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Neurodegenerative diseases are characterized by the progressive breakdown of neuronal structure and function and the pathological accumulation of misfolded protein aggregates and toxic protein oligomers. A major contributor to the deterioration of neuronal physiology is the disruption of protein catabolic pathways mediated by the proteasome, a large protease complex responsible for most cellular protein degradation. Previously, it was believed that proteolysis by the proteasome required tagging of protein targets with polyubiquitin chains, a pathway called the ubiquitin-proteasome system (UPS). Because of this, most research on proteasomal roles in neurodegeneration has historically focused on the UPS. However, additional ubiquitin-independent pathways and their importance in neurodegeneration are increasingly recognized. In this review, we discuss the range of ubiquitin-independent proteasome pathways, focusing on substrate identification and targeting, regulatory molecules and adaptors, proteasome activators and alternative caps, and diverse proteasome complexes including the 20S proteasome, the neuronal membrane proteasome, the immunoproteasome, extracellular proteasomes, and hybrid proteasomes. These pathways are further discussed in the context of aging, oxidative stress, protein aggregation, and age-associated neurodegenerative diseases, with a special focus on Alzheimer’s Disease, Huntington’s Disease, and Parkinson’s Disease. A mechanistic understanding of ubiquitin-independent proteasome function and regulation in neurodegeneration is critical for the development of therapies to treat these devastating conditions. This review summarizes the current state of ubiquitin-independent proteasome research in neurodegeneration.

Background: The COVID-19 pandemic prompted rapid expansion of telemedicine to access subspecialty care. However, potential disparities in access to telemedicine in cardiology remain to be fully characterized. Objectives: The authors aimed to study whether telemedicine visit modality (video or audio only) differed by sociodemographic characteristics in the outpatient cardiology population of a large academic health center. Methods: We conducted a retrospective cross-sectional study of telemedicine encounter data from all outpatient cardiology telemedicine visits from January 1, 2020, to December 31, 2021. We examined unique patients’ first telemedicine encounter during the study period. The primary outcome was visit modality, video versus audio-only visit. Predictors of audio-only visit modality were assessed using adjusted logistic regression analyses. Results: There were 47,961 total adult cardiology telemedicine encounters among 39,381 unique patients. Of all encounters, 20.4% were audio only. Odds of audio-only visit modality increased with age, with the highest odds of audio-only visits in patients aged >75 years (OR: 3.4; 95% CI: 2.8-4.2). Non-White race (OR: 1.2; 95% CI: 1.1-1.3), lack of private insurance (Medicaid OR: 2.8; 95% CI: 2.5-3.1 and Medicare OR: 1.7; 95% CI: 1.5-1.8), and higher social deprivation index quintile (social deprivation index 5, most deprived, OR: 2.0; 95% CI: 1.9-2.2) were also associated with increased odds of audio-only modality. Conclusions: We identified sociodemographic disparities in telemedicine visit modality in a large outpatient cardiology population. These findings highlight the important role of audio-only visits in accessing telemedicine, and opportunities to narrow the digital health divide.

Objective: Elevated lipoprotein(a) [Lp(a)] is an independent, genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD). We evaluated the frequency of testing for elevated Lp(a) and subsequent management at the Johns Hopkins Hospital, a large academic medical center, over a 5-year period. Methods: The Johns Hopkins Hospital (JHH) electronic medical record was queried to identify patients with an encounter between 2017 and 2021, either with established ASCVD or at increased risk, defined as being on any lipid lowering medication or having LDL-C ≥ 190 mg/dL. The frequency of Lp(a) testing and of elevated levels were identified for each year. Results: Among 111,350 unique adult patients, 2,785 (2.5 %) had at least one Lp(a) test. Patients with Lp(a) testing, compared to those without testing, were younger (mean age 56 years vs. 66 years), more often female (49 % vs. 44 %), Black (24.7 % vs. 24.6 %) or “other” race/ethnicity (12 % vs 10 %), and had higher LDL-C levels (median 118 vs. 91 mg/dL; p < 0.001). The number and frequency of Lp(a) testing increased from 167 (0.57 %) in 2017 to 1155 (5.67 %) in 2021. Lp(a) levels were abnormal in 43.4 % of patients (moderate [75–125 nmol/L]: 10.3 %, high [126–600 nmol/L]: 32.2 %, severe [>600 nmol/L]: 0.9 %). Among 920 patients with high or severe Lp(a) levels, 200 (22 %) had a subsequent referral to cardiology or lipid specialist, and 180 (20 %) had a new lipid-lowering medication prescribed in the subsequent 18 months. Conclusion: Based on a single-center experience, the frequency of incident Lp(a) testing among increased-risk patients was low but increased significantly over 5-years, likely due to Lipid Clinic referrals with reflex Lp(a) testing and greater awareness about this risk factor. Future work should target appropriate population based Lp(a) testing strategies and clinical decision-making regarding risk management once Lp(a) elevation is diagnosed.

Background Prior studies have shown that cardiovascular disease (CVD) can be effectively managed through telehealth. However, there are little national data on the use of telehealth in people with CVD or CVD risk factors. We aimed to determine the prevalence of telehealth visits and visit modality (video versus audio‐only) in people with CVD and CVD risk factors. We also assessed their rationale and satisfaction with telehealth visits. Methods and Results A nationally representative sample of 6252 participants from the 2022 Health Information National Trends Survey 6 was used. We defined the CVD risk categories as having no self‐reported CVD (coronary heart disease or heart failure) or CVD risk factors (hypertension, diabetes, obesity, or current smoking), CVD risk factors alone, and CVD. Multivariable logistic regression, adjusting for major sociodemographic factors, assessed the relationship between CVD risk and telehealth uptake. The weighted prevalence of using telehealth was 50% (95% CI, 44%–56%) for individuals with CVD and 40% (95% CI, 37%–43%) for those with CVD risk factors alone. Individuals with CVD had the highest odds of using any telehealth (audio‐only or video) (adjusted odds ratio [OR], 2.02 [95% CI, 1.39–2.93]) when compared with those without CVD or CVD risk factors. Notably, 21% (95% CI, 16.3%–25.6%) of patients with CVD used audio‐only visits (adjusted OR, 2.38 [95% CI, 1.55–3.64]) compared with patients without CVD or CVD risk factors. Conclusions In a nationally representative survey, there was high prevalence of any (video or audio‐only) telehealth visits in people with CVD, and audio‐only visits comprised a significant proportion of telehealth visits in this population.

Background The metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride‐rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease. Methods and Results We studied 1791 MESA (Multi‐Ethnic Study of Atherosclerosis) participants who took part in an ancillary study on body composition with adipokine levels measured (leptin, adiponectin, and resistin) at either visit 2 or visit 3. RC was calculated as non–high‐density lipoprotein cholesterol minus low‐density lipoprotein cholesterol, measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable‐adjusted linear mixed‐effects models were used to assess the cross‐sectional and longitudinal associations between adipokines and log‐transformed levels of RC. Mean±SD age was 64.5±9.6 years; mean±SD body mass index was 29.9±5.0 kg/m2; and 52.0% were women. In fully adjusted cross‐sectional models that included body mass index, diabetes, low‐density lipoprotein cholesterol, and lipid‐lowering therapy, for each 1‐unit increment in adiponectin, there was 14.6% (95% CI, 12.2–16.9) lower RC. With each 1‐unit increment in leptin and resistin, there was 4.8% (95% CI, 2.7–7.0) and 4.0% (95% CI, 0.2–8.1) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow‐up of 5 (interquartile range, 4–8) years. Conclusions Lower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for body mass index and low‐density lipoprotein cholesterol.

Cell Reports speaks with Seth S. Margolis and Eric Villalón Landeros about their scientific journeys, experiences, and interests that have led to their recent work in our journal, which demonstrates a role for the neuronal membrane proteasome in modulating the activity of sensory neurons.

Objective: Assess the yield of genetic testing for pathogenic variants in ABCG5, ABCG8, LIPA, and APOE in individuals with personal and family histories suggestive of familial hypercholesterolemia. Methods: Retrospective review of patients seen in the Advanced Lipid Disorders Clinic at Johns Hopkins Results: In the lipid clinic at a single center during the years 2015–2023, 607 patients underwent genetic testing for familial hypercholesterolemia, of which 263 underwent the expanded genetic testing for sitosterolemia. Eighty-eight patients had genetic testing which included APOE, and 22 patients had testing which included LIPA. Among these, one patient was identified to have a pathogenic variant in APOE and another patient with a pathogenic variant in ABCG5 (0.7 % yield). The frequency of a positive result was double that of a variant of uncertain significance. Conclusion: These data suggest in rare cases expanded testing can provide answers for patients and families with a minimal likelihood of a variant of uncertain significance.

BackgroundPeople living with HIV (PLWHA) smoke at three times the rate of the general population and respond poorly to cessation strategies. Previous studies examined repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (L. dlPFC) to reduce craving, but no studies have explored rTMS among PLWHA who smoke. The current pilot study compared the effects of active and sham intermittent theta-burst stimulation (iTBS) on resting state functional connectivity (rsFC), cigarette cue attentional bias, and cigarette craving in PLWHA who smoke.MethodsEight PLWHA were recruited (single-blind, within-subject design) to receive one session of iTBS (n=8) over the L. dlPFC using neuronavigation and, four weeks later, sham iTBS (n=5). Cigarette craving and attentional bias assessments were completed before and after both iTBS and sham iTBS. rsFC was assessed before iTBS (baseline) and after iTBS and sham iTBS.ResultsCompared to sham iTBS, iTBS enhanced rsFC between the L. dlPFC and bilateral medial prefrontal cortex and pons. iTBS also enhanced rsFC between the right insula and right occipital cortex compared to sham iTBS. iTBS also decreased cigarette craving and cigarette cue attentional bias.ConclusioniTBS could potentially offer a therapeutic option for smoking cessation in PLWHA.

IntroductionVascular and mitochondrial dysfunction are well-established consequences of multiple central nervous system (CNS) disorders, including neurodegenerative diseases and traumatic injuries. We previously reported that 5-hydroxytryptamine 1F receptor (5-HT1FR) agonism induces mitochondrial biogenesis (MB) in multiple organ systems, including the CNS.MethodsLasmiditan is a selective 5-HT1FR agonist that is FDA-approved for the treatment of migraines. We have recently shown that lasmiditan treatment induces MB, promotes vascular recovery and improves locomotor function in a mouse model of spinal cord injury (SCI). To investigate the mechanism of this effect, primary cerebral microvascular endothelial cells from C57bl/6 mice (mBMEC) were used.ResultsLasmiditan treatment increased the maximal oxygen consumption rate, mitochondrial proteins and mitochondrial density in mBMEC, indicative of MB induction. Lasmiditan also enhanced endothelial cell migration and tube formation, key components of angiogenesis. Trans-endothelial electrical resistance (TEER) and tight junction protein expression, including claudin-5, were also increased with lasmiditan, suggesting improved barrier function. Finally, lasmiditan treatment decreased phosphorylated VE-Cadherin and induced activation of the Akt-FoxO1 pathway, which decreases FoxO1-mediated inhibition of claudin-5 transcription.DiscussionThese data demonstrate that lasmiditan induces MB and enhances endothelial cell function, likely via the VE-Cadherin-Akt-FoxO1-claudin-5 signaling axis. Given the importance of mitochondrial and vascular dysfunction in neuropathologies, 5-HT1FR agonism may have broad therapeutic potential to address multiple facets of disease progression by promoting MB and vascular recovery.

Dietary supplements augment the nutritional value of everyday food intake and originate from the historical practices of ancient Egyptian (Ebers papyrus), Chinese (Pen Ts’ao by Shen Nung), Indian (Ayurveda), Greek (Hippocrates), and Arabic herbalists. In modern-day medicine, the use of dietary supplements continues to increase in popularity with greater than 50% of the US population reporting taking supplements. To further compound this trend, many patients believe that dietary supplements are equally or more effective than evidence-based therapies for lipoprotein and lipid-lowering. Supplements such as red yeast rice, omega-3 fatty acids, garlic, cinnamon, plant sterols, and turmeric are marketed to and believed by consumers to promote “cholesterol health.” However, these supplements are not subjected to the same manufacturing scrutiny by the Food and Drug Administration as pharmaceutical drugs and as such, the exact contents and level of ingredients in each of these may vary. Furthermore, supplements do not have to demonstrate efficacy or safety before being marketed. The holistic approach to lowering atherosclerotic cardiovascular disease risk makes dietary supplements an attractive option to many patients; however, their use should not come at the expense of established therapies with proven benefits. In this narrative review, we provide a historical and evidence-based approach to the use of some dietary supplements in lipoprotein and lipid-lowering and provide a framework for managing patient expectations.

Background Cardiac rehabilitation (CR) is an evidence‐based, guideline‐recommended intervention for patients recovering from a cardiac event, surgery or procedure that improves morbidity, mortality, and functional status. CR is traditionally provided in‐center, which limits access and engagement, most notably among underrepresented racial and ethnic groups due to barriers including cost, scheduling, and transportation access. This study is designed to evaluate the Corrie Hybrid CR, a technology‐based, multicomponent health equity‐focused intervention as an alternative to traditional in‐center CR among patients recovering from a cardiac event, surgery, or procedure compared with usual care alone. Methods The mTECH‐Rehab (Impact of a Mobile Technology Enabled Corrie CR Program) trial will randomize 200 patients who either have a diagnosis of type 1 myocardial infarction or who undergo coronary artery bypass grafting surgery, percutaneous coronary intervention, heart valve repair, or replacement presenting to 4 hospitals in a large academic health system in Maryland, United States, to the Corrie Hybrid CR program combined with usual care CR (intervention group) or usual care CR alone (control group) in a parallel arm, randomized controlled trial. The Corrie Hybrid CR program leverages 5 components: (1) a patient‐facing mobile application that encourages behavior change, patient empowerment, and engagement with guideline‐directed therapy; (2) Food and Drug Administration‐approved smart devices that collect health metrics; (3) 2 upfront in‐center CR sessions to facilitate personalization, self‐efficacy, and evaluation for the safety of home exercise, followed by a combination of in‐center and home‐based sessions per participant preference; (4) a clinician dashboard to track health data; and (5) weekly virtual coaching sessions delivered over 12 weeks for education, encouragement, and risk factor modification. The primary outcome is the mean difference between the intervention versus control groups in distance walked on the 6‐minute walk test (ie, functional capacity) at 12 weeks post randomization. Key secondary and exploratory outcomes include improvement in a composite cardiovascular health metric, CR engagement, quality of life, health factors (including low‐density lipoprotein‐cholesterol, hemoglobin A1c, weight, diet, smoking cessation, blood pressure), and psychosocial factors. Approval for the study was granted by the local institutional review board. Results of the trial will be published once data collection and analysis have been completed. Conclusions The Corrie Hybrid CR program has the potential to improve functional status, cardiovascular health, and CR engagement and advance equity in access to cardiac rehabilitation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05238103.

Abstract Background Nutritional counseling, which includes two‐way interactive education, has been hypothesized to improve the health and nutritional status of pregnant women, but little is known about the impact such practice of care might have on maternal and infant health and behavioral outcomes of pregnant women living in low income, low‐middle income, and upper‐middle‐income countries (LMIC)s. Objectives We conducted a systematic review to appraise the effectiveness and impact on health equity of two‐way nutritional counseling practices in LMICs on maternal and infant behavioral, nutritional, and health outcomes. Search Methods We conducted electronic searches for relevant studies on Medline, Embase, CINAHL, PsychInfo, and the Cochrane CENTRAL for randomized and non‐randomized trials on the effectiveness of two‐way interactive nutritional counseling among pregnant women from the date of database inception up to June 22, 2021. In addition, we searched references of included studies in systematic reviews, gray literature resources, and unpublished studies or reports that satisfied our eligibility criteria using a focused Google search. Selection Criteria We included randomized and non‐randomized controlled studies (NRS), controlled before and after, and interrupted time series that assessed the effectiveness of two‐way interactive nutrition counseling targeting pregnant women in LMICs. Data Collection and Analysis Data extraction and risk of bias were conducted in duplicate. The risk of bias (ROB) for randomized trials (RCT) was assessed according to the Cochrane Handbook of Systematic Reviews, and ROB for NRS was assessed using the Newcastle‐Ottawa scale (NOS). RCT and NRS were meta‐analyzed separately. Main Results Our search identified 6418 records and 52 studies met our inclusion criteria, but only 28 were used in the quantitative analysis. Twenty‐eight studies were conducted in Asia, the most in Iran. Eight studies were conducted in Africa. Two‐way interactive nutritional counseling during pregnancy may improve dietary caloric intake (mean difference [MD]: 81.65 calories, 95% confidence interval [CI], 15.37–147.93, three RCTs; I2 = 42%; moderate certainty of evidence using GRADE assessment), may reduce hemorrhage (relative risk [RR]: 0.63; 95% CI, 0.25–1.54, two RCTs; I2 = 40%; very low certainty of evidence using GRADE assessment), may improve protein (MD: 10.44 g, 95% CI, 1.83–19.05, two RCTs; I2 = 95%; high certainty of evidence using GRADE assessment), fat intake (MD: 3.42 g, 95% CI, −0.20 to 7.04, two RCTs; I2 = 0%; high certainty of evidence using GRADE assessment), and may improve gestational weight gain within recommendations (RR: 1.84; 95% CI, 1.10–3.09, three RCTs; I2 = 69%). Nutrition counseling probably leads to the initiation of breastfeeding immediately after birth (RR: 1.72; 95% CI, 1.42–2.09, one RCT). There was little to no effect on reducing anemia (RR: 0.77; 95% CI, 0.50–1.20, three RCTs; I2 = 67%; very low certainty of evidence using GRADE assessment) risk of stillbirths (RR: 0.81; 95% CI, 0.52–1.27, three RCTs; I2 = 0%; moderate certainty of evidence using GRADE assessment) and risk of cesarean section delivery (RR: 0.96; 95% CI, 0.76–1.20, four RCTs; I2 = 36%; moderate certainty of evidence using GRADE assessment). Authors’ Conclusions Our review highlights improvements in maternal behavioral and health outcomes through interactive nutrition counseling during pregnancy. However, we are uncertain about the effects of nutrition counseling due to the low certainty of evidence and a low number of studies for some key outcomes. Moreover, the effects on health equity remain unknown. More methodologically rigorous trials that focus on a precise selection of outcomes driven by the theory of change of nutrition counseling to improve maternal and infant behavioral and health outcomes and consider equity are required.

ABSTRACTBackground Special populations like people living with HIV/AIDS (PLWHA) and people with opioid use disorder (OUD) smoke tobacco cigarettes at rates three to four times greater than the general population. Patients with tobacco use disorder exhibit attentional bias (AB) for cigarette cues. Eye tracking can quantify this bias by measuring fixation time (FT) on cigarette and matched neutral cues, to calculate an AB score. Although previous studies have measured this bias in people who smoke without any other comorbid conditions, no study, to our knowledge, has measured or compared this bias in special populations.Methods We performed exploratory analyses on eye tracking data collected in two separate randomized clinical trials (RCTs) (NCT05049460, NCT05295953). We compared FT and cigarette-cue AB score (measured by subtracting FT on neutral cues from FT on cigarette cues) between PLWHA and people with OUD who smoke, using a visual probe task and Tobii Pro Fusion eye tracker. We used two cigarette cue types, one encompassing people smoking cigarettes and the other consisting of cigarette paraphernalia. We used two cue presentation times, 1000 and 2000 milliseconds (ms).Results Cues of people smoking cigarettes elicited greater AB than cues of cigarette paraphernalia across both subject groups when cues were presented for 2000 ms, but not 1000 ms. PLWHA who smoke exhibited greater AB for cues of people smoking cigarettes than cigarette paraphernalia when presented for 2000 ms compared to people with OUD who smoke.Conclusion We use cigarette-cue AB to quantify craving and cigarette consumption in two populations smoking at elevated rates. The addition of social cues potentiates cigarette cue AB, based on cue type and stimulus presentation time. Understanding the neurobiology of this relationship can help design novel smoking cessation treatments that target AB and prevent relapse in these populations with suboptimal response to smoking cessation treatments.Trial registration Clinical trials that provided the data for post hoc analyses are NCT05049460 and NCT05295953.

Introduction To evaluate the relationship between electronic nicotine delivery systems (ENDS) use and the risk of stroke when compared to non-smokers. Material and methods A comprehensive search was conducted until June 15, 2023. We included observational studies that assessed association of current or former usage of ENDS with risk of stroke compared with non-smokers, reported the risk estimate as odds ratio (OR) or hazard ratio (HR) and were adjusted for possible confounders. Results 6 studies with 1,024,401 participants were included in our analysis. ENDS use was associated with a significant increased risk of stroke (OR = 1.52; 95% CI: 1.17–1.97) compared with non-users. A non-significant association was found between former ENDS use and risk of stroke (OR = 1.03; 95% CI: 0.87–1.21). Conclusions The ENDS usage appears to be associated with a higher risk of stroke compared to non-use, whereas there was no association between former ENDS use and the risk of stroke.

The popularity of short-messaging formats, like text and chat, is on the rise in the workplace with many employees preferring this style over long-form options like email. While many businesses expect employees to communicate using short messages, students may be ill-equipped to effectively use these methods due to a lack of formal training. This study sets out to understand students’ experience, confidence, and education related to professional short messaging. Results indicate a correlation between confidence and experience levels in writing text and chat messages. Further, the participants who indicated they had training on writing short messages, indicated they learned it in a business communication class. Thus, this study highlights a need for education on short messaging in the business communication classroom to increase student experience, and thus, their confidence in writing these messages.

Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment‐resistant disorder characterized by early‐onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a “real‐world” setting. Untreated low‐density lipoprotein cholesterol levels were lower in adults than children (533 versus 776 mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow‐up, despite multiple lipid‐lowering treatment, low‐density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid‐lowering treatments were prescribed for 18%; 40% were on no lipid‐lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid‐lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.

Disclosures: EMS serves as a consultant to Corrie Health. Under a license agreement between Corrie Health and the Johns Hopkins University, the University owns equity in Corrie Health and the University, FAM, and SSM are entitled to royalty distributions related to technology described in the study discussed in this publication. Additionally, FAM and SSM are founders of and hold equity in Corrie Health. ML and JS have equity ownership in Corrie Health. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies. Therapeutic Area: Cardiac Rehabilitation; Secondary Prevention of CVD; Digital Health Background: Low participation in cardiac rehabilitation (CR) is a missed opportunity to improve outcomes in secondary prevention of cardiovascular disease. To increase participation in CR, a multidisciplinary team launched a 12-week hybrid CR program utilizing in-center and virtual CR sessions via an evidence-based digital health platform. Our early experience with >40 participants provides valuable lessons learned for creating a scalable hybrid CR program. Methods: We established a 5-phase approach from recruitment to graduation. Phase 1 - Pre-Bedside: We used the electronic medical record system, Epic, to identify low to moderate risk CR-eligible inpatients. Phase 2 - Bedside: Patient navigators approached inpatients to inform them about hybrid CR, conduct further screening, and for enrollment. Patients were coached how to use the digital health platform including a smartphone application, smartwatch, and blood pressure monitor. Phase 3 - Pre-CR: During hospitalization and after discharge, patients tracked medication use and vital signs, engaged with educational videos, and entered lab values (ex. LDL). Coaches conducted weekly check-in sessions to review progress, safety, and address any technical issues. Phase 4 - CR: Patients completed 2 in-center safety assessments prior to starting home-exercise. Phase 5 - Graduation: Patients received a graduation coaching session at week 12 to celebrate and plan for sustainable healthy lifestyle habits. Results: We identified multiple areas for improvement and enhanced our program. Phase 1: We streamlined patient identification using Epic reports and auto-referral ordersets for eligible patients. Phase 2: We developed flexible onboarding methods with instructional videos tailored for different levels of digital literacy. We also found that assembling a diverse CR team was key for recruiting patients traditionally underrepresented in CR. Phase 3: We created a structured weekly coaching curriculum to promote engagement. Phase 4: We refined low to moderate risk criteria to adjust for lack of exercise data during hospitalization and implemented 2 in-person safety assessments. Phase 5: Some patients expressed interest in advocacy after graduating, possibly through social media support groups. Conclusion: Drawing on lessons learned, we developed a hybrid CR program that adapted to patients’ experiences and provided a scalable solution for patients who cannot attend CR on a regular basis.

Therapeutic Area: CVD Prevention – Primary and Secondary; ASCVD/CVD Risk Assessment; Preventive Cardiology Best Practices Background: According to the 2022 American Heart Association Heart Disease and Stroke Statistics, coronary heart disease remains the leading cause of death attributable to cardiovascular disease (CVD). Opportunity exists to utilize electronic medical records (EMRs) and biomarkers to facilitate early identification of patients at high risk for CVD. Additionally, automatic or opt-out orders are EMR-based tools that have the potential to improve referral rates to prevention programs. The role of cardiovascular biomarkers and electronic medical records (EMRs) in optimizing identification and referral of patients at risk for CVD are explored in the ABCDs PREVENTION program. Methods: A multidisciplinary team of cardiologists, internists, engineers, and clinical informaticists defined the logic for the guideline based ABCDs PREVENTION tool. The EMR algorithm used the cardiovascular risk biomarker thresholds of lipoprotein(a) > 70 nmol/L, apolipoprotein B > 90 mg/dL, low-density lipoprotein cholesterol > 150 mg/dL, and triglycerides > 200 mg/dL, and/or a diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation MI (NSTEMI) based on ICD-10 codes to generate automatic referrals to (1) cardiac rehabilitation (CR), (2) the advanced lipid disorders clinic, and/or (3) Corrie Cardiovascular Health Program (Figure 1). Results: In a test environment, the algorithm was applied to 27 patients identified by the clinical team with STEMI or NSTEMI. The algorithm was 90% successful in triggering automatic referrals to CR and Corrie. Fail rates can be attributed to our current algorithm not detecting some ICD codes related to NSTEMI. The automatic referral to lipid disorders clinic based on abnormal lipid biomarkers is now live and undergoing automation optimization to validate accuracy. Conclusion: Building an EMR-based algorithm to individualize CVD prevention using cardiovascular risk biomarkers and diagnoses may enable early identification and intervention on high-risk patients. Future directions include applying the algorithm to clinical decision support tools as well as an automated order set to increase referral rates to evidenced-based programs focused on primary and secondary CVD prevention. Ultimately, use analysis will determine if the algorithm improves referral rates to CR, lipid clinic, and the Corrie Cardiovascular Health Program to improve access to these evidence-based services.

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10–25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease.The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Abstract Physical activity (PA) has numerous health benefits. Personalized coaching may increase adherence to PA recommendations, but it is challenging to deliver personalized coaching in a scalable manner. The objective of our study was to determine whether novel artificially intelligent (AI) coaching interventions increase PA among overweight or obese, physically inactive cancer survivors compared to a control arm that receives health information. We conducted a single-center, three-arm randomized trial with equal allocation to (1) voice-assisted AI coaching delivered by smart speaker (MyCoach), (2) autonomous AI coaching delivered by text message (SmartText), and (3) control. Data collection was automated via sensors and voice technology, effectively masking outcome ascertainment. The primary outcome was change in mean steps per day from baseline to the end of follow-up at 4 weeks. Of the 42 randomized participants, 91% were female, and 36% were Black; mean age was 62.1 years, and mean BMI was 32.9 kg/m2. The majority were breast cancer survivors (85.7%). At the end of 4 weeks follow-up, steps increased in the MyCoach arm by an average of 3618.2 steps/day; the net gain in this arm was significantly greater [net difference = 3568.9 steps/day (95% CI: 1483–5655), P value

Background Depression is a nontraditional risk factor for cardiovascular disease (CVD). Data on the association of depression and poor mental health with CVD and suboptimal cardiovascular health (CVH) among young adults are limited. Methods and Results We used data from 593 616 young adults (aged 18–49 years) from the 2017 to 2020 Behavioral Risk Factor Surveillance System, a nationally representative survey of noninstitutionalized US adults. Exposures were self‐reported depression and poor mental health days (PMHDs; categorized as 0, 1–13, and 14–30 days of poor mental health in the past 30 days). Outcomes were self‐reported CVD (composite of myocardial infarction, angina, or stroke) and suboptimal CVH (≥2 cardiovascular risk factors: hypertension, hypercholesterolemia, overweight/obesity, smoking, diabetes, physical inactivity, and inadequate fruit and vegetable intake). Using logistic regression, we investigated the association of depression and PMHDs with CVD and suboptimal CVH, adjusting for sociodemographic factors (and cardiovascular risk factors for the CVD outcome). Of the 593 616 participants (mean age, 34.7±9.0 years), the weighted prevalence of depression was 19.6% (95% CI, 19.4–19.8), and the weighted prevalence of CVD was 2.5% (95% CI, 2.4–2.6). People with depression had higher odds of CVD than those without depression (odds ratio [OR], 2.32 [95% CI, 2.13–2.51]). There was a graded association of PMHDs with CVD. Compared with individuals with 0 PMHDs, the odds of CVD in those with 1 to 13 PMHDs and 14 to 30 PHMDs were 1.48 (95% CI, 1.34–1.62) and 2.29 (95% CI, 2.08–2.51), respectively, after adjusting for sociodemographic and cardiovascular risk factors. The associations did not differ significantly by sex or urban/rural status. Individuals with depression had higher odds of suboptimal CVH (OR, 1.79 [95% CI, 1.65–1.95]) compared with those without depression, with a similar graded relationship between PMHDs and suboptimal CVH. Conclusions Depression and poor mental health are associated with premature CVD and suboptimal CVH among young adults. Although this association is likely bidirectional, prioritizing mental health may help reduce CVD risk and improve CVH in young adults.

Background Understanding current trends in cholesterol screening, lipid levels, and lipid management therapies may inform health policy and practice. Methods and Results In 50 928 US adult National Health and Nutrition Examination Survey (NHANES) participants, trends were assessed in cholesterol screening, mean levels of total cholesterol, triglycerides, low‐density‐lipoprotein cholesterol, and lipid‐lowering medication use from 1999 through 2018. Point estimates were also calculated using the 2017 to March 2020 prepandemic data set. The age‐ and sex‐adjusted proportion of having cholesterol screened within 5 years increased from 63.2% (95% CI, 60.0–66.3) in 1999 to 2000 to 72.5% (95% CI, 69.5–75.3) in 2017 to 2018 (P

Machine learning (ML) refers to computational algorithms that iteratively improve their ability to recognize patterns in data. The digitization of our healthcare infrastructure is generating an abundance of data from electronic health records, imaging, wearables, and sensors that can be analyzed by ML algorithms to generate personalized risk assessments and promote guideline-directed medical management. ML's strength in generating insights from complex medical data to guide clinical decisions must be balanced with the potential to adversely affect patient privacy, safety, health equity, and clinical interpretability. This review provides a primer on key advances in ML for cardiovascular disease prevention and how they may impact clinical practice.

Background:. The introduction of mesh for reinforcement of ventral hernia repair (VHR) led to a significant reduction in hernia recurrence rates. However, it remains controversial whether synthetic or biologic mesh leads to superior outcomes. Recently, hybrid mesh consisting of reinforced biosynthetic ovine rumen (RBOR) has been developed and aims to combine the advantages of biologic and synthetic mesh; however, outcomes after VHR with RBOR have not yet been compared with the standard of care. Methods:. We performed a retrospective analysis on 109 patients, who underwent VHR with RBOR (n = 50) or synthetic polypropylene mesh (n = 59). Demographic characteristics, comorbidities, postoperative complications, and recurrence rates were analyzed and compared between the groups. Multivariate logistic regression models were fit to assess associations of mesh type with overall complications and surgical site occurrence (SSO). Results:. Patients who underwent VHR with RBOR were older (mean age 63.7 versus 58.8 years, P = 0.02) and had a higher rate of renal disease (28.0 versus 10.2%, P = 0.01) compared with patients with synthetic mesh. Despite an unfavorable risk profile, patients with RBOR had lower rates of SSO (16.0 versus 30.5%, P = 0.12) and similar hernia recurrence rates (4.0 versus 6.78%, P = 0.68) compared with patients with synthetic mesh. The use of synthetic mesh was significantly associated with higher odds for overall complications (3.78, P < 0.05) and SSO (3.87, P < 0.05). Conclusion:. Compared with synthetic polypropylene mesh, the use of RBOR for VHR mitigates SSO while maintaining low hernia recurrence rates at 30-month follow-up.

Background: Using mobile health, vital signs such as heart rate (HR) can be used to assess a patient’s recovery process from acute events including acute myocardial infarction (AMI). Objective: We aimed to characterize clinical correlates associated with HR change in the subacute period among patients recovering from AMI. Methods: HR measurements were collected from 91 patients (4447 HR recordings) enrolled in the MiCORE study using the Apple Watch and Corrie smartphone application. Mixed regression models were used to estimate the associations of patient-level characteristics during hospital admission with HR changes over 30 days postdischarge. Results: The mean daily HR at admission was 78.0 beats per minute (bpm) (95% confidence interval 76.1 to 79.8), declining 0.2 bpm/day (-0.3 to -0.1) under a linear model of HR change. History of coronary artery bypass graft, history of depression, or being discharged on anticoagulants was associated with a higher admission HR. Having a history of hypertension, type 2 diabetes mellitus (T2DM), or hyperlipidemia was associated with a slower decrease in HR over time, but not with HR during admission. Conclusion: While a declining HR was observed in AMI patients over 30 days postdischarge, patients with hypertension, T2DM, or hyperlipidemia showed a slower decrease in HR relative to their counterparts. This study demonstrates the feasibility of using wearables to model the recovery process of patients with AMI and represents a first step in helping pinpoint patients vulnerable to decompensation.

Abstract In humans, loss-of-function mutations in the UBE3A gene lead to the neurodevelopmental disorder Angelman syndrome (AS). AS patients have severe impairments in speech, learning and memory, and motor coordination, for which there is currently no treatment. In addition, UBE3A is duplicated in > 1–2% of patients with autism spectrum disorders—a further indication of the significant role it plays in brain development. Altered expression of UBE3A, an E3 ubiquitin ligase, is hypothesized to lead to impaired levels of its target proteins, but identifying the contribution of individual UBE3A targets to UBE3A-dependent deficits remains of critical importance. Ephexin5 is a putative UBE3A substrate that has restricted expression early in development, regulates synapse formation during hippocampal development, and is abnormally elevated in AS mice, modeled by maternally-derived Ube3a gene deletion. Here, we report that Ephexin5 can be directly ubiquitylated by UBE3A. Furthermore, removing Ephexin5 from AS mice specifically rescued hippocampus-dependent behaviors, CA1 physiology, and deficits in dendritic spine number. Our findings identify Ephexin5 as a key driver of hippocampal dysfunction and related behavioral deficits in AS mouse models. These results demonstrate the exciting potential of targeting Ephexin5, and possibly other UBE3A substrates, to improve symptoms of AS and other UBE3A-related developmental disorders.

Background Mobile health (mHealth) has an emerging role in the prevention of cardiovascular disease. This study evaluated possible inequities in mHealth access in older adults. Methods and Results mHealth access was assessed from 2019 to 2020 in MESA (Multi‐Ethnic Study of Atherosclerosis) telephone surveys of 2796 participants aged 62 to 102 years. A multivariable logistic regression model adjusted for general health status assessed associations of mHealth access measures with relevant demographic, socioeconomic, and cognitive characteristics. There were lower odds of all access measures with older age (odds ratios [ORs], 0.37–0.59 per 10 years) and annual income

Background: Alternatives to the Friedewald low-density lipoprotein cholesterol (LDL-C) equation have been proposed. Objective: To compare the accuracy of available LDL-C equations with ultracentrifugation measurement. Methods: We used the second harvest of the Very Large Database of Lipids (VLDbL), which is a population-representative convenience sample of adult and pediatric patients (N = 5,051,467) with clinical lipid measurements obtained via the vertical auto profile (VAP) ultracentrifugation method between October 1, 2015 and June 30, 2019. We performed a systematic literature review to identify available LDL-C equations and compared their accuracy according to guideline-based classification. We also compared the equations by their median error versus ultracentrifugation. We evaluated LDL-C equations overall and stratified by age, sex, fasting status, and triglyceride levels, as well as in patients with atherosclerotic cardiovascular disease, hypertension, diabetes, kidney disease, inflammation, and thyroid dysfunction. Results: Analyzing 23 identified LDL-C equations in 5,051,467 patients (mean±SD age, 56±16 years; 53.3% women), the Martin/Hopkins equation most accurately classified LDL-C to the correct category (89.6%), followed by the Sampson (86.3%), Chen (84.4%), Puavilai (84.1%), Delong (83.3%), and Friedewald (83.2%) equations. The other 17 equations were less accurate than Friedewald, with accuracy as low as 35.1%. The median error of equations ranged from –10.8 to 18.7 mg/dL, and was best optimized using the Martin/Hopkins equation (0.3, IQR–1.6 to 2.4 mg/dL). The Martin/Hopkins equation had the highest accuracy after stratifying by age, sex, fasting status, triglyceride levels, and clinical subgroups. In addition, one in five patients who had Friedewald LDL-C 70 mg/dL by the Martin/Hopkins equation. Conclusions: Most proposed alternatives to the Friedewald equation worsen LDL-C accuracy, and their use could introduce unintended disparities in clinical care. The Martin/Hopkins equation demonstrated the highest LDL-C accuracy overall and across subgroups.

BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is a mediator of the immune response to sepsis. PCSK9 is also highly expressed in pneumocytes and pulmonary endothelial cells. We hypothesized that serum PCSK9 levels would be associated with death and ICU outcomes in patients with ARDS.MethodsUsing data and plasma samples from the NIH BioLINCC data repository, we assembled a cohort of 1,577 patients with the acute respiratory distress syndrome (ARDS) enrolled in two previously completed clinical trials, EDEN and SAILS. We measured PCSK9 levels in plasma within 24 h of intubation using commercially available ELISA kits (R&D Systems). We assessed the association of PCSK9 with mortality using Cox proportional hazard models. We also assessed clinical factors associated with PCSK9 level and the association of PCSK9 with the number of days free of mechanical ventilation and days free of ICU care.ResultsIn 1,577 ARDS patients, median age was 53 years (IQR 42–65 years) and median APACHE III score 91 (72–111) connoting moderate critical illness. PCSK9 levels were 339.3 ng/mL (IQR 248.0–481.0). In multivariable models, race, cause of ARDS, body mass index, pre-existing liver disease, body temperature, sodium, white blood cell count and platelet count were associated with PCSK9 level. Presence of sepsis, use of vasopressors and ventilator parameters were not associated with PCSK9 level. PCSK9 levels were not associated with in-hospital mortality (HR per IQR 0.96, 95% CI 0.84–1.08, P = 0.47). Higher PCSK9 levels were associated with fewer ICU and ventilator free days.ConclusionsPlasma PCSK9 is not associated with mortality in ARDS, however higher PCSK9 levels are associated with secondary outcomes of fewer ICU free and ventilator free days. Clinical factors associated with PCSK9 in ARDS are largely unmodifiable. Further research to define the mechanism of this association is warranted.

Stagnating COVID-19 vaccination rates and vaccine hesitancy remain a threat to public health. Improved strategies for real-time tracking and estimation of population-level behavior regarding vaccinations are needed. The aim of this study was to evaluate whether online search trends for COIVD-19 and influenza mirror vaccination rates. State-level weekly fraction of online searches for top vaccination-related search terms and CDC vaccination data were obtained from June 1, 2020, to May 31, 2021. Next, trends in online search and vaccination data for COVID-19 and influenza were analyzed for visual and quantitative correlation patterns using Spearman’s rank correlation analysis. Online searches in the US for COVID-19 vaccinations increased 2.71-fold (95% CI: 1.98-3.45) in the 4 weeks after the FDA emergency authorization compared to the precedent 4 weeks. In March-April 2021, US online searches reached a plateau that was followed by a decline of 83.3% (95% CI: 31.2%-135.3%) until May 31, 2021. The timing of peaks in online searches varied across US states. Online searches were strongly correlated with vaccination rates (r=0.71, 95% CI: 0.45 - 0.87), preceding actual reported vaccination rates in 44 of 51 states. Online search trends preceded vaccination trends by a median of 3.0 weeks (95% CI: 2.0-4.0 weeks) across all states. For influenza vaccination searches, seasonal peaks in September-October between 2016-2020 were noted. Influenza search trends highly correlated with the timing of actual vaccinations for the 2019-2020 (r=0.82, 95% CI: 0.64 – 0.93) and 2020-2021 season (r=0.91, 95% CI: 0.78 – 0.97). Search trends and real-world vaccination rates are highly correlated. Temporal alignment and correlation levels were higher for influenza vaccinations; however, only online searches for COVID-19 vaccination preceded vaccination trends. These findings indicate that US online search data can potentially guide public health efforts, including policy changes and identifying geographical areas to expand vaccination campaigns.

Background Aspirin is widely administered to prevent cardiovascular disease (CVD). However, appropriate use of aspirin depends on patient understanding of its risks, benefits, and indications, especially where aspirin is available over the counter (OTC). Methods and Results We did a survey of patient‐reported 10‐year cardiovascular risk; aspirin therapy status; form of aspirin access (OTC versus prescription); and knowledge of the risks, benefits, and role of aspirin in CVD prevention. Consecutive adults aged ≥50 years with ≥1 cardiovascular risk factor attending outpatient clinics in America and Europe were recruited. We also systematically reviewed national policies regulating access to low‐dose aspirin for CVD prevention. At each site, 150 responses were obtained (300 total). Mean±SD age was 65±10 years, 40% were women, and 41% were secondary prevention patients. More than half of the participants at both sites did not know (1) their own level of 10‐year CVD risk, (2) the expected magnitude of reduction in CVD risk with aspirin, or (3) aspirin’s bleeding risks. Only 62% of all participants reported that aspirin was routinely indicated for secondary prevention, whereas 47% believed it was routinely indicated for primary prevention (P=0.048). In America, 83.5% participants obtained aspirin OTC compared with 2.5% in Europe (P

Background Accurate measurement of the cholesterol within lipoprotein(a) (Lp[a]‐C) and its contribution to low‐density lipoprotein cholesterol (LDL‐C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)‐C from particle number using fixed conversion factors has been proposed (Lp[a]‐C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]‐C). The accuracy of this method, which theoretically can isolate “Lp(a)‐free LDL‐C,” has not been validated. Methods and Results In 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)‐C and Lp(a)‐free LDL‐C with measured values and quantified absolute and percent error. We compared findings with an analogous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)‐C and Lp(a)‐free LDL‐C increased with higher Lp(a)‐C values. Median error for estimated Lp(a)‐C

Objective: The 2018 AHA/ACC cholesterol guidelines recommend considering non-statin agents among very high-risk (VHR) patients with LDL-C ≥ 70 mg/dL after maximizing statin therapy. We aimed to evaluate the prevalence of VHR status in acute myocardial infarction (AMI) patients at hospital discharge and the adherence to guideline-directed cholesterol therapy (GDCT) within one-year follow-up post-AMI. Methods: We performed a retrospective analysis of patients who suffered a type 1 AMI between October 2015 and March 2019, and then were followed at our institution for 1 year after hospital discharge. We calculated the percentage of patients at VHR and among those with follow up lipid panels, we determined the proportion able to achieve GDCT. Results: The mean age of the 331 AMI patients was 61.0 (SD 11.9) years and 33.6% were women. Overall, 268 (81.0%) patients were categorized as having VHR at discharge. Among patients at VHR, a lipid panel was rechecked in 153 individuals (57.1%) within 1 year of discharge, with the median time to lipid recheck being 22.4 weeks (interquartile range: 10.9–40.7 weeks). Among those with a lipid panel re-check, 100 (65.4%) of patients achieved GDCT. Conclusions: Approximately 4 out of 5 AMI patients were considered VHR per the 2018 AHA/ACC guidelines, only about half had follow up lipid panels in the year following AMI, and about two-thirds of those with follow up lipid panels achieved GDCT.

Abstract The objective of this systematic review is to identify, appraise and synthesise the best available evidence on the effectiveness of nutritional counselling and education interventions on maternal, infant and child health outcomes, and assess the differences in effects across participants' PROGRESS+ characteristics. To achieve these objectives, we will aim to answer the following research questions: What is the effectiveness of nutrition counselling interventions for pregnant women in low‐ or middle‐income countries on maternal, infant and child health outcomes? What are the impacts of nutrition counselling interventions on maternal, infant and child health outcomes across participants' PROGRESS+ characteristics?

Background Caregivers provide critical support for patients with chronic diseases, including heart disease, but often experience caregiver stress that negatively impacts their health, quality of life, and patient outcomes. We aimed to inform health care teams on an evidence‐based approach to supporting the caregivers of patients with heart disease. Methods and Results We conducted a systematic review and meta‐analysis of randomized controlled trials written in English that evaluated interventions to support caregivers of patients with heart disease. We identified 15,561 articles as of April 2, 2020 from 6 databases; of which 20 unique randomized controlled trials were evaluated, representing a total of 1570 patients and 1776 caregivers. Most interventions focused on improving quality of life, and reducing burden, depression, and anxiety; 85% (17 of 20) of the randomized controlled trials provided psychoeducation for caregivers. Interventions had mixed results, with moderate non‐significant effects observed for depression (Hedges’ g=−0.64; 95% CI, −1.34 to 0.06) and burden (Hedges’ g=−0.51; 95% CI, −2.71 to 1.70) at 2 to 4 months postintervention and small non‐significant effects observed for quality of life and anxiety. These results were limited by the heterogeneity of outcome measures and intervention delivery methods. A qualitative synthesis of major themes of the interventions resulted in clinical recommendations represented with the acronym “CARE” (Caregiver‐Centered, Active engagement, Reinforcement, Education). Conclusions This systematic review highlights the need for greater understanding of the challenges faced by caregivers and the development of guidelines to help clinicians address those challenges. More research is necessary to develop clinical interventions that consistently improve caregiver outcomes.

Objective: Major guidelines recommend the use of secondary targets, such as non-HDL-C and apoB, to further reduce cardiovascular risk. We aimed to evaluate the proportion at which newer, more aggressive secondary lipid targets are exceeded in patients with LDL-C

Objective: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) Blood Cholesterol Guideline recommendation to classify patients with atherosclerotic cardiovascular disease (ASCVD) as very high-risk (VHR) vs not-VHR (NVHR) has important implications for escalation of medical therapy. We aimed to define the prevalence and clinical characteristics of these two groups within a large multi-state healthcare system and develop a simpler means to assist clinicians in identifying VHR patients using classification and regression tree (CART) analysis. Methods: We performed a retrospective analysis of all patients in a 28-hospital US healthcare system in 2018. ICD-10 codes were used to define the ASCVD population. Per the AHA/ACC Guideline, VHR status was defined by ≥2 major ASCVD events or 1 major ASCVD event and ≥2 high-risk conditions. CART analysis was performed on training and validation datasets. A random forest model was used to verify results. Results: Of 180,669 ASCVD patients identified, 58% were VHR. Among patients with a history of myocardial infarction (MI) or recent acute coronary syndrome (ACS), 99% and 96% were classified as VHR, respectively. Both CART and random forest models identified recent ACS, ischemic stroke, hypertension, peripheral artery disease, history of MI, and age as the most important predictors of VHR status. Using five rules identified by CART analysis, fewer than 50% of risk factors were required to assign VHR status. Conclusion: CART analysis helped to streamline the identification of VHR patients based on a limited number of rules and risk factors. This approach may help improve clinical decision making by simplifying ASCVD risk assessment at the point of care. Further validation is needed, however, in more diverse populations.

This case report describes a 50-year-old-woman from Southeast Asia with extensive atherosclerotic cardiovascular disease, found to have homozygous familial hypercholesterolemia caused by variants of uncertain significance in both the APOB and LDLR genes. Medications were insufficient, and thus LDL apheresis was initiated to further decrease LDL-C. (Level of Difficulty: Beginner.)

In recent years, improvement in outcomes related to cardiovascular disease is in part due to the prioritization and progress of primary and secondary prevention efforts. The Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease expanded ‘ABC's approach is used to highlight key findings in Preventive Cardiology from 2020 and further emphasize the importance of cardiovascular prevention. This simplified approach helps clinicians focus on the most relevant and up to date recommendations for optimizing cardiovascular disease risk through accurate risk assessment and appropriate implementation of lifestyle, behavioral and pharmacologic interventions. While 2020 not only provided practice changing updates by way of clinical guidelines and randomized controlled trials on topics related to antithrombotic and lipid lowering therapy, diabetes management and risk assessment, it also provided promising data on how to improve dietary and exercise adherence and manage genetic risk. By providing clinicians with a systematic approach to cardiovascular prevention and key highlights from the prior year, the goal of significantly reducing the burden of cardiovascular disease worldwide can be achieved.

Adult working-class Americans spend on average 50% of their workday awake time at their jobs. The vast majority of these jobs involve mostly physically inactive tasks and frequent exposure to unhealthy food options. Traditionally, the workplace has been a challenging environment for cardiovascular prevention, where cardiovascular guidelines have had limited implementation. Despite the impact that unhealthy lifestyles at the workplace may have on the cardiovascular health of U.S. workers, there is currently no policy in place aimed at improving this. In this review, we discuss recent evidence on the prevalence of physical inactivity among Americans, with a special focus on the time spent at the workplace; and the invaluable opportunity that workplace-based lifestyle interventions may represent for improving the prevention of cardiovascular disease. We describe the current regulatory context, the key stakeholders involved, and present specific, guideline-inspired initiatives to be considered by both Congress and employers to improve the “cardiovascular safety” of US jobs. Additionally, we discuss how the COVID-19 pandemic has forever altered the workplace, and what lessons can be taken from this experience and applied to cardiovascular disease prevention in the new American workplace. For many Americans, long sitting hours at their job represent a risk to their cardiovascular health. We discuss how a paradigm shift in how we approach cardiovascular health, from focusing on leisure time to also focusing on work time, may help curtail the epidemic of cardiovascular disease in this country.