Achievement of LDL-C <55 mg/dL among US Adults : Findings from the cvMOBIUS2 Registry.

BACKGROUND: Reflecting clinical trial data showing improved outcomes with lower LDL-C levels, guidelines across the globe are increasingly recommending a goal of LDL-C <55 mg/dL in persons with atherosclerotic cardiovascular disease (ASCVD). What proportion of patients with ASCVD are already meeting those goals in the US remains understudied. METHODS: Using electronic health record data from 8 large US health systems, we evaluated lipid-lowering therapy (LLT), LDL-C levels, and factors associated with an LDL-C <55 mg/dL in persons with ASCVD treated between 1/1/2021-12/31/2021. Multivariable modeling was used to evaluate factors associated with achievement of an LDL-C <55 mg/dL. RESULTS: Among 167,899 eligible patients, 22.6% (38,016) had an LDL-C <55 mg/dL. While 76.1% of individuals overall were on a statin, only 38.2% were on a high-intensity statin,;5.9% were on ezetimibe, and 1.7% were on a PCSK9i monoclonal antibody (mAb). Factors associated with lower likelihood of achieving an LDL-C <55 mg/dL included: younger age (odds ratio [OR] 0.91 per 10y), female sex (OR 0.69), Black race (OR 0.76), and non-coronary artery disease forms of ASCVD including peripheral artery disease (OR 0.72) and cerebrovascular disease (OR 0.85), while high-intensity statin use was associated with increased odds of LDL-C <55 mg/dL (OR 1.55). Combination therapy (statin+ezetimibe or statin+PCSK9i mAb) was rare (4.4% and 0.5%, respectively) and was associated with higher odds of an LDL-C <55 mg/dL (OR 1.39 and 3.13, respectively). CONCLUSION: Less than a quarter of US patients with ASCVD in community practice are already achieving an LDL-C <55 mg/dL. Marked increases in utilization of both high intensity statins and combination therapy with non-statin therapy will be needed to achieve LDL-C levels <55 mg/dL at the population level in secondary prevention.

Apolipoprotein B: Bridging the Gap Between Evidence and Clinical Practice.

Despite data suggesting that apolipoprotein B (apoB) measurement outperforms low-density lipoprotein cholesterol level measurement in predicting atherosclerotic cardiovascular disease risk, apoB measurement has not become widely adopted into routine clinical practice. One barrier for use of apoB measurement is lack of consistent guidance for clinicians on how to interpret and apply apoB results in clinical context. Whereas guidelines have often provided clear low-density lipoprotein cholesterol targets or triggers to initiate treatment change, consistent targets for apoB are lacking. In this review, we synthesize existing data regarding the epidemiology of apoB by comparing guideline recommendations regarding use of apoB measurement, describing population percentiles of apoB relative to low-density lipoprotein cholesterol levels, summarizing studies of discordance between low-density lipoprotein cholesterol and apoB levels, and evaluating apoB levels in clinical trials of lipid-lowering therapy to guide potential treatment targets. We propose evidence-guided apoB thresholds for use in cholesterol management and clinical care.

Individual Variation in the Distribution of Apolipoprotein B Levels Across the Spectrum of LDL-C or Non-HDL-C Levels.

Importance: Although apolipoprotein B (apoB) is a superior marker of lipid-related risk compared with low-density lipoprotein cholesterol (LDL-C), few data exist to translate the goals and thresholds from LDL-C to their apoB equivalent. In addition, although current American College of Cardiology/American Heart Association guidelines provide a relative indication for apoB measurement among individuals with hypertriglyceridemia, whether discordance is limited to those subgroups is unknown. Objectives: To assess the variability in apoB level across the spectrum of LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) levels and evaluate whether discordance between apoB and LDL-C or non-HDL-C is limited to specifiable subgroups. Design, Setting, and Participants: This cross-sectional study used data from a nationally representative sample of 12 688 adult participants not using statins in the National Health and Nutrition Examination Survey between 2005 and 2016. Statistical analysis was performed from April 2023 to February 2024. Main Outcomes and Measures: Quantile regression was used to assess the population distribution of apoB across LDL-C or non-HDL-C levels. Discordance between apoB and LDL-C was the difference between measured apoB and median apoB levels for an individual's LDL-C level. Discordance was evaluated by age, sex, race and ethnicity, obesity, diabetes, triglyceride level, hemoglobin A1c level, body mass index (BMI), statin use, and metabolic health (defined as a BMI between 18.5 and 24.9, triglyceride level <150 mg/dL, and no diabetes). Results: Among the sample of 12 688 participants (median age, 41.0 years [IQR, 29.0-54.0 years]; 52.9% women) for LDL-C values of 55, 70, 100, and 190 mg/dL, the corresponding population median apoB levels were 49, 60, 80, and 140 mg/dL, respectively. For given levels of LDL-C, a range of apoB values was observed. At an LDL-C level of 100 mg/dL, the 95% population distribution of apoB ranged from 66 mg/dL to 99 mg/dL. ApoB variability was highest for LDL-C values estimated using the Friedewald equation, lower when using Sampson or Martin-Hopkins equations, and lowest for non-HDL-C. Although individuals with metabolic risk factors were more likely to have discordantly high apoB levels (ie, had higher median observed apoB levels relative to what was estimated based on LDL-C), significant variability in apoB levels was observed even among metabolically healthy individuals. Conclusions and Relevance: This study suggests that even metabolically healthy individuals may have discordantly high apoB levels relative to LDL-C or non-HDL-C levels. The current guideline approach for apoB testing only for those with hypertriglyceridemia appears too narrow. Population percentile data can be used to translate LDL-C goals and thresholds to their apoB equivalent to facilitate clinical adoption.

Use of Dietary Supplements Among People With Atherosclerotic Cardiovascular Disease in the United States: A Population-Based Analysis From NHANES.

BACKGROUND: Dietary supplement use is prevalent in the general US population, but little is known regarding the driving reasons for their use among those with atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: Data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to March 2020 were used to identify adults with ASCVD. Supplement use was assessed by interviewers using label review, and surveys captured self-reported reasons for use. Demographic, clinical, medication, and laboratory characteristics were compared between supplement users and nonusers. Among individuals with ASCVD in the National Health and Nutrition Examination Survey (n=965; mean age, 65 years; 56.1% men; 73.7% White individuals), 73.1% reported taking ≥1 dietary supplements, most commonly multivitamins (35.4%), vitamin D (30.8%), and fish oil (19.8%). Of those taking supplements, 47.3% report taking them under the advisement of a health professional. Nearly one fifth (17.9%) reported taking at least 1 supplement for "heart health," most commonly fish oil (11.1%), followed by CoQ10 (4.2%) and resveratrol (1.5%). Supplement users were older (68 versus 62 years; P=0.003), included more women (45.8% versus 37.7%; P=0.17), were less likely to smoke (11.0% versus 36.4%; P<0.001), had higher levels of education (P=0.005) and income (P<0.001), and higher use of statins (69.4% versus 55.8%; P=0.046). CONCLUSIONS: Supplement use is common in people with ASCVD. Among the top 3 supplements, a substantial minority were being taken under the direction of health professionals. Supplement users often report taking supplements "for heart health," despite a lack of randomized trial evidence for benefit in ASCVD, indicating a need for more patient and clinician education regarding health benefits of dietary supplements in ASCVD.

A critical assessment of using ChatGPT for extracting structured data from clinical notes.

Existing natural language processing (NLP) methods to convert free-text clinical notes into structured data often require problem-specific annotations and model training. This study aims to evaluate ChatGPT's capacity to extract information from free-text medical notes efficiently and comprehensively. We developed a large language model (LLM)-based workflow, utilizing systems engineering methodology and spiral "prompt engineering" process, leveraging OpenAI's API for batch querying ChatGPT. We evaluated the effectiveness of this method using a dataset of more than 1000 lung cancer pathology reports and a dataset of 191 pediatric osteosarcoma pathology reports, comparing the ChatGPT-3.5 (gpt-3.5-turbo-16k) outputs with expert-curated structured data. ChatGPT-3.5 demonstrated the ability to extract pathological classifications with an overall accuracy of 89%, in lung cancer dataset, outperforming the performance of two traditional NLP methods. The performance is influenced by the design of the instructive prompt. Our case analysis shows that most misclassifications were due to the lack of highly specialized pathology terminology, and erroneous interpretation of TNM staging rules. Reproducibility shows the relatively stable performance of ChatGPT-3.5 over time. In pediatric osteosarcoma dataset, ChatGPT-3.5 accurately classified both grades and margin status with accuracy of 98.6% and 100% respectively. Our study shows the feasibility of using ChatGPT to process large volumes of clinical notes for structured information extraction without requiring extensive task-specific human annotation and model training. The results underscore the potential role of LLMs in transforming unstructured healthcare data into structured formats, thereby supporting research and aiding clinical decision-making.

US population qualifying for aspirin use for primary prevention of cardiovascular disease.

Objective: Aspirin has been used for primary prevention of atherosclerotic cardiovascular disease (ASCVD) for decades, but this indication has become controversial with recent trial data. The 2022 US Preventive Services Task Force (USPSTF) provided a recommendation to consider aspirin use for primary prevention in adults 40-59 years with a 10-year ASCVD risk ≥10 % and not at increased risk of bleeding, yet population estimates for the impact of this recommendation are unknown. The objective of this study is to determine the prevalence and demographics of the US population who meet eligibility criteria for aspirin under the new 2022 USPSTF guidelines. Methods: This is a serial cross-sectional study using data from the 2011-March 2020 National Health and Nutrition Examination Survey (NHANES) database. Individuals aged 40-59 years without a self-reported history of ASCVD were included. 10-year estimated ASCVD risk ≥10 % as calculated by the Pooled Cohort Equations (PCE) and increased bleeding risk determined using variables adapted from USPSTF guidelines were further applied as inclusion and exclusion criteria, respectively. The weighted frequencies of US adults aged 40-59 years qualifying for primary prevention aspirin, subgrouped by gender, age, and race/ethnicity, were calculated. Results: Among 72,840,734 US individuals aged 40-59 years, 7.2 million (10 %) are eligible for consideration of primary prevention aspirin by PCE criteria. Of these, approximately 30 % would be potentially excluded based on increased bleeding risks, resulting in a net eligible cohort of 5 million. This represents 7 % of US adults aged 40-59 years and only 2.6 % of adults ≥18 years. Men, age 50-59 years, and Black race have higher proportions meeting aspirin use eligibility. Conclusions: The overall prevalence of US individuals who qualify for aspirin for primary prevention under the 2022 USPSTF guidelines is modest, with larger proportional eligibility among men, older age, and Black individuals.

National Variation in Hospital MTEER Outcomes and Correlation With TAVR Outcomes: STS/ACC TVT Registry Analysis.

BACKGROUND: A single, multitiered valve center designation has been proposed to publicly identify centers with expertise for all valve therapies. The correlation between transcatheter aortic valve replacement (TAVR) and mitral transcatheter edge-to-edge repair (MTEER) procedures is unknown. OBJECTIVES: The authors sought to examine the relationship between site-level volumes and outcomes for TAVR and MTEER. We further explored variability between sites for MTEER outcomes. METHODS: Using the STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) national registry, TAVR and MTEER procedures at sites offering both therapies from 2013 to 2022 were examined. Sites were ranked into deciles of adjusted in-hospital and 30-day outcomes separately for TAVR and MTEER and compared. Stepwise, hierarchical multivariable models were constructed for MTEER outcomes, and the median OR was calculated. RESULTS: Between 2013 and 2022, 384,394 TAVRs and 53,274 MTEERs (median annualized volumes: 93.6 and 18.8, respectively) were performed across 453 U.S. sites. Annualized TAVR and MTEER volumes were moderately correlated (r = 0.48; P < 0.001). After adjustment, 14.3% of sites had the same decile rank for TAVR and MTEER 30-day composite outcome, 50.6% were within 2 decile ranks; 35% had more discordant outcomes for the 2 procedures (P = 0.0005). For MTEER procedures, the median OR for the 30-day composite outcome was 1.57 (95% CI: 1.51-1.64), indicating a 57% variability in outcome by site. CONCLUSIONS: There is modest correlation between hospital-level volumes for TAVR and MTEER but low interprocedural correlation of outcomes. For similar patients, site-level variability for mortality/morbidity following MTEER was high. Factors influencing outcomes and "centers of excellence" as a whole may differ for TAVR and MTEER.

Risk Prediction for Atherosclerotic Cardiovascular Disease With and Without Race Stratification.

Importance: Use of race-specific risk prediction in clinical medicine is being questioned. Yet, the most commonly used prediction tool for atherosclerotic cardiovascular disease (ASCVD)-pooled cohort risk equations (PCEs)-uses race stratification. Objective: To quantify the incremental value of race-specific PCEs and determine whether adding social determinants of health (SDOH) instead of race improves model performance. Design, Setting, and Participants: Included in this analysis were participants from the biracial Reasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort study. Participants were aged 45 to 79 years, without ASCVD, and with low-density lipoprotein cholesterol level of 70 to 189 mg/dL or non-high-density lipoprotein cholesterol level of 100 to 219 mg/dL at baseline during the period of 2003 to 2007. Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke. Study data were analyzed from July 2022 to February 2023. Main outcome/measures: Discrimination (C statistic, Net Reclassification Index [NRI]), and calibration (plots, Nam D'Agostino test statistic comparing observed to predicted events) were assessed for the original PCE, then for a set of best-fit, race-stratified equations including the same variables as in the PCE (model C), best-fit equations without race stratification (model D), and best-fit equations without race stratification but including SDOH as covariates (model E). Results: This study included 11 638 participants (mean [SD] age, 61.8 [8.3] years; 6764 female [58.1%]) from the REGARDS cohort. Across all strata (Black female, Black male, White female, and White male participants), C statistics did not change substantively compared with model C (Black female, 0.71; 95% CI, 0.68-0.75; Black male, 0.68; 95% CI, 0.64-0.73; White female, 0.77; 95% CI, 0.74-0.81; White male, 0.68; 95% CI, 0.64-0.71), in model D (Black female, 0.71; 95% CI, 0.67-0.75; Black male, 0.68; 95% CI, 0.63-0.72; White female, 0.76; 95% CI, 0.73-0.80; White male, 0.68; 95% CI, 0.65-0.71), or in model E (Black female, 0.72; 95% CI, 0.68-0.76; Black male, 0.68; 95% CI, 0.64-0.72; White female, 0.77; 95% CI, 0.74-0.80; White male, 0.68; 95% CI, 0.65-0.71). Comparing model D with E using the NRI showed a net percentage decline in the correct assignment to higher risk for male but not female individuals. The Nam D'Agostino test was not significant for all race-sex strata in each model series, indicating good calibration in all groups. Conclusions: Results of this cohort study suggest that PCE performed well overall but had poorer performance in both BM and WM participants compared with female participants regardless of race in the REGARDS cohort. Removal of race or the addition of SDOH did not improve model performance in any subgroup.

Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction: The CTS-AMI Randomized Clinical Trial.

Importance: Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Interventions: Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. Main Outcomes and Measures: The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Results: Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. Conclusions and Relevance: In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03792035.

Accuracy of incidental visual coronary artery calcium assessment compared with dedicated coronary artery calcium scoring.

INTRODUCTION: CAC can be detected on routine chest computed tomography (CT) scans and may contribute to CVD risk estimation, but the accuracy of visual CAC scoring may be affected by the specialty of the interpreting radiologist and/or the use of contrast. METHODS: The accuracy of visual CAC estimation on non-gated CT scans was evaluated at UT Southwestern Medical Center (UTSW) and Parkland Health and Hospital System (PHHS). All adults who underwent CAC scanning and a non-gated CT scan within 6 months were identified and the scores from the two CTs were compared overall and stratified by type of reader and whether contrast was used. Visual CAC categories of none, small, moderate, and large were compared to CAC â€‹= â€‹0, 1-99, 100-399, and ≥400, respectively. RESULTS: From 2016 to 2021, 934 patients (mean age 60 â€‹± â€‹12 â€‹y, 43% male, 61% White, 34% Black, 24% Hispanic, 54% from PHHS) had both CT scans. Of these, 441 (47%) had no CAC, 278 (30%) small, 147 (16%) moderate, and 66 (7%) large CAC on non-gated CT. Visual CAC estimates were highly correlated with CAC scores (Kendalls tau-b â€‹= â€‹0.76, p â€‹< â€‹0.0001). Among those with no visual CAC, 76% had CAC â€‹= â€‹0 (72% of contrast-enhanced vs 85% of non-contrast scans, 88% of scans interpreted by CT radiologist vs 78% of those interpreted by other radiologist). In those with moderate-to-large visual CAC, 99% had CAC >0 and 88% had CAC ≥100, including 89% of those with contrast, 90% of those without contrast, 80% of those read by a CT radiologist, and 88% of those read by a non-CT radiologist. DISCUSSION: Visual CAC estimates on non-gated CT scans are concordant with Agatston score categories from cardiac CT scans. A lack of visual CAC on non-gated CT scans may not be sufficient to "de-risk" patients, particularly for contrast-enhanced scans and those read by non-CT radiologists. However, the presence of moderate-to-large CAC, including on contrasted scans and regardless of radiologist type, is highly predictive of CAC and may be used to identify high-risk patients for prevention interventions.

Health Claims and Doses of Fish Oil Supplements in the US.

Importance: One in 5 US adults older than 60 years takes fish oil supplements often for heart health despite multiple randomized clinical trials showing no data for cardiovascular benefit for supplement-range doses. Statements on the supplement labels may influence consumer beliefs about health benefits. Objectives: To evaluate health claims made on the labels of fish oil supplements in the US, and to examine doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in commonly available formulations. Design, Setting, and Participants: This cross-sectional study used data from labels of on-market fish oil (and nonfish ω-3 fatty acid) supplements obtained from the National Institutes of Health Dietary Supplement Label Database. The study was conducted and data analyzed from February to June 2022. Main Outcome and Measures: The frequency and types of health claims made on fish oil labels (US Food and Drug Administration [FDA]-reviewed qualified health claim vs a structure/function claim) and the organ system referenced were evaluated. The total daily doses of combined EPA and DHA (EPA+DHA) were assessed for supplements from 16 leading manufacturers and retailers. Results: Across 2819 unique fish oil supplements, 2082 (73.9%) made at least 1 health claim. Of these, only 399 (19.2%) used an FDA-approved qualified health claim; the rest (1683 [80.8%]) made only structure/function claims (eg, "promotes heart health"). Cardiovascular health claims were the most common (1747 [62.0%]). Across 16 leading brands/manufacturers, 255 fish oil supplements were identified. Among these, substantial variability was found in the daily dose of EPA (median [IQR], 340 [135-647] mg/d), DHA (median [IQR], 270 [140-500] mg/d), and total EPA+DHA (median [IQR], 600 [300-1100] mg/d). Only 24 of 255 supplements (9.4%) evaluated contained a daily dose of 2 g or more EPA+DHA. Conclusions: Results of this cross-sectional study suggest that the majority of fish oil supplement labels make health claims, usually in the form of structure/function claims, that imply a health benefit across a variety of organ systems despite a lack of trial data showing efficacy. Significant heterogeneity exists in the daily dose of EPA+DHA in available supplements, leading to potential variability in safety and efficacy between supplements. Increasing regulation of dietary supplement labeling may be needed to prevent consumer misinformation.

Gaps in Guideline-Based Lipid-Lowering Therapy for Secondary Prevention in the United States: A Retrospective Cohort Study of 322†153 Patients.

BACKGROUND: Many patients with atherosclerotic cardiovascular disease (ASCVD) are not on guideline-recommended statin therapy. We evaluated utilization of statins and other lipid-lowering therapy (LLT), and changes in low-density lipoprotein cholesterol (LDL-C), among patients with ASCVD over a 1-year period. METHODS: LLT and LDL-C levels at the first outpatient visit (January 1, 2017-December 31, 2018) and 1-year follow-up were evaluated using data from Cerner Real-World Data, an electronic health record-derived data set from 92 US health systems. Logistic regression was used to evaluate factors associated with high-intensity statin use. RESULTS: We identified 322 153 patients with ASCVD (median age 69 years, 58.8% men, 81.8% White). Overall, 76.1% of patients were on statins, with only 39.4% on high-intensity statins. Men were more likely to receive high-intensity statins than women (multivariable-adjusted odds ratio, 1.34 [95% CI, 1.30-1.38]). Increasing age was associated with lower odds of statin use (odds ratio, 0.79 per 5-year increase at 60 years [95% CI, 0.78-0.81]). Patients with peripheral artery disease (odds ratio, 0.40 [95% CI, 0.37-0.42]) and cerebrovascular disease (odds ratio, 0.75 [95% CI, 0.70-0.80]) had lower odds of using high-intensity statins than those with coronary artery disease. At baseline, most patients (61.3%) had elevated LDL-C (≥70 mg/dL), including 59.8% of those on low/moderate-intensity statins and 76.1% on no statin; only 45.3% achieved an LDL-C <70 mg/dL at 1 year. Nonstatin LLT use was low (ezetimibe, 4.4%; proprotein convertase subtilisin/kexin type 9 inhibitors, 0.7%). Among patients on no statin or low/moderate-intensity statin at baseline, 14.8% and 13.4%, respectively, were on high-intensity statins at 1 year. CONCLUSIONS: Among patients with ASCVD in routine care, high-intensity statins are underutilized, and uptitration and use of nonstatin therapy are uncommon. Women, older adults, and individuals with noncardiac ASCVD are particularly undertreated. Concerted efforts are needed to address therapeutic inertia for lipid management in patients with ASCVD.

Predictors of intracranial hemorrhage in patients with atrial fibrillation treated with oral anticoagulants: Insights from the GARFIELD-AF and ORBIT-AF registries.

BACKGROUND: An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs). HYPOTHESIS: An externally validated model improves ICH risk stratification. METHODS: Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register. RESULTS: In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets. CONCLUSIONS: Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

Mitochondrial metabolites predict adverse cardiovascular events in individuals with diabetes.

Metabolic mechanisms underlying the heterogeneity of major adverse cardiovascular (CV) event (MACE) risk in individuals with type 2 diabetes mellitus (T2D) remain unclear. We hypothesized that circulating metabolites reflecting mitochondrial dysfunction predict incident MACE in T2D. Targeted mass-spectrometry profiling of 60 metabolites was performed on baseline plasma samples from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS; discovery cohort) and Exenatide Study of Cardiovascular Event Lowering (EXSCEL; validation cohort) biomarker substudy cohorts. A principal components analysis metabolite factor comprising medium-chain acylcarnitines (MCACs) was associated with MACE in TECOS and validated in EXSCEL, with higher levels associated with higher MACE risk. Meta-analysis showed that long-chain acylcarnitines (LCACs) and dicarboxylacylcarnitines were also associated with MACE. Metabolites remained associated with MACE in multivariate models and favorably changed with exenatide therapy. A third cohort (Cardiac Catheterization Genetics [CATHGEN]) with T2D was assessed to determine whether these metabolites improved discriminative capability of multivariate models for MACE. Nine metabolites (MCACs and LCACs and 1 dicarboxylacylcarnitine) were associated with time to MACE in the CATHGEN cohort. Addition of these metabolites to clinical models minimally improved the discriminative capability for MACE but did significantly down reclassify risk. Thus, metabolites reporting on dysregulated mitochondrial fatty acid oxidation are present in higher levels in individuals with T2D who experience subsequent MACE. These biomarkers may improve CV risk prediction models, be therapy responsive, and highlight emerging risk mechanisms.

Recent Vitamin K Antagonist Use and Intracranial Hemorrhage After Endovascular Thrombectomy for Acute Ischemic Stroke.

Importance: Use of oral vitamin K antagonists (VKAs) may place patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion at increased risk of complications. Objective: To determine the association between recent use of a VKA and outcomes among patients selected to undergo EVT in clinical practice. Design, Setting, and Participants: Retrospective, observational cohort study based on the American Heart Association's Get With the Guidelines-Stroke Program between October 2015 and March 2020. From 594 participating hospitals in the US, 32 715 patients with acute ischemic stroke selected to undergo EVT within 6 hours of time last known to be well were included. Exposure: VKA use within the 7 days prior to hospital arrival. Main Outcome and Measures: The primary end point was symptomatic intracranial hemorrhage (sICH). Secondary end points included life-threatening systemic hemorrhage, another serious complication, any complications of reperfusion therapy, in-hospital mortality, and in-hospital mortality or discharge to hospice. Results: Of 32 715 patients (median age, 72 years; 50.7% female), 3087 (9.4%) had used a VKA (median international normalized ratio [INR], 1.5 [IQR, 1.2-1.9]) and 29 628 had not used a VKA prior to hospital presentation. Overall, prior VKA use was not significantly associated with an increased risk of sICH (211/3087 patients [6.8%] taking a VKA compared with 1904/29 628 patients [6.4%] not taking a VKA; adjusted odds ratio [OR], 1.12 [95% CI, 0.94-1.35]; adjusted risk difference, 0.69% [95% CI, -0.39% to 1.77%]). Among 830 patients taking a VKA with an INR greater than 1.7, sICH risk was significantly higher than in those not taking a VKA (8.3% vs 6.4%; adjusted OR, 1.88 [95% CI, 1.33-2.65]; adjusted risk difference, 4.03% [95% CI, 1.53%-6.53%]), while those with an INR of 1.7 or lower (n = 1585) had no significant difference in the risk of sICH (6.7% vs 6.4%; adjusted OR, 1.24 [95% CI, 0.87-1.76]; adjusted risk difference, 1.13% [95% CI, -0.79% to 3.04%]). Of 5 prespecified secondary end points, none showed a significant difference across VKA-exposed vs VKA-unexposed groups. Conclusions and Relevance: Among patients with acute ischemic stroke selected to receive EVT, VKA use within the preceding 7 days was not associated with a significantly increased risk of sICH overall. However, recent VKA use with a presenting INR greater than 1.7 was associated with a significantly increased risk of sICH compared with no use of anticoagulants.

Challenge in Predicting Persistence to P2Y12 Inhibitors: A Perspective From the ARTEMIS Trial.

Background Premature discontinuation of P2Y12 inhibitor therapy has been associated with adverse cardiac events, which might be preventable by improving medication persistence. Current risk models have limited ability to predict patients at risk of P2Y12 inhibitor nonpersistence. Methods and Results ARTEMIS (Affordability and Real-World Antiplatelet Treatment Effectiveness after Myocardial Infarction Study) was a randomized, controlled trial testing the impact of a copayment assistance intervention on P2Y12 inhibitor persistence and outcomes. Among 6212 patients post myocardial infarction with a planned 1-year course of P2Y12 inhibitor therapy, nonpersistence was defined as a gap in P2Y12 inhibitor filled >30 days by pharmacy fill data. We developed a predictive model for 1-year P2Y12 inhibitor nonpersistence among patients randomized to usual care. P2Y12 inhibitor nonpersistence rates were 23.8% (95% CI, 22.7%-24.8%) at 30 days and 47.9% (46.6%-49.1%) at 1 year; the majority of these patients had in-hospital percutaneous coronary intervention. Patients who received the copayment assistance intervention had nonpersistence rates of 22.0% (20.7%-23.3%) at 30 days and 45.3% (43.8%-46.9%) at 1 year. A 53-variable multivariable model predicting 1-year persistence had a C-index of 0.63 (optimism-corrected C-index 0.58). Model discrimination did not improve with inclusion of patient-reported perceptions about disease, medication-taking beliefs, and prior medication-filling behavior in addition to demographic and medical history data (C-index 0.62). Conclusions Despite addition of patient-reported variables, models predicting persistence with P2Y12 inhibitor therapy performed poorly, thereby suggesting the need for continued patient and clinician education on the importance of P2Y12 inhibitor therapy after acute myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02406677.

Generalizability of an EHR-network dataset to the United States for cardiovascular disease conditions: Comparison of Cerner real world data with the national inpatient sample.

BACKGROUND: Electronic Health Record (EHR) data from health systems are increasingly being combined for clinical research purposes. Yet, it remains unclear whether these large EHR data sources provide a representative assessment of national disease prevalence and treatment. To evaluate this, we compared Cerner RealWorldData (CRWD), a large EHR data source, to those seen in the National Inpatient Sample (NIS) for 3 cardiovascular conditions (myocardial infarction (MI), congestive heart failure (CHF), and stroke. METHODS: Adult patients (age ≥18 years) hospitalized with MI, CHF, and stroke were identified in both CRWD (86 health systems) and the NIS (4,782 hospitals). Patient demographics, comorbidities, procedures, outcomes (length of stay and in-hospital mortality) and hospital type (teaching or nonteaching) were compared between NIS and CRWD patients. RESULTS: Of 86 health systems participating in CRWD, 33 were excluded for potential data quality issues which accounted for about 11% of hospitalizations in the dataset, leaving 53 for inclusion in analysis which accounted for about 89% of hospitalizations in the dataset. Between January 1, 2017 and December 31, 2018, 116,956 MI, 188,107 CHF, and 93,968 stroke hospitalizations were identified in CRWD vs 2,245,300 MI, 4,310,745 CHF, and 1,333,480 stroke hospitalizations in the NIS. Patient demographics were similar among patients in CWRD and the NIS for all 3 cardiovascular groups except for ethnicity, with underrepresentation of Hispanic individuals in CRWD vs the NIS. Patients hospitalized in CRWD had a slightly higher proportion of coded co-morbidities compared with NIS hospitalizations due to a longer potential look-back period. For patients with MI, hospital mortality, length of stay, coronary artery bypass graft (CABG) rates, and percutaneous coronary intervention (PCI) rates were similar between CRWD and NIS. Additionally, there was similar in hospital mortality and length of stay for those with CHF and stroke hospitalizations between CRWD and NIS. CONCLUSIONS: On aggregate, characteristics of hospitalizations for MI, CHF, and stroke using EHR data from one nationwide EHR-derived database, CRWD, appears similar to characteristics of hospitalizations in the nationally representative NIS. Important limitations of CRWD include lack of geographic representativeness, under-representation of Hispanic adults, and the need to exclude health systems for missing data.

Uptake of non-statin lipid-lowering therapies for secondary prevention in community practice.

Nearly two-thirds of individuals with atherosclerotic cardiovascular disease (ASCVD) do not reach target low-density lipoprotein cholesterol despite statin therapy. Three novel lipid-lowering therapies have proven to further reduce ASCVD beyond statins, including: ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), and icosapent ethyl. This study evaluated the use of these three agents in 728,423 individuals with ASCVD from 89 US health systems from 01/2018 through 03/2021 using the electronic health record. As of 2021, only 6.0% of ASCVD patients were on ezetimibe, 1.6% were on a PCSK9i, and 1.3% on icosapent ethyl, with utilization only marginally increasing over the study period. Addressing the underutilization of non-statin lipid-lowering therapy for secondary prevention is a critical step in improving the treatment gap of patients with residual risk of ASCVD.

Contemporary patterns of lipoprotein(a) testing and associated clinical care and outcomes.

Objective: Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease, yet little is known about Lp(a) testing patterns in real-world practice. The objective of this analysis was to determine how Lp(a) testing is used in clinical practice in comparison with low density lipoprotein cholesterol (LDL-C) testing alone, and to determine whether elevated Lp(a) level is associated with subsequent initiation of lipid-lowering therapy (LLT) and incident cardiovascular (CV) events. Methods: This is an observational cohort study, based on lab tests administered between Jan 1, 2015 and Dec 31, 2019. We used electronic health record (EHR) data from 11 United States health systems participating in the National Patient-Centered Clinical Research Network (PCORnet). We created two cohorts for comparison: 1) the Lp(a) cohort, of adults with an Lp(a) test and 2) the LDL-C cohort, of 4:1 date- and site-matched adults with an LDL-C test, but no Lp(a) test. The primary exposure was the presence of an Lp(a) or LDL-C test result. In the Lp(a) cohort, we used logistic regression to assess the relationship between Lp(a) results in mass units (< 50, 50-100, and > 100mg/dL) and molar units (<125, 125-250, > 250nmol/L) and initiation of LLT within 3 months. We used multivariable adjusted Cox proportional hazards regression to evaluate these Lp(a) levels and time to composite CV hospitalization, including hospitalization for myocardial infarction, revascularization and ischemic stroke. Results: Overall, 20,551 patients had Lp(a) test results and 2,584,773 patients had LDL-C test results (82,204 included in the matched LDL-C cohort). Compared with the LDL-C cohort, the Lp(a) cohort more frequently had prevalent ASCVD (24.3% vs. 8.5%) and multiple prior CV events (8.6% vs. 2.6%). Elevated Lp(a) was associated with greater odds of subsequent LLT initiation. Elevated Lp(a) reported in mass units was also associated with subsequent composite CV hospitalization [aHR (95% CI): Lp(a) 50-100mg/dL 1.25 (1.02-1.53), p<0.03, Lp(a) > 100mg/dL 1.23 (1.08-1.40), p<0.01]. Conclusion: Lp(a) testing is relatively infrequent in health systems across the U.S. As new therapies for Lp(a) emerge, improved patient and provider education is needed to increase awareness of the utility of this risk marker.