Effective Gene Therapy for Metachromatic Leukodystrophy Achieved with Minimal Lentiviral Genomic Integrations.

Metachromatic leukodystrophy (MLD) is a fatal lysosomal storage disease (LSD) characterized by the deficient enzymatic activity of arylsulfatase A (ARSA). Combined autologous hematopoietic stem cell transplant (HSCT) with lentiviral (LV) based gene therapy has great potential to treat MLD. However, if enzyme production is inadequate, this could result in continued loss of motor function, implying a high vector copy number (VCN) requirement for optimal enzymatic output. This may place children at increased risk for genomic toxicity due to higher VCN. We increased the expression of ARSA cDNA at single integration by generating novel LVs, optimizing ARSA expression, and enhancing safety. In addition, our vectors achieved optimal transduction in mouse and human HSC with minimal multiplicity of infection (MOI). Our top-performing vector (EA1) showed at least 4X more ARSA activity than the currently EU-approved vector and a superior ability to secrete vesicle-associated ARSA, a critical modality to transfer functional enzymes from microglia to oligodendrocytes. Three-month-old Arsa -KO MLD mice transplanted with Arsa -KO BM cells transduced with 0.6 VCN of EA1 demonstrated behavior and CNS histology matching WT mice. Our novel vector boosts efficacy while improving safety as a robust approach for treating early symptomatic MLD patients.

Regional variations in management and outcomes of patients with acute coronary syndrome in China: Evidence from the National Chest Pain Center Program.

Regional variations in acute coronary syndrome (ACS) management and outcomes have been an enormous public health issue. However, studies have yet to explore how to reduce the variations. The National Chest Pain Center Program (NCPCP) is the first nationwide, hospital-based, comprehensive, continuous quality improvement program for improving the quality of care in patients with ACS in China. We evaluated the association of NCPCP and regional variations in ACS healthcare using generalized linear mixed models and interaction analysis. Patients in the Western region had longer onset-to-first medical contact (FMC) time and time stay in non-percutaneous coronary intervention (PCI) hospitals, lower rates of PCI for ST-elevation myocardial infarction (STEMI) patients, and higher rates of medication usage. Patients in Central regions had relatively lower in-hospital mortality and in-hospital heart failure rates. Differences in the door-to-balloon time (DtoB) and in-hospital mortality between Western and Eastern regions were less after accreditation (ß = -8.82, 95% confidence interval (CI) -14.61 to -3.03; OR = 0.79, 95%CI 0.70 to 0.91). Similar results were found in differences in DtoB time, primary PCI rate for STEMI between Central and Eastern regions. The differences in PCI for higher-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients among different regions had been smaller. Additionally, the differences in medication use between Eastern and Western regions were higher after accreditation. Regional variations remained high in this large cohort of patients with ACS from hospitals participating in the NCPCP in China. More comprehensive interventions and hospital internal system optimizations are needed to further reduce regional variations in the management and outcomes of patients with ACS.

The American Heart Association at 100: A Century of Scientific Progress and the Future of Cardiovascular Science: A Presidential Advisory From the American Heart Association.

In 1924, the founders of the American Heart Association (AHA) envisioned an international society focused on the heart and aimed at facilitating research, disseminating information, increasing public awareness, and developing public health policy related to heart disease. This presidential advisory provides a comprehensive review of the past century of cardiovascular and stroke science, with a focus on the AHA's contributions, as well as informed speculation about the future of cardiovascular science into the next century of the organization's history. The AHA is a leader in fundamental, translational, clinical, and population science, and it promotes the concept of the "learning health system," in which a continuous cycle of evidence-based practice leads to practice-based evidence, permitting an iterative refinement in clinical evidence and care. This advisory presents the AHA's journey over the past century from instituting professional membership to establishing extraordinary research funding programs; translating evidence to practice through clinical practice guidelines; affecting systems of care through quality programs, certification, and implementation; leading important advocacy efforts at the federal, state and local levels; and building global coalitions around cardiovascular and stroke science and public health. Recognizing an exciting potential future for science and medicine, the advisory offers a vision for even greater impact for the AHA's second century in its continued mission to be a relentless force for longer, healthier lives.

Moderating Effect of Sex on the Relationship Between Physical Activity and Quality of Life in Coronary Heart Disease Patients in China.

PURPOSE: The aim of this study was to investigate the moderating effect of sex on the relationship between physical activity (PA) and quality of life (QoL) in Chinese patients with coronary heart disease (CHD) not participating in cardiac rehabilitation. METHODS: Chinese patients with CHD (aged 18-80 yr) were selected 12 mo after discharge from three Hebei Province tertiary hospitals. The International Physical Activity Questionnaire was used to assess PA in metabolic equivalents of energy (METs) and the Chinese Questionnaire of Quality of Life in Patients With Cardiovascular Disease was used to assess QoL. Data were analyzed using Student's t test and the χ2 test, multivariant and hierarchical regression analysis, and simple slope analysis. RESULTS: Among 1162 patients with CHD studied between July 1 and November 30, 2017, female patients reported poorer QoL and lower total METs in weekly PA compared with male patients. Walking (ß= .297), moderate-intensity PA (ß= .165), and vigorous-intensity PA (ß= .076) positively predicted QoL. Hierarchical regression analysis showed that sex moderates the relationship between walking (ß= .195) and moderate-intensity PA (ß= .164) and QoL, but not between vigorous-intensity PA (ß= -.127) and QoL. Simple slope analysis revealed the standardized coefficients of walking on QoL were 0.397 (female t = 8.210) and 0.338 (male t = 10.142); the standardized coefficients of moderate-intensity PA on QoL were 0.346 (female, t = 7.000) and 0.175 (male, t = 5.033). CONCLUSIONS: Sex moderated the relationship between PA and QoL among patients with CHD in China. There was a greater difference in QoL for female patients reporting higher time versus those with lower time for both walking and moderate-intensity PA than for male patients.

Contact-FP: A Dimerization-Dependent Fluorescent Protein Toolkit for Visualizing Membrane Contact Site Dynamics.

Membrane contact sites (MCSs) are sites of close apposition between two organelles used to exchange ions, lipids, and information. Cells respond to changing environmental or developmental conditions by modulating the number, extent, or duration of MCSs. Because of their small size and dynamic nature, tools to study the dynamics of MCSs in live cells have been limited. Dimerization-dependent fluorescent proteins (ddFPs) targeted to organelle membranes are an ideal tool for studying MCS dynamics because they reversibly interact to fluoresce specifically at the interface between two organelles. Here, we build on previous work using ddFPs as sensors to visualize the morphology and dynamics of MCSs. We engineered a suite of ddFPs called Contact-FP that targets ddFP monomers to lipid droplets (LDs), the endoplasmic reticulum (ER), mitochondria, peroxisomes, lysosomes, plasma membrane, caveolae, and the cytoplasm. We show that these probes correctly localize to their target organelles. Using LDs as a test case, we demonstrate that Contact-FP pairs specifically localize to the interface between two target organelles. Titration of LD-mitochondria ddFPs revealed that these sensors can be used at high concentrations to drive MCSs or can be titrated down to minimally perturb and visualize endogenous MCSs. We show that Contact-FP probes can be used to: (1) visualize LD-mitochondria MCS dynamics, (2) observe changes in LD-mitochondria MCS dynamics upon overexpression of PLIN5, a known LD-mitochondrial tether, and (3) visualize two MCSs that share one organelle simultaneously (e.g., LD-mitochondria and LD-ER MCSs). Contact-FP probes can be optimized to visualize MCSs between any pair of organelles represented in the toolkit.

Characterizing Social Connectedness and Associated Mental Health Symptoms among Sexual Minority Men Enrolled in a Substance Use Recovery Support Program.

BACKGROUND: Sexual minority men (SMM; gay, bisexual, and other men who have sex with men) report higher rates of substance use compared to other populations. Social connectedness is a critical component for promoting and maintaining recovery from substance use disorders. However, the degree of social connectedness among SMM who report substance use is largely unknown. OBJECTIVES: We examined substance use, social connectedness (past 30-d participation in formal recovery support, past 30-d interaction with supportive family/friends, relationship satisfaction, and types of support) and mental health among SMM at the time of their enrollment in a behavioral substance use program from September 2019 to October 2021. RESULTS: Of the107 SMM, 80% of the sample reported past 30-d illicit substance use, with methamphetamine representing the most commonly reported drug used (53%). Participants used a variety of social connections for support, including self-help groups (44% voluntary; 5% religious-affiliated; 20% other) and family/friends (81%). Importantly, 15% reported they had no one to turn to when having trouble and 36% were either dissatisfied or very dissatisfied with their relationships. Participants who endorsed significant depressive (58%) and anxiety (70%) symptoms were more likely to endorse relationship dissatisfaction than participants who did not endorse symptoms (p < 0.01). CONCLUSIONS: One-third of SMM enrolled in a substance use recovery program expressed relationship dissatisfaction, particularly those struggling with depression or anxiety. Future research and programming should examine ways of leveraging existing social connectedness or forging new social supports to enhance mental health and substance use recovery for SMM using substances.

Low Awareness of Diabetes as a Major Risk Factor for Cardiovascular Disease in Middle- and High-Income Countries.

OBJECTIVE: Awareness of diabetes as a major risk factor for cardiovascular disease (CVD) may enhance uptake of screening for diabetes and primary prevention of CVD. RESEARCH DESIGN AND METHODS: The American Heart Association conducted an online survey in 50 countries. The main outcome of this study was the proportion of individuals in each country who recognized diabetes as a CVD risk factor. We also examined variation by sex, age, geographic region, and country-level economic development. RESULTS: Among 48,988 respondents, 15,747 (32.1%) identified diabetes as a major CVD risk factor. Awareness was similar among men and women, but increased with age, and was greater in high-income than in middle-income countries. CONCLUSIONS: Two-thirds of adults in surveyed countries did not recognize diabetes as a major CVD risk factor. Given the increasing global burden of diabetes and CVD, this finding underscores the need for concerted efforts to raise public health awareness.

Percutaneous Coronary Intervention in Acute Coronary Syndrome with Mild-to-Moderate Thrombocytopenia.

BACKGROUND: Baseline thrombocytopenia is commonly observed in patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI). AIM: The purpose of this analysis was to investigate safety and effectiveness of PCI in ACS patients with baseline mild-to-moderate thrombocytopenia. METHODS: The data were collected from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. A total of 50,009 ACS patients were recruited between July 2017 and December 2019. Among them, there were 6,413 patients with mild-to-moderate thrombocytopenia, defined as a platelet count of ≥50 × 109/L and <150 × 109/L on admission. The primary outcome was in-hospital net adverse clinical events (NACE), consisting of major adverse cardiac events (MACE) and major bleeding events. The associations between PCI and in-hospital outcomes were analyzed by inverse probability treatment weighting (IPTW) method. RESULTS: PCI was performed in 4,023 of 6,413 patients (62.7%). The IPTW analysis showed that PCI was significantly associated with a reduced risk of in-hospital MACE (odd ratio [OR]: 0.45; 95% confidence interval [CI]: 0.31-0.67; p < 0.01) and NACE (OR: 0.59; 95% CI: 0.42-0.83; p < 0.01). PCI was also associated with an increased risk of any bleeding (OR: 1.56; 95% CI: 1.09-2.22; p = 0.01) and minor bleeding (OR: 1.52; 95% CI: 1.00-2.30; p = 0.05), but not major bleeding (OR: 1.51; 95% CI: 0.76-2.98; p = 0.24). CONCLUSION: Compared with medical therapy alone, PCI is associated with better in-hospital outcomes in ACS patients with mild-to-moderate thrombocytopenia. Further studies with long-term prognosis are needed.

Oral anti-coagulants use in Chinese hospitalized patients with atrial fibrillation.

BACKGROUND: Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China. METHODS: Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed. RESULTS: A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43-0.68; P  <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P  <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04-13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65-3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38-1.53; P <0.001). CONCLUSIONS: In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

A Nationwide Initiative to Improve Cardiology Quality: The Best Practice in Cardiology Program in Brazil. / Uma Iniciativa Nacional de Melhoria da Qualidade em Cardiologia: O Programa de Boas Práticas em Cardiologia no Brasil.

BACKGROUND: A Nationwide Initiative to Improve Cardiology Quality: The Best Practice in Cardiology Program in Brazil ACEI/ARB: angiotensin-converting enzyme inhibitor/angiotensin receptor blocker; LVEF: left ventricular ejection fraction; LVSD: left ventricular systolic dysfunction; AF: atrial fibrillation; PT/INR: prothrombin time/international normalized ratio. BACKGROUND: Despite significant progress in improving the quality of cardiovascular care, persistent gaps remain in terms of inconsistent adherence to guideline recommendations. OBJECTIVE: This study evaluates the effects of implementing a quality improvement program adapted from the American Heart Association's Get with the Guidelines™ initiative on adherence to guideline-directed medical therapy for acute coronary syndrome (ACS), atrial fibrillation (AF), and heart failure (HF). METHODS: We examined demographics, quality measures, and short-term outcomes in patients hospitalized with ACS, AF, and HF enrolled in the Best Practice in Cardiology (BPC) Program from 2016 to 2022. RESULTS: This study included 12,167 patients in 19 hospitals in Brazil. Mean age was 62.5 [53.8-71] y/o; 61.1% were male, 68.7% had hypertension, 32.0% diabetes mellitus, and 24.1% had dyslipidemia. Composite score had a sustainable performance in the period from baseline to the last quarter: 65.8±36.2% to 73± 31.2% for AF (p=0.024), 81.0± 23.6% to 89.9 ± 19.3% for HF (p<0.001), and from 88.0 ± 19.1 to 91.2 ±14.9 for ACS (p<0.001). CONCLUSIONS: The BPC program is a quality improvement program in Brazil in which real-time data, obtained using cardiology guideline metrics, were implemented in a quality improvement program resulting in an overall sustained improvement in AF, HF, and ACS management.

Sex Disparities in Management and Outcomes Among Patients With Acute Coronary Syndrome.

Importance: Sex disparities in the management and outcomes of acute coronary syndrome (ACS) have received increasing attention. Objective: To evaluate the association of a quality improvement program with sex disparities among patients with ACS. Design, Setting, and Participants: The National Chest Pain Centers Program (NCPCP) is an ongoing nationwide program for the improvement of quality of care in patients with ACS in China, with CPC accreditation as a core intervention. In this longitudinal analysis of annual (January 1, 2016, to December 31, 2020) cross-sectional data of 1 095 899 patients with ACS, the association of the NCPCP with sex-related disparities in the care of these patients was evaluated using generalized linear mixed models and interaction analysis. The robustness of the results was assessed by sensitivity analyses with inverse probability of treatment weighting. Data were analyzed from September 1, 2021, to June 30, 2022. Exposure: Hospital participation in the NCPCP. Main Outcomes and Measures: Differences in treatment and outcomes between men and women with ACS. Prehospital indicators included time from onset to first medical contact (onset-FMC), time from onset to calling an emergency medical service (onset-EMS), and length of hospital stay without receiving a percutaneous coronary intervention (non-PCI). In-hospital quality indicators included non-PCI, use of statin at arrival, discharge with statin, discharge with dual antiplatelet therapy, direct PCI for ST-segment elevation myocardial infarction (STEMI), PCI for higher-risk non-ST-segment elevation ACS, time from door to catheterization activation, and time from door to balloon. Patient outcome indicators included in-hospital mortality and in-hospital new-onset heart failure. Results: Data for 1 095 899 patients with ACS (346 638 women [31.6%] and 749 261 men [68.4%]; mean [SD] age, 63.9 [12.4] years) from 989 hospitals were collected. Women had longer times for onset-FMC and onset-EMS; lower rates of PCI, statin use at arrival, and discharge with medication; longer in-hospital delays; and higher rates of in-hospital heart failure and mortality. The NCPCP was associated with less onset-FMC time, more direct PCI rate for STEMI, lower rate of in-hospital heart failure, more drug use, and fewer in-hospital delays for both men and women with ACS. Sex-related differences in the onset-FMC time (ß = -0.03 [95% CI, -0.04 to -0.01), rate of direct PCI for STEMI (odds ratio, 1.11 [95% CI, 1.06-1.17]), time from hospital door to balloon (ß = -1.38 [95% CI, -2.74 to -0.001]), and rate of in-hospital heart failure (odds ratio, 0.90 [95% CI, 0.86-0.94]) were significantly less after accreditation. Conclusions and Relevance: In this longitudinal cross-sectional study of patients with ACS from hospitals participating in the NCPCP in China, sex-related disparities in management and outcomes were smaller in some aspects by regionalization between prehospital emergency and in-hospital treatment systems and standardized treatment procedures. The NCPCP should emphasize sex disparities to cardiologists; highlight compliance with clinical guidelines, particularly for female patients; and include the reduction of sex disparities as a performance appraisal indicator.

Asymptomatic atrial fibrillation among hospitalized patients: clinical correlates and in-hospital outcomes in Improving Care for Cardiovascular Disease in China-Atrial Fibrillation.

AIMS: The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients. METHODS AND RESULTS: We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS. CONCLUSION: Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms.

Clinical Profiles, Outcomes, and Sex Differences of Patients With STEMI: Findings From the NORIN-STEMI Registry.

Background: Low- and middle-income countries account for most of the global burden of coronary artery disease. There is a paucity of data regarding epidemiology and outcomes for ST-segment elevation myocardial infarction (STEMI) patients in these regions. Objectives: The authors studied the contemporary characteristics, practice patterns, outcomes, and sex differences in patients with STEMI in India. Methods: NORIN-STEMI (North India ST-Segment Elevation Myocardial Infarction Registry) is an investigator-initiated prospective cohort study of patients presenting with STEMI at tertiary medical centers in North India. Results: Of 3,635 participants, 16% were female patients, one-third were <50 years of age, 53% had a history of smoking, 29% hypertension, and 24% diabetes. The median time from symptom onset to coronary angiography was 71 hours; the majority (93%) presented first to a non-percutaneous coronary intervention (PCI)-capable facility. Almost all received aspirin, statin, P2Y12 inhibitors, and heparin on presentation; 66% were treated with PCI (98% femoral access) and 13% received fibrinolytics. The left ventricular ejection fraction was <40% in 46% of patients. The 30-day and 1-year mortality rates were 9% and 11%, respectively. Compared with male patients, female patients were less likely to receive PCI (62% vs 73%; P < 0.0001) and had a more than 2-fold greater 1-year mortality (22% vs 9%; adjusted HR: 2.1; 95% CI: 1.7-2.7; P < 0.001). Conclusions: In this contemporary registry of patients with STEMI in India, female patients were less likely to receive PCI after STEMI and had a higher 1-year mortality compared with male patients. These findings have important public health implications, and further efforts are required to reduce these gaps.

Dual Antiplatelet Therapy: A Concise Review for Clinicians.

Dual antiplatelet therapy (DAPT) combines two antiplatelet agents to decrease the risk of thrombotic complications associated with atherosclerotic cardiovascular diseases. Emerging data about the duration of DAPT is being published continuously. New approaches are trying to balance the time, benefits, and risks for patients taking DAPT for established cardiovascular diseases. Short-term dual DAPT of 3-6 months, or even 1 month in high-bleeding risk patients, is equivalent in terms of efficacy and effectiveness compared to long-term DAPT for patients who experienced percutaneous coronary intervention in an acute coronary syndrome setting. Prolonged DAPT beyond 12 months reduces stent thrombosis, major adverse cardiovascular events, and myocardial infarction rates but increases bleeding risk. Extended DAPT does not significantly benefit stable coronary artery disease patients in reducing stroke, myocardial infarction, or cardiovascular death. Ticagrelor and aspirin reduce cardiovascular events in stable coronary artery disease with diabetes but carry a higher bleeding risk. Antiplatelet therapy duration in atrial fibrillation patients after percutaneous coronary intervention depends on individual characteristics and bleeding risk. Antiplatelet therapy is crucial for post-coronary artery bypass graft and transcatheter aortic valve implantation; Aspirin (ASA) monotherapy is preferred. Antiplatelet therapy duration in peripheral artery disease depends on the scenario. Adding vorapaxar and cilostazol may benefit secondary prevention and claudication, respectively. Carotid artery disease patients with transient ischemic attack or stroke benefit from antiplatelet therapy and combining ASA and clopidogrel is more effective than ASA alone. The optimal duration of DAPT after carotid artery stenting is uncertain. Resistance to ASA and clopidogrel poses an incremental risk of deleterious cardiovascular events and stroke. The selection and duration of antiplatelet therapy in patients with cardiovascular disease requires careful consideration of both efficacy and safety outcomes. The use of combination therapies may provide added benefits but should be weighed against the risk of bleeding. Further research and clinical trials are needed to optimize antiplatelet treatment in different patient populations and clinical scenarios.

Mortality in Patients Hospitalized With Acute Myocardial Infarction Without Standard Modifiable Risk Factors: The ARIC Study Community Surveillance.

Background Prevention strategies targeting standard modifiable cardiovascular risk factors (SMuRFs; diabetes, hypertension, smoking, hypercholesterolemia) are critical to improving cardiovascular disease outcomes. However, acute myocardial infarction (AMI) among individuals who lack 1 or more SMuRFs is not uncommon. Moreover, the clinical characteristics and prognosis of SMuRFless individuals are not well characterized. Methods and Results We analyzed AMI hospitalizations from 2000 to 2014 captured by the ARIC (Atherosclerosis Risk in Community) study community surveillance. AMI was classified by physician review using a validated algorithm. Clinical data, medications, and procedures were abstracted from the medical record. Main study outcomes included short- and long-term mortality within 28 days and 1 year of AMI hospitalization. Between 2000 and 2014, a total of 742 (3.6%) of 20 569 patients with AMI were identified with no documented SMuRFs. Patients without SMuRFs were less likely to receive aspirin, nonaspirin antiplatelet therapy, or beta blockers and less often underwent angiography and revascularization. Compared with those with one or more SMuRFs, patients without SMuRFs had significantly higher 28-day (odds ratio, 3.23 [95% CI, 1.78-5.88]) and 1-year (hazard ratio, 2.09 [95% CI, 1.29-3.37]) adjusted mortality. When examined across 5-year intervals from 2000 to 2014, the incidence of 28-day mortality significantly increased for patients without SMuRFs (7% to 15% to 27%), whereas it declined for those with 1 or more SMuRFs (7% to 5% to 5%). Conclusions Individuals without SMuRFs presenting with AMI have an increased risk of all-cause mortality with an overall lower prescription rate for guideline-directed medical therapy. These findings highlight the need for evidence-based pharmacotherapy during hospitalization and the need to discover new markers and mechanisms for early risk identification in this population.

Mobile-phone text messaging to promote ideal cardiovascular health in women.

OBJECTIVE: Ideal cardiovascular health (CVH) was developed to promote CVH as a key component of primordial prevention. Mobile short message service (SMS) is useful for improving health behaviours. We aim to test the effectiveness of SMS intervention in women to improve CVH. METHODS: In a single-blinded, randomised, controlled study, 620 women, aged 35-70 years, without cardiovascular disease, were enrolled in SMS intervention versus no SMS. CVH metrics by self-report, and biochemical laboratory, anthropometric and blood pressure measurements were collected during home visits at baseline and 9 months. Women were categorised as having poor (0-2), intermediate (3-4) or ideal (5-7) CVH according to the number of ideal CVH metrics. Participants were randomised 1:1 to SMS intervention versus control. SMS was sent every 5-6 days for 9 months. The primary outcome was the difference in the proportion of women with ideal CVH between SMS and control groups at 9 months. Rates of intermediate CVH, poor CVH and each of the seven ideal CV health metrics at 9 months were key secondary endpoints. RESULTS: At 9 months, there was no significant difference between groups for the primary outcome (16.3% at baseline and 13.3% at 9 months, and 10.1% and 11.1%, in SMS and control groups, respectively, adjusted RR 1.0; 95% CI 0.6 to 1.6). Similarly, there were no significant differences between groups for the key secondary endpoints. SMS had an acceptance rate of 94.9%. CONCLUSIONS: Behavioural SMS intervention did not improve rates of ideal CVH in women, despite being feasible and well received. TRIAL REGISTRATION NUMBER: 6377.

External applicability of the Effect of ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) trial: An analysis of patients with diabetes and coronary artery disease in the REduction of Atherothrombosis for Continued Health (REACH) registry.

AIMS: THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry. METHODS AND RESULTS: The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a 'THEMIS-eligible population' of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy. CONCLUSIONS: In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be 'THEMIS eligible.' CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov identifier: NCT01991795.

Risk Factors for In-Hospital Cardiac Arrest in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: In-hospital cardiac arrest (IHCA) is one of the most deleterious complications of ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: We systematically analyzed the clinical characteristics of STEMI patients with IHCA, as well as predictors and treatments associated with risk of IHCA, using a nationwide database. METHODS: In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we stratified patients presenting with STEMI within 24 hours after symptom onset according to IHCA or no IHCA during the index hospitalization. We analyzed patients' clinical characteristics, mortality, and independent correlates of IHCA. RESULTS: Of 40,670 STEMI patients, 2.2% (95% CI: 2.1%-2.4%) experienced IHCA. Among IHCA patients, the in-hospital mortality was 53.0% (95% CI: 49.7%-56.3%). IHCA represents 55.0% (95% CI: 51.6%-58.4%) of inpatient deaths. Age ≥75 years, female, nonsmoker, prior diabetes mellitus, prior renal failure, out-of-hospital cardiac arrest, heart rate >100 beats/min, systolic blood pressure <90 mm Hg, and Killip IV were identified as predictors of IHCA. IHCA patients were less likely to receive ß-blockers and ticagrelor during the first 24 hours after first medical contact and were less likely to undergo primary percutaneous coronary intervention. After adjustment, primary percutaneous coronary intervention (adjusted HR: 0.82; 95% CI: 0.71-0.95), ß-blockers (adjusted HR: 0.63; 95% CI: 0.47-0.86), and ticagrelor (adjusted HR: 0.57; 95% CI: 0.42-0.76) were associated with a reduced risk of IHCA. CONCLUSIONS: IHCA is rare in STEMI but is associated with high mortality. Multiple modifiable and unmodifiable factors are associated with its occurrence, suggesting that early intervention and rational drug treatment may improve its prognosis. (CCC Project- Acute Coronary Syndrome; NCT02306616).

Early ACEI/ARB use and in-hospital outcomes of acute myocardial infarction patients with systolic blood pressure <100 mmHg and undergoing percutaneous coronary intervention: Findings from the CCC-ACS project.

Background: Few studies have evaluated whether acute myocardial infarction (AMI) patients with relatively low blood pressure benefit from early ACEI/ARB use in the era of percutaneous coronary intervention (PCI). Objectives: This study evaluated the associations of ACEI/ARB use within 24 h of admission with in-hospital outcomes among AMI patients with SBP < 100 mmHg and undergoing PCI. Methods: This study was based on the Improving Care for Cardiovascular Disease in China-ACS project, a collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. Between November 2014 and December 2019, a total of 94,623 patients with AMI were enrolled. Of them, 4,478 AMI patients with SBP < 100 mmHg and undergoing PCI but without clinically diagnosed cardiogenic shock at admission were included. Multivariable logistic regression and propensity score-matching analysis were used to evaluate the association between early ACEI/ARB use and in-hospital major adverse cardiac events (MACEs), a combination of all-cause death, cardiogenic shock, and cardiac arrest. Results: Of AMI patients, 24.41% (n = 1,093) were prescribed ACEIs/ARBs within 24 h of admission. Patients with early ACEI/ARB use had a significantly lower rate of MACEs than those without ACEI/ARB use (1.67% vs. 3.66%, p = 0.001). In the logistic regression analysis, early ACEI/ARB use was associated with a 45% lower risk of MACEs (odds ratio: 0.55, 95% CI: 0.33-0.93; p = 0.027). Further propensity score-matching analysis still showed that patients with early ACEI/ARB use had a lower rate of MACEs (1.96% vs. 3.93%, p = 0.009). Conclusion: This study found that among AMI patients with an admission SBP < 100 mmHg undergoing PCI, early ACEI/ARB use was associated with better in-hospital outcomes. Additional studies of the early use of ACEIs/ARBs in AMI patients with relatively low blood pressure are warranted.