tbuckley/cabot-search huggingface dataset:
Abstract P407: Decreased Peripheral Mitochondrial Respiration in Pre-Adolescent Hispanic Children With Hepatic Steatosis
Authors: Ana Ramirez Tovar, Cristian Sanchez Torres, Helaina Huneault, Zhulin He, Jean A Welsh, Miriam B Vos
Journal: Circulation (2024)

Introduction: Mitochondria plays a significant role in the functioning of the liver. Its function and structure have been associated with diseases outside the organelle by producing reactive oxygen species (ROS), causing generalized oxidative stress, improper function to several metabolic pathways, and perpetuating a pro-inflammatory state in conditions like obesity, diabetes, and metabolic dysfunction associated steatotic liver disease (MASLD). These diseases are on the rise and increase future atherosclerotic cardiovascular disease. Little is known regarding the pathophysiology of the earliest stages of hepatic steatosis, although mitochondrial dysfunction has been shown in later stages. In young children with and without MASLD, we aimed to measure mitochondrial respiration and compare it to hepatic steatosis and other cardiometabolic parameters. The hypothesis of the sub-study was that children with MASLD will have a decreased mitochondrial function compared with healthy children. Methods: We report data on 9 subjects, (all Latino subjects, mean age of 8.1 years, mean BMIp of 78%) who participated in screening for an ongoing clinical trial (ClinicalTrials No. NCT05292352). After consent and assent, procedures included drawing whole blood and transferring it immediately to the lab. Monocyte isolation was performed using RosetteSep™ Cocktail and measurement of fatty acid oxidation and glycolysis using the Seahorse Bioscience XFp extracellular flux analyzer. We measured the Oxygen Consumption Rate (OCR) as a proxy for mitochondrial respiration. Association with the mitochondrial parameters was evaluated with the percentage of hepatic steatosis (Hepafat), levels of ALT, insulin, and BMI percentile (BMIp). Data were analyzed using the R software program version 4.2.3 Results: Mean hepatic steatosis (HS) was 5.97% with a low of 2.4% and a high of 13%. The mean OCR for the subjects without MASLD (n=4, HS ≤5% by MRI) was 404.64 and the mean for subjects with MASLD (n=5, HS ≥5% by MRI) was 349.88. The mean OCR of subjects with a normal, overweight, and obese BMIp was 441.58, 397.45, 309.08, respectively. We found peripheral mitochondrial respiration tends to decrease as hepatic steatosis, BMIp, ALT and insulin levels increase. Conclusion: Hepatic steatosis is associated with decreased mitochondrial respiration and perhaps perpetuates an inflammatory state at very young ages in this vulnerable population. More subjects from the NAFLD prevention study will increase the significance of the study in the future.
Abstract P414: Serum Potassium Trajectories Among Chronic Kidney Disease Patients: The Chronic Renal Insufficiency Cohort Study
Authors: Jenilee Cueto, Andrei R Stefanescu, Hua He, Jing Chen, Morgan Grams, Amanda H Anderson, Jiang He, Katherine T Mills
Journal: Circulation (2024)

Background: Patients with chronic kidney disease (CKD) are at an increased risk for blood electrolyte imbalances and compromised cardiac and renal regulatory functions. Our objective is to characterize serum potassium trajectories in patients with CKD. Methods: Data from the Chronic Renal Insufficiency Cohort Study were used to analyze 5,625 participants with CKD. Serum potassium measurements were collected annually. Hyperkalemia was defined as &gt;5.0 mmol/L, hypokalemia as &lt;3.5 mmol/L, and normokalemia as 3.5 - 5.0 mmol/L. Trajectory analysis using a semiparametric modeling strategy was conducted, incorporating hierarchical modeling and latent class models. Group-based trajectory models were used to fit longitudinal data and estimate probabilities for multiple trajectories. Models were tested using a censored normal model with various numbers of trajectory groups and functional forms (e.g., linear, quadratic, cubic). Maximum likelihood was used to estimate model parameters and model fit was assessed by comparing Bayesian Information Criterion. Posterior predicted probabilities for each individual were estimated for each trajectory group and participants were assigned the highest posterior predicted probability. Results: Participants were 56% male, 43% Black, and had a median age of 67.0 years. Overall mean serum potassium was 4.3 mmol/L over 12 annual visits with a median follow-up of 9 years. Based on model fit and statistical significance, five distinct trajectory groups were identified (Figure). Four trajectories (one hyperkalemia and three normokalemia) were stable over time. One trajectory started in the normokalemia range and increased into hyperkalemia. Conclusions: Five trajectories of serum potassium were identified among CKD patients. Characterizing serum potassium trajectories over time can help to understand who may be at increased risk for abnormal potassium and related complications and potentially inform the development of interventions to maintain normokalemia in patients with CKD.
Abstract P527: Acculturation and Family History Are Associated With Sleep Disturbances in US Americans of South Asian Origin
Authors: Krish Vasudev, Eshaan Vasudev, Lisa Yanek, Dhananjay Vaidya
Journal: Circulation (2024)

Introduction: Sleep disorders are an important risk for cardiovascular disease. Although the effects of sleep-disordered breathing have been widely studied in general populations, there is a gap in understanding its prevalence and determinants among South Asians in the United States of America (US), a group with high risk of cardiometabolic disease that presents unique genetic burdens and acculturation issues. We examined the association of family history of sleep disturbances and acculturation in a survey of South Asian immigrants. Methods: We surveyed 105 US South Asian participants (20-75 years, 69% male, 92% born in South Asia) recruited at a community event. Respondents provided information on age, gender, acculturation (measured by the adoption of English spoken at home), and family history of severe snoring in first degree relatives. We used a modified Berlin Sleep Questionnaire, where the obesity criterion was replaced with current diabetes to identify persons with high-risk sleep disturbances and asked about severe snoring in first degree relatives to identify family history of sleep disturbances. We examined the association of high-risk sleep disturbances with family history and acculturation metrics using Chi-squared tests, followed by logistic regression analysis. Results: Of the 105 participants, 28 (26.7%) were identified as high-risk for sleep disturbances. Those at high risk had a median age of 61 years, significantly older than their low-risk counterparts (median age 53; p=0.015). Of the 55% individuals who were acculturated to now speak English at home, 34% had high risk sleep disturbances as compared to 17% with sleep disturbances among those that continued to speak their native non-English language (p=0.044). Of the 10% individuals whose siblings had severe snoring problems, 50% had high risk sleep disturbances vs. 24% in those without sibling history (p = 0.079). In logistic regression models adjusting for age and gender, both sibling history (Odds Ratio 4.6, 95% CI 1.0 to 20.3, p = 0.047) and acculturation (Odds Ratio 3.0, 95% CI 1.1 to 8.6, p = 0.037) were associated with high-risk sleep disturbances. Conclusions: Acculturation as measured by adoption of English as the home language and family history of severe snoring are both associated with sleep disturbances among US South Asians in. Healthcare providers should be especially vigilant for sleep disorders in acculturated South Asian patients and those with such family and social history. Further studies are needed to understand the relationships between genetic predispositions, acculturation, and environmental factors in this population.
Abstract P175: Total Fasting and Post-Load and Individual Fasting Non-Esterified Fatty Acids and Total and Cause-Specific Mortality: The Cardiovascular Health Study
Authors: Yakubu Bene-Alhasan, Sanyog G Shitole, Nirupa R Matthan, Alice H Lichtenstein, Joachim H Ix, Petra Buzkova, Calvin Hirsch, David S Siscovick, JORGE R KIZER, Luc Djousse, Ken J Mukamal
Journal: Circulation (2024)

Background: Total fasting non-esterified fatty acid (NEFA) levels have been associated with total and cause-specific mortality in older adults, but the corresponding associations with NEFA levels following the metabolic challenge of an oral glucose tolerance test (OGTT) and with individual fasting NEFA species have not been quantified Methods: We studied 1996 participants from the Cardiovascular Health Study with a mean age of 78 years who had total serum NEFA measured enzymatically before and two hours after an OGTT and fasting individual NEFA measured using gas chromatography in samples collected in 1996-1997. 1678 participants died over a median follow-up of 11 years. Multivariable Cox proportional hazard models were used to evaluate adjusted hazard ratios (aHR) for mortality associated with standard deviation increments of fasting and post-load total NEFA and fasting individual and subclasses (saturated, monounsaturated, n-3 and n-6 polyunsaturated, and trans) Results: Fasting NEFA were associated with an increased risk of all-cause mortality (aHR 1.17, 95% CI 1.10 - 1.23). In contrast, levels of post-load NEFA were not associated with mortality (aHR 0.98, 95% CI 0.93 - 1.03). Among NEFA subclasses, only monounsaturated fatty acid (MUFA) were associated with total mortality (aHR 1.24, 95% CI 1.09 - 1.41). In cause-specific analyses, MUFA were associated with higher risk of death from dementia, cardiovascular, respiratory, infectious and kidney disease. For individual NEFAs, nervonic acid (aHR 1.06, 95% CI 1.01 - 1.12) and petroselaidic acid (aHR 1.21, 95% CI 1.03 - 1.42) were associated with higher risk of all-cause mortality whereas eicosapentaenoic acid (aHR 0.90, 95% CI 0.82 - 0.99) was associated with lower risk Conclusion: Among community-dwelling older adults, total fasting but not post-load NEFA were associated with higher risk of death. Among subclasses and individual species, MUFA, nervonic, and petroselaidic acids were associated with higher risk, and eicosapentanoic acid with lower risk, of mortality.
Abstract P299: Alteration of Cardiac Autonomic Function Through Inhalation of Biogenic Volatile Organic Compounds
Authors: Cameron K Stopforth, Jacqueline Gallagher, Aruni Bhatnagar, Rachel J Keith
Journal: Circulation (2024)

Background: There is an inverse relationship between exposure to greenspaces and prevalence of cardiovascular disease and cardiovascular disease risk factors. More specifically, green exposure is associated with electrocardiogram (ECG) changes, suggesting a potential alteration of cardiac autonomic balance. One proposed mechanism by which cardiac autonomic balance may be altered is a direct physiologic effect of inhalable plant derived compounds, or biogenic volatile organic compounds (bVOCs), including limonene, α- and β-pinene which are commonly released from vegetation. Therefore, we examined the relationship between acute exposure of isolated bVOCs and cardiac autonomic tone. Hypothesis: We hypothesize that controlled exposure to isolated individual bVOCs will decrease cardiac sympathetic tone. Methods: Under controlled conditions after a bVOC washout period, healthy adults ages 18-70 were exposed to limonene (n=32), α-pinene (n=24), β-pinene (n=17), and a control (room air, n=9). Exposure consisted of one inhalation every 30 seconds for a total of 5 minutes (10 inhalations total). Pre- and post-exposure measurements of supine heart rate variability (HRV) were conducted following a 10-minute rest period. HRV was analyzed using a clean, 5-minute epoch with &gt;95% effective data length. Statistical analysis was performed using paired t-tests to determine changes in HR and HRV. Significance level was set at p&lt;0.05, a priori . Results: Our population was primarily female (56%, 18 of 32), white (53%, 17 of 32), high income (47%, 15 of 32), and had an education higher than a 4-year degree (62.5%, 20 of 32). There were significant decreases in HR when exposed to limonene (pre: 64.87±9.86bpm vs. post: 63.26±9.10bpm, p&lt;.001) and α-pinene (pre: 63.98±9.32bpm vs. post: 61.64±9.72bpm, p=.008), along with trends seen in β-pinene (pre: 65.78±10.60bpm vs. post: 63.74±9.65bpm, p=.066). Control exposure showed no difference (pre: 65.40±8.38bpm vs. post: 64.14±9.35bpm, p=.301). Normalized low- (LF) and high-frequency (HF) HRV parameters showed no change across isolated bVOCs, however the LF/HF ratio scores decreased significantly following β-pinene exposure (pre: 1.62±1.69 vs. post: 0.96±0.96, p=.039). HRV time-domain parameters RMSSD and SDNN did not change following isolate exposure. Conclusions: Post-exposure decreases in HR and LFHF ratios indicate the potential for cardiovascular disease risk reduction from bVOC exposure leading to decreased sympathetic tone. Additional work is required to determine the mechanism of exposure-related changes.
Abstract P524: Prolonged Mild Sleep Restriction Results in Specific Alterations in Genome-Wide DNA Methylation: A Randomized Crossover Trial
Authors: Rocio Barragan, Oscar Coltell, Christian Dye, Bin Cheng, Lawrence Honig, Dolores Corella, Marie-Pierre St-Onge
Journal: Circulation (2024)

Introduction: Short sleep duration is associated with increased cardiometabolic risk. DNA methylation plays a critical role in the regulation of gene expression and studies suggest that sleep deprivation may alter DNA-methylation patterns. However, most findings are from acute sleep deprivation or short duration studies. Hypothesis: Prolonged sleep restriction study that mimics real-life situations is associated with differentially methylated CpG loci (DML) in the core clock candidate genes and across the epigenome in an epigenome-wide association study (EWAS) Methods: Sixty participants (65% women) aged 21-73 y were included in randomized crossover studies with 2 phases of 6 weeks each. Phases differed in sleep duration: either adequate sleep (AS; sleep ≥7h/night) or sleep restriction (SR; -1.5h/night relative to AS). DNA was isolated from whole blood at wk 0 and wk 6 of each phase. DNA methylation (DNAm) was quantified the Illumina Infinium MethylationEPIC BeadChip array v.2.0 (&gt;900K methylation sites) and Partek Genomic Suite v.720.0831. After quality control and normalization, several global and stratified EWASs were performed to test the impact of sleep condition on DNAm. Analyses were adjusted for week, phase, sex, age, BMI and cell type composition. We also focused on methylation changes of the selected core-clock candidate genes ( RORA, CRY1, NR1D2, TIMELESS, NPAS2, NFIL3, RORB, PER3, CSNK1E, ARNTL2, CRY2, CLOCK, ARNTL, RORC, PER2, BHLHE40, NR1D1, CSNK1D, BHLHE41 and PER1 ). Results: In the candidate gene approach, we detected several significant DML. Top-ranked DML in selected core clock genes with significant interactions between condition and time were: cg02394126 at ARNTL (p&lt;0.001), cg23506964 at CLOCK (p=0.001), cg03701037 at NPAS2 (p=0.009), cg06606972 at NPAS2 (p=0.009), and cg13576304 at RORA (p=0.008). Hypermethylation was primarily observed after 6 wk of SR vs AS for cg02394126, cg23506964, cg03701037, and cg06606972, while hypomethylation was observed cg13576304 ( RORA ). In our EWAS, we detected some suggestive significant condition x time interactions in cg23738833 at SNHG3-RCC1 (p=1,34E-06), cg13280380 in the FAF1 gene (p=2,25E-05), cg03179866 in the MMP12 gene (p=2,78E-05), and cg13063696 (p=3,21E-05). All but cg23738833 ( SNHG3-RCC1 ) showed hypermethylation after 6 wk of SR vs AS. Conclusion: Six weeks of mild SR was associated with changes in DNAm in core-clock candidate genes and in other genes in the EWAS. However, further studies are needed to confirm these findings and determine the functional pathways.
Abstract P421: Smoking Timing, Healthy Diet, and Risk of Incident CKD Among Smokers: A Cohort Study in UK Biobank
Authors: Rui Tang, Ying Hu, Jian Zhou, Xuan Wang, Xiang Li, Yoriko Heianza, Lu Qi
Journal: Circulation (2024)

Introduction: While smoking is a recognized risk factor for chronic kidney disease (CKD), the relationship between the smoking timing and CKD remains largely unstudied. Hypothesis: We assessed the hypothesis that there is an association between the smoking timing and the risk of CKD. Method: A total of 32,776 participants with complete data on the time from waking to the first cigarette and free of prevalent CKD from UK Biobank were included in this prospective study. The Cox proportional hazard model was used to investigate the associations between smoking timing and risk of CKD. The potential interactions of smoking timing with risk factors in relation to CKD risk were assessed on both multiplicative and additive scales. Results: During a median follow-up of 12 years, 940 incident CKD cases were reported. Shorter time from waking to the first cigarette was significantly associated with a higher risk of incident CKD ( P -trend=0.012). The adjusted hazard ratio (HR) associated with smoking timing was 1.28 (95% CI: 0.92-1.80) for 61-120 minutes, 1.48 (95% CI: 1.11-1.96) for 30-60 minutes, 1.36 (95% CI: 1.01-1.88) for 5-15 minutes, and 1.70 (95% CI: 1.22-2.37) for &lt;5 minutes, respectively. Those who smoke within 5 minutes of waking had a 70% increased risk of CKD incident compared to those who delayed for over 120 minutes. Furthermore, there was a significant positive additive interaction between the timing of smoking and a healthy diet score ( P for additive interaction=0.01). Conclusion: Our findings indicate a significant association between the shorter time from waking to the first cigarette and a higher CKD risk; and the associations are exacerbated in the presence of an unhealthy diet.
Abstract P196: The Effects of Initiating a 24-hour Fast With a Low versus a High Carbohydrate Protein Shake on Heart Rate Variability in the Elderly
Authors: Landon Deru, Elizabeth Gipson, Katelynn Hales, Bruce Bailey
Journal: Circulation (2024)

Introduction: While multiple studies demonstrate the potential cardiovascular benefits of fasting, the effects of the fast-initiating meal have not been evaluated. The aim of this secondary analysis was to examine the effects of the macronutrient composition of a fast-initiating meal on the autonomic nervous system through measurements of heart rate variability (HRV) in older, sedentary adults with abdominal obesity. Methods: Using a crossover design, each of the 24 participants (13 male, 11 female) completed two 24-hour fasts (8:00 am to 8:00 am) separated by 6-10 days. Participants were 59.54 ± 6.67 years old and had a body mass index of 31.59 ± 5.59 kg/m 2 . Each fast was initiated with either a low carbohydrate protein shake or an isocaloric and isovolumetric high carbohydrate protein shake (592.13 ± 104.57 kcal). Heart rate variability was measured for 10 minutes immediately prior to, one hour after, and then 24 hours after shake consumption. Results: A mixed effects model with repeated measures was used to assess the effects of the fasting conditions on various HRV outcomes. The sympathetic (SNS) index increased significantly over the time of each fast (p = 0.0033), but was not different between conditions (p = 0.7229). The parasympathetic PNS index experienced no change over time (p = 0.1521) and no change between conditions (p = 0.8961). The stress index increased over time (p = 0.0021), but was not different between conditions (p = 0.7308). There was no difference in standard deviation of the normal-to-normal interval (SDNN) or root mean square of successive difference (RMSSD) over time (p = 0.2022 and p = 0.2770, respectively) or between condition (p = 0.9054 and p = 0.9857, respectively). The High Frequency (HF) reading was elevated in the high-carbohydrate condition compared to the low-carbohydrate condition (p &lt; 0.0001), and the low frequency to high frequency (LF/HF) ratio showed no difference between conditions (p = 0.3460), but increased over time (p = 0.0044) and demonstrated a time by condition interaction (p = 0.0089). Conclusions: Acute fasting places strain on the cardiometabolic systems as evident by the increased SNS index and stress index as well as the increase in LF/HF ratio over the course of both fasts. A low carbohydrate shake reduced HF readings, indicating more anxiety or panic in this condition. These results agree with previous works and are unique in demonstrating that most HRV parameters are neither strengthened nor weakened by the composition of the pre-fast meal.
Abstract P405: Calibrating Routine Blood Pressures Among Preterm Infants: A Retrospective, Cross-Sectional Analysis
Authors: Matthew S Loop, Jieun Park
Journal: Circulation (2024)

Background: Among preterm infants (&lt; 12 months postnatal age and born &lt; 37 weeks gestation), oscillometric systolic blood pressure (SBP) measurements are error-prone. However, some preterm infants have “gold standard” SBPs measured using an arterial line, in addition to the error-prone oscillometric SBPs. Objective: To compare different statistical methods to calibrate oscillometric SBPs to mimic arterial line SBPs Methods: We sampled participants from an existing pilot study of preterm infants treated with an antihypertensive therapy at the University of Alabama at Birmingham. Participants' data was obtained from the hospital's data warehouse for electronic medical records. Participants for this analysis had at least one arterial line SBP measurement, and for each of these "gold standard" measurements we identified the closest paired oscillometric SBP measurement (&lt;10 minutes apart). We also collected participant factors such as race (white vs. black/African American), gender, gestational age at birth (weeks), postnatal age at arterial line SBP measurement (weeks), and whether the participant had received an antihypertensive medication. We predicted the arterial line SBPs from oscillometric SBPs and covariates using linear regression, linear regression with restricted cubic splines, random forest, and Bayesian additive regression trees (BART). Prediction errors were calculated using 10-fold cross-validation. We used complete case analysis. Results: We identified 822 measurements among 28 participants. Ten of 28 (36%) participants were black and 13 of 28 (46%) were female. The median (Q1, Q3) gestational age at birth was 33 (29, 35) weeks. The root mean squared error for predicting arterial line SBP from oscillometric SBP by itself was 17.1 mmHg. The root mean squared error of the predicted arterial line SPBs from different statistical methods varied little from the most error (linear regression with restricted cubic splines: 13.5 mmHg) to the least error (BART: 12.6 mmHg), meaning that any calibration resulted in at least a 21% reduction in error compared to the oscillometric SBPs. BART tended to underpredict the arterial line SBPs that were above 100 mmHg. Conclusions: Among preterm infants, statistical calibration is a viable strategy for reducing the variability of error-prone oscillometric SBPs. The different statistical models performed similarly in this small pilot study, but a larger sample size using additional important variables (e.g., birth weight) is required to confirm this finding.