Variation in cardiovascular care completion is well documented. However, less is known about differences originating from earlier, intermediate stages such as ordering or scheduling of testing or referrals, despite their role as key prerequisites for care access. To examine the care cascades for coronary artery disease (CAD) after emergency department (ED) visits and to identify the specific stages at which variation emerges for CAD testing and cardiology referrals. This was a retrospective cohort study using data and metadata from electronic health records from a large multicenter health system. Participants were adult patients with established primary care and no history of ischemic heart disease or cardiology care who presented to an ED from January 1, 2020, to June 30, 2022, and underwent a troponin test, a proxy for clinically suspected myocardial ischemia. Variation in cardiovascular follow-up care (CAD testing and cardiology referrals) was identified and analyzed. Analyses were restricted to patients with above-median electrocardiogram (ECG)-derived ischemia risk scores to enrich for higher likelihood of benefit from cardiovascular follow-up. Receipt of an order for CAD testing (stress tests, coronary computed tomography angiography) or cardiology referral, scheduling of the service, and completion within 6 months. Outcomes were compared by insurance type, race and ethnicity, language, and sex using multivariable logistic regression adjusted for demographic characteristics, clinical factors, and ECG-derived cardiovascular risk. Among 16 475 patients with an ED visit (median [IQR] age, 67.4 [54.9-77.9] years; 36% female and 64% male individuals) and elevated cardiovascular risk, marked variation in follow-up care emerged. Compared to commercially insured patients, those with Medicare dual or disabled coverage had lower adjusted odds of completing CAD testing (adjusted odds ratio [aOR], 0.45; 95% CI, 0.36-0.56) and cardiology referrals (aOR, 0.47; 95% CI, 0.39-0.57); similar patterns were seen for Medicaid coverage. Patients whose primary language was not English were less likely to complete either service (CAD testing aOR, 0.77; 95% CI, 0.61-0.98; referral aOR, 0.75, 95% CI, 0.61-0.92), and female patients had lower adjusted odds of completing CAD testing (aOR, 0.86; 95% CI, 0.77- 0.96). Adjusted differences by race and ethnicity were modest. Variation was primarily associated with ordering differences and with additional scheduling barriers for select groups. Once scheduled, completion rates exceeded 75%, without differences between groups. This retrospective cohort study found that among patients who visited the ED with elevated ischemic risk, attrition in follow-up care was concentrated early in care cascades and most pronounced among those with noncommercial health insurance. This stepwise analytic framework offers a novel, reproducible approach for health systems to identify where and for whom care gaps arise, which can enable targeted interventions to improve equity and efficiency.
Patient-facing large language model (LLM) outputs for inflammatory bowel disease (IBD) must be decision-relevant, readable, and verifiable. In a cross-sectional benchmark using a guideline-derived question set, five publicly available LLMs provided answers to 20 single-intent patient IBD questions, mapped to prespecified decision-critical domains across the care pathway (100 model-question responses). Queries were conducted from January 17-24, 2026, via official web interfaces under default settings (privacy mode; new chat per prompt). Two blinded raters evaluated informational quality and completeness (using DISCERN, EQIP, and the Global Quality Scale), transparency proxies (based on JAMA benchmark criteria), and readability through the Automated Readability Index, Flesch Reading Ease, Gunning Fog Index, Flesch-Kincaid Grade Level, Coleman-Liau Index, and SMOG. Overall differences were assessed using within-question paired Friedman tests with Holm adjustment, and effect size was quantified with Kendall's W. Interrater agreement was high [DISCERN ICC(A,1) = 0.842; EQIP ICC(A,1) = 0.760; GQS weighted κ = 0.812; JAMA weighted κ = 0.936]. Median DISCERN scores ranged from 43.5 to 57.5, and EQIP scores ranged from 67.5 to 77.5, while transparency remained limited (JAMA median 0-1/4). Readability consistently failed to meet patient targets, with grade-level indices exceeding sixth grade and Flesch Reading Ease medians ranging from 15 to 36 (compared to a target of ≥80 for "easy" readability). All 10 outcomes varied significantly across models (Holm-adjusted P < 0.001; W = 0.238-0.702). Under default settings, publicly available LLMs exhibit variable informational quality for IBD but consistently poor transparency and readability. Patient-facing deployment should mandate provenance, currency, and disclosure fields, as well as outputs targeted to appropriate grade levels.
This JAMA Clinical Guidelines Synopsis summarizes the 2024 recommendations from the American Heart Association and American College of Cardiology on perioperative cardiovascular medication management for noncardiac surgery.
Transcatheter tricuspid valve replacement (TTVR) demonstrated superior outcomes over medical therapy in patients with severe tricuspid regurgitation (TR) in the Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy Using a Novel Device II (TRISCEND II) randomized clinical trial, and received regulatory approval in the US in 2024. Contemporary real-world data on its effectiveness and safety remain limited. To evaluate 30-day clinical, echocardiographic, and health status outcomes of TTVR in real-world use. Retrospective cohort study of all consecutive patients who underwent TTVR in the US from February 2024 through March 2025 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients had symptomatic, severe TR despite optimal medical therapy and TTVR was deemed appropriate by a heart team. Statistical analysis was conducted from September 2025 to February 2026. Device-enabled TTVR. Thirty-day event rates (all-cause death, stroke, bleeding, new cardiac implantable electronic device [CIED] implantation, heart failure hospitalizations), TR reduction, and changes in health status (New York Heart Association [NYHA] functional class and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) are reported. Subgroup analyses examined the impact of baseline CIED status on outcomes. Among 1034 attempted procedures at 82 centers (mean [SD] age, 77.1 [10.6] years; 69.1% female; 73.2% NYHA functional class III/IV), a valve was successfully implanted in 1017 patients (98.4%). Mild or less TR was achieved in 98.4% of patients post procedure and in 97.7% at 30 days. At 30 days, all-cause mortality was 3.1%; stroke, 0.2%; bleeding, 7.9%; new CIED, 15.9% in CIED-naive patients; and heart failure hospitalization, 3.1%. There were significant improvements in NYHA functional class (class I/II, 82.7%; P < .001) and mean KCCQ-OS score (22.4 points; P < .001) from baseline to 30 days. There were no significant differences in 30-day mortality (P = .47), heart failure hospitalization (P > .99), and functional outcomes (P = .55) when patients were stratified by baseline CIED status. Early US real-world experience with TTVR confirms safety and effectiveness in patients with severe TR. Thirty-day outcomes are consistent with the TRISCEND II pivotal trial, demonstrating acceptable safety, near-complete TR elimination, and significant health status improvements in an older, comorbid population. Rates of new CIED implantation and bleeding were lower than randomized clinical trial experience.
This JAMA Clinical Guidelines Synopsis summarizes the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndrome.
Clonal hematopoiesis of indeterminate potential (CHIP) is linked to an increased incidence of cardiovascular and malignant diseases. To determine whether CHIP is associated with cardiotoxic effects in patients with breast cancer receiving trastuzumab. Analyses of human cohorts with complementary animal experimentation were performed using a nationwide population-based cohort (UK Biobank), 1 tertiary referral center (Seoul National University Hospital [SNUH]), and a controlled laboratory setting. UK Biobank participants were enrolled between 2006 and 2010, and SNUH patients were enrolled from January 2004 to March 2024. Data were analyzed from March 2021 to February 2026. Incident heart failure (HF) in the UK Biobank cohort and trastuzumab-related cardiotoxic effects in the SNUH cohort were the main outcome measures. Trastuzumab-related cardiotoxic effects were defined using established clinical criteria (European Society of Cardiology [ESC], Canadian Trastuzumab Working Group, and Cardiac Review and Evaluation Committee [CREC]). Fine-Gray competing risk models were used to account for death and myocardial infarction; multivariable models were adjusted for age and cardiovascular risk factors in both cohorts, with additional adjustment for anthracycline use in the SNUH cohort. Changes in left ventricular ejection fraction (LVEF) were assessed in Tet2-deficient bone marrow chimeric mice following trastuzumab exposure. Overall, 15 729 patients with breast cancer from the UK Biobank cohort (mean [SD] age, 58.8 [7.3] years; 107 [0.68%] male) and 454 female patients with breast cancer who received trastuzumab from the SNUH cohort (mean [SD] age, 52.0 [9.6] years) were included. The corresponding 2-year cumulative incidence values for trastuzumab-related cardiotoxic effects were 15.7% vs 5.0% by ESC criteria (Gray test P = .001), 19.9% vs 10.8% by Canadian criteria (P = .01), and 20.9% vs 11.3% by CREC criteria (P = .02). Using the ESC definition, CHIP positivity (variant allele frequency ≥1.0%) was associated with cardiotoxic effects in multivariable competing risk analysis (adjusted subdistribution hazard ratio, 1.91; 95% CI, 1.32-2.76). Tet2-deficient mice demonstrated a significant LVEF reduction following trastuzumab treatment (effect size, -4.2%; 95% CI, -7.91 to -0.49; P = .03); other experimental groups showed no significant change. In this cohort study, the presence of CHIP was associated with increased susceptibility to trastuzumab-related cardiotoxic effects.
Apolipoprotein B (apoB) is a superior marker of residual atherosclerotic cardiovascular disease risk in patients treated with lipid-lowering therapy (LLT) compared with low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). The cost-effectiveness of LDL-C, non-HDL-C, and apoB goals has not been established. To determine the relative cost-effectiveness of intensifying LLT for primary prevention based on LDL-C, non-HDL-C, and apoB goals. This economic evaluation used a computer simulation model to evaluate the cost-effectiveness of intensifying LLT with high-intensity statins or ezetimibe according to LDL-C, non-HDL-C, or apoB goals. A cohort of 250 000 statin-eligible and atherosclerotic cardiovascular disease-free US adults was constructed from 2005 to 2016 National Health and Nutrition Examination Survey participants (N = 4149). Individuals commenced the simulation after lipid screening and received statin therapy based on 2018 American Heart Association/American College of Cardiology guidelines. Model inputs were derived from national survey data, pooled longitudinal cohort studies, and published literature. Uncertainty was explored with traditional and probabilistic sensitivity analysis. Lipid-lowering therapy was intensified if individuals did not achieve treated LDL-C level less than 100 mg/dL, non-HDL-C level less than 118 mg/dL, or apoB level less than 78.7 mg/dL. Lifetime quality-adjusted life-years (QALYs) and costs (in 2025 US dollars), discounted 3.0% annually. The primary outcome was the incremental cost-effectiveness ratio. Strategies were considered cost-effective if they cost less than $120 000 per QALY gained. Compared with an LDL-C goal, 965 QALYs (95% uncertainty interval [UI], -3551 to 5341 QALYs) would be gained with a non-HDL-C goal, alongside a $2.1 million (95% UI, -$94.2 million to $92.0 million) reduction in costs. Compared with a non-HDL-C goal, 1324 QALYs (95% UI, -2602 to 5669 QALYs) would be gained with an apoB goal, alongside a $40.2 million (95% UI, -$43.6 million to $134 million) increase in costs, yielding an incremental cost-effectiveness ratio of $30 300 per QALY gained. At a willingness-to-pay threshold of $120 000 per QALY gained, an apoB goal was optimal in 65% of probabilistic analyses and a non-HDL-C goal was optimal in 25%. The cost of apoB testing was marginal; higher costs reflected longer life expectancy and prolonged preventive treatment. The results of this computer simulation study suggest that apoB can be used as a cost-effective marker to guide primary prevention LLT and improve population health.
Timely prescription of quadruple guideline-directed medical therapies (GDMTs) for patients with heart failure with reduced ejection fraction (HFrEF) is associated with improved morbidity and mortality, yet contemporary estimates of time to quadruple therapy (TTQ) and the factors associated with its achievement remain unknown. To characterize TTQ and factors associated with TTQ in HFrEF. This was a retrospective cohort study including patients with incident HFrEF from the Veterans Health Administration database during the January 1, 2020, to December 31, 2023, period. Study data were analyzed from November 2024 to December 2025. Primary factors included race and ethnicity, sex, and copay status (priority group). Secondary factors included clinical characteristics. The main outcome included quadruple therapy according to pharmacy fill data-concurrent use of evidence-based β-blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors. TTQ was defined as the first date that all 4 medication classes overlapped, based on dispense date and days' supply. Among 52 850 patients with incident HFrEF (median [SD] age, 71.8 [11] years; 51 473 male [97%]; 10 791 Black [20%]; 2528 Hispanic [5%]; 35 867 White [68%]; 3664 other [7%]), 11 217 (21.2%) achieved quadruple therapy over a median (IQR) follow-up of 2.9 (1.9-3.9) years. The median (IQR) TTQ was 197 (49-528) days. After adjustment, Black patients (hazard ratio [HR], 1.22; 95% CI, 1.15-1.30), Hispanic patients (HR, 1.21; 95% CI, 1.09-1.33), and those from other racial or ethnic groups (HR, 1.11; 95% CI, 1.02-1.20) had higher rates of quadruple therapy than White patients. There was no difference in TTQ in females vs males (HR, 0.97; 95% CI, 0.86-1.09). Prescription copays (priority groups 2-8) were associated with an 8% lower rate of achieving quadruple therapy (HR, 0.92; 95% CI, 0.87-0.96) than no prescription copay (priority group 1). Rates of quadruple therapy were higher among veterans with an outpatient HFrEF diagnosis vs inpatient (22.2% vs 14.2%), with diabetes vs without diabetes (23.6% vs 19.3%), and without chronic kidney disease vs with chronic kidney disease (22.5% vs 18.1%). Results of this cohort study suggest that opportunities exist to improve both the rate and timeliness of quadruple therapy as only 21.2% of patients with HFrEF achieved it, with a median follow-up of 2.9 years and TTQ of 6 months. Medication copays represent a modifiable barrier, providing a potential target for interventions to enhance TTQ.
Membership in both the Alpha Omega Alpha (AOA) and Gold Humanism Honor Society (GHHS) is positively associated with career advancement. Prior studies have shown that Asian American medical students are less likely to be selected for these societies, but it is unknown whether representation among specific Asian American subgroups differ. To examine the association between AOA and GHHS membership and self-reported ethnicity among Asian American students at US doctor of medicine (MD)-granting medical schools. This retrospective cross-sectional study analyzed deidentified data from the Association of American Medical Colleges, focusing on allopathic medical students graduating between 2018 and 2021. Data analysis was conducted from July 10, 2024, to January 26, 2026. Self-reported race and Asian ethnicity. The primary outcome was AOA and GHHS membership at graduation. Multivariable logistic regression was performed, adjusting for Medical College Admission Test score, childhood income, sex, and sexual orientation, and clustered by medical school. Among 55 632 graduating medical students, 28 127 (50.6%) self-identified as female and 10 867 (19.5%) as Asian American. AOA membership was reported by 10 126 students (18.2%), and GHHS membership was reported by 8623 students (15.5%). Bangladeshi (odds ratio [OR], 0.35; 95% CI, 0.20-0.61), Chinese (OR, 0.51; 95% CI, 0.44-0.58), Filipino (adjusted OR, 0.44; 95% CI, 0.29-0.65), Indian (OR, 0.56; 95% CI, 0.50-0.63), Japanese (OR, 0.48; 95% CI, 0.28-0.81), Korean (OR, 0.41; 95% CI, 0.33-0.51), Pakistani (OR, 0.46; 95% CI, 0.34-0.63), Taiwanese (OR, 0.38; 95% CI, 0.28-0.51), and Vietnamese (OR, 0.56; 95% CI, 0.45-0.71) students were less likely to be AOA members than White students. Chinese (OR, 0.67; 95% CI, 0.58-0.78), Korean (OR, 0.55; 95% CI, 0.43-0.69), and Taiwanese (OR, 0.67; 95% CI, 0.49-0.91) students were less likely to be GHHS members compared with White students. This cross-sectional study of graduating medical students found widespread underrepresentation of most Asian American subgroups in AOA membership and for Chinese, Korean, and Taiwanese medical students in GHHS membership. This underscores the importance of disaggregating Asian American individuals in medicine to unmask disparities and provide opportunities to promote greater inclusion in medicine.
Low-quality dietary intake is associated with adverse heart failure (HF) outcomes, yet evidence evaluating food-as-medicine interventions that supply high-quality dietary content is limited. To determine the feasibility of providing food supplementation with medically tailored meals or fresh produce and explore the association of food supplementation vs usual care with clinical outcomes in patients recently hospitalized with HF and whether it differs by conditioning food supplementation to health care engagement. This open-label factorial randomized clinical trial was conducted between April 2024 and October 2025 at 2 hospitals in Dallas, Texas. The study included patients who were hospitalized for HF and enrolled within 14 days of discharge, excluding those with prior heart transplant, a left ventricular assist device, or inotropic support at discharge; current enrollment in meal delivery programs; and inability to receive home deliveries. Participants were followed up with for 12 weeks. Of 150 participants enrolled, 2 were withdrawn due to clinical deterioration, 1 died, and 6 were lost to follow-up; all were included in the intention-to-treat analysis. Participants were randomized 1:1:1 to medically tailored meals, fresh produce, or usual care. Those receiving food supplementation underwent secondary 1:1 randomization to conditional (linked to clinic attendance and medication fills) vs unconditional delivery. Implementation outcomes included delivery completion, adherence, and acceptability and exploratory clinical outcomes. The primary clinical outcome was defined as readmission for HF or emergency department (ED) visits for HF over 90-day follow-up. Secondary clinical outcomes included a win-ratio-based hierarchical composite (all-cause death, total HF hospitalizations or ED visits, and ≥10-point Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score [KCCQ-CSS] improvement). Among 150 participants (median [IQR] age, 59.5 [52.0-66.0] years; 91 [60.7%] male), the baseline median (IQR) left ventricular ejection fraction was 35% (25.0-54.0), the baseline median (IQR) KCCQ-CSS was 56.6 (36.8-72.9), and 79 (52.7%) had food insecurity. Food delivery completion was 93.6% with a mean (SD) reported consumption adherence of 4.7 (2.4) days per week (medically tailored meals) and 5.5 (2.3) days per week (fresh produce), with high retention (96.0%). Fresh produce demonstrated superior acceptability compared with medically tailored meals (Net Promoter Score: 8.6 vs 7.3; P = .02). There was no significant difference in the primary clinical outcome (HF readmission or ED visit) between food supplementation (23 events among 100 participants) vs usual care (9 events among 50 participants) (adjusted rate ratio, 1.09; 95% CI, 0.49-2.43; P = .83). The hierarchical composite favored food supplementation vs usual care (win ratio, 1.21; 95% CI, 1.14-1.29; P < .001). Among participants receiving food supplementation, conditional delivery (vs unconditional) was not associated with risk of HF events. In this randomized clinical trial, 90-day food supplementation was feasible and well accepted in individuals with recent HF. Food supplementation was not associated with an improvement in the primary clinical outcome and there was no difference when conditioning food supplementation on health care engagement. ClinicalTrials.gov Identifier: NCT06115369.
This Viewpoint discusses a novel, biology-driven concept aligning antiplatelet therapy with evolving thrombotic risk after coronary artery bypass graft (CABG) surgery.
Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction predominantly affecting women. There is a paucity of reproductive health data surrounding pregnancy-associated SCAD (P-SCAD). To examine detailed reproductive variables as well as demographics, psychosocial, and SCAD-event factors among women with a history of at least 1 prior pregnancy in a large, multicenter registry (iSCAD Registry). This cohort study compared data of women with P-SCAD vs women with non-pregnancy-associated SCAD (NP-SCAD) between the years 2019 and 2024 and rates of certain reproductive health features among the general reproductive-aged population in US states. Differences were analyzed using the Kruskal-Wallis test for continuous variables and χ2 test for categorical variables. Pregnancy and SCAD. Patient survey-based clinical and reproductive history variables were collected and corroborated with investigator-extracted clinical and imaging data, including detailed characterization of the SCAD event. Among 907 women (median [IQR] age at enrollment, 52.0 [45.1-59.4] years; median [IQR] age at first SCAD event, 49.2 [42.3-57.1] years) with SCAD and 1 or more pregnancies, 98 had P-SCAD with median (IQR) age of 36.7 (33.7-39.1) years at time of SCAD event. Those with P-SCAD had a lower prevalence of fibromuscular dysplasia (27 of 86 [31%] vs 309 of 681 [45%]; P = .01) but similar rates of extracoronary abnormalities. Greater use of assisted reproductive technology (ART; 25 of 97 [26%] vs 98 of 804 [12%]), greater multigravida with more than 5 gestations (13 of 98 [13%] vs 55 of 809 [7%]), and preeclampsia (24 of 98 [25%] vs 101 of 809 [13%]; P = .001) were reported among women with P-SCAD. Those with P-SCAD had a more severe SCAD phenotype including higher incidence of STEMI (16 of 86 [18.6%] vs 40 of 733 [5.5%]; P < .001), multivessel segment involvement (22 of 70 [31%] vs 101 of 588 [17%]; P = .004), and left ventricular ejection fraction (LVEF) lower than 40% (4 of 15 [27%] vs 6 of 105 [7%]; P = .006). They also experienced less LVEF recovery by 1-year follow-up. The majority (661 of 887 [75%]) of both groups were primarily medically managed. From this large, multisite registry, results reveal that women with P-SCAD had greater median ages at gestation, greater history of ART use, and greater instances of multigravida and preeclampsia than women with NP-SCAD and the general reproductive-aged US population. With high percentages of vascular imaging among participants, women with P-SCAD had less fibromuscular dysplasia but similar rates of extracoronary abnormalities including dissection and aneurysms as women with NP-SCAD. In this contemporary cohort, women with P-SCAD continue to represent a higher-risk phenotype with predominantly conservative management; however, they had less LVEF recovery.
Familial hypercholesterolemia is a common genetic disorder associated with premature cardiovascular disease. Genetic cascade screening is recommended but remains underused due to privacy laws that prevent clinicians from directly contacting at-risk relatives. To examine whether implementing a web-based communication platform in a patient-mediated genetic cascade screening program for familial hypercholesterolemia increases uptake compared with usual care. This open-label, multicenter, implementation randomized clinical trial (CATCH) was conducted between November 1, 2020, and October 31, 2023, at 7 cardiovascular prevention or lipid clinics across Switzerland, representing French-, German-, and Italian-speaking regions. Adults aged 16 years or older with genetically confirmed familial hypercholesterolemia and at least 1 eligible first-degree relative living in Switzerland participated. A total of 87 index patients with 359 eligible first-degree relatives were randomized by family cluster (1:1) to the intervention or usual care arm. A secure web-based platform allowing participants to send preprepared electronic messages (email or text) to their relatives, linking them directly to participating centers for genetic testing. The primary outcome was cascade screening uptake, defined as the proportion of eligible first-degree relatives undergoing genetic testing within 6 months. The secondary outcome was new cases identified. Among 221 adults screened across multiple families, 87 (39.4%) had genetically confirmed familia hypercholesterolemia (median [IQR] age, 49.2 [16.4-83.7] years; 46 [52.9%] female; median [IQR] highest low-density lipoprotein cholesterol, 289.58 [139.00-498.07] mg/dL); 43 were randomized to the usual care arm, and 44 were randomized to the intervention arm. Among the 359 eligible relatives (median family size, 4), 99 (27.6%) underwent genetic testing. Uptake was higher in the intervention arm (30.4%; 95% CI, 22.0%-40.4%) than in usual care arm (16.7%; 95% CI, 10.1%-26.3%), yielding an odds ratio of 2.18 (95% CI, 1.06-4.51; P = .03). New case identification was also greater (17.0% vs 8.1%; odds ratio, 2.32; 95% CI, 1.07-5.05; P = .03). Newly identified patients were often untreated or had modifiable risk factors. In this randomized clinical trial of patient-mediated genetic cascade screening supported by a web-based platform, participation in genetic testing and detection of familial hypercholesterolemia was increased compared with usual care. These results suggest that the use of digital communication tools enhanced the reach and effectiveness of genetic screening programs within privacy-regulated health systems. ClinicalTrials.gov Identifier: NCT04419090.
This cross-sectional study examines the association of Chronic Condition Special Needs Plans vs conventional Medicare Advantage plans with quality of care and outcomes after hospitalization in patients with heart failure.
Guidelines on primary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend considering risk enhancing factors (REFs) to inform decisions on use of lipid-lowering therapies for the 44 million Americans with borderline or intermediate estimated ASCVD risk. To quantify REF burden and estimate whether REFs are associated with higher likelihood of statin use. Cross-sectional using National Health and Nutrition Examination Survey pooled 2015 to March 2020. Adults aged 40-75 without known ASCVD. Nine REFs were measurable in NHANES including family history of premature ASCVD, rheumatoid arthritis, metabolic syndrome, premature menopause, chronic kidney disease and biomarkers of hypercholesteremia, hypertriglyceridemia, elevated low-density lipoprotein cholesterol and elevated C-reactive protein. Prevalence of REFs and association with statin use were calculated overall and across ASCVD treatment categories based on diabetes and 10-year ASCVD risk.  KEY RESULTS: In the sample of 3,111 participants (mean age 56 years; 52.6% female) weighted to represent 115.7 million US adults, 77% had at least one REF and 28% had at least three. The most common REFs were elevated high sensitivity C-reactive protein (49.6%) metabolic syndrome (48.3%), and hypertriglyceridemia (18.9%). The presence of any REF was associated with a 2.17 (95% CI, 1.42-3.33) greater odds of statin use. Metabolic syndrome, family history of premature ASCVD, hypertriglyceridemia and hypercholesteremia were associated with greater odds of statin use (aORs ranging from 1.5 to 2.3). The presence of any REF was associated with higher likelihood of statin use in participants with low (< 5%), intermediate (7.5-19%), and high ASCVD risk (≥ 20%), but not borderline ASCVD risk (5-7.4%) or diabetes categories. REFs are highly prevalent and inconsistently associated with statin use. Achieving the potential benefit of individualizing ASCVD risk estimates will require clearer guidance on when and how to incorporate REFs into primary prevention prescribing decisions.
Prepregnancy care and counseling optimize maternal health before conception to improve outcomes for mothers and infants. In the US, 66.4% of reproductive-aged women have at least 1 modifiable risk factor for adverse pregnancy outcomes. For all individuals desiring pregnancy, recommended interventions include folic acid supplementation; cessation of tobacco, alcohol, cannabis, and opioids; immunizations against hepatitis B virus, varicella, and rubella; and screening for syphilis and HIV. Folic acid use before pregnancy is associated with reduced fetal neural tube defects (relative risk [RR], 0.67; 95% CI, 0.52-0.87). Maternal tobacco smoking is associated with increased risks of stillbirth (summary RR [sRR], 1.46; 95% CI, 1.38-1.54), neonatal death (sRR, 1.22; 95% CI, 1.14-1.30), and perinatal death (sRR, 1.33; 95% CI, 1.25-1.41). Screening for and treatment of syphilis and HIV prior to and during pregnancy decrease rates of fetal and neonatal infection. Prepregnancy immunizations against hepatitis B virus, varicella, and rubella decrease neonatal infection and mortality. Individuals using tobacco, alcohol, cannabis, and opioids should receive counseling and treatment prior to pregnancy (eg, buprenorphine or methadone for opioid use disorder). For individuals with chronic disease, routine health examinations and contraceptive care in the year before conception can optimize pregnancy timing and are associated with decreased risk of severe maternal morbidity. Compared with planned pregnancies, unintended pregnancies are associated with increased risk of postpartum depression (15.7% vs 9.6%; adjusted odds ratio [aOR], 1.51; 95% CI, 1.40-1.70), preterm birth (9.4% vs 7.7%; aOR, 1.21; 95% CI, 1.12-1.31), and low infant birth weight (7.3% vs 5.2%; aOR, 1.09; 95% CI, 1.02-1.21). Weight loss prior to conception is recommended for individuals with a body mass index of 25 or greater because overweight and obesity are associated with increased risk of gestational diabetes, gestational hypertension, and cesarean delivery. Among patients with pregestational diabetes (type 1 or 2), hemoglobin A1c of less than 6.5% is associated with a decreased risk of fetal anomaly compared with hemoglobin A1c of 6.5% or greater. Cardiovascular complications such as hypertension and heart failure occur in 15% of pregnancies and are more common among those with preexisting cardiovascular disease. These patients should receive counseling on maternal and neonatal risk, monitoring, and medication management by specialists in cardiology and maternal fetal medicine. Prepregnancy counseling and care reduce maternal morbidity and neonatal morbidity and mortality. Primary care-based discussion of reproductive goals, immunizations, screening for infections and substance use, and risk-reducing interventions such as folate supplementation can optimize outcomes in individuals contemplating pregnancy.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disorder caused by destabilization of serum transthyretin (sTTR). Acoramidis, an approved therapy that achieves near-complete (≥90%) sTTR stabilization, demonstrated clinical benefit through month 30 in ATTRibute-CM, which was incremental through month 42 in the open-label extension (OLE); however, the longer-term durability of outcomes has not been reported. To evaluate the long-term efficacy and safety of acoramidis through month 54. This OLE of the ATTRibute-CM randomized clinical trial is an international, multicenter, ongoing OLE study. Data accumulated between October 2021 and April 2025 through month 24 of the OLE (month 54) are reported. Participants (aged 18-90 years) who completed ATTRibute-CM and met the OLE eligibility criteria were invited to enroll in the OLE. Data were analyzed from May 2025 through November 2025. All OLE participants received open-label oral acoramidis, 800 mg, twice daily. Acoramidis recipients from ATTRibute-CM continued therapy (continuous acoramidis) and placebo recipients switched to acoramidis (placebo to acoramidis). The primary outcome was time to event for all-cause mortality (ACM), cardiovascular-related mortality (CVM), and first cardiovascular hospitalization (CVH), which was assessed for both groups. Biomarkers of disease progression (N-terminal pro-B-type natriuretic peptide [NT-proBNP]), sTTR, functional capacity (6-minute walk distance [6MWD]), and heart failure-related health status (Kansas City Cardiomyopathy Questionnaire-Overall Summary [KCCQ-OS] score) were analyzed. In ATTRibute-CM, 632 participants were randomized to receive acoramidis (n = 421) or placebo (n = 211); mean (SD) age was 77.3 (6.6) years, and 62 participants (9.8%) were female. Overall, 389 participants enrolled in the OLE (263 in the continuous acoramidis group; 126 in the placebo-to-acoramidis group). Continuous acoramidis treatment reduced risks of ACM (hazard ratio [HR], 0.55; 95% CI, 0.42-0.74; P < .001) and CVM (HR, 0.51; 95% CI, 0.36-0.71; P < .001) through month 54, with consistent efficacy across all prespecified subgroups. Continuous acoramidis reduced time to first CVH (HR, 0.53; 95% CI, 0.42-0.69; P < .001) through month 54. Through month 54, continuous acoramidis stabilized increases in NT-proBNP, sustained higher sTTR levels, and stabilized KCCQ-OS score and 6MWD. Switching from placebo to acoramidis at month 30 was associated with stabilization of NT-proBNP and KCCQ-OS score and improvements in sTTR and 6MWD through month 54. No new long-term safety concerns were identified. In this OLE of the ATTRibute-CM randomized clinical trial, early and continuous acoramidis treatment resulted in sustained incremental reductions in ACM, CVM, and first CVH through month 54. These findings support the importance of early and continuous long-term treatment with acoramidis in ATTR-CM. ClinicalTrials.gov Identifier: NCT04988386.