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Digital health technologies can generate data that can be used to train artificial intelligence (AI) algorithms, which have been particularly transformative in cardiovascular health-care delivery. However, digital and health-care data repositories that are used to train AI algorithms can introduce bias when data are homogeneous and health-care processes are inequitable. AI bias can also be introduced during algorithm development, testing, implementation, and post-implementation processes. The consequences of AI algorithmic bias can be considerable, including missed diagnoses, misclassification of disease, incorrect risk prediction, and inappropriate treatment recommendations. This bias can disproportionately affect marginalised demographic groups. In this Series paper, we provide a brief overview of AI applications in cardiovascular health care, discuss stages of algorithm development and associated sources of bias, and provide examples of harm from biased algorithms. We propose strategies that can be applied during the training, testing, and implementation of AI algorithms to mitigate bias so that all those at risk for or living with cardiovascular disease might benefit equally from AI.

High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease.

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. 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/m2or ≥27 kg/m2and 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. 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. 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.

Patterns and disparities in guideline-directed medical therapy (GDMT) uptake for heart failure with reduced ejection fraction (HFrEF) across rural vs urban regions are not well described.

Implantable cardioverter-defibrillator (ICD) therapy is recommended to reduce mortality risk in patients with heart failure with reduced ejection fraction (HFrEF). Frailty is common among patients with HFrEF and is associated with increased mortality risk. Whether the therapeutic efficacy of ICD is consistent among frail and nonfrail patients with HFrEF remains unclear.

Individuals with acute decompensated heart failure (ADHF) have a varying response to diuretic therapy. Strategies for the early identification of low diuretic efficiency to inform decongestion therapies are lacking.

Frailty is common among older patients with heart failure (HF). The efficacy of coronary artery bypass grafting (CABG) on the risk of mortality among frail patients with ischemic cardiomyopathy and HF is uncertain, and whether frailty burden modifies the treatment benefits of CABG among these patients is unknown. We performed a post hoc analysis of the STICHES trial, a randomized trial of CABG with medical therapy vs medical therapy alone among participants with ischemic cardiomyopathy with ejection fraction ≤ 35%. Baseline frailty was assessed through a Rockwood Frailty Index (FI), and based on FI cut-offs from prior HF studies, participants with FI ≥ 0.311 were classified as more frail, and those with FI < 0.311 were classified as less frail. A multivariable Cox proportional hazard model with multiplicative interaction terms was constructed to evaluate whether frailty status modified the treatment effect of CABG on mortality in the overall trial cohort and among those < 60 vs ≥ 60 years of age. Of 1187 participants (12.4% female, 2.6% Black, median FI = 0.33 [IQR 0.27–0.39]), 678 were characterized as more frail. Frailty burden did not modify the efficacy of CABG on the risk of all-cause death in the overall cohort (PintCABG × frailty = 0.2). In age stratified analysis, Baseline frailty status did not modify the treatment effect of CABG on the risk of all-cause mortality among younger (< 60 years,PintCABG × frailty = 0.2) as well as older participants (≥60 years, PintCABG × frailty = 0.6). In this post hoc analysis of the STICHES trial, baseline frailty status did not modify the efficacy of CABG in the overall cohort as well as among younger or older participants. Frailty alone should not be used as a criterion to determine the utilization of CABG among patients with ischemic cardiomyopathy.

Obesity is associated with incident heart failure (HF), independent of other cardiovascular risk factors. Despite rising rates of both obesity and incident HF, the associations remain poorly understood between: 1) obesity and HF outcomes; and 2) weight loss and HF outcomes. Evidence shows that patients with HF and obesity have high symptom burdens, lower exercise capacity, and higher rates of hospitalization for HF when compared with patients with HF without obesity. However, the impact of weight loss on these outcomes for patients with HF and obesity remains unclear. Recent advances in medical therapies for weight loss have offered a new opportunity for significant and sustained weight loss. Ongoing and recently concluded cardiovascular outcomes trials will offer new insights into the role of weight loss through these therapies in preventing HF and mitigating HF outcomes and symptom burdens among patients with established HF, particularly HF with preserved ejection fraction.

Polypharmacy is common among patients with heart failure with reduced ejection fraction (HFrEF). However, its impact on the use of optimal guideline-directed medical therapy (GDMT) is not well established.

At least half of all patients with heart failure (HF) are affected by frailty, a syndrome that limits an individual ability to recover from acute stressors. While frailty affects up to 90% of patients with HF with preserved ejection fraction, it is also seen in ~30–60% of patients with HF with reduced ejection fraction, with ~26% higher prevalence in women compared with men. The relationship between frailty and HF is bidirectional, with both conditions exacerbating the other. Frailty is further complicated by a higher prevalence of sarcopenia (by ~20%) in HF patients compared with patients without HF, which negatively affects outcomes. Several frailty assessment methods have been employed historically including the Fried frailty phenotype and Rockwood Clinical Frailty Scale to classify HF patients based on the severity of frailty; however, a validated HF‐specific frailty assessment tool does not currently exist. Frailty in HF is associated with a poor prognosis with a 1.5‐fold to 2‐fold higher risk of all‐cause death and hospitalizations compared to non‐frail patients. Frailty is also highly prevalent in patients with worsening HF, affecting >50% of patients hospitalized for HF. Such patients with multiple readmissions for decompensated HF have markedly poor outcomes compared to younger, non‐frail cohorts, and it is hypothesized that it may be due to major physical and functional limitations that limit recovery from an acute episode of worsening HF, a care aspect that has not been addressed in HF guidelines. Frail patients are thought to confer less benefit from therapeutic interventions due to an increased risk of perceived harm, resulting in lower adherence to HF interventions, which may worsen outcomes. Multiple studies report that <40% of frail patients are on guideline‐directed medical therapy for HF, of which most are on suboptimal doses of these medications. There is a lack of evidence generated from randomized trials in this incredibly vulnerable population, and most current practice is governed by post hoc analyses of trials, observational registry‐based data and providers' clinical judgement. The current body of evidence suggests that the treatment effect of most guideline‐based interventions, including medications, cardiac rehabilitation and device therapy, is consistent across all age groups and frailty subgroups and, in some cases, may be amplified in the older, more frail population. In this review, we discuss the characteristics, assessment tools, impact on prognosis and impact on therapeutic interventions of frailty in patients with HF.

The burden of heart failure among people with type 2 diabetes is increasing globally. People with comorbid type 2 diabetes and heart failure often have worse outcomes than those with only one of these conditions—eg, higher hospitalisation and mortality rates. Therefore, it is essential to implement optimal heart failure prevention strategies for people with type 2 diabetes. A detailed understanding of the pathophysiology underlying the occurrence of heart failure in type 2 diabetes can aid clinicians in identifying relevant risk factors and lead to early interventions that can help prevent heart failure. In this Review, we discuss the pathophysiology and risk factors of heart failure in type 2 diabetes. We also review the risk assessment tools for predicting heart failure incidence in people with type 2 diabetes as well as the data from clinical trials that have assessed the efficacy of lifestyle and pharmacological interventions. Finally, we discuss the potential challenges in implementing new management approaches and offer pragmatic recommendations to help overcome these challenges.

In the CANVAS (Canagliflozin Cardiovascular Assessment Study) program, canagliflozin reduced the risk of heart failure (HF) hospitalization among individuals with type 2 diabetes mellitus (T2DM).

IMPORTANCE: The burden of atherosclerotic cardiovascular disease (ASCVD) in the US is higher among Black and Hispanic vs White adults. Inclusion of race in guidance for statin indication may lead to decreased disparities in statin use. OBJECTIVE: To evaluate prevalence of primary prevention statin use by race and ethnicity according to 10-year ASCVD risk. DESIGN, SETTING, AND PARTICIPANTS: This serial, cross-sectional analysis performed in May 2022 used data from the National Health and Nutrition Examination Survey, a nationally representative sample of health status in the US, from 2013 to March 2020 (limited cycle due to the COVID-19 pandemic), to evaluate statin use for primary prevention of ASCVD and to estimate 10-year ASCVD risk. Participants aged 40 to 75 years without ASCVD, diabetes, low-density lipoprotein cholesterol levels 190 mg/dL or greater, and with data on medication use were included. EXPOSURES: Self-identified race and ethnicity (Asian, Black, Hispanic, and White) and 10-year ASCVD risk category (5%-&lt;7.5%, 7.5%-&lt;20%, ≥20%). MAIN OUTCOMES AND MEASURES: Prevalence of statin use, defined as identification of statin use on pill bottle review. RESULTS: A total of 3417 participants representing 39.4 million US adults after applying sampling weights (mean [SD] age, 61.8 [8.0] years; 1289 women [weighted percentage, 37.8%] and 2128 men [weighted percentage, 62.2%]; 329 Asian [weighted percentage, 4.2%], 1032 Black [weighted percentage, 12.7%], 786 Hispanic [weighted percentage, 10.1%], and 1270 White [weighted percentage, 73.0%]) were included. Compared with White participants, statin use was lower in Black and Hispanic participants and comparable among Asian participants in the overall cohort (Asian, 25.5%; Black, 20.0%; Hispanic, 15.4%; White, 27.9%) and within ASCVD risk strata. Within each race and ethnicity group, a graded increase in statin use was observed across increasing ASCVD risk strata. Statin use was low in the highest risk stratum overall with significantly lower rates of use among Black (23.8%; prevalence ratio [PR], 0.90; 95% CI, 0.82-0.98 vs White) and Hispanic participants (23.9%; PR, 0.90; 95% CI, 0.81-0.99 vs White). Among other factors, routine health care access and health insurance were significantly associated with higher statin use in Black, Hispanic, and White adults. Prevalence of statin use did not meaningfully change over time by race and ethnicity or by ASCVD risk stratum. CONCLUSIONS AND RELEVANCE: In this study, statin use for primary prevention of ASCVD was low among all race and ethnicity groups regardless of ASCVD risk, with the lowest use occurring among Black and Hispanic adults. Improvements in access to care may promote equitable use of primary prevention statins in Black and Hispanic adults.

IMPORTANCE: Frailty is common among older patients with acute decompensated heart failure (ADHF) and is associated with worse quality of life (QOL) and a higher risk of clinical events. Frailty can also limit recovery and response to interventions. In the Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial, a 3-month innovative, early, transitional, tailored, multidomain physical rehabilitation intervention improved physical function and QOL (vs usual care) in older patients with ADHF. OBJECTIVE: To evaluate whether baseline frailty modified the benefits of the physical rehabilitation intervention among patients with ADHF enrolled in the REHAB-HF trial and to assess the association between changes in frailty with the risk of adverse clinical outcomes on follow-up. DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of the REHAB-HF trial, a multicenter randomized clinical trial, included 337 patients 60 years and older hospitalized for ADHF. Patients were enrolled from September 17, 2014, through September 19, 2019. Participants were stratified across baseline frailty strata as assessed using modified Fried criteria. Data were analyzed from July 2021 to September 2022. INTERVENTIONS: Physical rehabilitation intervention or attention control. MAIN OUTCOMES AND MEASURES: Primary outcome was the Short Physical Performance Battery (SPPB) score at 3 months. Clinical outcomes included all-cause hospitalization or mortality at 6 months. RESULTS: This prespecified secondary analysis included 337 participants; 181 (53.7%) were female, 167 (49.6%) were Black, and the mean (SD) age was 72 (8) years. A total of 192 (57.0%) were frail and 145 (43.0%) were prefrail at baseline. A significant interaction was observed between baseline frailty status and the treatment arm for the primary trial end point of overall SPPB score, with a 2.6-fold larger improvement in SPPB with intervention among frail patients (2.1; 95% CI, 1.3-2.9) vs prefrail patients (0.8; 95% CI, −0.1 to 1.6; P for interaction = .03). Trends consistently favored a larger intervention effect size, with significant improvement among frail vs prefrail participants for 6-minute walk distance, QOL, and the geriatric depression score, but interactions did not achieve significance. CONCLUSIONS AND RELEVANCE: In this prespecified secondary analysis of the REHAB-HF trial, patients with ADHF with worse baseline frailty status had a more significant improvement in physical function in response to an innovative, early, transitional, tailored, multidomain physical rehabilitation intervention than those who were prefrail. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT02196038

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The majority of cardiovascular randomized controlled trials (RCTs) test interventions in selected patient populations under explicitly protocol-defined settings. Although these ‘explanatory’ trial designs optimize conditions to test the efficacy and safety of an intervention, they limit the generalizability of trial findings in broader clinical settings. The concept of ‘pragmatism’ in RCTs addresses this concern by providing counterbalance to the more idealized situation underpinning explanatory RCTs and optimizing effectiveness over efficacy. The central tenets of pragmatism in RCTs are to test interventions in routine clinical settings, with patients who are representative of broad clinical practice, and to reduce the burden on investigators and participants by minimizing the number of trial visits and the intensity of trial-based testing. Pragmatic evaluation of interventions is particularly important in cardiovascular diseases, where the risk of death among patients has remained fairly stable over the past few decades despite the development of new therapeutic interventions. Pragmatic RCTs can help to reveal the ‘real-world’ effectiveness of therapeutic interventions and elucidate barriers to their implementation. In this Review, we discuss the attributes of pragmatism in RCT design, conduct and interpretation as well as the general need for increased pragmatism in cardiovascular RCTs. We also summarize current challenges and potential solutions to the implementation of pragmatism in RCTs and highlight selected ongoing and completed cardiovascular RCTs with pragmatic trial designs.

The U.S. population is aging with concurrent increases in heart failure (HF) burden. However, HF-related mortality trends among adults ≥75 years have not been investigated.

IMPORTANCE: There are limited data on mortality trends in young adults with heart failure (HF). OBJECTIVE: To study the trends in HF-related mortality among young adults. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort analysis used mortality data of young adults aged 15 to 44 years with HF listed as a contributing or underlying cause of death in the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 1999 to December 2019. Analysis took place in October 2021. EXPOSURES: Age 15 to 44 years with HF listed as a contributing or underlying cause of death. MAIN OUTCOMES AND MEASURES: HF-related age-adjusted mortality rates (AAMR) per 100 000 US population stratified by sex, race and ethnicity, and geographic areas. RESULTS: Between 1999 and 2019, a total of 61 729 HF-related deaths occurred in young adults. Of these, 38 629 (62.0%) were men and 23 460 (38.0%) were women, and 22 156 (35.9%) were Black, 6648 (10.8%) were Hispanic, and 30 145 (48.8%) were White. The overall AAMR per 100 000 persons for HF in young adults increased from 2.36 in 1999 to 3.16 in 2019. HF mortality increased in young men and women, with men having higher AAMRs throughout the study period. AAMR increased for all race and ethnicity groups, with Black adults having the highest AAMRs (6.41 in 1999 and 8.58 in 2019). AAMR for Hispanic adults and White adults increased from 1.62 to 2.04 and 1.83 to 2.45 over the same time period, respectively. Across most demographic and regional subgroups, HF-related mortality stayed stable or decreased between 1999 and 2012, followed by an increase between 2012 and 2019. There were significant regional differences in the burden of HF-related mortality, with states in the upper 90th percentile of HF-related mortality (Oklahoma, South Carolina, Louisiana, Arkansas, Alabama, and Mississippi) having a significantly higher mortality burden compared with those in the bottom tenth percentile. CONCLUSIONS AND RELEVANCE: Following an initial period of stability, HF-related mortality in young adults increased from 2012 to 2019 in the United States. Black adults have a 3-fold higher AAMR compared with White adults, with significant geographic variation. Targeted health policy measures are needed to address the rising burden of HF in young adults, with a focus on prevention, early diagnosis, and reduction in disparities.

Supranormal ejection fraction by echocardiography in clinically referred patient populations has been associated with an increased risk of cardiovascular disease (CVD). The prognostic implication of supranormal left ventricular ejection fraction (LVEF)—assessed by cardiac magnetic resonance (CMR)—in healthy, community-dwelling individuals is unknown.

Excess adiposity is a well-known risk factor for heart failure (HF). Fat accumulation in and around the peripheral skeletal muscle may further inform risk for HF.

The aim of this study was to assess trends in heart failure (HF) hospitalizations among young adults.

The health benefits of exercise are well-recognized and are observed across multiple organ systems. These beneficial effects enhance overall resilience, healthspan and longevity. The molecular mechanisms that underlie the beneficial effects of exercise, however, remain poorly understood. Since the discovery in 2000 that muscle contraction releases IL-6, the number of exercise-associated signalling molecules that have been identified has multiplied. Exerkines are defined as signalling moieties released in response to acute and/or chronic exercise, which exert their effects through endocrine, paracrine and/or autocrine pathways. A multitude of organs, cells and tissues release these factors, including skeletal muscle (myokines), the heart (cardiokines), liver (hepatokines), white adipose tissue (adipokines), brown adipose tissue (baptokines) and neurons (neurokines). Exerkines have potential roles in improving cardiovascular, metabolic, immune and neurological health. As such, exerkines have potential for the treatment of cardiovascular disease, type 2 diabetes mellitus and obesity, and possibly in the facilitation of healthy ageing. This Review summarizes the importance and current state of exerkine research, prevailing challenges and future directions.

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Current guidelines for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend targeting a low-density lipoprotein cholesterol (LDL-C) of < 70 mg/dL. However, temporal trends and racial/ethnic- and sex-differences in achievement of LDL-C targets are not well described. We assessed trends and racial/ethnic- and sex-differences in achievement of LDL-C < 70 mg/dL using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008 to 2017-March 2020.

In this study, we sought to evaluate the association of frailty with the use of optimal guideline-directed medical therapy (GDMT) and outcomes in heart failure with reduced ejection fraction (HFrEF).

This study evaluated the association of transthyretin (TTR) gene variant, in which isoleucine substitutes for valine at position 122 (V142I), with cardiac structure, function, and heart failure (HF) risk among middle-aged Black adults.

Supplemental Digital Content is available in the text.

IMPORTANCE: Elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro–B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable. OBJECTIVE: To test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering. DESIGN, SETTING, AND PARTICIPANTS: This is a nonprespecified post hoc analysis of the multicenter, prospective, randomized clinical Systolic Blood Pressure Intervention Trial (SPRINT), conducted from October 20, 2010, to August 20, 2015. A total of 9361 patients without diabetes with increased risk for cardiovascular disease were randomized to receive intensive vs standard SBP lowering. Statistical analysis was performed on an intention-to-treat basis from September 30, 2019, to July 29, 2021. INTERVENTIONS: Participants were randomized to undergo intensive (&lt;120 mm Hg) or standard (&lt;140 mm Hg) SBP lowering. High-sensitivity cardiac troponin T and NTproBNP levels were measured from stored specimens collected at enrollment, with elevated levels defined as 14 ng/L or more for hscTnT (to convert to micrograms per liter, multiply by 0.001) and 125 pg/mL or more for NTproBNP (to convert to nanograms per liter, multiply by 1.0). MAIN OUTCOMES AND MEASURES: The primary outcome of this ancillary study was HF and mortality. RESULTS: Of the 9361 participants enrolled in SPRINT, 8828 (5578 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured hscTnT levels and 8836 (5585 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured NTproBNP levels; 2262 of 8828 patients (25.6%) had elevated hscTnT levels, 3371 of 8836 patients (38.2%) had elevated NTproBNP, and 1411 of 8828 patients (16.0%) had both levels elevated. Randomization to the intensive SBP group led to a 4.9% (95% CI, 1.7%-7.5%) absolute risk reduction (ARR) over 4 years in death and HF (421 events) for those with elevated hscTnT and a 1.7% (95% CI, 0.7%-2.5%) ARR for those without elevated levels. Similarly, for those with elevated NTproBNP, the ARR for death and HF over 4 years was 4.6% (95% CI, 2.3%-6.5%) vs 1.8% (95% CI, 0.9%-2.5%) in those without elevated levels. For those with elevated levels of both biomarkers, the ARR for death and HF over 4 years was 7.8% (95% CI, 3.3%-11.3%) vs 1.7% (95% CI, 0.8%-2.3%) in those with neither biomarker elevated. No significant treatment group by biomarker category interactions were detected. CONCLUSIONS AND RELEVANCE: Intensive SBP control led to large absolute differences in death and HF among patients with abnormal hscTnT and NTproBNP levels. These findings demonstrate that risk associated with elevation of these biomarkers is modifiable with intensive BP control. A prospective, randomized clinical trial is needed to evaluate whether these biomarkers may help guide selection of patients for intensive SBP lowering. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062

For patients with shortness of breath, a new, simplified screening tool — relying only on basic clinical information — can estimate the probability of heart failure with preserved ejection fraction, providing the opportunity for improved detection in non-specialist settings.

Visceral and ectopic fat are key drivers of adverse cardiometabolic outcomes in obesity. We aimed to evaluate the effects of injectable liraglutide 3·0 mg daily on body fat distribution in adults with overweight or obesity without type 2 diabetes at high cardiovascular disease risk.

IMPORTANCE: The American Heart Association/American College of Cardiology pooled cohort equations (PCEs) are used for predicting 10-year atherosclerotic cardiovascular disease (ASCVD) risk. Pooled cohort equation risk prediction capabilities across self-reported leisure-time physical activity (LTPA) levels and the change in model performance with addition of LTPA to the PCE are unclear. OBJECTIVE: To evaluate PCE risk prediction performance across self-reported LTPA levels and the change in model performance by adding LTPA to the existing PCE model. DESIGN, SETTING, AND PARTICIPANTS: Individual-level pooling of data from 3 longitudinal cohort studies—Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Cardiovascular Health Study—was performed. A total of 18 824 participants were stratified into 4 groups based on self-reported LTPA levels: inactive (0 metabolic equivalent of task [MET]-min/wk), less than guideline-recommended (&lt;500 MET-min/wk), guideline-recommended (500-1000 MET-min/week), and greater than guideline-recommended (>1000 MET-min/wk). Pooled cohort equation risk discrimination was studied using the C statistic and reclassification capabilities were studied using the Greenwood Nam-D’Agostino χ2 goodness-of-fit test. Change in risk discrimination and reclassification on adding LTPA to PCEs was evaluated using change in C statistic, integrated discrimination index, and categorical net reclassification index. MAIN OUTCOMES AND MEASURES: Adjudicated ASCVD events during 10-year follow-up. RESULTS: Among 18 824 participants studied, 10 302 were women (54.7%); mean (SD) age was 57.6 (8.2) years. A total of 5868 participants (31.2%) were inactive, 3849 (20.4%) had less than guideline-recommended LTPA, 3372 (17.9%) had guideline-recommended LTPA, and 5735 (30.5%) had greater than guideline-recommended LTPA level. Higher LTPA levels were associated with a lower risk of ASCVD after adjustment for risk factors (hazard ratio [HR] per 1-SD higher LTPA, 0.91; 95% CI, 0.86-0.96). Across LTPA groups, PCE risk discrimination (C statistic, 0.76-0.78) and risk calibration (all χ2 P > .10) was similar. Addition of LTPA to the PCE model resulted in no significant change in the C statistic (0.0005; 95% CI, −0.0004 to 0.0015; P = .28) and categorical net reclassification index (−0.003; 95% CI, −0.010 to 0.010; P = .95), but a minimal improvement in the integrated discrimination index (0.0008; 95% CI, 0.0002-0.0013; P = .005) was observed. Similar results were noted when cohort-specific coefficients were used for creating the baseline model. CONCLUSIONS AND RELEVANCE: Higher self-reported LTPA levels appear to be associated with lower ASCVD risk and increasing LTPA promotes cardiovascular wellness. These findings suggest the American Heart Association/American College of Cardiology PCEs are accurate at estimating the probability of 10-year ASCVD risk regardless of LTPA level. The addition of self-reported LTPA to PCEs does not appear to be associated with improvement in risk prediction model performance.

•GLP1-RAs and SGLT2Is lower the risk of adverse cardiac-kidney events in diabetes.•Only 10 % used GLP1-RAs or SGLT2Is, regardless of level of cardiac-kidney risk.•Few people who would benefit most from GLP1-RAs or SGLT2Is, were receiving them from 2015 to 2020.

IMPORTANCE: Self-identified Black race is associated with higher hypertension prevalence and worse blood pressure (BP) control compared with other race/ethnic groups. The contribution of genetic West African ancestry to these racial disparities appears not to have been completely determined. OBJECTIVE: To determine the association between the proportion of West African ancestry with the response to antihypertensive medication, BP control, kidney function, and risk of adverse cardiovascular (CV) events among self-identified Black individuals in the Systolic Blood Pressure Intervention Trial (SPRINT). DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of the SPRINT trial incorporated data from a multicenter study of self-identified Black participants with available West African ancestry proportion, estimated using 106 biallelic autosomal ancestry informative genetic markers. Recruitment started on October 20, 2010, and ended on August 20, 2015. Data were analyzed from May 2020 to September 2020. MAIN OUTCOMES AND MEASURES: Trajectories of BP and kidney function parameters on follow-up of the trial were assessed across tertiles of the proportion of West African ancestry using linear mixed-effect modeling after adjustment for potential confounders. Multivariable adjusted Cox models evaluated the association of West African ancestry with the risk of composite CV events (nonfatal myocardial infarction, CV death, and heart failure event). RESULTS: Among 2466 participants in the current analysis (1122 women [45.5%]; median West African ancestry, 81% [interquartile range, 73%-87%]), there were 120 composite CV events (4.9%) over a mean (SD) of 3.2 (0.9) years of follow-up. At baseline, mean (SD) high-density lipoprotein cholesterol levels were higher (tertile 3: 56.5 [15.0] mg/dL vs tertile 1: 54.2 [14.9] mg/dL; P = .006), smoking prevalence (never smoking: tertile 3: 367 [47.9%] vs tertile 1: 372 [42.2%]; P = .009) and mean (SD) Framingham Risk scores (tertile 3: 16.7 [9.7] vs tertile 1: 18.1 [10.2]; P = .01) were lower, and baseline BP was not different across increasing tertiles of West African ancestry. On follow-up, there was no evidence of differences in longitudinal trajectories of BP, kidney function parameters, or left ventricular mass (Cornell voltage by electrocardiogram) across tertiles of West African ancestry in either intensive or standard treatment arms. In adjusted Cox models, higher West African ancestry was associated with a lower risk of a composite CV event after adjustment for potential confounders (adjusted hazard ratio per 5% higher West African ancestry, 0.92 [95% CI, 0.85-0.99]). CONCLUSIONS AND RELEVANCE: Among self-reported Black individuals enrolled in SPRINT, the trajectories of BP, kidney function, and left ventricular mass over time were not different across tertiles of the proportion of West African ancestry. A higher proportion of West African ancestry was associated with a modestly lower risk for CV events. These findings suggest that extrinsic and structural societal factors, more than genetic ancestry, may be the major drivers of the well-established racial disparity in cardiovascular health associated with hypertension.

This study evaluated the application of a biomarker-based risk score to identify individuals with dysglycemia who are at high risk for incident heart failure (HF) and to inform allocation of effective preventive interventions.

This study investigates the prevalence and prognostic significance of mitral regurgitation (MR) in acute decompensated heart failure (ADHF) patients.

IMPORTANCE: Thirty-day home time, defined as time spent alive and out of a hospital or facility, is a novel, patient-centered performance metric that incorporates readmission and mortality. OBJECTIVES: To characterize risk-adjusted 30-day home time in patients discharged with heart failure (HF) as a hospital-level quality metric and evaluate its association with the 30-day risk-standardized readmission rate (RSRR), 30-day risk-standardized mortality rate (RSMR), and 1-year RSMR. DESIGN, SETTING, AND PARTICIPANTS: This hospital-level cohort study retrospectively analyzed 100% of Medicare claims data from 2 968 341 patients from 3134 facilities from January 1, 2012, to November 30, 2017. EXPOSURES: Home time, defined as time spent alive and out of a short-term hospital, skilled nursing facility, or intermediate/long-term facility 30 days after discharge. MAIN OUTCOMES AND MEASURES: For each hospital, a risk-adjusted 30-day home time for HF was calculated similar to the Centers for Medicare & Medicaid Services risk-adjustment models for 30-day RSRR and RSMR. Hospitals were categorized into quartiles (lowest to highest risk-adjusted home time). The correlations between hospital rates of risk-adjusted 30-day home time and 30-day RSRR, 30-day RSMR, and 1-year RSMR were estimated using the Pearson correlation coefficient. Distribution of days lost from a perfect 30-day home time were calculated. Reclassification of hospital performance using 30-day home time vs 30-day RSRR was also evaluated. RESULTS: Overall, 2 968 341 patients (mean [SD] age, 81.0 [8.3] years; 53.6% female) from 3134 hospitals were included in this study. The median hospital risk-adjusted 30-day home time for patients with HF was 21.77 days (range, 8.22-28.41 days). Hospitals in the highest quartile of risk-adjusted 30-day home time (best-performing hospitals) were larger (mean [SD] number of beds, 285 [275]), with a higher volume of patients with HF (median, 797 patients; interquartile range, 395-1484) and were more likely academic hospitals (59.9%) with availability of cardiac surgery (51.1%) and cardiac rehabilitation (68.8%). A total of 72% of home time lost was attributable to stays in an intermediate- or long-term care facility (mean [SD], 2.65 [6.44] days) or skilled nursing facility (mean [SD], 3.96 [9.04] days), 13% was attributable to short-term readmissions (mean [SD], 1.25 [3.25] days), and 15% was attributable to death (mean [SD], 1.37 [6.04] days). Among 30-day outcomes, the 30-day RSRR and 30-day RSMR decreased in a graded fashion across increasing 30-day home time categories (correlation coefficients: 30-day RSRR and 30-day home time, −0.23, P &lt; .001; 30-day RSMR and 30-day home time, −0.31, P &lt; .001). Similar patterns of association were also noted for 1-year RSMR and 30-day home time (correlation coefficient, −0.35, P &lt; .001). Thirty-day home time meaningfully reclassified hospital performance in 30% of the hospitals compared with 30-day RSRR and in 25% of hospitals compared with 30-day RSMR. CONCLUSIONS AND RELEVANCE: In this study, 30-day home time among patients discharged after a hospitalization for HF was objectively assessed as a hospital-level quality metric using Medicare claims data and was associated with readmission and mortality outcomes and with reclassification of hospital performance compared with 30-day RSRR and 30-day RSMR.

IMPORTANCE: Although kidney dysfunction and abnormalities in serum electrolyte levels are associated with poor clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF), the association of visit-to-visit variability in such laboratory measures with long-term outcomes is unclear. OBJECTIVE: To evaluate the associations of visit-to-visit variability in indexes of kidney function (creatinine and blood urea nitrogen [BUN] levels) and serum electrolyte (sodium, chloride, and potassium) with the risk of adverse clinical outcomes among patients with chronic, stable HFpEF. DESIGN, SETTING, AND PARTICIPANTS: This cohort analysis used data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. All participants with 3 or more serial laboratory measurements who were event free within the first 4 months of enrollment were included. Data were analyzed from March 1, 2019, to January 31, 2020. MAIN OUTCOMES AND MEASURES: Adjusted associations between indexes of variability in serum laboratory measurements during the first 4 months of follow-up and risk of the primary composite outcome (a composite of aborted cardiac arrest, hospitalization for heart failure, or cardiovascular death) and all-cause mortality were assessed using Cox proportional hazards regression models. RESULTS: Of the 3445 patients enrolled in the TOPCAT trial (mean [SD] age, 68-69 [10] years; 49.7%-51.5% female), 2479 (BUN) to 3195 (potassium) were analyzed, depending on availability of serial measurements. Participants with higher laboratory variability in kidney function parameters were older, had more comorbidities, and had more severe symptoms of HFpEF. Higher visit-to-visit variability in BUN (hazard ratio [HR] per 1-SD higher average successive variability [ASV], 1.21; 95% CI, 1.10-1.33) and creatinine (HR per 1-SD higher ASV, 1.13; 95% CI, 1.04-1.22) were independently associated with a higher risk of the primary composite outcome as well as mortality independent of other baseline confounders, changes in kidney function, changes in medication dosages, and variability in other cardiometabolic parameters (systolic blood pressure and body mass index). The higher risk associated with greater variability in kidney function was consistent across subgroups of patients stratified by the presence of chronic kidney disease (CKD) at baseline (CKD: HR per 1-SD higher ASV, 1.39; 95% CI, 1.16-1.67 and no CKD: HR per 1-SD higher ASV, 1.13; 95% CI, 1.01-1.27), among placebo and spironolactone treatment arms separately (spironolactone arm: 1.30; 95% CI, 1.03-1.65 and placebo arm: HR per 1-SD higher ASV, 1.27; 95% CI, 1.04-1.56). Among serum electrolytes, variability in sodium and potassium measures were also significantly associated with a higher risk of primary composite events (sodium: HR per 1-SD higher ASV, 1.14; 95% CI, 1.01-1.30 and potassium: HR per 1-SD higher ASV, 1.21; 95% CI, 1.02-1.44). CONCLUSIONS AND RELEVANCE: In HFpEF, visit-to-visit variability in laboratory indexes of kidney function and serum electrolytes is common and independently associated with worse long-term clinical outcomes.

IMPORTANCE: Low-density lipoprotein cholesterol (LDL-C)–lowering therapies are a cornerstone of prevention in atherosclerotic cardiovascular disease. With the introduction of generic formulations and the release of new therapies, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, contemporary Medicare utilization of these therapies remains unknown. OBJECTIVE: To determine trends in utilization and spending on brand-name and generic LDL-C–lowering therapies and to estimate potential savings if all Medicare beneficiaries were switched to available therapeutically equivalent generic formulations. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed prescription drug utilization and cost trend data from the Medicare Part D Prescription Drug Event data set from 2014 to 2018 for LDL-C–lowering therapies. A total of 11 LDL-C–lowering drugs with 25 formulations, including 16 brand-name and 9 generic formulations, were included. Data were collected and analyzed from October 2019 to June 2020. MAIN OUTCOMES AND MEASURES: Number of Medicare Part D beneficiaries, annual spending, and spending per beneficiary for all formulations. RESULTS: The total number of Medicare Part D beneficiaries ranged from 37 720 840 in 2014 to 44 249 461 in 2018. The number of Medicare beneficiaries taking LDL-C–lowering therapies increased by 23% (from 20.5 million in 2014 to 25.2 million in 2018), while the associated Medicare expenditure decreased by 46% (from $6.3 billion in 2014 to $3.3 billion in 2018). Lower expenditure was driven by greater uptake of generic statin and ezetimibe and a concurrent rapid decline in the use of their brand-name formulations. Medicare spent $9.6 billion on brand-name statins and ezetimibe and could have saved $2.1 billion and $0.4 billion, respectively, if brand-name formulations were switched to equivalent generic versions when available. The number of beneficiaries using PCSK9 inhibitors since their introduction in 2015 has been modest, although use has increased by 144% (from 25 569 in 2016 to 62 476 in 2018) and total spending has increased by 199% (from $164 million in 2016 to $491 million in 2018). CONCLUSIONS AND RELEVANCE: Between 2014 and 2018, LDL-C–lowering therapies were used by 4.8 million more Medicare beneficiaries annually, with an associated $3.0 billion decline in Medicare spending. This cost reduction was driven by the rapid transition from brand-name formulations to lower-cost generic formulations of statins and ezetimibe. Use of PCSK9 inhibitions, although low, increased over time and could have broad implications on future Medicare spending.