Publications by Year: 2025

IMPORTANCE: Heterozygous familial hypercholesterolemia (FH), a genetic condition, results in lifelong increased low-density lipoprotein cholesterol (LDL-C) and increases lifetime cardiovascular disease (CVD) risk. Most individuals with FH remain undiagnosed, so early FH identification and treatment could lower CVD burden.

OBJECTIVE: To evaluate the projected cost-effectiveness of population sequential FH screening (lipid testing followed by genetic testing after a high LDL-C measurement) at 10 or 18 years of age.

DESIGN, SETTING, AND PARTICIPANTS: The CVD Policy Model, a validated discrete event simulation of CVD risk factor management and CVD outcomes in National Health and Nutrition Examination Survey participants, was used to simulate lifetime health and economic outcomes from a health care sector perspective for a hypothetical cohort of 4.2 million US 10-year-olds. Individual characteristics and health care processes informed CVD events (coronary heart disease or stroke) and survival probabilities. Model inputs included national data sources, clinical trials, pooled longitudinal cohort studies, and published literature.

INTERVENTIONS: Usual care assumed only opportunistic lipid testing and LDL-C and CVD risk-guided treatment. When added to usual care, sequential FH screening strategies examined combinations of childhood (age 10 years) or early adulthood (age 18 years) screening with 3 LDL-C thresholds (≥130 mg/dL, ≥160 mg/dL, or ≥190 mg/dL) to select patients for genetic testing.

MAIN OUTCOMES AND MEASURES: Primary outcomes were direct health care costs (2021 US dollars), quality-adjusted life-years (QALYs), and an incremental cost-effectiveness ratio (ICER). Future costs and QALYs were discounted 3% annually. Strategies with an ICER of less than $100 000 per QALY gained were considered cost-effective.

RESULTS: For the simulated cohort, usual care would lead to 3 118 000 (95% uncertainty interval, 3 061 000-3 192 000) total lifetime CVD events, with 16 182 (95% uncertainty interval, 15 683-16 827) among those with FH. Childhood FH screening could avert between 1385 and 1820 CVD events (<0.1% reduction in overall population), and early adulthood FH screening could avert between 1154 and 1448 CVD events (<0.1% reduction). While effective, no FH screening strategies were cost-effective relative to usual care; screening at age 18 years using an LDL-C threshold of 190 mg/dL or greater had the lowest ICER, at $289 700 per QALY gained. Sequential FH screening could become cost-effective vs usual care if lifetime lipid monitoring plus lifestyle therapy increased after a high screening LDL-C result, including for patients with non-FH dyslipidemias.

CONCLUSIONS AND RELEVANCE: Sequential FH screening in childhood or early adulthood could be effective but not cost-effective vs usual care. However, sequential FH screening could become cost-effective under highly optimistic assumptions about increased lifestyle therapy and increased lifetime lipid monitoring for patients with non-FH dyslipidemias.

INTRODUCTION: Self-measured blood pressure (SMBP) monitoring with clinical support is an evidence-based practice to improve hypertension control. However, it can be challenging to implement in safety-net systems that disproportionately serve low-income and/or racial/ethnic minority populations at risk of worse hypertension outcomes. We therefore propose a hybrid effectiveness-implementation trial to evaluate the effectiveness of multi-level implementation strategies to increase the use of SMBP monitoring in two urban safety-net systems.

METHODS: We will conduct a patient-level randomized controlled trial with 330 English-, Spanish-, and Chinese (Cantonese)-speaking patients with uncontrolled hypertension across six study sites with patients randomized to a low-intensity (SMBP education, text message education and reminders) vs high-intensity intervention (adds group classes and engagement of identified caregivers). To support increased use of SMBP data by the clinical team, we will concurrently deliver a staggered roll-out of a clinic-level implementation strategy (clinic education, shadowing, auditing with feedback, and optimization of electronic health record [EHR] use).

RESULTS: The primary outcomes will be clinic-measured systolic BP (SBP) among enrolled participants for the patient-level intervention and among all patients assigned to the clinic for the clinic-level intervention. We will additionally collect secondary clinical outcomes (BP control, home SBP), implementation outcomes (adoption, reach, and costs), and patient-reported outcomes (patient activation).

DISCUSSION: The results of this trial will address gaps in identifying cost-conscious implementation strategies for increasing adoption of SMBP in safety-net systems with the overarching goal of improving blood pressure control in low-income, diverse patient populations. Trial registration NCT, NCT06871462. Registered 4 March 2025, https://clinicaltrials.gov/study/NCT06871462.

AIM: The "2025 AHA/ACC Statement on Cost/Value Methodology in Clinical Practice Guidelines (Update From 2014 Statement)" describes a systematic approach for consistent implementation of "economic value statements" across ACC/AHA guidelines. It updates the cost-effectiveness threshold and proposes a new level of certainty framework that summarizes the strength of the available evidence. Additionally, it describes how cost-effectiveness analyses (CEAs) can help advance equity in population cardiovascular health.

METHODS: A focused literature search was conducted from January 9, 2024, to February 2, 2024, encompassing English-language publications related to CEA methodology in PubMed, EMBASE, and the Cochrane Library, with publication dates ranging from 1973 to the present. Additional relevant studies published during the writing process (through June 25, 2024) were also considered by the writing committee.

STRUCTURE: This Cost/Value Methodology Statement updates prior guidance regarding the incorporation of evidence from published CEAs into clinical guidelines. It provides guidance for identifying and synthesizing relevant high-quality evidence, developing economic value statements, and communicating level of certainty in such statements. It defines the US cost-effectiveness threshold as $120,000 per quality-adjusted life year gained, highlights special considerations related to cardiovascular drugs and devices, emphasizes health equity considerations when interpreting CEAs, and defines a reference case for future CEAs.

AIM: The "2025 AHA/ACC Statement on Cost/Value Methodology in Clinical Practice Guidelines (Update From 2014 Statement)" describes a systematic approach for consistent implementation of "economic value statements" across ACC/AHA guidelines. It updates the cost-effectiveness threshold and proposes a new level of certainty framework that summarizes the strength of the available evidence. Additionally, it describes how cost-effectiveness analyses (CEAs) can help advance equity in population cardiovascular health.

METHODS: A focused literature search was conducted from January 9, 2024, to February 2, 2024, encompassing English-language publications related to CEA methodology in PubMed, EMBASE, and the Cochrane Library, with publication dates ranging from 1973 to the present. Additional relevant studies published during the writing process (through June 25, 2024) were also considered by the writing committee.

STRUCTURE: This Cost/Value Methodology Statement updates prior guidance regarding the incorporation of evidence from published CEAs into clinical guidelines. It provides guidance for identifying and synthesizing relevant high-quality evidence, developing economic value statements, and communicating level of certainty in such statements. It defines the US cost-effectiveness threshold as $120 000 per quality-adjusted life year gained, highlights special considerations related to cardiovascular drugs and devices, emphasizes health equity considerations when interpreting CEAs, and defines a reference case for future CEAs.

BACKGROUND: Compared with the 2003 Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) guideline, the 2017 American College of Cardiology and American Heart Association guideline (ACC/AHA 2017) expanded hypertension diagnostic criteria to blood pressure (BP) ≥130/80 mm Hg and intensified treatment goals to <130/80 mm Hg. The cost-effectiveness of ACC/AHA 2017 guideline treatment has not been quantified.

METHODS: We used the Cardiovascular Disease (CVD) Policy Model to simulate hypertension treatment according to ACC/AHA 2017 compared with JNC7 in untreated US adults aged 35 to 79 years. Outcomes were projected over 10 years and included CVD events and deaths, quality-adjusted life-years (QALYs), and total health care costs (ie, costs of antihypertensive treatment and costs of health care utilization for cardiovascular and noncardiovascular care, regardless of payer). Cost-effectiveness was calculated from a health care sector perspective as incremental health care costs divided by incremental QALYs.

RESULTS: Under ACC/AHA 2017, 4.9 million more US adults are indicated for treatment and 14.9 million are recommended more intensive treatment goals compared with JNC7. Over 10 years, ACC/AHA 2017 versus JNC7 treatment would cost $48 300 per QALY gained ($38 300/QALY in men; $65 200/QALY in women). Overall, 34% of CVD events prevented by ACC/AHA 2017 versus JNC7 would be from expanded diagnosis (at $120 900/QALY gained), and 66% from intensified BP treatment goals (at $18 900/QALY gained). Cost-effectiveness improved with a longer time horizon ($17 600 per QALY gained at 30 years) and when generic drug costs were assumed in place of median US drug costs ($27 900 per QALY gained in 10 years). ACC/AHA 2017 is cost-saving in adults with BP ≥140/90 mm Hg and prior CVD or 10-year CVD risk ≥10%.

CONCLUSIONS: Initiating hypertension treatment according to the ACC/AHA 2017 guideline in untreated US adults is cost-effective compared with JNC7 at 10 years. Prioritizing low-cost generic medicines and intensive BP treatment of high-CVD-risk adults with BP ≥140/90 mm Hg returns the most value.

BACKGROUND: Elevated low-density lipoprotein cholesterol (LDL-C) levels are a leading risk factor for atherosclerotic cardiovascular disease (ASCVD), a major global cause of illness and death. Patients' qualitative insights about experiences, priorities, and needs are essential for creating more targeted, patient-centered quality improvement interventions.

OBJECTIVES: To document the experiences of people with high levels of low-density LDL-C in three countries.

METHODS: Qualitative study of 60-min in-depth interviews with 50 adult patients from Australia, Brazil, and the United States. The study was overseen by a Steering Committee comprising patients, patient advocates, researchers, and cardiologists. The interviews explored pathways and barriers to high LDL-C diagnosis; the burden of managing high LDL-C and the awareness of the association between high LDL-C and cardiovascular risks. The data were analyzed by applying a structured, team-based approach to coding qualitative data.

RESULTS: There were three main pathways to diagnosing high cholesterol: routine physical exams conducted by primary care providers; symptomatic presentations or incidental findings during emergency visits and through a healthcare visit for another condition, frequently diabetes. Healthcare providers' communication styles influenced patients' perceptions of their conditions. Two-thirds of participants (n = 33) attempted lifestyle changes after their high cholesterol diagnosis, but work schedules and daily routines posed barriers to maintaining healthy habits. Some participants who experienced ASCVD events waited hours or days before seeking care, assuming their symptoms were not serious. After diagnosis of an ASCVD event, many patients feared death and worried about their families' futures. When asked about potential improvements to their current therapy, 21 patients mentioned reduced administration frequency.

CONCLUSIONS: This pilot study provides insights into patients' experiences living with and managing elevated LDL-C. It describes opportunities for policymakers and healthcare providers to improve the detection of elevated LDL-C and support patients in understanding risks and strategies for reducing the risk of ASCVD events.

BACKGROUND: Obesity is an established risk factor for venous thromboembolism (VTE). Observational data suggest that glucagon-like peptide 1 receptor agonists (GLP-1RAs) may reduce the risk of VTE. However, the effects of GLP-1RAs on VTE have not been tested in randomized controlled trials (RCTs).

OBJECTIVES: To investigate the impact of GLP-1RAs on VTE risk using data from RCTs.

METHODS: We conducted a systematic review and meta-analysis of placebo-controlled RCTs focusing on GLP-1RA use in patients with type 2 diabetes mellitus (T2DM) or obesity. Five databases were searched from inception to October 2024. The primary outcome was VTE, which was a composite of pulmonary embolism (PE), deep vein thrombosis (DVT), and VTE at other sites, and the secondary outcomes were the individual events.

RESULTS: Twenty-seven RCTs with 84,003 patients were analyzed. The median incidence of VTE was 1.1 and 2.5 per 1,000 patient-years in the GLP-1RA and placebo groups, respectively. There was no statistically significant difference in overall VTE risk between GLP-1RA and placebo groups (RR 0.70, 95% CI 0.46-1.07). However, GLP-1RAs were associated with a significantly lower risk of PE (RR 0.60, 95% CI 0.39-0.94). In contrast, there were no significant differences in the risk of DVT (RR 1.24, 95% CI 0.67-2.27) or VTE at other sites (RR 0.56, 95% CI 0.25-1.26).

CONCLUSIONS: In this meta-analysis of randomized trials, GLP-1RAs were not associated with a significant reduction in overall VTE risk but were associated with a lower risk of PE among patients with T2DM or obesity.

BACKGROUND: Studying trends in mortality is essential to advance understanding of population health. Further evaluation of long-term heart disease mortality trends and subtypes in the United States is needed to guide public health and clinical interventions.

METHODS: This study used the National Vital Statistics System Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data for adults aged 25 years and older in the United States from 1970 to 2022. Outcomes included absolute number and age-adjusted mortality of total heart disease, ischemic heart disease, and other heart disease subtypes.

RESULTS: From 1970 to 2022, overall age-adjusted heart disease mortality decreased by 66% from 1970 to 2022 (from 761 to 258 per 100 000). In 1970, 91% of all heart disease deaths were ischemic, declining to 53% of all heart disease deaths in 2022. From 1970 to 2022, age-adjusted mortality decreased by 89% for acute myocardial infarction (from 354 to 40 per 100 000) and 81% for all ischemic heart disease (from 693 to 135 per 100 00). In contrast, from 1970 to 2022 age-adjusted mortality for other heart disease subtypes increased by 81% (from 68 to 123 per 100 000), with the greatest increases in heart failure (146% increase), hypertensive heart disease (106% increase) and arrhythmias (450% increase).

CONCLUSIONS: Heart disease mortality has decreased over the past 5 decades. There is an increasing burden of mortality from other heart conditions including heart failure, hypertensive heart disease, and arrhythmias. Further efforts must be undertaken to address the growing challenge of these other heart conditions.