tbuckley/cabot-search huggingface dataset:
Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio—Experience from the Swedish AMORIS cohort: A cohort study
Authors: Göran Walldius, Ulf de Faire, Lars Alfredsson, Karin Leander, Peter Westerholm, Håkan Malmström, Torbjörn Ivert, Niklas Hammar
Journal: PLoS Medicine (2021)

Background Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop. Methods and findings In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25–84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan–Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case–control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study. Conclusions An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines.
Abstract 11414: Transplantation of Epididymal Adipose Tissue from Mice with Myeloid Deletion of RAGE Induces Insulin Resistance in Wild-Type Mice
Authors: Lakshmi Arivazhagan, Robin Wilson, Henry Ruiz, Ravichandran Ramasamy, Ann Marie Schmidt
Journal: Circulation (2021)

Introduction: Obesity is a major global health problem and often associated with insulin resistance (IR). Our previous work showed that global and adipose tissue specific Ager deletion provide protection from HFD induced weight gain and insulin resistance. We identified that myeloid-specific of Ager deletetion (MDR) further impairs insulin sensitivity in mice fed HFD without further increasing body weight vs. control animals. These effects of myeloid Ager deletion were reversed upon simultaneous deletion of adipocyte Ager in HFD feeding. In parallel, the expression of inflammatory genes was significantly higher in the epididymal adipose tissue (eWAT) of MDR vs. all other mice groups. We tested the hypothesis that eWAT-borne factors from mice bearing myeloid Ager deletion induce IR upon transplantation to wild-type mice fed low fat chow. Methods: We generated mice with myeloid-specific (MDR) LyzMCre(+/+).Ager flox/flox and adipocyte and myeloid-specific (Double Knockouts (KO)) AdipoQCre(-/+)LyzMCre(+/+).Ager flox/flox deletion of Ager and LysMCre mice (Cre control) were used as control. Mice were fed HFD (60% kcal/fat) for 3 months starting at age 6 weeks. Mice were assessed for body mass and glucose and insulin sensitivities. After 12 weeks of HFD feeding, eWAT from these HFD fed mice was transplanted into C57BL/6 (WT) mice. The transplanted recipient mice were maintained on a low fat diet and their body mass, blood glucose and insulin sensitivity were monitored. Results: 6 weeks after eWAT transplantation into WT mice, only the WT low fat diet-fed recipients of MDR eWAT displayed IR in comparison to recipients of Cre control or Double KO eWAT. Despite no difference in the body weight, native eWAT adipocyte size was significantly higher in the recipients of MDR eWAT vs. all other groups. Differences in F4/80-positive crown like structures were also observed in native recipient eWAT, which might underlie mechanisms of IR. Conclusion: Transplantation of eWAT from mice devoid of myeloid Ager and previously fed HFD confers IR to low fat diet WT mice. The molecular mechanisms mediating these effects are under investigation.
Abstract 11661: Associations of Macronutrient and Sodium Intake With Cardiac Structure and Function in the Hispanic Community Health Study/Study of Latinos
Authors: David Flomenbaum, Ayana April-Sanders, Un Jung Lee, Robert Kaplan, Yasmin Mossavar-Rahmani, Robert Ostfeld, Daniela Sotres-Alvarez, Josiemer Mattei, Martha L Daviglus, Mayank M Kansal, Amanda McClain, Barry E Hurwitz, Bonnie Shook-Sa, Carlos Rodriguez
Journal: Circulation (2021)

Introduction: Dietary macronutrient balance and reduced sodium intake are key modifiable risk factors for prevention of cardiovascular disease. Pre-heart failure (HF) (evidence of structural heart disease or abnormal cardiac function) is an independent risk factor for incident clinical HF development. We assessed associations of macronutrient and sodium intake with cardiac structure and function from the Echocardiographic Study of Latinos (Echo-SOL), an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hypothesis: We hypothesized that higher intake of protein and lower intake of fat, carbohydrate and sodium would be associated with healthier cardiac structure and function. Methods: Cross-sectional data from HCHS/SOL interviews were analyzed among 1818 adults (57% female, mean age 56 ± 0.17) with complete echo assessments. Intake of carbohydrates, proteins, fats, and sodium in relation to total caloric intake was derived from two 24-hour recalls. Associations between nutrients and pre-HF outcomes were estimated via simple linear regression as well as ANOVA across quintiles of each nutrient. All analyses were weighted and account for complex survey design. Results: Mean ± SE macronutrient intake for the overall target population was 52.3 ± 0.1% carbohydrates, 17.1 ± 0.05% protein, and 29.7 ± 0.1% fat. Mean dietary sodium intake was 3,107.2 ± 47.7mg. Higher percent of total daily calories from carbohydrates was associated with lower LV mass (-13.7g per 5%, p&lt;0.01) and lower e’ velocity (-0.37cm/s per 5%, p&lt;0.01). Higher fat consumption was associated with higher LV mass (11.23g per 5%, p&lt;0.01). No significant associations were seen with protein intake. Higher sodium intake was associated with higher LV mass (1.35g per 100mg, p&lt;0.01) and lower ejection fraction (-0.091% per 100mg, p&lt;0.01). Quintile analysis confirmed the presence and monotonicity of the observed associations. Conclusions: Our results suggest that a macronutrient balance favoring higher carbohydrate and lower fat consumption along with reduced sodium intake is associated with better cardiac structure and function. These findings have important implications for HF prevention. Future studies should explore the role of specific nutrient types.
Abstract 11846: Excess Healthcare Costs and Bed Days Associated With Complications Following Catheter Ablation of Atrial Fibrillation
Authors: Linh T Ngo, Anand N Ganesan, Billingsley Kaambwa, Richard Woodman, Karen Hay, Isuru Ranasinghe
Journal: Circulation (2021)

Background: Complications following catheter ablation of atrial fibrillation (AF) have been extensively examined but little is known about their associated economic burden. Hypothesis: Complications of AF ablations were associated with a significant increase in healthcare resources utilization. Methods: All patients &gt;18 years undergoing AF ablations in the financial years of 2011-2017 in Australia with available cost data from the National Hospital Cost Data Collection were included. The primary outcome was occurrence of any complications up to 30-days post-discharge. All costs were adjusted to 2021 Australian dollars. The increase in length of stay (LOS) and in cost associated with complications, adjusting for patient characteristics, was evaluated using generalized linear models and negative binomial regression. Results: Our study included 19,916 patients (mean age 62.6±11.3 years, 30.2% females). The median length of stay was 1 day (interquartile range [IQR] 1-2 days) and the median cost per hospitalization was $6,646.5 (IQR $5,979.7-$10,210.5). A total of 1,074 patients (5.39%) experienced a complication (4.24% during the hospital stay and 1.37% post-discharge). The most common complications were bleeding (3.18%), pericardial effusion (0.66%), and vascular injury (0.43%). On average, the occurrence of a complication was associated with 2.8 excess bed-days and a $6,119.4 (95%CI $5,491.2-$6,747.7) increase in hospitalization cost (totaling nearly $6.6 millions). Complications that required cardiac surgery were associated with the highest incremental cost per patient ($19,958.5 [95%CI $17,304.5-$22,612.6]) but most of excess cost was attributable to bleeding ($4,808.5 per patient, $3,048,596.1 in total, 44.4% of total excess cost) and pericardial effusion ($6,064.8 per patient, $1,073,094.9 in total, 16.3% of total excess cost). Conclusions: The occurrence of any complication following AF ablation is associated with a significant economic burden, most of which was attributable to bleeding and pericardial effusion. Strategies to improve procedural safety and reduce healthcare cost should focus on these complications.
Abstract 11487: Individualizing the Cardiovascular Benefits of Intensive Blood Pressure Reduction Using Computational Phenomaps of the SPRINT and ACCORD Trials
Authors: Evangelos K Oikonomou, Marc Suchard, Rohan Khera
Journal: Circulation (2021)

Introduction: Intensive systolic blood pressure (SBP) control reduces major adverse cardiovascular events (MACE) in patients without type 2 diabetes mellitus (T2DM). However, these benefits are less clear in T2DM. We evaluated an application of machine learning to clinical trials of patients without and with T2DM in assessing a personalized cardiovascular benefit of intensive SBP control. Methods: In SPRINT, a trial of intensive (n=4678, SBP&lt;120 mmHg) versus standard (n=4683, SBP&lt;140 mmHg) SBP control in 9361 patients without T2DM, we created a topological representation of the trial patients using 59 baseline variables (trial phenomaps). Within each patient’s 5% topological neighborhood, we calculated hazard ratios (HR) for recurrent MACE (cardiovascular death, acute coronary syndrome, stroke, acute decompensated heart failure). We trained an extreme gradient boosting algorithm to predict the personalized effects of intensive SBP control using features linked to topological benefit. We then tested this machine learning tool in the ACCORD BP trial of patients with T2DM (n=2362 &amp; 2371 in the intensive and standard arms respectively). Results: In SPRINT (age 68±9 years, 36% women) there were a total of 1046 recurrent MACE endpoints. The median individual patient HR was 0.58 [IQR, 0.38-0.82] ( A ). We developed a 10-variable tool in SPRINT ( B ) and subsequently tested in ACCORD BP (age 63±7 years, 48% women) where it identified individual patients with a higher benefit with intensive vs standard SBP control (adj. HR for time-to-MACE 0.77 [95% CI 0.61-0.98] in individuals with above median predicted benefit [high responders] ( C ) vs 0.97 [95% CI 0.77-1.23] ( D ) for below median predicted benefit [low responders]). Conclusions: We present a clinical trial-based, machine learning tool that identifies an individual’s personalized benefit from intensive versus standard SBP goals in patients with and without T2DM and may be used to guide clinical decision-making.
Abstract 6961: Anesthetic Management During Pre-Stage II Intracardiac Hemodynamic Assessment: An Analysis of the Single Ventricle Reconstruction Trial Dataset
Authors: Andrew H Smith, Steven Healan, George Nicholson, Fred S Lamb
Journal: Circulation (2021)

Background: Intracardiac hemodynamics are often obtained with cardiac catheterization prior to proceeding with Stage II palliation for infants with single ventricle anatomy. There is little data examining the hemodynamic impact of anesthetic strategy during catheterization. Methods: Data from the Pediatric Heart Network Single Ventricle Reconstruction Trial was used for analysis. In addition to anesthetic strategy, data reported from cardiac catheterization prior to Stage II palliation included mean systemic venous atrial pressure (MSVAP), end diastolic ventricular pressure (EDVP), pulmonary flow (Q p )/systemic flow (Q s ) ratio, and indexed pulmonary vascular resistance (PVRi). Indexed systemic vascular resistance (SVRi), Q p , and Q s were calculated using available hemodynamic data. Results: Of 549 subjects, pre-Stage II cardiac catheterization data following palliation with a modified Blalock-Taussig-Thomas shunt (mBTTS) or right ventricle to pulmonary artery conduit (RV2PA) was available for 390, of which 219 had adequate hemodynamic data for inclusion in analysis. Intracardiac hemodynamic comparisons were made with respect to anesthetic approach and shunt type. Moderate sedation was utilized in 90 (41%) and general anesthesia in the remaining 129 subjects. A moderate sedation strategy was associated with significantly higher Q p /Q s (1.2 [0.9, 1.6] v. 1.0 [0.7, 1.3], p&lt;0.001) and estimated SVRi (15 Wu•m 2 [11,19] v. 10 [7.8,15], p&lt;0.001), a difference consistent among both mBTTS and RV2PA subgroups. There were no differences between anesthetic groups with respect to PVRi or calculated Q s in either shunt group. Independent of shunt type, PVRi, and patient weight at catheterization, moderate sedation at catheterization was associated with a two-fold odds of a reported Q p /Q s &gt;1 (OR 2.03, 95%CI 1.13-3.63, p=0.017). Conclusions: Anesthetic strategy and alterations in SVRi represent an important consideration when evaluating hemodynamics in a shunt dependent single ventricle circulation. Future investigations may aid in understanding the relationship between anesthetic approach during catheterization and the resulting hemodynamic data employed in perioperative decision-making.
Mapping the Food Allergy Quality of Life Questionnaire Parent Form onto the Short‐Form Six‐Dimensions version 2
Authors: Yan Watts, Élise Dufresne, Kathryn Samaan, François Graham, Roxane Labrosse, Louis Paradis, Anne Des Roches, Thomas G. Poder, Philippe Bégin
Journal: Allergy (2021)

The Food Allergy Quality of Life Questionnaire Parent Form (FAQLQ-PF) is the most widely used quality of life questionnaire in food allergy. The objective of this study was to develop a mapping algorithm to convert FAQLQ-PF scores into health state utilities.The Short-Form Six-Dimensions version 2 (SF-6Dv2) and FAQLQ-PF questionnaires were collected from an academic center oral immunotherapy referral cohort. Utility estimates were derived from the SF-6Dv2 using the food allergy preference set. Candidate mapping algorithm models were developed using seven regression methods starting from either the total average score, the average scores of each of the three domains or the individual item scores of FAQLQ-PF. The process was repeated twice, including only section A, common to all age groups, or including all age-applicable sections of the FAQLQ-PF. The mean absolute error (MAE) and root mean squared error (RMSE) were used to select the best fitting model. An independent cohort from a previous national online survey was used for external validation.In the index cohort, 1000 of 1257 respondents had completed both questionnaires. The lowest MAE (0.0791) and RMSE (0.1020) were recorded when entering individual item scores in a categorical regression model. The model including only FAQLQ-PF section A was found to be most consistent when tested in the external validation cohort (n = 248) (MAE of 0.0898).The FAQLQ-PF was mapped onto SF-6Dv2 utilities with good predictive accuracy in two independent cohorts. This will enable calculation of health utility for cost-effectiveness analyses in food allergy.
Abstract 12079: Demographic and State-Level Trends in Mortality Due to Ischemic Heart Disease in the United States From 1999 to 2019
Authors: Mohammed Essa, Alireza Ghajar, Augustin DeLago, Matthew Hammond-Haley, Joseph Shalhoub, Dominic Marshall, Justin Salciccioli, Lissa Sugeng, Harlan M Krumholz, Binu Philips, Kamil Faridi
Journal: Circulation (2021)

Introduction: Mortality from ischemic heart disease (IHD) in the United States (U.S.) has decreased recently, yet variation in IHD-related mortality trends for different demographic across U.S. states is not well described. Hypothesis: IHD mortality differs based on geography, gender, ethnicity, and race. Methods: We performed analysis using CDC WONDER database to evaluate IHD mortality trends in the U.S. between 1999 and 2019. Age-adjusted mortality rates (AAMR) per 100,000 people were evaluated and stratified by sex, race, and state. Joinpoint regression was used to assess annual rates of change in IHD-related mortality. Results: From 1999 to 2019, AAMR due to IHD decreased from 194.6/100,000 to 88.0/100,000 nationally. Black men had the highest AAMR, and Hispanic white women had the lowest AAMR throughout this period. AAMR for white men decreased nationally by 51.4% from 251.2 to 122.1; 59.1% for white women from 150.5 to 61.5; 51.8% for black men from 278.7 to 134.2; 59.9% for black women from 188 to 75.4; 54.3% for Hispanic men from 200.1 to 91.4; and 63.1% for Hispanic women from 133.1 to 49.0 (Figure). Relative decreases in AAMR across states ranged from 27.0%-70.9% for white men, 30.9%-68.9% for white women, 7.3%-80.9% for black men, 27.2%-74.7% for black women, 30.5%-79.8% for Hispanic men, and 35.8%-76.8% for Hispanic women. Based on the regression model, the annual average percent decline in IHD-related AAMR for all groups has decreased since 2011 (Figure). Conclusions: AAMR due to IHD in the U.S. has decreased from 1999 to 2019 for all demographic groups, though the rate of decline has lessened since 2011. There is significant geographic variation in reductions of IHD-related AAMR across U.S. states. These findings indicate that race, ethnicity, and geography are strongly associated with trends in mortality due to IHD. Given the ongoing disparities in mortality, further investigation into geographic differences in prevention and treatment of IHD is needed.
Integration of Targeted Gene Expression Profiling and FDG-PET Radiomics Uncovers Radiometabolic Signatures Associated with Outcome in Diffuse Large B-Cell Lymphoma
Authors: Saveria Mazzara, Laura L. Travaini, Francesca Botta, Chiara Granata, Giovanna Motta, Federica Melle, Stefano Fiori, Valentina Tabanelli, Anna Vanazzi, Safaa M. Ramadan, Tommaso Radice, Sara Raimondi, Giuliana Lo Presti, Mahila E. Ferrari, Marta Cremonesi, Francesco Ceci, Corrado Tarella, Stefano A Pileri, Enrico Derenzini
Journal: Blood (2021)
Comorbid insomnia and sleep apnoea is associated with all-cause mortality
Authors: Bastien Lechat, Sarah Appleton, Yohannes Adama Melaku, Kristy Hansen, R. Doug McEvoy, Robert Adams, Peter Catcheside, Leon Lack, Danny J. Eckert, Alexander Sweetman
Journal: European Respiratory Journal (2021)

Background Increased mortality has been reported in people with insomnia and in those with obstructive sleep apnoea (OSA). However, these conditions commonly co-occur and the combined effect of comorbid insomnia and sleep apnoea (COMISA) on mortality risk is unknown. This study used Sleep Heart Health Study (SHHS) data to assess associations between COMISA and all-cause mortality risk. Methods Insomnia was defined as difficulties falling asleep, maintaining sleep and/or early morning awakenings from sleep ≥16 times per month, and daytime impairments. OSA was defined as an apnoea–hypopnoea index ≥15 events·h −1 . COMISA was defined if both conditions were present. Multivariable adjusted Cox proportional hazards models were used to determine the association between COMISA and all-cause mortality (n=1210) over 15 years of follow-up. Results 5236 participants were included. 2708 (52%) did not have insomnia/OSA (reference group), 170 (3%) had insomnia-alone, 2221 (42%) had OSA-alone and 137 (3%) had COMISA. COMISA participants had a higher prevalence of hypertension (OR 2.00, 95% CI 1.39–2.90) and cardiovascular disease (CVD) (OR 1.70, 95% CI 1.11–2.61) compared with the reference group. Insomnia-alone and OSA-alone were associated with higher risk of hypertension but not CVD compared with the reference group. Compared with the reference group, COMISA was associated with a 47% (hazard ratio 1.47, 95% CI 1.06–2.07) increased risk of mortality. The association between COMISA and mortality was consistent across multiple definitions of OSA and insomnia. Conclusions COMISA was associated with higher rates of hypertension and CVD at baseline, and an increased risk of all-cause mortality compared with no insomnia/OSA.
Induction of the p51/p63 gene expression in mouse tissues by administration of cisplatin
Authors: Ken-Ichi Aisaki, Iyoko Katoh, Yoshiya Tomimori, Takeshi Okuyama, Shun-Ichi Kurata, Jun Kanno, Yoji Ikawa
Journal: Cancer Research (2004)

2546  The transactivator proteins encoded by the members of p53 gene family are alleviated by DNA damage through post-transcriptional regulation. Since p53, p51/p63 and p73 share the PuPuPuC(A/T)(A/T)GPyPyPy target sequences, many of the p53-regulated genes are also sensitive to p51/p63 and p73. Interestingly, the transcriptional control region of p51/p63 contains a p53-binding sequence. As reported recently, p51/p63 gene expression is induced by p53 in cell lines. To analyze the transcriptional activation of the p53 family members and their target genes by genotoxic stress in vivo, 12-week-old male C57BL/6 mice (three mice per group) were given cisplatin of 0, 5, 15, and 50mg/kg in corn oil containing 10% of DMSO by gavage (10ml/kgbw). At 2, 4, 8 and 24 hours after administration, liver (tissue blocks) and colon epithelium (mechanically striped off with care) were sampled for transcriptome analysis using Affymetrix GeneChip Mouse Expression Array 430A (22690 probe sets). The gene expression data were processed with our original absolutization system including original unsupervised clustering algorisms to elucidate gene responses in time and dose dependent manner. Results indicate that the levels of p51/p63 and p73 mRNAs were elevated significantly in liver 24 h after the drug administration, whereas p53 expression was kept constant. Upregulation of p53(p51/p63)-responsive genes including p21waf1 and Gadd45 was also detectable. These results suggest that in vivo genotoxic stress responses involve cooperative actions of p53 with the sister molecules. Furthermore, we cloned the p51/p63 TA and ΔN promoter regions to analyze their responsiveness to DNA damage in culture. Results of reporter gene expression assays in combination with DNA-damaging drugs supported our speculation.