follow up of 3.4 years. Compared to placebo, BA reduced mean LDL-C by 21% and median hsCRP by 22% at 6 months. Quartiles of increasing baseline RDW were assessed as predictors of future adverse events after adjustment for traditional risk factors, hsCRP, and randomized treatment assignment. Results Compared to placebo, BA reduced mean RDW by 0.28% at 6 months and 0.13% at 36 months (p&amp;lt;0.0001). There was a weak positive correlation between hsCRP and RDW at baseline (Figure 1). In the placebo group, higher baseline RDW was associated with an increase in the likelihood of MACE-4 and CV death, and the hazard ratios (HR) associated with a 1% increase in RDW after adjusting for covariates and hsCRP were 1.06 (95% CI 1.02-1.11) and 1.22 (1.15-1.29), respectively. When grouped by quartiles of baseline RDW, compared with a reference group with lowest RDW (&amp;lt;13.7%), there was a notable increase in the risk of MACE-4 and CV death among the higher quartiles in the placebo group (Table 1). Those in the 4th quartile demonstrated a 3-fold increase in the risk of CV death (HR, 3.03, 2.00-4.60). The adjusted HRs (95% CI) for BA vs placebo for MACE-4 were generally lower in individuals with elevated baseline RDW than in those in the first quartile [Q1: RDW≤13.7%; 0.96 (0.79-1.17), Q2: RDW 13.7%-14.4%; 0.81 (0.67-0.97), Q3: RDW 14.4%-15.2%; 0.90 (0.75-1.09), and Q4: RDW&amp;gt;15.2%; 0.84 (0.7-1.01)]. Conclusions In a large randomized controlled clinical trial setting, we confirmed an association between elevated RDW and MACE-4. Compared with placebo, BA demonstrated efficacy in reducing CV risk in patients with moderately increased RDW.Figure 1.Correlation of hsCRP and RDWTable 1.Risk of Outcome by RDW Quartile

Education level and the incidence of heart failure, acute myocardial infarction, and stroke in patients with atrial fibrillation

Abstract Background Education level is an important socioeconomic factor affecting the incidence, symptoms, and treatment of atrial fibrillation (AF). Despite this, data on the association between education level and the incidence of major AF consequences – heart failure (HF), acute myocardial infarction (AMI), and stroke – are limited. Aim To investigate the association between education level and the risk of HF, AMI, and stroke in patients hospitalized with AF. Methods This retrospective cohort study is based on data generated by crosslinking of several Swedish national registries. All patients hospitalized between 1998 and 2003 with a diagnosis of AF were included. The relative risk for incident HF, AMI, and stroke were assessed according to education level categories during a 5–year follow–up. Education levels were categorised as primary, secondary, and academic. Kaplan-Meier curves and Cox regression models adjusted for age, sex, time of AF diagnosis, and the variables of Charlson´s Comorbidity Index were used to estimate the relative risk of the examined outcomes. Hazard ratios (HR) with 95% confidence intervals (CI) were used as estimate of associations and statistical significance level was 5%. Results The study included 263,172 patients (56.2% male; mean age 72.5±10.4 years). There was a statistically significant dose-dependent association between education level and the risk of AMI and HF in both sexes. Compared to primary education, the HR for AMI was 0.89 (95% CI: 0.85-0.93) for secondary education and 0.71 (95% CI: 0.65-0.78) for academic education in women; and 0.91 (95% CI: 0.87-0.94) for secondary education and 0.75 (95% CI: 0.71-0.80) for academic education in men. The relative risk for HF was similar, with HRs of 0.96 (95% CI: 0.93-1.00) for secondary and 0.82 (95% CI: 0.77-0.87) for academic education in women, and HRs of 0.93 (95% CI: 0.90-0.96) for secondary and 0.76 (95% CI: 0.72-0.80) for academic education in men. Patients with academic education had a significantly lower risk for stroke compared to those with primary education (HR 0.77 (95% CI: 0.71-0.84) in women; HR 0.84 (95% CI: 0.79-0.90) in men), while patients with secondary education did not have a significantly different relative risk for stroke compared to those with primary education. Conclusion Secondary and academic education levels were associated with a significantly lower risk of HF and AMI in both women and men with AF compared to primary education. Furthermore, academic education was associated with a lower risk of stroke. In conclusion, , higher education levels were associated with a lower 5-year risk of HF, AMI, and stroke compared to primary education

Device-measured vigorous intermittent lifestyle physical activity (VILPA) and major adverse cardiovascular events: evidence of sex differences.

Vigorous intermittent lifestyle physical activity (VILPA) refers to brief bouts of intense physical activity embedded into daily life. To examine sex differences in the dose-response association of VILPA with major adverse cardiovascular events (MACE) and its subtypes. Using multivariable-adjusted cubic splines, we examined the associations of daily VILPA duration with overall MACE and its subtypes (incident myocardial infarction, heart failure and stroke) among non-exercisers (individuals self-reporting no leisure-time exercise and no more than one recreational walk per week) in the UK Biobank. We also undertook analogous analyses for vigorous physical activity among exercisers (individuals self-reporting participation in leisure-time exercise and/or recreational walking more than once a week). Among 13 018 women and 9350 men, there were 331 and 488 all MACE, respectively, over a 7.9-year follow-up. In women, daily VILPA duration exhibited a near-linear dose-response association with all MACE, myocardial infarction and heart failure. In men, dose-reponse curves were less clear with less evidence of statistical signifigance. Compared with women with no VILPA, women's median daily VILPA duration of 3.4 min was associated with hazard ratios (HRs; 95% confidence intervals) of 0.55 (0.41 to 0.75) for all MACE and 0.33 (0.18 to 0.59) for heart failure. Women's minimum doses of 1.2-1.6 min of VILPA per day were associated with HRs of 0.70 (0.58 to 0.86) for all MACE, 0.67 (0.50 to 0.91) for myocardial infarction, and 0.60 (0.45 to 0.81) for heart failure. The equivalent analyses in UK Biobank's accelerometry sub-study exercisers suggested no appreciable sex differences in dose-response. Among non-exercising women, small amounts of VILPA were associated with a substantially lower risk of all MACE, myocardial infarction and heart failure. VILPA may be a promising physical activity target for cardiovascular disease prevention, particularly in women unable or not willing to engage in formal exercise.