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Weight loss induced by glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucagon-like peptide-1 receptor (GLP-1R)/glucose-dependent insulinotropic polypeptide receptor agonists is coming closer to the magnitudes achieved with surgery. However, with greater weight loss there is concern about potential side effects on muscle quantity (mass), health and function. There is heterogeneity in the reported effects of GLP-1-based therapies on lean mass changes in clinical trials: in some studies, reductions in lean mass range between 40% and 60% as a proportion of total weight lost, while other studies show lean mass reductions of approximately 15% or less of total weight lost. There are several potential reasons underlying this heterogeneity, including population, drug-specific/molecular, and comorbidity effects. Furthermore, changes in lean mass may not always reflect changes in muscle mass as the former measure includes not only muscle but also organs, bone, fluids, and water in fat tissue. Based on contemporary evidence with the addition of magnetic resonance imaging-based studies, skeletal muscle changes with GLP-1RA treatments appear to be adaptive: reductions in muscle volume seem to be commensurate with what is expected given ageing, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function. Nevertheless, factors such as older age and severity of disease may influence the selection of appropriate candidates for these therapies due to risk of sarcopenia. To further improve muscle health during weight loss, several pharmacological treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. Future research on GLP-1-based and other therapies designed for weight loss should focus on more accurate and meaningful assessments of muscle mass, composition, as well as function, mobility or strength, to better define their impact on muscle health for the substantial number of patients who will likely be taking these medications well into the future., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Obesity is a recognized public health epidemic with a prevalence that continues to increase dramatically in nearly all populations, impeding progress in reducing incidence rates of cardiovascular disease. Over the past decade, obesity science has evolved to improve knowledge of its multifactorial causes, identifying important biological causes and sociological determinants of obesity. Treatments for obesity have also continued to develop, with more evidence-based programs for lifestyle modification, new pharmacotherapies, and robust data to support bariatric surgery. Despite these advancements, there continues to be a substantial gap between the scientific evidence and the implementation of research into clinical practice for effective obesity management. Addressing barriers to obesity science implementation requires adopting feasible methodologies and targeting multiple levels (eg, clinician, community, system, policy) to facilitate the delivery of obesity-targeted therapies and maximize the effectiveness of guideline-driven care to at-need patient populations. This scientific statement (1) describes strategies shown to be effective or promising for enhancing translation and clinical application of obesity-based research; (2) identifies key gaps in the implementation of obesity science into clinical practice; and (3) provides guidance and resources for health care professionals, health care systems, and other stakeholders to promote broader implementation and uptake of obesity science for improved population-level obesity management. In addition, advances in implementation science that hold promise to bridge the know-do gap in obesity prevention and treatment are discussed. Last, this scientific statement highlights implications for health research policy and future research to improve patient care models and optimize the delivery and sustainability of equitable obesity-related care.

Aim: To evaluate the impact of the Dexcom G6 continuous glucose monitoring (CGM) device on glycaemic control and cardiometabolic risk in patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk who are not on insulin therapy., Materials and Methods: Adults with T2DM with glycated haemoglobin (HbA1c) >7% and body mass index (BMI) ≥30 kg/m 2 not using insulin were enrolled in a two-phase cross-over study. In phase 1, CGM data were blinded, and participants performed standard glucose self-monitoring. In phase 2, the CGM data were unblinded, and CGM, demographic and cardiovascular risk factor data were collected through 90 days of follow-up and compared using paired tests., Results: Forty-seven participants were included (44% women; 34% Black; mean age 63 years; BMI 37 kg/m 2 ; HbA1c 8.4%; 10-year predicted atherosclerotic cardiovascular disease risk 24.0%). CGM use was associated with a reduction in average glucose (184.0 to 147.2 mg/dl, p < .001), an increase in time in range (57.8 to 82.8%, p < .001) and a trend towards lower glucose variability (26.2 to 23.8%). There were significant reductions in HbA1c, BMI, triglycerides, blood pressure, total cholesterol, diabetes distress and 10-year predicted risk for atherosclerotic cardiovascular disease (p < .05 for all) and an increase in prescriptions for sodium-glucose cotransporter 2 inhibitors (36.2 to 83.0%) and glucagon-like peptide-1 receptor agonists (42.5 to 87.2%, p < .001 for both)., Conclusions: Dexcom G6 CGM was associated with improved glycaemic control and cardiometabolic risk in patients with T2DM who were not on insulin. CGM can be a safe and effective tool to improve diabetes management in patients at high risk for adverse cardiovascular outcomes., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Excess muscle fat is observed in obesity and associated with greater burden of cardiovascular risk factors and higher risk of mortality. Liraglutide reduces total body weight and visceral fat but its effect on muscle fat and adverse muscle composition is unknown., Methods: This is a pre-specified secondary analysis of a randomized, double-blind, placebo-controlled trial that examined the effects of liraglutide plus a lifestyle intervention on visceral adipose tissue and ectopic fat among adults without diabetes with body mass index ≥30 kg/m 2 or ≥27 kg/m 2 and metabolic syndrome. Participants were randomly assigned to a once-daily subcutaneous injection of liraglutide (target dose 3.0 mg) or matching placebo for 40 weeks. Body fat distribution and muscle composition was assessed by magnetic resonance imaging at baseline and 40-week follow-up. Muscle composition was described by the combination of thigh muscle fat and muscle volume. Treatment difference (95% confidence intervals [CI]) was calculated by least-square means adjusted for baseline thigh muscle fat. The association between changes in thigh muscle fat and changes in body weight were assessed using Spearman correlation coefficients. The effect of liraglutide versus placebo on adverse muscle composition, denoted by high thigh muscle fat and low thigh muscle volume, was explored., Results: Among the 128 participants with follow-up imaging (92.2% women, 36.7% Black), median muscle fat at baseline was 7.8%. The mean percent change in thigh muscle fat over median follow-up of 36 weeks was -2.87% among participants randomized to liraglutide (n = 73) and 0.05% in the placebo group (absolute change: -0.23% vs. 0.01%). The estimated treatment difference adjusted for baseline thigh muscle fat was -0.24% (95% CI, -0.41 to -0.06, P-value 0.009). Longitudinal change in thigh muscle fat was significantly associated with change in body weight in the placebo group but not the liraglutide group. The proportion of participants with adverse muscle composition decreased from 11.0% to 8.2% over follow-up with liraglutide, but there was no change with placebo., Conclusions: In a cohort of predominantly women with overweight or obesity in the absence of diabetes, once-daily subcutaneous liraglutide was associated with a reduction in thigh muscle fat and adverse muscle composition compared with placebo. The contribution of muscle fat improvement to the cardiometabolic benefits of liraglutide requires further study., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Aims: To describe the overall fat distribution patterns independent of body mass index (BMI) in participants with type 2 diabetes (T2D) in the SURPASS-3 MRI substudy by comparison with sex- and BMI-matched virtual control groups (VCGs) derived from the UK Biobank imaging study at baseline and Week 52., Methods: For each study participant at baseline and Week 52 (N = 296), a VCG of ≥150 participants with the same sex and similar BMI was identified from the UK Biobank imaging study (N = 40 172). Average visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT) and liver fat (LF) levels and the observed standard deviations (SDs; standardized normal z-scores: z-VAT, z-aSAT and z-LF) were calculated based on the matched VCGs. Differences in z-scores between baseline and Week 52 were calculated to describe potential shifts in fat distribution pattern independent of weight change., Results: Baseline fat distribution patterns were similar across pooled tirzepatide (5, 10 and 15 mg) and insulin degludec (IDeg) arms. Compared with matched VCGs, SURPASS-3 participants had higher baseline VAT (mean [SD] z-VAT +0.42 [1.23]; p < 0.001) and LF (z-LF +1.24 [0.92]; p < 0.001) but similar aSAT (z-aSAT -0.13 [1.11]; p = 0.083). Tirzepatide-treated participants had significant decreases in z-VAT (-0.18 [0.58]; p < 0.001) and z-LF (-0.54 [0.84]; p < 0.001) but increased z-aSAT (+0.11 [0.50]; p = 0.012). Participants treated with IDeg had a significant change in z-LF only (-0.46 [0.90]; p = 0.001), while no significant changes were observed for z-VAT (+0.13 [0.52]; p = 0.096) and z-aSAT (+0.09 [0.61]; p = 0.303)., Conclusion: In this exploratory analysis, treatment with tirzepatide in people with T2D resulted in a significant reduction of z-VAT and z-LF, while z-aSAT was increased from an initially negative value, suggesting a possible treatment-related shift towards a more balanced fat distribution pattern with prominent VAT and LF loss., (© 2024 Eli Lilly and Company and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Competing Interests: Disclosures N. Sattar has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; he has received grant support paid to his university from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics outside the submitted work. Dr Neeland has consulted for and/or received speaker honoraria from Boehringer Ingelheim, Eli Lilly and Co, Novo Nordisk, Bayer Pharmaceuticals, and Nestle Health Sciences outside the submitted work. Dr McGuire reports research support for Clinical Trials Leadership from Boehringer Ingelheim, Pfizer, AstraZeneca, Novo Nordisk, Esperion, Lilly USA, and CSL Behring, as well as honoraria for consultancy from Lilly USA, Pfizer, Boehringer Ingelheim, Lexicon, Novo Nordisk, Applied Therapeutics, Altimmune, CSL Behring, Bayer, Intercept, and New Amsterdam.

Objective: To evaluate the association between trimethylamine N-oxide (TMAO) and related metabolites with adverse cardiovascular events in a multiethnic urban primary prevention population., Methods: We performed a case-control study of 361 participants of the Dallas Heart Study, including 88 participants with an incident atherosclerotic cardiovascular disease (ASCVD) event and 273 controls matched for age, sex, and body mass index without an ASCVD event during 12 years of follow-up (January 1, 2000, through December 31, 2015). Plasma levels of TMAO, choline, carnitine, betaine, and butyrobetaine were measured by mass spectrometry. The differential odds for incident ASCVD by metabolite levels between cases and controls were compared by a conditional logistic regression model adjusted for cardiovascular risk factors., Results: Participants with incident ASCVD had higher levels of TMAO and related metabolites compared with those without ASCVD (P<.05 for all). Those with plasma TMAO concentrations in quartile 4 had a more than 2-fold higher odds of ASCVD compared with those in quartile 1 (odds ratio, 2.77 [95% CI, 1.05 to 7.7; P=.04] for hard ASCVD and 2.41 [95% CI, 1.049 to 5.709; P=.04]). Similar trends were seen with the related metabolites choline, betaine, carnitine, and butyrobetaine., Conclusion: Our results suggest that TMAO and related metabolites are independently associated with ASCVD events. Although further studies are needed, measurement of TMAO and related metabolites may have a role in ASCVD risk stratification for primary prevention., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Urban environments contribute substantially to the rising burden of cardiometabolic diseases worldwide. Cities are complex adaptive systems that continually exchange resources, shaping exposures relevant to human health such as air pollution, noise, and chemical exposures. In addition, urban infrastructure and provisioning systems influence multiple domains of health risk, including behaviors, psychological stress, pollution, and nutrition through various pathways (eg, physical inactivity, air pollution, noise, heat stress, food systems, the availability of green space, and contaminant exposures). Beyond cardiometabolic health, city design may also affect climate change through energy and material consumption that share many of the same drivers with cardiometabolic diseases. Integrated spatial planning focusing on developing sustainable compact cities could simultaneously create heart-healthy and environmentally healthy city designs. This article reviews current evidence on the associations between the urban exposome (totality of exposures a person experiences, including environmental, occupational, lifestyle, social, and psychological factors) and cardiometabolic diseases within a systems science framework, and examines urban planning principles (eg, connectivity, density, diversity of land use, destination accessibility, and distance to transit). We highlight critical knowledge gaps regarding built-environment feature thresholds for optimizing cardiometabolic health outcomes. Last, we discuss emerging models and metrics to align urban development with the dual goals of mitigating cardiometabolic diseases while reducing climate change through cross-sector collaboration, governance, and community engagement. This review demonstrates that cities represent crucial settings for implementing policies and interventions to simultaneously tackle the global epidemics of cardiovascular disease and climate change., Competing Interests: Disclosures None.

In the past 2 decades, health care has witnessed technological and pharmacological advancements leading to innovations in diabetes management. Despite these advances, published guidelines, and treatment algorithms, most people with diabetes remain above glycemic targets. Thus, the authors designed a novel care model aimed at improving several causative factors, including therapeutic inertia, limited access to endocrinology and cardiovascular specialists, time constraints, and complexity in incorporating clinical practice guidelines. The model involves collaboration between the diabetes specialty team and primary care providers (PCPs). The intervention reviewed uncontrolled diabetes data and the patient's electronic medical record (EMR) and sent personalized, evidence-based recommendations to the provider using the task function in the EMR. Other services (eg, diabetes education) were utilized to optimize patient care to achieve optimal glycemic targets and address cardiometabolic risk. The overall mean hemoglobin A1c (HbA1c) decreased pre-post intervention by almost 1%, and 52.1% (347 of 666) of the cohort had ≥-0.5% change in HbA1c post-intervention. All pathways exhibited a decrease in HbA1c. Team-based approaches to managing diabetes patient care were the most effective. The interventions effectively utilized the resources across the health system without placing additional load or burden on primary care or diabetes specialty care teams. In the future, the authors hope to address the limitations of the current gap caused by increasing diabetes numbers, decreasing availability of PCPs and endocrinologists, and fee-for-service models using the innovative specialty consultant-primary care connection and knowledge exchange offered by this novel model, which can only be sustained with payer's support.

Background and Aims: Identifying the association of novel plasma biomarkers with coronary artery calcium (CAC) incidence or progression may provide insights into the pathophysiology of atherogenesis and plaque formation., Methods: Participants of the Dallas Heart Study (DHS), a multi-ethnic cohort of ambulatory individuals at low-intermediate risk for future atherosclerotic cardiovascular disease (ASCVD), who had their blood tested for 31 biomarkers reflecting multiple pathophysiological pathways, underwent 2 serial non-contrast computed tomography assessments for CAC a median ∼7 years apart. The collected biomarkers were explored for association with CAC incidence or progression using univariate and multivariate analysis., Results: A total of 1424 participants were included; mean age 43 years, 39 % male, and nearly half African-American. Over a 7-year interval between the two CAC measurements, 340 participants (23.9 %) had CAC incidence or progression, 105 (7.4 %) with incident CAC, and 309 (21.7 %) with CAC progression. Although several plasma biomarkers were associated with CAC incidence or progression in a univariate model, only soluble intercellular adhesion molecule-1 (sICAM-1), related to atherosclerosis by the inflammatory pathway, remained independently associated in a multivariate model adjusted for traditional risk factors., Conclusions: Further studies are needed to characterize the role of sICAM-1 in CAC evolvement to establish whether it has a pivotal mechanistic contribution or is rather an innocent bystander. Alternate measures of coronary atherosclerosis may be needed to elucidate contributors to atherosclerosis incidence or progression., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Neeland has been a speaker/consultant for Boehringer-Ingelheim/Lilly Alliance and Bayer Pharmaceuticals and has been an advisory board member for AMRA Medical, Boehringer Ingelheim, Bayer, and Lilly. Dr. Eisen has been a speaker/consultant/ Advisory board member for Boehringer-Ingelheim, Bayer, Novo Nordisk, AstraZeneca, Pfizer, Neopharm, Medison Pharma, and Sanofi. Dr. de Lemos reports grant support from Roche Diagnostics and Abbott Diagnostics, consulting fees from Quidel Cardiovascular, Inc., Cytokinetics and Glaxo Smith Kline, honoraria for participation in endpoint committees from Beckman Coulter and Siemens Health Care Diagnostics, and fees for participation in Data Monitoring Committees from Astra Zeneca, Novo Nordisk, Eli Lilly, Regeneron, Amgen, and Verve Therapeutics., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: The effects of weight loss with a partial or total meal replacement programme (MRP) on atherosclerotic cardiovascular disease (ASCVD) risk factors are not fully understood, in particular in people at higher CV risk. In the 52-week randomized controlled OPTIWIN study in men and women with obesity, meal replacement programme (total for first 26 weeks, partial for the ensuing 26 weeks) with OPTIFAST (OP) resulted in significantly greater weight loss compared with a low-calorie food-based (FB) dietary plan, both as part of a comprehensive lifestyle intervention [OP (n = 135)/FB (n = 138) week 26: -12.4%/-6.0%, p < .001; week 52: -10.5%/-5.5%, p < .001]. Here, we examined effects on ASCVD risk factors and 10-year ASCVD risk., Materials and Methods: Participants with body mass index 30-55 kg/m 2 and age 18-70 years, and not on anti-obesity medications, were recruited. The effects on systolic and diastolic blood pressure (SBP, DBP), lipid parameters and 10-year ASCVD risk were analysed as changes over time using linear mixed models. Subgroup analyses were conducted for changes in SBP, DBP and ASCVD risk by categories of age (<40, 40-59, ≥60 years), baseline SBP (2 , 10-year ASCVD risk <5% 87%/74%, dysglycaemia 52%/50%). At week 26, SBP/DBP were significantly reduced with OP versus FB, and a greater proportion achieved BP ≤130/80 mmHg [odds ratio 2.11 (95% confidence interval 1.10, 4.03), p = .024]. All lipid parameters as well as 10-year ASCVD risk were significantly improved with OP versus FB. A similar, but slightly attenuated pattern was observed at 52 weeks. Across subgroups, greater reductions for SBP, DBP and ASCVD risk were generally seen with OP versus FB with quantitatively higher baseline SBP and age, and in men., Conclusions: In people with obesity at low ASCVD risk, OP significantly reduced cardiovascular risk factors and 10-year predicted risk for ASCVD., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: Fat distribution pattern could help determine cardiometabolic risk profile. This study aimed to evaluate the association of balance/imbalance between visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and liver fat (LF) with incident type 2 diabetes (T2D) and cardiovascular disease (CVD) in the UK Biobank prospective cohort study., Methods: Magnetic resonance images of 40 174 participants were analyzed for VAT, aSAT, and LF using AMRA® Researcher. To assess fat distribution patterns independent of body mass index (BMI), fat z-scores (z-VAT, z-aSAT, z-LF) were calculated. Participants without prevalent T2D/CVD (N = 35 138) were partitioned based on balance between (1) z-VAT and z-LF (z-scores = 0 as cut-points for high/low), (2) z-VAT and z-aSAT, and (3) z-LF and z-aSAT. Associations with T2D/CVD were investigated using Cox regression (crude and adjusted for sex, age, BMI, lifestyle, arterial hypertension, statin treatment)., Results: T2D was significantly associated with z-LF (hazard ratio, [95% CI] 1.74 [1.52-1.98], P < .001) and z-VAT (1.70 [1.49-1.95], P < .001). Both remained significant after full adjustment. For z-scores balance, strongest associations with T2D were z-VAT > 0 and z-LF > 0 (4.61 [2.98-7.12]), z-VAT > 0 and z-aSAT < 0 (4.48 [2.85-7.06]), and z-LF > 0 and z-aSAT < 0 (2.69 [1.76-4.12]), all P < .001. CVD was most strongly associated with z-VAT (1.22 [1.16-1.28], P < .001) which remained significant after adjustment for sex, age, BMI, and lifestyle. For z-scores balance, strongest associations with CVD were z-VAT > 0 and z-LF < 0 (1.53 [1.34-1.76], P < .001) and z-VAT > 0 and z-aSAT < 0 (1.54 [1.34-1.76], P < .001). When adjusted for sex, age, and BMI, only z-VAT > 0 and z-LF < 0 remained significant., Conclusion: High VAT in relation to BMI (z-VAT > 0) was consistently linked to both T2D and CVD; z-LF > 0 was linked to T2D only. Skewed fat distribution patterns showed elevated risk for CVD (z-VAT > 0 and z-LF < 0 and z-VAT > 0 and z-aSAT < 0) and T2D (z-VAT > 0 and z-aSAT < 0)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD., Methods: The derivation sample included individual-level participant data from 25 data sets (N=3 281 919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular filtration rate. Models were sex-specific, race-free, developed on the age scale, and adjusted for competing risk of non-CVD death. Analyses were conducted in each data set and meta-analyzed. Discrimination was assessed using the Harrell C-statistic. Calibration was calculated as the slope of the observed versus predicted risk by decile. Additional equations to predict each CVD subtype (atherosclerotic CVD and heart failure) and include optional predictors (urine albumin-to-creatinine ratio and hemoglobin A1c), and social deprivation index were also developed. External validation was performed in 3 330 085 participants from 21 additional data sets., Results: Among 6 612 004 adults included, mean±SD age was 53±12 years, and 56% were women. Over a mean±SD follow-up of 4.8±3.1 years, there were 211 515 incident total CVD events. The median C-statistics in external validation for CVD were 0.794 (interquartile interval, 0.763-0.809) in female and 0.757 (0.727-0.778) in male participants. The calibration slopes were 1.03 (interquartile interval, 0.81-1.16) and 0.94 (0.81-1.13) among female and male participants, respectively. Similar estimates for discrimination and calibration were observed for atherosclerotic CVD- and heart failure-specific models. The improvement in discrimination was small but statistically significant when urine albumin-to-creatinine ratio, hemoglobin A1c, and social deprivation index were added together to the base model to total CVD (ΔC-statistic [interquartile interval] 0.004 [0.004-0.005] and 0.005 [0.004-0.007] among female and male participants, respectively). Calibration improved significantly when the urine albumin-to-creatinine ratio was added to the base model among those with marked albuminuria (>300 mg/g; 1.05 [0.84-1.20] versus 1.39 [1.14-1.65]; P =0.01)., Conclusions: PREVENT equations accurately and precisely predicted risk for incident CVD and CVD subtypes in a large, diverse, and contemporary sample of US adults by using routinely available clinical variables., Competing Interests: Disclosures Dr Coresh reports grants from the National Institutes of Health (NIH) and from the National Kidney Foundation during the conduct of the study and personal fees and other support from Healthy.io outside the submitted work. Dr Khan reports grants from NIH during the conduct of the study (R21 HL165376). Dr Chang reports consulting fees from Novartis, Reata, and Amgen, and grants from Novartis, Novo Nordisk, NIH, and the National Kidney Foundation. Dr Palaniappan reports grants from NIH during the conduct of the study (K24 HL150476). Dr Tuttle reports unpaid support from the American Heart Association and grant support from NIH (01MD014712, OT2OD032581, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, and UM1AI109568); the Centers for Disease Control and Prevention (75D301-21-P-12254), as well as Bayer and Travere, paid to the institution; consulting fees from Eli Lilly, Boehringer Ingelheim, AstraZeneca, Goldfinch Bio, Novo Nordisk, Bayer, and Travere Therapeutics Inc; honoraria from Eli Lilly, AstraZeneca, Novo Nordisk, and Bayer; unpaid participation as a Data Safety and Monitoring Board chair for National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)/NIH and George Clinical Institute; and unpaid participation as a Diabetic Kidney Disease collaborative chair for the American Society of Nephrology. Dr Neeland reports speaker and consulting fees from Boehringer Ingelheim, Eli Lilly and Co, Nestle Health Science, and Bayer Pharmaceuticals. Dr Virani reports grants from NIH, US Department of Veterans Affairs, Tahir and Jooma Family. The views expressed in this article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the US Department of Health and Human Services. All other coauthors have nothing to disclose.

Background: The care for patients with type 2 diabetes mellitus (T2DM) necessitates a multidisciplinary team approach to reduce cardiovascular (CV) risk but implementation of effective integrated strategies has been limited., Methods and Results: We report 2-year results from a patient-centered, team-based intervention called CINEMA at University Hospitals Cleveland Medical Center. Patients with T2DM or prediabetes at high-risk for CV events, including those with established atherosclerotic CVD, elevated coronary artery calcium score ≥100, chronic heart failure with reduced ejection fraction, chronic kidney disease (CKD) stages 2-4, and/or prevalent metabolic syndrome were included. From May 2020 through September 2022, 426 patients were enrolled in the CINEMA program. A total of 227 (54%) completed ≥1 follow-up visit after an initial baseline visit with median (IQR) follow-up time 4 [3], [4], [5], [6], [7] months with maximum follow-up time 19 months. Mean age was 60 years, 47 % were women, and 37 % were Black and 85% had prevalent T2DM, 48 % had established ASCVD, 29% had chronic HF, 27% had CKD and mean baseline 10-year ASCVD risk estimate was 25.1 %; baseline use of a SGLT2i or GLP-1RA was 21 % and 18 %, respectively. Patients had significant reductions from baseline in body weight (-5.5 lbs), body mass index (-0.9 kg/m 2 ), systolic (-3.6 mmHg) and diastolic (-1.2 mmHg) blood pressure, Hb A1c (-0.5 %), total (-10.7 mg/dL) and low-density lipoprotein (-9.0 mg/dL) cholesterol, and triglycerides (-13.5 mg/dL) ( p <0.05 for all). Absolute 10-year predicted ASCVD risk decreased by ∼2.4 % ( p <0.001) with the intervention. In addition, rates of guideline-directed cardiometabolic medication prescriptions significantly increased during follow-up with the most substantive changes seen in rates of SGLT2i and GLP-1RA use which approximately tripled from baseline (21 % to 57 % for SGLT2i and 18 % to 65 % for GLP-1RA, p <0.001 for both)., Conclusions: The CINEMA program, an integrated, patient-centered, team-based intervention for patients with T2DM or prediabetes at high risk for cardiovascular disease has continued to demonstrate effectiveness with significant improvements in ASCVD risk factors and improved use of evidence-based therapies. Successful implementation and dissemination of this care delivery paradigm remains a key priority., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ian Neeland reports a relationship with Boehringer Ingelheim GmbH that includes: consulting or advisory and speaking and lecture fees. Ian Neeland reports a relationship with Eli Lilly and Company that includes: consulting or advisory and speaking and lecture fees. Ian Neeland reports a relationship with Bayer AG that includes: consulting or advisory and speaking and lecture fees. Ian Neeland reports a relationship with AMRA that includes: consulting or advisory. Sanjay Rajagopalan reports a relationship with Novo Nordisk Inc that includes: consulting or advisory. Sanjay Rajagopalan reports a relationship with Bayer AG that includes: consulting or advisory., (© 2023 The Author(s).)

Cardiovascular-kidney-metabolic (CKM) syndrome is a novel construct recently defined by the American Heart Association in response to the high prevalence of metabolic and kidney disease. Epidemiological data demonstrate higher absolute risk of both atherosclerotic cardiovascular disease (CVD) and heart failure as an individual progresses from CKM stage 0 to stage 3, but optimal strategies for risk assessment need to be refined. Absolute risk assessment with the goal to match type and intensity of interventions with predicted risk and expected treatment benefit remains the cornerstone of primary prevention. Given the growing number of therapies in our armamentarium that simultaneously address all 3 CKM axes, novel risk prediction equations are needed that incorporate predictors and outcomes relevant to the CKM context. This should also include social determinants of health, which are key upstream drivers of CVD, to more equitably estimate and address risk. This scientific statement summarizes the background, rationale, and clinical implications for the newly developed sex-specific, race-free risk equations: PREVENT (AHA Predicting Risk of CVD Events). The PREVENT equations enable 10- and 30-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure), include estimated glomerular filtration rate as a predictor, and adjust for competing risk of non-CVD death among adults 30 to 79 years of age. Additional models accommodate enhanced predictive utility with the addition of CKM factors when clinically indicated for measurement (urine albumin-to-creatinine ratio and hemoglobin A1c) or social determinants of health (social deprivation index) when available. Approaches to implement risk-based prevention using PREVENT across various settings are discussed.

Background: Inflammatory bowel disease (IBD) is associated with higher incidence of atherosclerotic cardiovascular disease (ASCVD). Data investigating the role of coronary artery calcium (CAC) scoring in identifying subclinical atherosclerotic disease in IBD patients is scarce., Methods: Using data obtained from the CLARIFY registry, a prospective study of no-charge coronary artery calcium (CAC) testing at University Hospitals, we reviewed patients with ulcerative colitis (UC) or Crohn's disease (CD) who underwent CAC scoring from 2014 to 2020. We investigated the concordance between CAC risk and 10-year estimated ASCVD risk by AHA/ACC pooled cohort equation using pre-established thresholds for statin prescription (CAC≥100, 10-year ASCVD risk ≥7.5%). We additionally investigated the association between CAC, preventive therapy initiation and Major Adverse Cardiovascular Events (MACE)., Results: A total of 369 patients with IBD were included (174 UC, 195 CD), with median age of 60 years. The median CAC score was 14.9 with no significant difference between UC and CD (P = .76). Overall, 151 (41%) had CAC of 0, 108 (29%) had CAC 1-99, 61 (17%) had CAC 100 to 399, and 49 (13%) had CAC ≥400 with no difference in CAC distribution between CD and UC (P = .17). There was no difference in median CAC between IBD or age/sex-matched controls (P = .34). Approximately half of the patients (52%) with IBD had 10-year estimated ASCVD risk of 7.5% or higher. Among patients with ASCVD risk <7.5% (n = 163), 29 (18%) had CAC≥100 and among patients with ASCVD risk ≥7.5% (n = 178), 102 (57%) had CAC <100. There was no difference between CAC<100 vs CAC≥100 with respect to CRP, use of immunosuppressive or amino-salicylate therapy, IBD severity or complications. CAC score (AUROC 0.67 [0.56-0.78]), but not PCE ASCVD risk (AUROC 0.60 [0.48-0.73]), was predictive of MACE. The best cut-off for CAC score was 76 (sensitivity = 60%, specificity = 69%), and was associated with 4-fold increase in MACE (Hazard Ratio 4.0 [2.0-8.1], P < .001)., Conclusion: Subclinical atherosclerosis, as evaluated by CAC scoring, is prevalent in patients with IBD, and is associated with cardiovascular events. Further studies are needed to understand underlying biological processes of increased atherosclerotic disease risk among adults with IBD., Competing Interests: Conflict of interest None to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.

Background: The Epitomee Capsule (EC) is an, oral, self-use, bio-degradable device for weight management, composed of absorbent polymers that self-expands in the stomach (pH-sensitive) and creates a triangular shape, space-occupying super-absorbent gel structure. A recent study reported that 42 % of study completers obtained >5 % weight reduction at 12 weeks. We performed exploratory analyses of this study to evaluate its effect on cardiovascular risk factors and on self-reported satiety, between-meal snacking and meal-size., Methods: This single-center observational study (Israel) enrolled 78 volunteers, with mean age 41 years, BMI 32.5 kg/m 2 , systolic/diastolic blood pressure (SBP/DBP) 124/77 mmHg. The EC was given in addition to diet and physical activity counseling. Assessments included anthropometrics, BP, lipids, and three questions (translated from Hebrew) scored 1 (not at all) to 5 (very much) for "Do you feel the EC - Q1:helps you to consume less snacks in between meals? Q2:helps you to eat less in the meal?; Q3:is causing an early sense of satiety?". Changes from baseline were assessed using a mixed model and included all patients with at least one measure. Correlation-analysis between weight-change and PROs used Kendall's tau., Result: Compared to baseline, at 12 weeks, SBP/DBP were reduced (ΔSBP: -5.5 mmHg, p = 0.0003/ΔDBP: -1.9 mmHg, p = 0.1341), with a larger effect in people with hypertension at baseline (ΔSBP: -13.2 mmHg, p < 0.00001/ΔDBP: -6.1, p = 0.008). Triglyceride-level was also significantly reduced, but not other lipids. Mean scores to Q1-3 were high throughout, with slight decreases (Q1 at W2 3.9 ± 1.1/W12 3.0 ± 1.6; Q2 at W2 3.7 ± 1.1/W12 3.1 ± 1.6; Q3 at W2 3.8 ± 1.2/W12 2.9 ± 1.6). There was a moderate correlation between PROs and weight reduction, although significance was not observed for all weeks., Conclusions: Exploratory analyses of 12 weeks treatment with EC demonstrated significant reductions in SBP, DBP, and triglycerides. The weight reduction correlated with satiety, less snacking, and reduced meal size., Competing Interests: HS has received investigator fee from Epitomee, Israel, IJN has received consulting fees/speaking honoraria from Nestlé Health Science, US, 10.13039/100001003Boehringer Ingelheim, Germany, Lilly, US, and AMRA, Sweden, DHR has received investigator fee from Epitomee, Israel. DdL and AL has received investigator fee and consulting fee from Pronokal, a Nestlé Health Science company, Spain, ZM is employed by Aimmune therapeutics, UK, a Nestlé Health Science company. YK and RA are employees and stock-owner of Epitomee, Israel. DLC has nothing to report. OEJ is employed by Nestlé Health Science, Switzerland., (© 2023 The Authors.)

Purpose of Review: Specific measures of body fat distribution may have particular value in the development and treatment of cardiometabolic conditions, such as cardiovascular disease (CVD) and diabetes mellitus (DM). Here, we review the pathophysiology, epidemiology, and recent advances in the identification and management of body fat distribution as it relates to DM and CVD risk., Recent Findings: Accumulation of visceral and ectopic fat is a major contributor to CVD and DM risk above and beyond the body mass index (BMI), yet implementation of fat distribution assessment into clinical practice remains a challenge. Newer imaging-based methods offer improved sensitivity and specificity for measuring specific fat depots. Lifestyle, pharmacological, and surgical interventions allow a multidisciplinary approach to reduce visceral and ectopic fat. A focus on implementation of body fat distribution measurements into clinical practice should be a priority over the next 5 to 10 years, and clinical assessment of fat distribution can be considered to refine risk evaluation and to develop improved and effective preventive and therapeutic strategies for high-risk obesity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The sodium-glucose transporter 2 inhibitor (SGLT2i) empagliflozin may reduce the incidence of obstructive sleep apnea (OSA) in patients with type 2 diabetes (T2D) and cardiovascular (CV) disease. This analysis of VERTIS CV, the CV outcome trial for the SGLT2i ertugliflozin conducted in a similar group of patients, explored the effects of ertugliflozin on reported incident OSA., Methods: In VERTIS CV, patients ≥ 40 years with T2D and atherosclerotic CV disease (ASCVD) were randomized to ertugliflozin 5 or 15 mg or placebo. The primary endpoint was the composite of major adverse CV events. This exploratory analysis evaluated the impact of ertugliflozin (5 and 15 mg pooled) on incident OSA. Patients with prevalent OSA were excluded. Incident OSA events were based on investigator-reported events using the MedDRA SMQ term "sleep apnea syndrome." A multivariable Cox proportional hazards regression model was constructed to assess the association between ertugliflozin and incident OSA., Results: Of 8246 patients enrolled, 7697 (93.3%) were without baseline OSA (placebo, n = 2561; ertugliflozin, n = 5136; mean age 64.4 years; BMI 31.7 kg/m 2 ; HbA1c, 8.2%; 69.2% male; 88.3% White). The OSA incidence rate was 1.44 per 1000 person-years versus 2.61 per 1000 person-years among patients treated with ertugliflozin versus placebo, respectively, corresponding to a 48% relative risk reduction (HR 0.52; 95% CI 0.28-0.96; P = 0.04)., Conclusions: In VERTIS CV, ertugliflozin reduced by nearly half the incidence of OSA in patients with T2D and ASCVD. These data contribute to the literature that SGLT2is may have a significant beneficial impact on OSA., Clinicaltrials: gov identifier: NCT01986881., (© 2022. Pfizer Inc. and The Author(s).)

Introduction: Cardiovascular disease (CVD) risk amongst those with type 2 diabetes (T2D) is heterogenous. The role of imaging-based cardiometabolic biomarkers (e.g., coronary artery calcium [CAC] score, and hepatic triglyceride content [HTC]) in CVD risk stratification in T2D is unclear. To better understand this, we sought to evaluate the individual and joint associations between CAC and hepatic steatosis (HS) with clinical atherosclerotic CVD (ASCVD) in Dallas Heart Study (DHS) participants with and without T2D., Methods: We examined participants in the DHS, a multi-ethnic cohort study, without self-reported ASCVD. CAC scoring was performed via computed tomography with the mean of two consecutive scores used. HTC was measured using magnetic resonance spectroscopy, and HS was defined as HTC >5.5% The primary outcome was incident ASCVD, defined as coronary heart disease (CHD; myocardial infarction, percutaneous coronary intervention, or coronary artery bypass graft surgery), ischemic stroke, transient ischemic attack, or CVD death. Cox regression analyses, and interaction testing was performed to evaluate the individual and joint associations between CAC and HS with ASCVD. The association between HS and coronary heart disease was validated in the UK Biobank (UKB)., Results: A total of 1252 DHS participants were included with mean age 44.8 ± 9.3 years, mean body mass index 28.7 ± 5.9 kg/m 2 , 55% female, and 59% black with an overall prevalence of T2D of 9.7%. CAC scores were significantly higher (p < 0.01) and HS was significantly more prevalent in those with T2D (p < 0.01). Over a median of 12.3 years, 8.3% of participants experienced ASCVD events. The ASCVD event rate was significantly higher in participants with T2D (20.5% vs 7.0%, p < 0.01). Continuous CAC was associated with ASCVD events in the overall cohort regardless of T2D status with a significant interaction present between CAC and T2D status on ASCVD, P interaction  = 0.02. HTC was not associated with ASCVD risk in participants without T2D but was inversely associated with risk in participants with T2D (HR 0.91, 95% CI 0.83-0.99 per 1% increase in HTC, p = 0.02), P interaction  = 0.02. Amongst 37,266 UKB participants, 4.5% had T2D. CHD events occurred in 2.2% of participants, with 10.2% of events occurring amongst those with T2D. An inverse relationship between HTC and CHD was also found amongst those with T2D in UKB with a significant interaction between T2D status and HTC on CHD (HR per 1% increase in HTC 0.95, 95% CI 0.91-0.99, p = 0.01, P interaction  = 0.02)., Conclusions: In the DHS, we found that CAC was associated with ASCVD risk independent of T2D status. We did not observe an association between HTC and ASCVD in participants without T2D, but there was an inverse association between HTC and ASCVD in those with T2D that was replicated in the UKB cohort. Further investigation is warranted to understand the possible protective association of HS in participants with T2D., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Severe hypercholesterolemia (SH), defined as a low-density lipoprotein cholesterol (LDL-C) level ≥ 190 mg/dl, is associated with an increased risk for premature atherosclerotic cardiovascular disease. Despite guideline recommendations, many patients with severe hypercholesterolemia remain untreated. We conducted an observational analysis of a large pool of SH patients, exploring demographic and social factors contributing to disparities in the prescription of statin and other lipid-lowering therapies., Methods: We included all adults (age 18 or older) in the University Hospitals Health Care System, with an LDL-C ≥ 190 mg/dl on a lipid profile drawn between January 2, 2014, and March 15, 2022. Variables were compared across relevant categories of age, gender, race and ethnicity, medical history, prescription medication status, insurance type, and provider referral type. We used the Fischer exact test and Pearson Chi-square (χ 2) for variable comparisons., Results: A total of 7,942 patients were included in the study. The median age was 57 [IQR 48-66] years with 64% female, and 17% Black patients. Only 58% of the total cohort was prescribed statin therapy. Higher age was independently associated with a higher likelihood of receiving a statin, with an odds ratio of 1.25 (95% CI [1.21 - 1.30] per 10 years, p <0.001). Additional factors that were associated with higher rates of statin prescription in patients with SH were Black race (OR 1.90, 95% CI [1.65 - 2.17], p <0.001), smoking (OR 2.42, 95% CI [2.17 -2.70], p <0.001), and presence of diabetes (OR 3.88, 95% CI [3.27 - 4.60], p <0.001). Similar trends were also seen with other lipid-lowering therapies such as ezetimibe and fibrates., Conclusions: In our Northeast Ohio healthcare system, less than two-thirds of patients with severe hypercholesterolemia are prescribed a statin. Statin prescription rates were highly dependent on age and the presence of additional ASCVD risk factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©2023TheAuthors.PublishedbyElsevierB.V.)

Aims: To evaluate the associations between liver fat content and cardiometabolic parameters to explore potential threshold values that define metabolically healthy liver fat content, and to examine the association of liver fat content with cardiovascular events as well as its longitudinal progression., Methods: Participants in the Dallas Heart Study underwent clinical evaluation, including laboratory testing, and liver fat quantification by magnetic resonance spectroscopy (MRS) at baseline (N = 2287) and at follow-up (N = 343) after a mean of 7.3 years. Cardiovascular events were adjudicated (>12 years)., Results: The mean age at study entry was 44 years, 47% of participants were men, and 48% were African American. The following cardiometabolic biomarkers worsened across liver fat quintiles (P < 0.0001): body mass index (BMI); waist circumference; prevalence of hypertension; prevalence of diabetes; cholesterol, triglyceride, high-sensitivity C-reactive protein (CRP), leptin and fasting glucose levels; homeostatic model assessment of insulin resistance index (HOMA-IR); coronary artery calcium score; visceral adipose tissue; abdominal subcutaneous adipose tissue; and lower body subcutaneous adipose tissue. Cardiovascular events were comparable across groups defined by tertile of baseline liver fat content. Change in BMI (R = 0.40), waist circumference (R = 0.35), CRP (R = 0.31), alanine aminotransferase (R = 0.27), HOMA-IR (R = 0.26), aspartate transaminase (R = 0.15) and triglycerides (R = 0.12) significantly correlated with change in liver fat content (P < 0.01 for all)., Conclusion: Clinically relevant metabolic abnormalities were higher across quintiles of liver fat, with increases noted well within normal liver fat ranges, but cardiovascular events were not associated with liver fat content. Longitudinal changes in metabolic parameters, especially adiposity-related parameters, were correlated with change in liver fat content., (© 2022 John Wiley & Sons Ltd.)

Objectives: Adults with diabetes are at an increased risk of atherosclerotic cardiovascular disease (ASCVD), and food insecurity may be a major and underappreciated risk compounder in this population. We sought to analyze the prevalence of food insecurity and its association with ASCVD in adults with diabetes., Methods: A total of 6424 participants with diabetes were included from the 2019 and 2020 National Health Interview Survey. Food insecurity was determined with a 10-question U.S. Adult Food Security Survey Module, and classified as high, marginal, low, and very low. ASCVD was defined as a self-reported history of coronary artery disease, myocardial infarction, or stroke., Results: Of the 6424 included participants (weighted: n = 21 690 217), 5 405 543 (24.4%) reported a history of ASCVD and 2 946 061 (13.3%) were identified as food insecure (low or very low food security). Adults with food insecurity were more likely to have ASCVD than adults who were food secure (28.9% vs 23.7%; P = 0.008). In the multivariate analyses adjusted for traditional cardiovascular risk factors, all levels of food insecurity were associated with ASCVD compared with food-secure adults (marginal security: odds ratio [OR]: 1.60; 95% confidence interval [CI], 1.18-2.18]; P = 0.003; low security: OR: 2.09; 95% CI, 1.58-2.74]; P < 0.001; very low security: OR: 1.69; 95% CI, 1.22-2.34]; P = 0.001). The association persisted when adjusted for income, location, education, and insurance status. In adults with diabetes and ASCVD, income was a negative factor for food insecurity (OR: 0.71; 95% CI, 0.62-0.80; P < 0.001), but female sex and smoking were positive factors (OR: 1.90; 95% CI, 1.29-2.80; P = 0.001; and OR: 1.97; 95% CI, 1.23-3.18; P = 0.005; respectively). At younger ages, the prevalence of food insecurity increased, especially in adults with ASCVD., Conclusions: We showed that 13% of U.S. adults with diabetes are food insecure, which was associated with ASCVD independent of traditional and socioeconomic risk factors. Our findings emphasize the importance of recognizing food insecurity as a driver of ASCVD in adults with diabetes, and encourage future efforts at reducing this disparity., (Copyright © 2022. Published by Elsevier Inc.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction: Coronary artery calcium (CAC) scoring is not routinely performed in patients with diabetes based on an existing class I indication for statin therapy in these patients. However, CAC scoring may improve risk classification and prediction of atherosclerotic cardiovascular disease (ASCVD) events beyond risk scores in asymptomatic individuals with prediabetes and diabetes, warranting CAC assessment in this population. The routine availability through provision of no-charge CAC as an alternative to routine probabilistic risk scores may improve utilization of preventive therapies especially in traditionally underserved populations., Methods: Prospective observational study in a large health system offering no-charge CAC scoring for primary prevention risk prediction with available glycosylated hemoglobin (HbA1c) measurements between June 2015 and March 2019 were divided according to no diabetes (HbA1c <5.7 %), prediabetes (HbA1c 5.7 %-6.4 %), or diabetes (HbA1c ≥ 6.5 % or charted history) and followed for major adverse cardiovascular events [myocardial infarction, stroke, death (MACE) or coronary revascularization]. Patient characteristics, health history, laboratory data, and statin prescription rates were measured at baseline and at one year after CAC scoring., Results: A total of 12,194 subjects with available HbA1c underwent CAC scoring during the study period (6462 diabetes, 2062 prediabetes, and 3670 without diabetes). At a median follow-up of 1.2 years, there were 458 MACE events (71 patients without diabetes, 66 patients with prediabetes, and 321 patients with diabetes). Among patients with diabetes or prediabetes, increased CAC was associated with MACE (HR 1.38 [1.26-1.51], p < 0.001) and MACE or revascularization (HR 1.70 [1.57-1.85], p < 0.001). In patients with diabetes, CAC category was associated with greater statin initiation (89.6 % for CAC≥400 vs 60.1 % for CAC = 0, p < 0.001) and high intensity statin initiation (42.2 % for CAC≥400 vs 16.8 % for CAC = 0, p < 0.001) at one year post CAC scoring. Patients with diabetes had greater reductions in systolic blood pressure, LDL-C, total cholesterol, and triglycerides from baseline with a CAC ≥400 compared to a lower CAC category (p = 0.007)., Conclusions: CAC burden is associated with ASCVD risk in patients with diabetes. CAC scoring increases statin prescriptions and reduces ASCVD risk in patients with diabetes, potentially warranting routine CAC assessment in this population., (Copyright © 2022. Published by Elsevier Inc.)

Background: Left ventricular hypertrophy (LVH) combined with elevations in cardiac biomarkers reflecting myocardial injury and neurohormonal stress (malignant LVH) is associated with a high risk for heart failure and death., Objectives: The aim of this study was to determine the impact of intensive systolic blood pressure (SBP) control on the prevention of malignant LVH and its consequences., Methods: A total of 8,820 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were classified into groups based on the presence or absence of LVH assessed by 12-lead ECG, and elevations in biomarker levels (high-sensitivity cardiac troponin T ≥14 ng/L or N-terminal pro-B-type natriuretic peptide ≥125 pg/mL) at baseline. The effects of intensive vs standard SBP lowering on rates of acute decompensated heart failure (ADHF) events and death and on the incidence and regression of malignant LVH were determined., Results: Randomization to intensive SBP lowering led to similar relative reductions in ADHF events and death across the combined LVH/biomarker groups (P for interaction = 0.68). The absolute risk reduction over 4 years in ADHF events and death was 4.4% (95% CI: -5.2% to 13.9%) among participants with baseline malignant LVH (n = 449) and 1.2% (95% CI: 0.0%-2.5%) for those without LVH and nonelevated biomarkers (n = 4,361). Intensive SBP lowering also reduced the incidence of malignant LVH over 2 years (2.5% vs 1.1%; OR: 0.44; 95% CI: 0.30-0.63)., Conclusions: Intensive SBP lowering prevented malignant LVH and may provide substantial absolute risk reduction in the composite of ADHF events and death among SPRINT participants with baseline malignant LVH., Competing Interests: Funding Support and Author Disclosures This ancillary study was supported by the National Heart, Lung, and Blood Institute (1R01HL144112-01 for Dr Berry). Analytical reagents for hs-cTnT and NT-proBNP measurements were donated by Roche. SPRINT was sponsored by the National Institutes of Health, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under Contract Numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, HHSN268200900049C, and Inter-Agency Agreement Number A-HL-13–002-001. It was also supported in part with resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the U.S. Department of Veterans Affairs, or the United States Government. Support was also received from the following CTSAs funded by the National Center for Advancing Translational Sciences: CWRU: UL1TR000439, OSU: UL1RR025755, U Penn: UL1RR024134 and UL1TR000003, Boston: UL1RR025771, Stanford: UL1TR000093, Tufts: UL1RR025752, UL1TR000073 and UL1TR001064, University of Illinois: UL1TR000050, University of Pittsburgh: UL1TR000005, UT Southwestern: 9U54TR000017–06, University of Utah: UL1TR000105–05, Vanderbilt University: UL1 TR000445, George Washington University: UL1TR000075, University of California, Davis: UL1 TR000002, University of Florida: UL1 TR000064, University of Michigan: UL1TR000433, Tulane University: P30GM103337 COBRE Award NIGMS, Wake Forest University: UL1TR001420. Dr de Lemos has received grant support from Roche Diagnostics and Abbott Diagnostics; has received consulting fees from Roche Diagnostics, Abbott Diagnostics, Ortho Clinical Diagnostics, Quidel Cardiovascular, Inc, and Siemen’s Health Care Diagnostics; and has been named a co-owner on a patent awarded to the University of Maryland (US Patent Application Number: 15/309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure.” Dr Kitzman has received honoraria as a consultant outside the present study from Bayer, Merck, Pfizer, Corvia Medical, Boehringer Ingelheim, Ketyo, Rivus, Novo Nordisk, AstraZeneca, and Novartis; has received grant funding from Novartis, Bayer, Pfizer, Novo Nordisk, and AstraZeneca; and has stock ownership in Gilead Sciences. Dr Berry has received grant support from the National Institutes of Health, Roche Diagnostics, and Abbott Diagnostics; and has received consulting fees from Roche Diagnostics and the Cooper Institute. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Prior studies have suggested significant underutilization of statins in women and worse cardiovascular outcomes. Data examining the impact of real-world coronary artery calcium (CAC) scoring to improve utilization of preventive therapies and outcomes is limited., Methods: In a prospective registry study of low cost or no-cost CAC scoring between 2014 and 19 (CLARIFY Study, Clinicaltrials.gov NCT04075162), we sought to study the association of CAC scoring on statin utilization, blood lipids (LDL, total cholesterol, triglycerides), downstream ischemic testing (coronary angiography and stress testing), coronary revascularization and outcomes (MI, stroke, death) in women compared with men. Eligibility for statin initiation was defined as atherosclerotic cardiovascular disease pooled cohort equation (ASCVD-PCE) ≥ 7.5% and CAC≥100/≥75th percentile., Results: A total of 52,151 patients (26,336 women and 25,815 men) were enrolled. Women were more likely to have CAC 0 (51% vs 30%, P <0.001). Among patients not eligible for statin by PCE, CAC reclassified statin eligibility in a smaller proportion of women than men (25.4% vs 30%, P <0.001), while among patients eligible for statin by PCE, CAC was more likely to downgrade risk/statin eligibility in women than men (30.1% vs 48.4%, P <0.001). After CAC scoring, statin initiation was similar in women and men, but high-intensity statin use was lower in women (CAC-adjusted HR 0.76 [0.70-0.83], P <0.001). Women had similar reduction in LDL cholesterol levels compared with men. There was no difference between men and women with respect to CAC-stratified major adverse cardiovascular events., Conclusion: CAC scoring primarily served to downgrade statin eligibility in women compared with men. Women had similar CAC risk-guided reductions in LDL cholesterol compared with men., Competing Interests: None of the authors have disclosures related to the contents of this manuscript., (© 2022 The Author(s). Published by Elsevier B.V.)

Background The care for patients with type 2 diabetes necessitates a multidisciplinary team approach to reduce cardiovascular risk, but implementation of effective integrated strategies has been limited. Methods and Results We conceptualized and initiated a patient-centered, team-based intervention called Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) at University Hospitals Cleveland Medical Center. Patients with type 2 diabetes at high risk for cardiovascular events, including those with established atherosclerotic cardiovascular disease, elevated coronary artery calcium score >100, chronic heart failure with reduced ejection fraction, and/or chronic kidney disease stages 2 to 4 were included. Herein, we present the year 1 results for the program. From May 2020 through August 2021, there were 417 referrals. Among 206 eligible patients, 113 (55%) completed a baseline and ≥1 follow-up visit through December 2021, with mean (SD) time of 105 (34) days between baseline and first follow-up visits. Mean age was 59 years, with 49% women and 37% Black patients. Patients had significant reductions from baseline in glycosylated hemoglobin (-10.8%), total cholesterol (-7.9%), low-density lipoprotein cholesterol (-13.5%), systolic blood pressure (-4.0%), and body mass index (-2.7%) ( P ≤0.001 for all). In addition, among the 129 (63%) eligible patients not on sodium-glucose cotransporter 2 inhibitor or glucagon-like peptide-1 receptor agonist at baseline, 81% were prescribed evidence-based therapy with sodium-glucose cotransporter 2 inhibitor (n=66 [51%]) and/or glucagon-like peptide-1 receptor agonist (n=67 [52%]) to reduce the risk of cardiovascular disease in the initial 3-month follow-up period. Conclusions A team-based, patient-centered approach to high-risk disease management appears to be a promising paradigm for care delivery associated with greater use of evidence-based therapies and improved control of multiple cardiovascular risk factors.

Visceral adipose tissue (VAT) is a strong prognostic factor for cardiovascular disease and a potential target for cardiovascular risk stratification. Because VAT is difficult to measure in clinical practice, we estimated prediction models with predictors routinely measured in general practice and VAT as outcome using ridge regression in 2,501 middle-aged participants from the Netherlands Epidemiology of Obesity study, 2008-2012. Adding waist circumference and other anthropometric measurements on top of the routinely measured variables improved the optimism-adjusted R2 from 0.50 to 0.58 with a decrease in the root-mean-square error (RMSE) from 45.6 to 41.5 cm2 and with overall good calibration. Further addition of predominantly lipoprotein-related metabolites from the Nightingale platform did not improve the optimism-corrected R2 and RMSE. The models were externally validated in 370 participants from the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS, 2006-2009) and 1,901 participants from the Multi-Ethnic Study of Atherosclerosis (MESA, 2000-2007). Performance was comparable to the development setting in PIVUS (R2 = 0.63, RMSE = 42.4 cm2, calibration slope = 0.94) but lower in MESA (R2 = 0.44, RMSE = 60.7 cm2, calibration slope = 0.75). Our findings indicate that the estimation of VAT with routine clinical measurements can be substantially improved by incorporating waist circumference but not by metabolite measurements., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Objective: To evaluate the cardiometabolic outcomes associated with discordant visceral adipose tissue (VAT) and liver fat (LF) phenotypes in 2 cohorts., Patients and Methods: Participants in the Dallas Heart Study underwent baseline imaging from January 1, 2000, through December 31, 2002, and were followed for incident cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) through 2013. Associations between VAT-LF groups (low-low, high-low, low-high, and high-high) and outcomes were assessed using multivariable-adjusted regression and were replicated in the independent UK Biobank., Results: The Dallas Heart Study included 2064 participants (mean ± SD age, 44±9 years; 54% female; 47% black). High VAT-high LF and high VAT-low LF were associated with prevalent atherosclerosis, whereas low VAT-high LF was not. Of 1731 participants without CVD/T2DM, 128 (7.4%) developed CVD and 95 (5.5%) T2DM over a median of 12 years. High VAT-high LF and high VAT-low LF were associated with increased risk of CVD (hazard ratios [HRs], 2.0 [95% CI, 1.3 to 3.2] and 2.4 [95% CI, 1.4 to 4.1], respectively) and T2DM (odds ratios [ORs], 7.8 [95% CI, 3.8 to 15.8] and 3.3 [95% CI, 1.4 to 7.8], respectively), whereas low VAT-high LF was associated with T2DM (OR, 2.7 [95% CI, 1.1 to 6.7]). In the UK Biobank (N=22,354; April 2014-May 2020), only high VAT-low LF remained associated with CVD after multivariable adjustment for age and body mass index (HR, 1.5 [95% CI, 1.2 to 1.9])., Conclusion: Although VAT and LF are each associated with cardiometabolic risk, these observations demonstrate the importance of separating their cardiometabolic implications when there is presence or absence of either or both in an individual., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Obesity and diabetes are associated with a higher risk of heart failure (HF). The interrelationships between different measures of adiposity-overall obesity, central obesity, fat mass (FM)-and diabetes status for HF risk are not well-established., Methods: Participant-level data from the ARIC study (Atherosclerosis Risk in Communities; visit 5) and the CHS (Cardiovascular Health Study; visit 1) cohorts were obtained from the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center, harmonized, and pooled for the present analysis, excluding individuals with prevalent HF. FM was estimated in all participants using established anthropometric prediction equations additionally validated using the bioelectrical impedance-based FM in the ARIC subgroup. Incident HF events on follow-up were captured across both cohorts using similar adjudication methods. Multivariable-adjusted Fine-Gray models were created to evaluate the associations of body mass index (BMI), waist circumference (WC), and FM with risk of HF in the overall cohort as well as among those with versus without diabetes at baseline. The population attributable risk of overall obesity (BMI≥30 kg/m 2 ), abdominal obesity (WC>88 and 102 cm in women and men, respectively), and high FM (above sex-specific median) for incident HF was evaluated among participants with and without diabetes., Results: The study included 10 387 participants (52.9% ARIC; 25.1% diabetes; median age, 74 years). The correlation between predicted and bioelectrical impedance-based FM was high ( R 2 =0.90; n=5038). During a 5-year follow-up, 447 participants developed HF (4.3%). Higher levels of each adiposity measure were significantly associated with higher HF risk (hazard ratio [95% CI] per 1 SD higher BMI=1.15 [1.05, 1.27], WC=1.22 [1.10, 1.36]; FM=1.13 [1.02, 1.25]). A significant interaction was noted between diabetes status and measures of BMI ( P interaction=0.04) and WC ( P interaction=0.004) for the risk of HF. In stratified analysis, higher measures of each adiposity parameter were significantly associated with higher HF risk in individuals with diabetes (hazard ratio [95% CI] per 1 SD higher BMI=1.29 [1.14-1.47]; WC=1.48 [1.29-1.70]; FM=1.25 [1.09-1.43]) but not those without diabetes, including participants with prediabetes and euglycemia. The population attributable risk percentage of overall obesity, abdominal obesity, and high FM for incident HF was higher among participants with diabetes (12.8%, 29.9%, and 13.7%, respectively) versus those without diabetes (≤1% for each)., Conclusions: Higher BMI, WC, and FM are strongly associated with greater risk of HF among older adults, particularly among those with prevalent diabetes.

The introduction of coronavirus 2019 (COVID-19) vaccination has been an integral force in stopping the spread of COVID-19 across the globe. While reported side effects of vaccination have predominantly been mild, in the last year reports have emerged of myocarditis following the BNT162b2 (Pfizer-BioNtech) and mRNA-1273 (Moderna) vaccinations. The adolescent and young adult population have been the population most reported, with over 1000 cases under review by the Centers for Disease Control (CDC) since April 2021. Here we report a case of a previously healthy 21-year-old male who developed Multisystem Inflammatory Syndrome in Adults (MIS-A) and following the second dose of the Pfizer-BioNtech vaccine. The young male initially presented with fever, leukocytosis with high neutrophil-lymphocyte ratio, severe cardiac illness, and positive COVID-19 nucleocapsid serology, consistent with MIS-A diagnosis. His case was complicated by cardiogenic shock, requiring brief venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. While this report does not detract from the overwhelming benefit of vaccination from COVID-19, clinicians should be aware of this possible relationship in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Purpose of Review: The obesity epidemic is on the rise, and while it is well known that obesity is associated with an increase in cardiovascular risk factors such as type 2 diabetes mellitus, hypertension, and obstructive sleep apnea, recent data has highlighted that the degree and type of fat distribution may play a bigger role in the pathogenesis of cardiovascular disease (CVD) than body mass index (BMI) alone. We aim to review updated data on adipose tissue inflammation and distribution and CVD., Recent Findings: We review the pathophysiology of inflammation secondary to adipose tissue, the association of obesity-related adipokines and CVD, and the differences and significance of brown versus white adipose tissue. We delve into the clinical manifestations of obesity-related inflammation in CVD. We discuss the available data on heterogeneity of adipose tissue-related inflammation with a focus on subcutaneous versus visceral adipose tissue, the differential pathophysiology, and clinical CVD manifestations of adipose tissue across sex, race, and ethnicity. Finally, we present the available data on lifestyle modification, medical, and surgical therapeutics on reduction of obesity-related inflammation. Obesity leads to a state of chronic inflammation which significantly increases the risk for CVD. More research is needed to develop non-invasive VAT quantification indices such as risk calculators which include variables such as sex, age, race, ethnicity, and VAT concentration, along with other well-known CVD risk factors in order to comprehensively determine risk of CVD in obese patients. Finally, pre-clinical biomarkers such as pro-inflammatory adipokines should be validated to estimate risk of CVD in obese patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)