A newborn's perspective on immune responses to food.

In this review, we will highlight infants' immune responses to food, emphasizing the unique aspects of early-life immunity and the critical role of breast milk as a food dedicated to infants. Infants are susceptible to inflammatory responses rather than immune tolerance at the mucosal and skin barriers, necessitating strategies to promote oral tolerance that consider this susceptibility. Breast milk provides nutrients for growth and cell metabolism, including immune cells. The content of breast milk, influenced by maternal genetics and environmental exposures, prepares the infant's immune system for the outside world, including solid foods. To do this, breast milk promotes immune system development through antigen-specific and non-antigen-specific immune education by exposing the newborn to food and respiratory allergens and acting on three key targets for food allergy prevention: the gut microbiota, epithelial cells, and immune cells. Building knowledge of how the maternal exposome and human milk composition influence offspring's healthy immune development will lead to recommendations that meet the specific needs of the developing immune system and increase the chances of promoting an appropriate immune response to food in the long term.

Opportunities in the Postpartum Period to Reduce Cardiovascular Disease Risk After Adverse Pregnancy Outcomes: A Scientific Statement From the American Heart Association.

Adverse pregnancy outcomes are common among pregnant individuals and are associated with long-term risk of cardiovascular disease. Individuals with adverse pregnancy outcomes also have an increased incidence of cardiovascular disease risk factors after delivery. Despite this, evidence-based approaches to managing these patients after pregnancy to reduce cardiovascular disease risk are lacking. In this scientific statement, we review the current evidence on interpregnancy and postpartum preventive strategies, blood pressure management, and lifestyle interventions for optimizing cardiovascular disease using the American Heart Association Life's Essential 8 framework. Clinical, health system, and community-level interventions can be used to engage postpartum individuals and to reach populations who experience the highest burden of adverse pregnancy outcomes and cardiovascular disease. Future trials are needed to improve screening of subclinical cardiovascular disease in individuals with a history of adverse pregnancy outcomes, before the onset of symptomatic disease. Interventions in the fourth trimester, defined as the 12 weeks after delivery, have great potential to improve cardiovascular health across the life course.

Genomic Innovation in Early Life Cardiovascular Disease Prevention and Treatment.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Although CVD events do not typically manifest until older adulthood, CVD develops gradually across the life-course, beginning with the elevation of risk factors observed as early as childhood or adolescence and the emergence of subclinical disease that can occur in young adulthood or midlife. Genomic background, which is determined at zygote formation, is among the earliest risk factors for CVD. With major advances in molecular technology, including the emergence of gene-editing techniques, along with deep whole-genome sequencing and high-throughput array-based genotyping, scientists now have the opportunity to not only discover genomic mechanisms underlying CVD but use this knowledge for the life-course prevention and treatment of these conditions. The current review focuses on innovations in the field of genomics and their applications to monogenic and polygenic CVD prevention and treatment. With respect to monogenic CVD, we discuss how the emergence of whole-genome sequencing technology has accelerated the discovery of disease-causing variants, allowing comprehensive screening and early, aggressive CVD mitigation strategies in patients and their families. We further describe advances in gene editing technology, which might soon make possible cures for CVD conditions once thought untreatable. In relation to polygenic CVD, we focus on recent innovations that leverage findings of genome-wide association studies to identify druggable gene targets and develop predictive genomic models of disease, which are already facilitating breakthroughs in the life-course treatment and prevention of CVD. Gaps in current research and future directions of genomics studies are also discussed. In aggregate, we hope to underline the value of leveraging genomics and broader multiomics information for characterizing CVD conditions, work which promises to expand precision approaches for the life-course prevention and treatment of CVD.

One-Year Effects of High-Intensity Statin on Bioactive Lipids: Findings From the JUPITER Trial.

BACKGROUND: Statin effects extend beyond low-density lipoprotein cholesterol reduction, potentially modulating the metabolism of bioactive lipids (BALs), crucial for biological signaling and inflammation. These bioactive metabolites may serve as metabolic footprints, helping uncover underlying processes linked to pleiotropic effects of statins and yielding a better understanding of their cardioprotective properties. This study aimed to investigate the impact of high-intensity statin therapy versus placebo on plasma BALs in the JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; NCT00239681), a randomized primary prevention trial involving individuals with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L. METHODS: Using a nontargeted mass spectrometry approach, over 11 000 lipid features were assayed from baseline and 1-year plasma samples from cardiovascular disease noncases from 2 nonoverlapping nested substudies: JUPITERdiscovery (n=589) and JUPITERvalidation (n=409). The effect of randomized allocation of rosuvastatin 20 mg versus placebo on BALs was examined by fitting a linear regression with delta values (∆=year 1-baseline) adjusted for age and baseline levels of each feature. Significant associations in discovery were analyzed in the validation cohort. Multiple comparisons were adjusted using 2-stage overall false discovery rate. RESULTS: We identified 610 lipid features associated with statin randomization with significant replication (overall false discovery rate, <0.05), including 26 with annotations. Statin therapy significantly increased levels of 276 features, including BALs with anti-inflammatory activity and arterial vasodilation properties. Concurrently, 334 features were significantly lowered by statin therapy, including arachidonic acid and proinflammatory and proplatelet aggregation BALs. By contrast, statin therapy reduced an eicosapentaenoic acid-derived hydroxyeicosapentaenoic acid metabolite, which may be related to impaired glucose metabolism. Additionally, we observed sex-related differences in 6 lipid metabolites and 6 unknown features. CONCLUSIONS: Statin allocation was significantly associated with upregulation of BALs with anti-inflammatory, antiplatelet aggregation and antioxidant properties and downregulation of BALs with proinflammatory and proplatelet aggregation activity, supporting the pleiotropic effects of statins beyond low-density lipoprotein cholesterol reduction.

Sudden cardiac death after myocardial infarction: individual participant data from pooled cohorts.

BACKGROUND AND AIMS: Risk stratification of sudden cardiac death after myocardial infarction and prevention by defibrillator rely on left ventricular ejection fraction (LVEF). Improved risk stratification across the whole LVEF range is required for decision-making on defibrillator implantation. METHODS: The analysis pooled 20 data sets with 140 204 post-myocardial infarction patients containing information on demographics, medical history, clinical characteristics, biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging. Separate analyses were performed in patients (i) carrying a primary prevention cardioverter-defibrillator with LVEF ≤ 35% [implantable cardioverter-defibrillator (ICD) patients], (ii) without cardioverter-defibrillator with LVEF ≤ 35% (non-ICD patients ≤ 35%), and (iii) without cardioverter-defibrillator with LVEF > 35% (non-ICD patients >35%). Primary outcome was sudden cardiac death or, in defibrillator carriers, appropriate defibrillator therapy. Using a competing risk framework and systematic internal-external cross-validation, a model using LVEF only, a multivariable flexible parametric survival model, and a multivariable random forest survival model were developed and externally validated. Predictive performance was assessed by random effect meta-analysis. RESULTS: There were 1326 primary outcomes in 7543 ICD patients, 1193 in 25 058 non-ICD patients ≤35%, and 1567 in 107 603 non-ICD patients >35% during mean follow-up of 30.0, 46.5, and 57.6 months, respectively. In these three subgroups, LVEF poorly predicted sudden cardiac death (c-statistics between 0.50 and 0.56). Considering additional parameters did not improve calibration and discrimination, and model generalizability was poor. CONCLUSIONS: More accurate risk stratification for sudden cardiac death and identification of low-risk individuals with severely reduced LVEF or of high-risk individuals with preserved LVEF was not feasible, neither using LVEF nor using other predictors.

Risk prediction of cardiovascular disease in the Asia-Pacific region: the SCORE2 Asia-Pacific model.

BACKGROUND AND AIMS: To improve upon the estimation of 10-year cardiovascular disease (CVD) event risk for individuals without prior CVD or diabetes mellitus in the Asia-Pacific region by systematic recalibration of the SCORE2 risk algorithm. METHODS: The sex-specific and competing risk-adjusted SCORE2 algorithms were systematically recalibrated to reflect CVD incidence observed in four Asia-Pacific risk regions, defined according to country-level World Health Organization age- and sex-standardized CVD mortality rates. Using the same approach as applied for the original SCORE2 models, recalibration to each risk region was completed using expected CVD incidence and risk factor distributions from each region. RESULTS: Risk region-specific CVD incidence was estimated using CVD mortality and incidence data on 8,405,574 individuals (556,421 CVD events). For external validation, data from 9,560,266 individuals without previous CVD or diabetes were analysed in 13 prospective studies from 12 countries (350,550 incident CVD events). The pooled C-index of the SCORE2 Asia-Pacific algorithms in the external validation data sets was 0.710 (95% confidence interval [CI] 0.677-0.745). Cohort-specific C-indices ranged from 0.605 (95% CI 0.597-0.613) to 0.840 (95% CI 0.771-0.909). Estimated CVD risk varied several-fold across Asia-Pacific risk regions. For example, the estimated 10-year CVD risk for a 50-year-old non-smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and high-density lipoprotein-cholesterol of 1.3 mmol/L, ranged from 7% for men in low-risk countries to 14% for men in very-high-risk countries, and from 3% for women in low-risk countries to 13% for women in very-high-risk countries. CONCLUSIONS: The SCORE2 Asia-Pacific algorithms have been calibrated to estimate 10-year risk of CVD for apparently healthy people in Asia and Oceania, thereby enhancing the identification of individuals at higher risk of developing CVD across the Asia-Pacific region.

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Integration of a polygenic score into guideline-recommended prediction of cardiovascular disease.

BACKGROUND AND AIMS: It is not clear how a polygenic risk score (PRS) can be best combined with guideline-recommended tools for cardiovascular disease (CVD) risk prediction, e.g. SCORE2. METHODS: A PRS for coronary artery disease (CAD) was calculated in participants of UK Biobank (n = 432 981). Within each tenth of the PRS distribution, the odds ratios (ORs)-referred to as PRS-factor-for CVD (i.e. CAD or stroke) were compared between the entire population and subgroups representing the spectrum of clinical risk. Replication was performed in the combined Framingham/Atherosclerosis Risk in Communities (ARIC) populations (n = 10 757). The clinical suitability of a multiplicative model 'SCORE2 × PRS-factor' was tested by risk reclassification. RESULTS: In subgroups with highly different clinical risks, CVD ORs were stable within each PRS tenth. SCORE2 and PRS showed no significant interactive effects on CVD risk, which qualified them as multiplicative factors: SCORE2 × PRS-factor = total risk. In UK Biobank, the multiplicative model moved 9.55% of the intermediate (n = 145 337) to high-risk group increasing the individuals in this category by 56.6%. Incident CVD occurred in 8.08% of individuals reclassified by the PRS-factor from intermediate to high risk, which was about two-fold of those remained at intermediate risk (4.08%). Likewise, the PRS-factor shifted 8.29% of individuals from moderate to high risk in Framingham/ARIC. CONCLUSIONS: This study demonstrates that absolute CVD risk, determined by a clinical risk score, and relative genetic risk, determined by a PRS, provide independent information. The two components may form a simple multiplicative model improving precision of guideline-recommended tools in predicting incident CVD.

Feasibility of prevention of type 2 diabetes in low- and middle-income countries.

Type 2 diabetes is a leading cause of global mortality and morbidity. Nearly 80% of individuals with diabetes live in low- and middle-income countries (LMICs), where nearly half of those with the condition remain undiagnosed. The majority of known cases have sub-optimal clinical outcomes. Moreover, large populations with impaired glucose tolerance and/or impaired fasting glucose contribute to the rapid increase in type 2 diabetes. Globally, priority should be given to limit the population with diabetes, especially in LMICs, alongside actions to optimise the care of people diagnosed with diabetes. Primary prevention studies in LMICs have generated evidence to show the efficacy and scalability of strategies to fully prevent or delay the development of diabetes in high-risk groups. However, these are mainly limited to certain countries in Asia, particularly China and India. The studies have indicated that prevention policies are effective in populations with a high risk of type 2 diabetes, and they also have long-term benefits, not only for the risk of type 2 diabetes but also for the risk of associated metabolic disorders, such as CVDs. For the effective conduct of national programmes, innovative mechanisms must be implemented, such as the use of information technology, joint efforts of multiple teams implementing similar programmes, and involvement of governmental and non-governmental partnerships. Continuous monitoring and long-term studies are required to assess the utility of these programmes. The effectiveness of such programmes in LMICs has not been proven over the longer term, except in China. Despite the available evidence, the feasibility of prevention strategies for type 2 diabetes in LMICs at population level remains an enigma. There remain challenges in the form of cultural, societal and economic constraints; insufficient infrastructure and healthcare capacity; and the non-fully elucidated natural history and determinants of type 2 diabetes in LMICs.

Optimizing Prepregnancy Cardiovascular Health to Improve Outcomes in Pregnant and Postpartum Individuals and Offspring: A Scientific Statement From the American Heart Association.

This scientific statement summarizes the available preclinical, epidemiological, and clinical trial evidence that supports the contributions of prepregnancy (and interpregnancy) cardiovascular health to risk of adverse pregnancy outcomes and cardiovascular disease in birthing individuals and offspring. Unfavorable cardiovascular health, as originally defined by the American Heart Association in 2010 and revised in 2022, is prevalent in reproductive-aged individuals. Significant disparities exist in ideal cardiovascular health by race and ethnicity, socioeconomic status, and geography. Because the biological processes leading to adverse pregnancy outcomes begin before conception, interventions focused only during pregnancy may have limited impact on both the pregnant individual and offspring. Therefore, focused attention on the prepregnancy period as a critical life period for optimization of cardiovascular health is needed. This scientific statement applies a life course and intergenerational framework to measure, modify, and monitor prepregnancy cardiovascular health. All clinicians who interact with pregnancy-capable individuals can emphasize optimization of cardiovascular health beginning early in childhood. Clinical trials are needed to investigate prepregnancy interventions to comprehensively target cardiovascular health. Beyond individual-level interventions, community-level interventions must include and engage key stakeholders (eg, community leaders, birthing individuals, families) and target a broad range of antecedent psychosocial and social determinants. In addition, policy-level changes are needed to dismantle structural racism and to improve equitable and high-quality health care delivery because many reproductive-aged individuals have inadequate, fragmented health care before and after pregnancy and between pregnancies (interpregnancy). Leveraging these opportunities to target cardiovascular health has the potential to improve health across the life course and for subsequent generations.

Incidental Coronary Artery Calcium: Opportunistic Screening of Previous Nongated Chest Computed Tomography Scans to Improve Statin Rates (NOTIFY-1 Project).

BACKGROUND: Coronary artery calcium (CAC) can be identified on nongated chest computed tomography (CT) scans, but this finding is not consistently incorporated into care. A deep learning algorithm enables opportunistic CAC screening of nongated chest CT scans. Our objective was to evaluate the effect of notifying clinicians and patients of incidental CAC on statin initiation. METHODS: NOTIFY-1 (Incidental Coronary Calcification Quality Improvement Project) was a randomized quality improvement project in the Stanford Health Care System. Patients without known atherosclerotic cardiovascular disease or a previous statin prescription were screened for CAC on a previous nongated chest CT scan from 2014 to 2019 using a validated deep learning algorithm with radiologist confirmation. Patients with incidental CAC were randomly assigned to notification of the primary care clinician and patient versus usual care. Notification included a patient-specific image of CAC and guideline recommendations regarding statin use. The primary outcome was statin prescription within 6 months. RESULTS: Among 2113 patients who met initial clinical inclusion criteria, CAC was identified by the algorithm in 424 patients. After chart review and additional exclusions were made, a radiologist confirmed CAC among 173 of 194 patients (89.2%) who were randomly assigned to notification or usual care. At 6 months, the statin prescription rate was 51.2% (44/86) in the notification arm versus 6.9% (6/87) with usual care (P<0.001). There was also more coronary artery disease testing in the notification arm (15.1% [13/86] versus 2.3% [2/87]; P=0.008). CONCLUSIONS: Opportunistic CAC screening of previous nongated chest CT scans followed by clinician and patient notification led to a significant increase in statin prescriptions. Further research is needed to determine whether this approach can reduce atherosclerotic cardiovascular disease events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04789278.

Cardiovascular Disease Risk Factors in Women: The Impact of Race and Ethnicity: A Scientific Statement From the American Heart Association.

Cardiovascular disease is the leading cause of death in women, yet differences exist among certain racial and ethnic groups. Aside from traditional risk factors, behavioral and environmental factors and social determinants of health affect cardiovascular health and risk in women. Language barriers, discrimination, acculturation, and health care access disproportionately affect women of underrepresented races and ethnicities. These factors result in a higher prevalence of cardiovascular disease and significant challenges in the diagnosis and treatment of cardiovascular conditions. Culturally sensitive, peer-led community and health care professional education is a necessary step in the prevention of cardiovascular disease. Equitable access to evidence-based cardiovascular preventive health care should be available for all women regardless of race and ethnicity; however, these guidelines are not equally incorporated into clinical practice. This scientific statement reviews the current evidence on racial and ethnic differences in cardiovascular risk factors and current cardiovascular preventive therapies for women in the United States.

Baseline breast tissue characteristics determine the effect of tamoxifen on mammographic density change.

Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk-reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition influences tamoxifen-associated density change. This biopsy-based study included 83 participants randomised to 6 months daily intake of placebo, 20, 10, 5, 2.5, or 1 mg tamoxifen. The study is nested within the double-blinded tamoxifen dose-determination trial Karolinska Mammography Project for Risk Prediction of Breast Cancer Intervention (KARISMA) Study. Ultrasound-guided core-needle breast biopsies were collected at baseline before starting treatment. Biopsies were quantified for epithelial, stromal, and adipose distributions, and epithelial and stromal expression of proliferation marker Ki67, oestrogen receptor (ER) and progesterone receptor (PR). Mammographic density was measured using STRATUS. We found that greater mammographic density at baseline was positively associated with stromal area and inversely associated with adipose area and stromal expression of ER. Premenopausal women had greater mammographic density and epithelial tissue, and expressed more epithelial Ki67, PR, and stromal PR, compared to postmenopausal women. In women treated with tamoxifen (1-20 mg), greater density decrease was associated with higher baseline density, epithelial Ki67, and stromal PR. Women who responded to tamoxifen with a density decrease had on average 17% higher baseline density and a 2.2-fold higher PR expression compared to non-responders. Our results indicate that features in the normal breast tissue before tamoxifen exposure influences the tamoxifen-associated density decrease, and that the age-associated difference in density change may be related to age-dependant differences in expression of Ki67 and PR.

Population Attributable Fraction of Total Stroke Associated with Modifiable Risk Factors in the United States.

Stroke is a leading cause of death in the United States across all race/ethnicity and sex groups, though disparities exist. We investigated the potential for primary prevention of total first stroke for Americans aged 20 and older, stratified by sex and race/ethnicity. Specifically, we calculated population attributable fractions (PAF) of first stroke for 7 potentially modifiable risk factors: smoking, physical inactivity, poor diet, obesity, hypertension, diabetes, and atrial fibrillation. PAFs are a function of (1) the relative risk of first stroke for people with the exposure and (2) the prevalence of the risk factor in the population. Relative risks came from recent meta-analyses and sex-race/ethnicity-specific prevalence estimates came from the 2015-2018 NHANES or Multi-Ethnic Study of Atherosclerosis (for atrial fibrillation only). Approximately 1/3 (35.7% [CI: 21.6%-49.0%]) for women, 32.7% [CI: 19.2%-45.1%] for men) of strokes were attributable to the 7 risk factors we considered. A 20% proportional reduction in stroke risk factors would result in approximately 37,000 fewer strokes annually in the United States. The estimated PAF was highest for non-Hispanic Black women (39.3% [CI: 24.8%-52.3%]) and lowest for non-Hispanic Asian men (25.5% [CI: 14.6%-36.2%]). For most groups, obesity and hypertension were the largest contributors to stroke rates.

Association between colchicine use and adverse cardiovascular events in patients with gout: a nationwide nested case-control study.

OBJECTIVE: The association between colchicine use and the primary prevention of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to explore the association between colchicine use and new development of ASCVD and ASCVD-related mortality in patients with incident gout. METHODS: This nested case-control study utilized the nation-wide claims database of the Korean National Health Insurance System. Patients without a history of ASCVD who developed incident gout and were newly started on allopurinol as first-line therapy between 2011 and 2016 were initially screened. Individuals who experienced ASCVD event or ASCVD-related mortality during the follow-up period were matched with four controls for age, sex, income, residential area, co-morbidities, and medications. The main exposure was colchicine use, assessed by 1) the cumulative defined daily doses (cDDDs) and 2) the cumulative duration. For secondary analyses, the risk of ASCVD events and ASCVD-related mortality were examined, separately. RESULTS: Overall, 9,346 patients with ASCVD event or ASCVD-related mortality were matched with 35 070 controls. The patient population was predominantly male. Compared with non-users, a curvilinear relationship between higher cDDDs of colchicine and the odds of ASCVD event was observed; the odds ratios (95% confidence interval) were were 1.09 (1.04-1.15) for <90 cDDDs, 1.20 (1.07-1.33) for 80-179 cDDDs, and 1.21 (1.09-1.35) for ≥180 cDDDs. This association was similarly observed for ASCVD events and ASCVD-related mortality, respectively. CONCLUSION: Colchicine use was associated with an increased risk of ASCVD in patients with newly diagnosed gout who did not have a prior history of ASCVD.

Ten years of subcutaneous defibrillator therapy: Consolidated clinical evidence and future perspectives.

The subcutaneous implantable cardioverter defibrillator (S-ICD) was developed as an alternative to the traditional transvenous implantable cardioverter defibrillator (TV-ICD), aiming to provide easier implantation, simplified detection algorithm of malignant ventricular arrhythmias and prevention from placing components in the cardiovascular system. The S-ICD is implanted subcutaneously or intramuscularly with the generator placed in the left midaxillary line and the lead tunneled subcutaneously in the left para-sternal region. Preimplant electrocardiogram screening is recommended to prevent implantation in patients at high risk of T wave over-sensing. Currently, the S-ICD is unsuitable for patients requiring pacing or cardiac resynchronization. Since the beginning, the S-ICD underwent extensive preclinical investigation until the first prospective multicentre trial demonstrating high efficacy and safety led to market release. While earlier studies focused on younger patients with higher ejection fraction, more recent studies showed favorable outcomes even in patients with comorbidities similar to those typically observed in patients receiving TV-ICD. The development of second and third generation devices has contributed to reduce inappropriate shocks and overcome previous limitations. The aim of this paper is to review the evidence in the literature over the past decade supporting S-ICD as a valid alternative to TV-ICD in terms of safety and efficacy, highlighting the improvements in technology, as well as outcomes.

The impact of supraventricular arrhythmias on the outcomes of guideline-compliant implantable cardioverter defibrillator programming.

INTRODUCTION: Several implantable cardioverter defibrillators (ICD) programming strategies are applied to minimize ICD therapy, especially unnecessary therapies from supraventricular arrhythmias (SVA). However, it remains unknown whether these optimal programming recommendations only benefit those with SVAs or have any detrimental effects from delayed therapy on those without SVAs. This study aims to assess the impact of SVA on the outcomes of ICD programming based on 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement and 2019 focused update on optimal ICD programming and testing guidelines. METHODS: Consecutive patients who underwent ICD insertion for primary prevention were classified into four groups based on SVA status and ICD programming: (1) guideline-concordant group (GC) with SVA, (2) GC without SVA, (3) nonguideline concordant group (NGC) with SVA, and (4) NGC without SVA. Cox proportional hazard models were analyzed for freedom from ICD therapies, shock, and mortality. RESULTS: Seven hundred and seventy-two patients (median age, 64 years) were enrolled. ICD therapies were the most frequent in NGC with SVA (24.0%), followed by NGC without SVA (19.9%), GC without SVA (11.6%), and GC with SVA (8.1%). Guideline concordant programming was associated with 68% ICD therapy reduction (HR 0.32, p = .007) and 67% ICD shock reduction (HR 0.33, p = .030) in SVA patients and 44% ICD therapy reduction in those without SVA (HR 0.56, p = .030). CONCLUSION: Programming ICDs in primary prevention patients based on current guidelines reduces therapy burden without increasing mortality in both SVA and non-SVA patients. A greater magnitude of reduced ICD therapy was found in those with supraventricular arrhythmias.

Clinician use of the Statin Choice Shared Decision-making Encounter Tool in a Major Health System.

BACKGROUND: Effective shared decision-making (SDM) tools for use during clinical encounters are available, but, outside of study settings, little is known about clinician use of these tools in practice. OBJECTIVE: To describe real-world use of an SDM encounter tool for statin prescribing, Statin Choice, embedded into the workflow of an electronic health record. DESIGN: Cross-sectional study. PARTICIPANTS: Clinicians and their statin-eligible patients who had outpatient encounters between January 2020 and June 2021 in Cleveland Clinic Health System. MAIN MEASURES: Clinician use of Statin Choice was recorded within the Epic record system. We categorized each patient's 10-year atherosclerotic cardiovascular disease risk into low (< 5%), borderline (5-7.5%), intermediate (7.5-20%), and high (≥ 20%). Other patient factors included age, sex, insurance, and race. We used mixed effects logistic regression to assess the odds of using Statin Choice for statin-eligible patients, accounting for clustering by clinician and site. We generated a residual intraclass correlation coefficient (ICC) to characterize the impact of the clinician on Statin Choice use. KEY RESULTS: Statin Choice was used in 7% of 68,505 eligible patients. Of 1047 clinicians, 48% used Statin Choice with ≥ 1 patient, and these clinicians used it with a median 9% of their patients (interquartile range: 3-22%). In the mixed effects logistic regression model, patient age (adjusted OR per year: 1.04; 95%CI 1.03-1.04) and 10-year ASVCD risk (aOR for 5-7.5% versus < 5% risk: 1.28; 95%CI: 1.14-1.44) were associated with use of Statin Choice. Black versus White race was associated with a lower odds of Statin Choice use (aOR: 0.83; 95%CI: 0.73-0.95), as was female versus male sex (aOR: 0.83; 95%CI: 0.76-0.90). The model ICC demonstrated that 53% of the variation in use of Statin Choice was clinician-driven. CONCLUSIONS: Patient factors, including race and sex, were associated with clinician use of Statin Choice; half the variation in use was attributable to individual clinicians.

Cholesterol Lowering in Older Adults: Should We Wait for Further Evidence?

PURPOSE OF REVIEW: Current guidelines for primary and secondary prevention of cardiovascular events in adults up to age 75 years are well-established. However, recommendations for lipid-lowering therapies (LLT), particularly for primary prevention, are inconclusive after age 75. In this review, we focus on adults ≥ 75 years to assess low-density lipoprotein-cholesterol (LDL-C) as a marker for predicting atherosclerotic cardiovascular disease (ASCVD) risk, review risk assessment tools, highlight guidelines for LLT, and discuss benefits, risks, and deprescribing strategies. RECENT FINDINGS: The relationship between LDL-C and all-cause mortality and cardiovascular outcomes in older adults is complex and confounded. Current ASCVD risk estimators heavily depend on age and lack geriatric-specific variables. Emerging tools may reclassify individuals based on biologic rather than chronologic age, with coronary artery calcium scores gaining popularity. After initiating LLT for primary or secondary prevention, target LDL-C levels for older adults are lacking, and non-statin therapy thresholds remain unknown, relying on evidence from younger populations. Shared decision-making is crucial, considering therapy's time to benefit, life expectancy, adverse events, and geriatric syndromes. Deprescribing is recommended in end-of-life care but remains unclear in fit or frail older adults. After an ASCVD event, LLT is appropriate for most older adults, and deprescribing can be considered for those approaching the last months of life. Ongoing trials will guide statin prescription and deprescribing among older adults free of ASCVD. In the interim, for adults ≥ 75 years without a limited life expectancy who are free of ASCVD, an LLT approach that includes both lifestyle and medications, specifically statins, may be considered after shared decision-making.

When Does Primary Prevention Encroach on Secondary Prevention?

PURPOSE OF REVIEW: The risk of incident atherosclerotic cardiovascular disease (ASCVD) in primary prevention is typically lower than in secondary prevention. However, there is a spectrum of risk among individuals undergoing primary prevention with the risk in some individuals approaching those of secondary prevention. We review the clinical conditions wherein the risk in primary prevention is similar to that observed in secondary prevention. RECENT FINDINGS: Among individuals without established ASCVD, coronary artery calcium (CAC) scores ≥ 300 AU are associated with ASCVD event rates similar to secondary prevention populations. CAC score ≥ 1,000 AU are associated with an ASCVD risk seen in very high-risk secondary prevention populations. Interpretation of these observations must however consider differences in the risk reduction strategies. Current guidelines dichotomize ASCVD prevention into primary and secondary prevention, but certain primary prevention patients have an ASCVD risk equivalent to that of secondary prevention populations. Identifying higher risk primary prevention populations will allow for better risk mitigation strategies.