tbuckley/cabot-search huggingface dataset:
Abstract 4144303: Long-Term Blood Pressure Variability is Associated With Risk for Sudden Cardiac Death: Cardiovascular Lifetime Risk Pooling Project (LRPP)
Authors: Ritam Patel, Hongyan Ning, John Wilkins, Donald Lloyd-Jones
Journal: Circulation (2024)

Background: Higher blood-pressure variability (BPV) across multiple visits has been associated with greater risk for mortality and adverse cardiovascular and neurocognitive outcomes. However, no studies have examined associations of BPV with sudden cardiac death (SCD), a leading mechanism of death among adults. Methods: We used individual-level participant (ppt) data from 5 cohorts that are included in the LRPP dataset, (CARDIA, ARIC, Framingham Original and Offspring, and CHS), using baseline visits from the 1980s-2000s. We included ppts aged 40-80 years with at least 3 blood pressure (BP) measurements. Visit-to-visit BPV was quantified over 15 years using the standard deviation (SD) across all visits or the average real variability (ARV; average absolute difference between successive BP measurements, also taking the order of the BP measurements into account). SCD was adjudicated by each cohort using standardized definitions. Cox models (adjusted for covariates) were assessed to examine associations of BPV measures with SCD. Results: There were 23,499 ppts (mean age 52.7±8.7 years, 55.3% women, 16.9% Black) followed for 15 years for BPV data and then for 10.3±6.6 years for SCD; 484 ppts (2.1%) experienced SCD. The mean SD and ARV were 11.1±6.3 and 11.9±7.3 mm Hg for systolic BP, 6.4±3.5 and 7.0±4.0 mm Hg for diastolic BP, and 7.0±3.9 and 7.8±4.6 mmHg for mean arterial pressure (MAP), respectively. After adjustment for age, sex, and race, each 1 mm Hg greater SD or ARV in MAP was associated with 9% (95% CI, 7-11%) or 6% (95% CI, 5-8%) higher hazards for SCD, respectively (Table). Associations of BPV with SCD were partially attenuated but remained significant after adjustment for other risk factors, baseline BP, and change in BP from baseline to end of observation. The pattern of results was overall similar for MAP, systolic BP, and diastolic BP. Ppts in the highest vs lowest quartiles of BPV were at approximately 50% higher adjusted risk for SCD (Table). Conclusions: Long-term BPV in middle age is associated with SCD, even after adjusting for underlying BP change with age and other risk factors. BPV may be useful as a marker to identify individuals in the general population at higher risk for sudden death.
Abstract 4144284: A Novel RNA Interference Agent RN0191 Lowering Proprotein Convertase Subtilisin/Kexin Type 9, Low-density Lipoprotein Cholesterol and Other Lipid Biomarkers in Healthy Volunteers with Elevated LDL Cholesterol: A Randomized, Single-blind, Placebo-controlled, Phase 1 Trial
Authors: fangfang wang, Haiyan Li, Jie Zeng, Stella Shi, Hongmei Li
Journal: Circulation (2024)

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, leading to their degradation and decreasing serum LDL-cholesterol (LDL-C) to reduce risk of coronary heart disease. We aimed to investigate the safety, tolerability, pharmacodynamic characteristics of RN0191, a novel structure small interfering RNA that inhibits PCSK9 mRNA translation process, in healthy Chinese adults with elevated LDL-C who were not on lipid-lowering treatment. Methods: We did a randomized, single-blind, placebo-controlled, Phase 1 dose-ascending study in healthy Chinese volunteers with serum LDL-C≥100 mg/dL (2.6 mmol/L). Subjects were randomly assigned in a 6:2 ratio to receive single subcutaneous injection of RN0191 (dose ranging from 60mg to 600mg) or placebo. Primary endpoint was the safety and tolerability of RN0191. Secondary endpoints included RN0191's pharmacodynamic effects on PCSK9, LDL-C and other lipid biomarkers. All subjects were masked to treatment assignment. The study registered in ClinicalTrials.gov (NCT06132360) and is still on-going. Results: Of 32 subjects, 24 were randomly allocated to receive a single dose (60mg/200mg/400mg/600mg) of RN0191 (6 in each active arm) and 8 to placebo. The analysis spans all cohorts at Day 56 post-administration. All the adverse events are mild or moderate. There is no severe treatment-emergent AE (TEAE), death or TEAE leading to study discontinuation. The numbers of subjects affected by TEAEs in each cohort of RN0191 (3,4,2,2) are similar to that of placebo (3). The interim data indicates a profound dose-dependent lowering impact of RN0191 on several key lipid biomarkers. Substantial PCSK9 protein reduction is demonstrated in a dose-dependent manner. In high dose (400 mg and 600 mg) cohorts, mean maximal decreases of PCSK9 level of 85.84% on Day 21 and 86.14% on Day 28 are achieved respectively. Notably, LDL-C exhibits progressively greater reductions across escalating doses. The mean maximal decreases of LDL-C are achieved as 54.65% of 400mg cohort on Day 42 and 51.35% of 600mg cohort on Day 21 respectively. Additionally, a significant lipoprotein (a) reduction is observed with mean maximal lowering level of 43.95% at 400mg cohort on Day 21 and 52.95% at 600mg on Day 28 respectively. Conclusions: The preliminary safety and efficacy profile of RN0191 underscoring its comprehensive lipid-lowering capacity as a promising therapeutic candidate for managing dyslipidemia.
Abstract 4144299: Association of Sleep and Exercise with Chronic Disease: Insights from Long-Term Wearable Data Among All of Us Participants
Authors: Asanish Kalyanasundaram, Jacob Barber, Michael Mi, Michelle Keyes, Usman Tahir, Jeremy Robbins, Nicholas Peters, Tamar Sofer, Daniel Kramer, Robert Gerszten, Prashant Rao
Journal: Circulation (2024)

Introduction: Sleep and physical activity (PA) are essential components of ideal health. However, epidemiological data assessing PA and sleep have been limited by short measurement periods, small samples, or recall bias. We assess the relationship between objective measures of long-term PA and sleep across the human phenome. Methods: We included 9399 individuals in the All of Us cohort with &gt;6 months of wearable (Fitbit) data and linked electronic health records. Fitbit data included daily total sleep duration (TSD) and moderate and vigorous physical activity (MVPA) over a median time of 1103 days. We used Cox regression to model the association of MVPA and TSD across 1711 phecodes (Cox pheWAS), adjusting for age, sex, and race. Top associations were investigated individually using restricted spline curves to quantify the change in hazard ratio (HR) of disease per minute of sleep or MVPA. Individual phenotype associations were further adjusted for smoking status, alcohol intake, education level, and BMI. We performed interaction analyses to assess whether TSD modifies the effect of MVPA on disease. We accounted for multiple hypothesis testing with Bonferroni correction. Results: TSD and MVPA levels were uncorrelated (r2: 0.004) and independently associated with several cardiometabolic and non-cardiometabolic diseases, including obesity (MVPA: HR 0.97, p 4e-14; TSD: HR 0.99, p 2e-16), hypertension (TSD: HR 0.99, p 4e-5), major depressive disorder (MVPA: HR 0.98, p 2e-7; TSD: HR 0.99, p 3e-3), and chronic migraine (MVPA: HR 0.97, p 3e-5) (Fig.1). The association between MVPA and chronic disease often demonstrated a linear or curvilinear dose-response curve. By contrast, the association of TSD and chronic disease was often sigmoidal, with increasing benefit of longer sleep between ~5hr20min and 6hr40min of sleep/day, but relatively constant health benefits/risks for longer/shorter sleep durations. Conclusion: In All of Us participants, TSD and MVPA are independently and inversely associated with chronic disease based on objective, long-term measures. These data highlight the importance of both sleep and MVPA in maintaining ideal health, and will help inform personalized, disease-specific sleep and PA recommendations.
Abstract 4144462: Prevalence and Risk Factors of Peripheral Artery Disease Identified by Multimodalities in Hispanics
Authors: Maya Salameh, Hairong Liu, Shoshana Ballew, Pablo Martinez-Amezcua, Jennifer Schrack, Olga Garcia-Bedoya, Gregory Talavera, Martha Daviglus, Daniela Sotres-Alvarez, Franklyn Gonzalez, Matthew Allison, Robert Kaplan, Kuni Matsushita
Journal: Circulation (2024)

Introduction: The prevalence of peripheral artery disease (PAD) has been assessed with the ankle-brachial index (ABI), but some studies have raised concerns about its sensitivity. Aims: Using data from a community-based cohort study, the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we estimated the prevalence of PAD in US Hispanics using the toe-brachial index (TBI), pulse volume recordings (PVR), continuous Doppler waveforms, and post-exercise ABI, in addition to resting ABI. We also explored the associations of known risk factors with PAD identified by these methods. Methods: The HCHS/SOL sampled Hispanics/Latinos from four US regions (CA, IL, FL, and NY). During its third visit, participants aged ≥45 years were invited for a comprehensive evaluation of PAD. PAD was defined as having at least one of the following: 1) resting ABI ≤0.9; 2) post-exercise (heel-raise) drop in ABI ≥20% or drop in ankle blood pressure ≥30 mmHg; or 3) abnormality in at least two of TBI (≤0.6), PVR (mild or greater abnormality), and continuous Doppler waveforms (monophasic/nonpulsatile in either dorsalis pedis or posterior tibial artery or biphasic without good acceleration in both arteries). Certified technicians conducted the measurements using a vascular diagnostic instrument (the Unetixs MultiLab Series II). Major cardiovascular risk factors were measured according to the standard protocol in HCHS/SOL. Results: Among 3,130 participants (mean age 62.9 years, 2121 female [67.8%]), the prevalence of PAD was 4.1% with only resting ABI ≤0.9 but 17.8% considering all modalities. The prevalence of PAD exceeded 22% in participants aged 65+ (Figure) and was similar between men and women. PAD prevalence was significantly higher in Cubans, Puerto Ricans, and Central Americans compared to Mexicans (Figure). The higher prevalence in these ethnic groups remained consistent even after adjusting for traditional risk factors. Among traditional risk factors, smoking, diabetes, and systolic blood pressure were robustly associated with the presence of PAD. Conclusion: In this cohort of US Hispanics/Latinos, the prevalence of PAD is substantially higher when multiple modalities are used to detect PAD. Disparities in the prevalence of PAD across ethnic groups in Hispanics could not be explained by traditional risk factors and should be further investigated.
Abstract 4144394: Cardiac Resynchronization Therapy is Associated with Increased All-Cause Mortality in Patients with Chronic Chagas Cardiomyopathy: Systematic Review and Meta-analysis
Authors: Beatriz Maria Franco Hondermann, Juan Bosco franco Hondermann, Ana Karla Jansen amorim
Journal: Circulation (2024)

Introduction: Cardiac resynchronization therapy (CRT) reduces mortality in patients with moderate to severe heart failure (HF) and reduced ejection fraction. However, outcomes associated with CRT in CCC patients are still controversial. We conducted a meta-analysis to quantify total mortality in patients with chronic Chagas cardiomyopathy compared to HF of other etiologies (Non-Chagas). Objectives: To perform a meta-analysis of studies to measure all-cause mortality in CCC patients compared to patients of other etiologies (Non-Chagas) when undergoing CRT. Methods: A literature search was conducted in PubMed, Cochrane, Embase, Scielo for English, Portuguese, and Spanish comparing all-cause mortality in patients undergoing CRT in CCC and other etiologies (Non-Chagas). The Non-Chagas group included patients with HF of ischemic, dilated, or idiopathic etiology. Statistical analysis was performed in RevMan 5.18. Heterogeneity was assessed by I2 statistics. Results: 577 patients from 3 studies were included, with 170 patients having Chronic Chagas Cardiomyopathy. Follow-up time ranged from 12 to 41 months. Mean age was 61.7 +/- 11.6 years and 61.5% were male. Mean ejection fraction across studies was 25.8% +/- 6.4. All-cause mortality (OR: 2.41; 95% CI: 1.65-3.53; p &lt; 0.00001, I2 = 0%) was significantly higher in patients with Chronic Chagas Cardiomyopathy compared to the Non-Chagas group. Conclusion: Patients with CCC had higher all-cause mortality compared to Non-Chagas patients when undergoing CRT. These results highlight the importance of prospective controlled studies comparing Cardiac Resynchronization Therapy with other treatments to define the optimal therapy for patients with heart failure with reduced ejection fraction due to Chagas disease.
Abstract 4144346: Gender, Racial/Ethnic and Regional Differences in Trends of Stroke-related Mortality in Atrial Fibrillation: a National Database Analysis 1999-2020
Authors: Rabbia Siddiqi, Syed Husain Farhan, sadik khuder, Ehab Eltahawy, Blair Grubb, George Moukarbel
Journal: Circulation (2024)

Background: Stroke is a leading cause of death globally. Atrial fibrillation (AF) is an important modifiable risk factor for stroke. Ascertaining the burden of stroke in AF, its temporal trends and demographic disparities can inform public health policy measures. Aims To describe national temporal trends of ischemic stroke-related mortality in patients with AF and identify any differences by gender, race, ethnicity, or region. Methods: In this cross-sectional analysis we used death certificate data from the national CDC Wide-Ranging ONline Data for Epidemiologic Research (WONDER) database for adults aged 35-84 years between 1999 and 2020. We queried for both ischemic stroke and AF as contributing or underlying cause of death. Crude and age-adjusted mortality rates (AAMR) were computed for the overall population and stratified by sex, race/ethnicity, geographic region, state, and rural/urban status. Joinpoint Regression Analysis software was used for trend analysis. Average annual percentage change (APC) in AAMR were computed using log-linear regression models. Results A total of 32,386 ischemic-stroke related deaths occurred in patients with AF between 1999 and 2020. Overall mortality trends were stable until 2014, sharply rose between 2014 and 2017 (APC 27.6% [95% confidence interval, CI, 18.8-33.4]), slowing down between 2017 and 2020 (APC 2.48 [95% CI, -4.81-7.03]). Overall AAMR per 100,000 was higher in men (1.00 vs 0.86 in women; Figure 1); Non-Hispanic Whites (0.98 versus 0.81 in Non-Hispanic Blacks and 0.70 in Hispanics; Figure 2), individuals in the Western census region (1.07 vs 0.95 in Southern, 0.92 in Midwestern and 0.78 in Northeast regions; Figure 3) and non-metropolitan areas (1.06 versus 0.91 in metropolitan). The rate of increase in AAMR over recent years was significantly greater in Black populations. Conclusion: Stroke mortality in AF rose sharply since 2014. Our findings underscore racial and geographic differences that exist in stroke-related deaths in the US.
Abstract 4144340: Attributing Ischemic Heart Disease Patients to Physicians: An Assessment of Claims-based Accountable Care Organization Attribution Methods
Authors: David Magid, Qian Luo, Ali Moghtaderi, Richard Klasco, Vinay Kini
Journal: Circulation (2024)

Background: Accountable care organizations (ACOs) often assess provider care quality by using attribution algorithms to determine the provider most responsible for a patient’s care. However, patients with ischemic heart disease (IHD) may receive care from more than one physician, and secondary prevention for IHD is often provided by both primary care physicians (PCPs) and cardiologists. Aim: To assess the performance of two commonly used claims-based ACO attribution methods for identifying the provider responsible for managing IHD-related outpatient care for patients in the year following incident acute myocardial infarction (AMI). Methods: Retrospective analysis of Medicare claims data for 491,391 AMI patients who survived for at least 1-year. Assignment of responsibility was made to the physician who saw the patient for the 1) plurality of PCP visits (PCP-method) or 2) plurality of PCP or cardiologist visits (PCP-Cardiologist method). For each method we assessed a) the proportion of patients that could be attributed to a physician, and b) how often the attributed physician and non-attributed physicians provided IHD care. IHD visits were identified using a previously validated list of IHD diagnosis codes. Results: The PCP-method attributed 352,261 patients (72%) and the PCP-Cardiologist method attributed 396,618 patients (81%) to a physician. The PCP-method attributed physician did not see the patient for an IHD visit in 38% of cases and did not provide the plurality of IHD visits in 67% of cases. The PCP-cardiologist method attributed physician did not see the patient for an IHD visit in 30% of cases and did not provide the plurality of IHD visits in 35% of cases. Overall, the proportion of IHD visits provided by other, non-attributed physicians was 69% for the PCP-method and 39% for the PCP-Cardiologist method. Conclusions: Patients with IHD often obtain care from multiple physicians. Commonly used ACO attribution methods to identify a single physician responsible for a patient’s IHD care results in a significant number of patients being unattributed. Attribution methods that focus on visit frequency alone often attribute patients to physicians that do not provide any IHD care or less than a plurality of IHD care. Multi-attribution methods which attribute patients to more than one physician and consider both visit frequency and clinical context could result in a more appropriate appraisal and distribution of the responsibility of IHD care.
Abstract 4144308: Re-Exploration of the Pulmonary Resistance-Compliance Relationship: a Universal Time Constant and Hyperbolic Fit?
Authors: Sara Hungerford, Audrey Adji, Hannah Kempton, Navin Kapur, Daniel Burkhoff
Journal: Circulation (2024)

Background: Pulmonary vascular resistance (PVR) and arterial compliance (PAC) represent the two major hemodynamic determinants of PA load, and their interdependence (the PVR-PAC relationship), critical to our understanding of RV-PA coupling. Previously, it has been reported that the two are physiologically linked through an inverse hyperbolic relationship, such that any rise in PVR is followed by an inverse reduction in PAC, and vice versa. Recent modelling has questioned the 'physiological correctedness' of this relationship as both share stroke volume (SV) in their determination. Accordingly, we sought to re-explore the PVR-PAC relationship, comparing PAC clinical with a new, modified area under the curve method, termed PAC pcwp. Methods: PAC clinical was calculated as the ratio of SV to PA PP . For PAC pcwp , the time constant was estimated as: τ = (A-dt*PCWP)/(P 1 -P 2 ) , where A is the integral over the time period from t 1 to t 2 of the pressure wave, dt is the time difference between P 1 and P 2 , PCWP is the mean post capillary wedge pressure, P 1 is the arterial pressure at t 1 and P 2 the arterial pressure at t 2 . Once τ was determined, PAC pcwp was measured as the τ/PVR ratio. Results: Hemodynamic data from 79-patients with dyspnoea who underwent sequential right heart catheterisation/cardiac magnetic resonance for investigation of PH were analysed (24 pre-capillary PH, 25 post-capillary, 17 combined and 13 controls). PAC pcwp values were significantly higher than PAC clinical (5.5±4.0 vs 3.4±1.6 mL/mmHg; P&lt;0.01), with a non-signifcant increase in τ amongst subjects with PH (Figure 1a). Whereas PVR demonstrated a strong inverse hyperbolic correlation with PAC clinical (R 2 -0.77, P&lt;0.01), it did not with PAC pcwp (R 2 -0.09, P=0.59; Figure 1b) where there was significant random scatter at lower PVR values. Compared with data in those with a PCWP &lt;15mmHg, the relationship was predictably shift downward in an almost parallel manner for PVR-PAC clinical but not so PVR-PAC pcwp (Figure 1c&amp;d). Conclusions: Although these observations may seem trivial at first, they bring into question the invariability of (i) a constant R-C time product and (ii) a hyperbolic resistance-compliance relationship, signalling the potential for greater fluctuations in PAC for any given change in PVR. Reconsideration of PAC determination using the PAC pcwp method in those with a low PVR and/or PA M (i.e., at the steep end of the PVR-PAC curve) may be the key to unlocking the prognostic utility of this index.
Abstract 4144315: Impact of Smartphone-based Atrial Fibrillation Burden (SMURDEN) on Quality-of-Life Improvement; Insights from DECAAF II
Authors: ghassan bidaoui, Chanho Lim, Francisco Tirado Polo, Mayana Bsoul, Ala' Assaf, Hadi Younes, Nour Chouman, Han Feng, Yingshuo Liu, Yishi Jia, Abboud Hassan, Eli Tsakiris, Joe Abi-Rached, Yanpei Hui, Besim Ademi, Mario Mekhael, Charbel Noujaim, Swati Rao, Omar Kreidieh, eoin donnellan, Amitabh Pandey, Nassir Marrouche
Journal: Circulation (2024)

Background: While numerous studies and clinical trials utilize smartphone based 30-second electrocardiogram (ECG) strips to assess the outcome of AF treatment, the direct association of AF burden with the quality of life (QoL) is yet to be established. Purpose: To discover the influence of smartphone-based AF Burden on QoL and symptom improvement after catheter ablation. Methods: We study the AF burden collected from the DECAAF II trial. The trial consists of persistent AF patients who provided daily single-lead ECG strips after ablation. We defined AF burden as the ratio of days with AF detected to the number of days with submitted ECG strips. A total number of 230,892 single-lead ECG strips were submitted. The AFSS and SF-36 questionnaires were administered pre-ablation, at 3 months, and at 12 months post-ablation. Our analyses include all patients with AF burden and completed questionnaires and those who had arrhythmia recurrence. With the two groups, we assessed the associations amongst AF burden, AFSS symptom severity score improvement, and SF-36 improvement through multiple linear regression analysis, controlling for possible confounders. Results: 507 persistent AF patients with a mean of 62 ±9 met our inclusion criteria. Patients submitted ECG strips on most days each month throughout the follow-up period, suggesting high compliance as shown. AFSS symptom score was 12±8 at baseline and improved by 7±8 points on average. AF burden was 19%±7 in the follow-up period. After controlling for age, sex, comorbidities, baseline AFSS score, and left atrial volume, AF burden was found to be inversely associated with AFSS symptom score improvement (beta=-5.201 p=&lt;0.001). This association was also significant in patients who recurred (Beta=-3.45 p=0.04). Similarly, AF burden was associated with improved functional status through SF-36 after ablation even after controlling for all the aforementioned factors including baseline SF-36(Beta= 20.641, p-value= &lt;0.001). These results highlight the importance of AF burden as a measure of treatment success compared to the binary outcome of recurrence. Conclusion: Smartphone-based AF burden adversely affects symptom severity and functional status improvement after ablation in persistent AF patients even in patients who had a recurrence, highlighting to need to incorporate it in our definition of ablation success.