tbuckley/cabot-search huggingface dataset:
Abstract P262: Atherosclerotic Cardiovascular Disease Risk in Hispanic United States Veterans
Authors: Yuk-Lam Ho, David R Gagnon, Yojin Park, Ashley Galloway, Kelly Cho, Peter W Wilson
Journal: Circulation (2020)

Background: Atherosclerotic cardiovascular disease (ASCVD) incidence is greater in Hispanic population. Traditional 2013 Pooled Cohort Equation (PCE) models tend to over-predict risks among Veterans by two-fold. Assessment of ASCVD risk with statin therapy has not been extensively investigated in Hispanic Veterans. Objective: We compared 5-year ASCVD incidence of White Hispanic vs White Non-Hispanic Veterans, 18-79 years at baseline in a cohort during 2002-2014. Methods: Ethnicity was determined from census and electronic health data where a Veteran’s last name has a 0.76 positive predictive value for Hispanic ethnicity. We used sex and ethnicity specific Cox models to predict 5-year ASCVD morbidity and mortality. The analyses included PCE variables (age, cholesterol, HDL-C, systolic pressure, blood pressure treatment, smoking, diabetes) plus statin use. Results: A total of 1,383,993 Veterans were in our study with 69,055 (4.9%) females and 81,773 (5.9%) Hispanics. Mean age, cholesterol and HDL-C levels were similar for Hispanics and Non-Hispanics. Smoking, BP therapy, and statin use were less common in Hispanics. Over 5 years of follow-up, 3.9% of Hispanic and 4% of Non-Hispanics developed ASCVD, and 1.3% of Hispanics and 2% of Non-Hispanics experienced ASCVD death. Discrimination of ASCVD events was improved by retraining prediction models using traditional ASCVD risk factors and statin use, with the following concordance statistics: Male Hispanic (0.73), Male Non-Hispanic (0.66), Female Hispanic (0.80), Female Non-Hispanic (0.79). Statin use was associated with a 17% lower ASCVD risk in Hispanics of both sexes and 9% lower ASCVD risk for Non-Hispanics of both sexes. Conclusions and Relevance: Traditional variables plus statin use are efficient predictors of ASCVD morbidity and mortality in a contemporary cohort of Hispanic U.S. Veterans. Baseline statin use was associated with lower risk of ASCVD events in Hispanics compared to Non-Hispanics.
Markers of Early Life Infection in Relation to Adult Diabetes: Prospective Evidence From a National Birth Cohort Study Over Four Decades
Authors: Mark Hamer, G. David Batty
Journal: Diabetes Care (2020)

Pathogen burden has been linked to the occurrence of selected noncommunicable health events, particularly coronary heart disease (1). In addition to an inflammatory hypothesis, pathogen burden may contribute to features of immune senescence, such as the accumulation of differentiated cytotoxic T cells that are associated with impaired glucose homeostasis (2). This raises the possibility of a link between early life infection and diabetes, although longitudinal studies are scarce. Existing data on acquired infections and diabetes risk have been inconsistent, which may be ascribed to methodological weaknesses such as small sample sizes ( n < 150) in studies largely on patient groups rather than the general population and a scarcity of prospective cohort studies. In the only prospective evidence of which we are aware, childhood illness of sufficient severity to warrant hospitalization was associated with markers of metabolic health, including fasting glucose (3). In the present analysis we use data from a national birth cohort of the general population in which exposure to infection was assessed in childhood before the onset of diabetes that was ascertained some 35 years later.

We used data from the 1970 …
Expanding Access and Reducing Prices for Drugs to Prevent HIV
Authors: Lawrence O. Gostin, Arti K. Rai
Journal: JAMA (2020)

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Abstract P228: Do Cardiometabolic Risk Profiles Differ Across Race-Ethnicity? An Analysis of the Most Active U.S. Adults in the 2003-2006 NHANES
Authors: William Boyer, Michael R Richardson, James R Churilla, Lindsay Toth, Eugene Fitzhugh, David R Bassett
Journal: Circulation (2020)

Introduction: Previous studies have revealed a significant, inverse dose-response relationship between total activity counts/day (TAC/d) and several cardiometabolic risk factors (CMRF). An ongoing line of research is the examination of the contributions of behavioral, environmental, and physiological factors to CMRF differences across race-ethnicity. However, it is unknown if these differences exist among the most physically active adults. Hypothesis: Among the most active U.S. adults, we hypothesize that CMRF measures will differ across race-ethnic groups. Methods: Study sample (n=1,059) included adult (20-79 years of age) participants from the 2003-2006 NHANES who wore an ActiGraph model 7164 accelerometer on the right hip. The top quartile of accelerometer-derived age- and gender-specific TAC/d was used as a cutpoint to define the “most active”. All participants were without T2D (fasting glucose &lt;126 mg/dL, no medication, no self-reported diagnosis) and without CVD (self-report). CMRF included HOMA-IR, fasting insulin and glucose, systolic (SBP) and diastolic blood pressure (DBP), HDL, LDL, triglycerides, BMI, waist circumference (WC) and C-reactive protein (CRP). Multiple linear regression was used to examine CMRF differences between non-Hispanic white (NHW), non-Hispanic black (NHB) and Mexican American (MA) participants. Regression models were adjusted for age, sex, education, smoking, wear time, BMI (except BMI and WC models), objectively-measure MVPA (≥760 counts/min) and race-ethnicity. Results: No significant differences were found in mean TAC/d across race-ethnicity. When compared to NHW, NHB had significantly higher HOMA-IR, fasting insulin, SBP, WC, and BMI. Compared to NHW, MA had significantly higher HOMA-IR, fasting insulin, triglycerides, WC and BMI. When comparing NHB to MA, MA had significantly higher triglycerides and HDL and significantly lower SBP. Conclusions: It has been proposed that the race-ethnic differences in PA participation could be contributing to disparities in elevated CMRF, but even among U.S. adults in the 75th percentile for total activity volume (i.e. TAC/d), race-ethnic differences in CMRF still exist. It is probable that other social, environmental, and genetic factors are responsible for moderating the beneficial effects PA has on CMRF specifically among NHB and MA adults.
Abstract P426: Cumulative 30-year Alcohol Use From Young Adulthood and Mid-life Cognitive Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Stephen Sidney, Julian Jakob, Paola Gilsanz, Catherine Lee, David Jacobs, Mark J Pletcher, Jamal S Rana, Jared P Reis, Veronique L Roger, Kristine Yaffe, Reto Auer
Journal: Circulation (2020)

Introduction: Alcohol use is common in the United States. Most studies describe a J-shaped relationship between alcohol consumption and cognitive function: frequent heavy consumption alters brain functions and decreases cognitive performance; regular light and moderate consumption may have protective impact. We are unaware of any reports utilizing longitudinally collected data to derive a cumulative exposure of alcohol use and assess its association with cognitive function. Hypothesis: Cumulative 30-year exposure to alcohol has a J-shaped association with mid-life cognitive function. Methods: We included 3,068 participants aged 18-30 years at the baseline examination (1985-86) and having up to 8 follow-up exams at 2- to 5-year intervals including at 30 years (2015-16). Cumulative “drink-years” exposure to alcohol was estimated at each exam by multiplying the usual number of drinks/day reported by the number of years since last exam, and then summing across exams. We used multivariable adjusted linear regression models to assess the independent associations of number of drink-years with 6 measures of cognitive function studied at Year 30: Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), Stroop Test, Montreal Cognitive Assessment (MoCA), Category Fluency Test, and Letter Fluency Test. We used inverse probability of censoring weighting to account for potential informative censoring. Linear regression models estimated standardized mean test scores for the cumulative alcohol use categories (drink-years: &gt;0 and &lt;15, 15-29.9, 30+). Too few participants were available for assessment of higher categories of use. Results: Compared with never drinking, the 3 categories of cumulative exposure were unassociated with any of the cognitive function measures. Conclusions: Cumulative 30-year alcohol use is not associated with cognitive function in middle-aged adults in the CARDIA study.
Abstract P491: Serum Fatty Acids Concentrations and Compositions, Lipids Concentrations and Their Correlation in Acute Ischemic Stroke Patients Aged 50 Years or Older
Authors: Takahisa Mori, Kazuhiro Yoshioka
Journal: Circulation (2020)

Background: Compositions of serum fatty acids (s-FAs), such as palmitic acid (PA), oleic acid (OlA), linoleic acid (LiA) and docosahexaenoic acid (DHA), and their correlation with serum lipids (s-LPs), such as total cholesterol (T-CHO) and triglycerides (TG), have been reported in healthy young or middle subjects. However, little is known about s-FAs features in acute ischemic stroke (AIS) patients. Hypothesis: Serum FAs features in AIS elderly patients are different from those in healthy young subjects and concentrations of s-FAs provide different correlation with s-LPs from compositions. Methods: We conducted a cross-sectional study of patients aged 50 years or older who were admitted to our institution between August 2016 and July 2019 within 24 hours of first AIS onset. We evaluated concentrations and compositions of s-FAs and their association with s-LPs, age and ischemic stroke subtype. Results: Three hundred sixty-six patients met our inclusive criteria. Their average age was 74.7 years, median T-CHO and TG were 203.5 and 102 mg/dl, respectively and median concentrations of PA, OlA, LiA and DHA were 642.5, 566.0, 723.0 and 129.8 μg/ml, respectively, and their median or mean compositions were 23.6, 20.9, 26.5 and 4.7 %, respectively. Concentrations of s-FAs had positive correlation with s-LPs. Concentrations of s-LPs and most of s-FAs had negative correlation with age. In stroke subtype of large-artery atherosclerosis or small-vessel occlusion (LAA_SVO) and in stroke subtype of cardioembolism or others (CE_O), mean age was 72.6 and 76.4 years (p&lt;0.001), median TCHO was 214 and 194 mg/dl (p&lt;0.0001), median TG was 113 and 95 mg/dl (p&lt;0.05), median PA was 678.8 and 611.2 μg/ml (p&lt;0.0001), median OlA was 613.8 and 532.4 μg/ml (p&lt;0.001), median LiA was 767.2 and 696.1 μg/ml (p&lt;0.001), and mean DHA was 131.4 and 127.9 μg/ml (ns). Compositions of PA, OlA, LiA and DHA had no correlation with T-CHO and compositions of PA and OlA had positive correlation with TG, whereas compositions of LiA and DHA had negative correlation with TG. Compositions of OlA had negative correlation with age, whereas DHA composition had positive correlation with age. There was little difference of compositions between stroke subtypes. Conclusions: In first AIS elderly patients, concentrations of most of s-FAs had positive correlation with s-LPs. In LAA_SVO, patients were younger and their concentrations of s-LPs and most of s-FAs were larger than in CE_O. On the other hand, correlation of s-FAs compositions with s-LPs was not constant and there was little difference of compositions between ischemic stroke subtypes.
Abstract P327: Inflammation Associates With Lower Myocardial Function Among Antiretroviral-Treated Persons Living With HIV in South Africa
Authors: Tess E Peterson, Mpiko Ntsekhe, Scott Shuldiner, Lye-Yeng Wong, Julian Wolfson, Stephen Jermy, Hadil Saad, Ackim Justin Mbalabu Lumbamba, Achita Singh, Muki Shey, Graeme Meintjes, Ntobeko Ntusi, Jason Baker
Journal: Circulation (2020)

Introduction: HIV-associated inflammation contributes to higher CVD risk among persons living with HIV (PLWH). Heart failure (HF) is a prominent CVD manifestation in sub-Saharan Africa where HIV prevalence is high. Systolic dysfunction is a well-known complication of untreated, advanced HIV disease, but it is unknown if ongoing inflammation contributes to myocardial dysfunction during antiretroviral therapy (ART). We evaluated myocardial function via cardiac magnetic resonance (CMR) and studied associations with inflammatory biomarkers among ART-treated PLWH residing in Khayelitsha township near Cape Town, South Africa. Methods: CMR images were ascertained via a large bore 3T Siemens Skyra MRI scanner using standardized protocols. Biomarkers were measured from stored plasma using immunoassays and were log 2 -transformed for analyses. Linear regression was used to evaluate cross-sectional associations between CMR parameters and biomarker concentrations, adjusted for age, sex, current smoking, and hypertension. Results: Among 133 ART-treated PLWH without known CVD, 64% (85) were female, 99% (132) were Black African, 29% (39) were smokers, 92% (123) had undetectable HIV viral load, mean (SD) age was 50 (9) years, and current and nadir CD4+ count were 535 (270) and 271 (213) cells/μL, respectively. Higher TNFR1, TNF-α, and IFN-γ were associated with lower left ventricular ejection fraction (p=0.03, 0.05, and 0.03, respectively) and systolic global circumferential strain (p=0.01, 0.04, and 0.02) ( Table ). Higher TNFR1 was also associated with lower diastolic strain rate in circumferential (p=0.02), longitudinal (p=0.05), and radial (p=0.01) planes. Conclusion: These data suggest inflammation may contribute to lower myocardial function among ART-treated PLWH prior to development of clinical HF. The magnitude of this effect was modest, but potential long-term effects on myocardial tissue remodeling and subsequent HF risk warrant further investigation among a growing ART-treated population in South Africa.
CCL2-CCR2 axis recruits tumor associated macrophages to induce immune evasion through PD-1 signaling in esophageal carcinogenesis
Authors: Hui Yang, Qiannan Zhang, Miao Xu, Lei Wang, Xuewei Chen, Yongquan Feng, Yongning Li, Xin Zhang, Wenming Cui, Xudong Jia
Journal: Molecular Cancer (2020)

The poor prognosis of esophageal squamous cell carcinoma (ESCC) highlights the need for novel strategies against this disease. Our previous study suggested the involvement of CCL2 and tumor associated macrophages (TAMs) in esophageal carcinogenesis. Despite the recognition of TAMs as a promising target for cancer treatment, mechanisms underlying its infiltration, activation and tumor-promotive function in ESCC remain unknown.Human esophageal tissue array and TCGA database were used to evaluate the clinical relevance of CCL2 and TAMs in ESCC. F344 rats and C57BL/6 mice were treated with N-nitrosomethylbenzylamine (NMBA) to establish orthotopic models of esophageal carcinogenesis. CCL2/CCR2 gene knockout mice and macrophage-specific PPARG gene knockout mice were respectively used to investigate the role of infiltration and polarization of TAMs in ESCC. CCL2-mediated monocyte chemotaxis was estimated in malignantly transformed Het-1A cells. THP-1 cells were used to simulate TAMs polarization in vitro. RNA-sequencing was performed to uncover the mechanism.Increasing expression of CCL2 correlated with TAMs accumulation in esophageal carcinogenesis, and they both predicts poor prognosis in ESCC cohort. Animal studies show blockade of CCL2-CCR2 axis strongly reduces tumor incidence by hindering TAMs recruitment and thereby potentiates the antitumor efficacy of CD8+ T cells in the tumor microenvironment. More importantly, M2 polarization increases PD-L2 expression in TAMs, resulting in immune evasion and tumor promotion through PD-1 signaling pathway.This study highlights the role of CCL2-CCR2 axis in esophageal carcinogenesis. Our findings provide new insight into the mechanism of immune evasion mediated by TAMs in ESCC, suggesting the potential of TAMs-targeted strategies for ESCC prevention and immunotherapy.
Correction: Role of growth arrest-specific gene 6-mer axis in multiple myeloma
Authors: J. S. Waizenegger, I. Ben-Batalla, N. Weinhold, T. Meissner, M. Wroblewski, M. Janning, K. Riecken, M. Binder, D. Atanackovic, H. Taipaleenmaeki, D. Schewe, S. Sawall, V. Gensch, M. Cubas-Cordova, A. Seckinger, W. Fiedler, E. Hesse, N. Kröger, B. Fehse, D. Hose, B. Klein, M. S. Raab, K. Pantel, C. Bokemeyer, S. Loges
Journal: Leukemia (2020)
Abstract P149: Association Between Disabilities And Cardiovascular Disease Mortality In Diabetic Men And Women
Authors: Chong-Do Lee, Samuel Lee
Journal: Circulation (2020)

The associations of physical disabilities with cardiovascular disease (CVD) mortality in diabetic patients remains less explored. Purpose: We investigated the associations of activities of daily living (ADL), instrumental ADL (IADL), and functional limitation (FL) disabilities with CVD mortality among diabetic men and women in the National Health and Nutrition Examination Surveys. Methods: Cox proportional hazards regressions were used to examine the associations of ADL, IADL, and FL disabilities with CVD mortality in men and women after adjustment for covariates. We followed 2,255 men and women, aged 20 to 90 years, who participated in the National Health and Nutrition Examination Surveys (1988-1994, 199-2014). All participants completed baseline demographics and health factors, including blood lipid profiles. Diabetes mellitus was defined as fasting glucose level ≥126 mg/dL, a nonfasting glucose level ≥200 mg/dL, use of hypoglycemic agents, or a history of physician-diagnosed diabetes mellitus. ADL disability was defined as those who had any difficulties in dressing, eating, getting out of bed, or walking a room to another room. IADL disability was defined as those who had any difficulties in preparing meals, managing money, or doing chores around the house. FL disability was defined as those who had any limitations in mobility performance (walking 0.25 mile, climbing 10 stairs, lifting/carrying 10 pounds, or standing from a chair). Results: During an average of 15.5 years of follow-up (34,939 person-years), there were a total of 382 CVD deaths. There were direct relationships between the number of ADL, IADL, and FL with CVD mortality after adjustment for age, sex, race, and other CVD risk covariates (All P&lt;0.007). After adjustment for multiple risk factors, the risks of CVD mortality for ADL, IADL, and FL disabilities were (95% CI) 2.01 (1.60, 2.51), 1.99 (1.60, 2.48), and 1.97 (1.59, 2.44), respectively, compared with their counterparts. After further adjustment for chronic medical conditions (personal history of coronary heart disease, stroke, or cancer), diabetic persons with ADL disability had 1.94 times (1.5, 2.43), with IADL disability had 1.93 times (1.54, 2.41), and with FL disability had 1.94 times (1.56, 2.40) the risk of CVD mortality as compared with their counterparts, respectively. The associations remained but were attenuated after further excluding these patients with chronic diseases. The risks of CVD mortality in diabetic persons with ADL, IADL, and FL disabilities were (95% CI) 1.78 (1.30, 2.43), 1.66 (1.22, 2.27), and 1.43 (1.09, 1.89), respectively, compared with their counterparts, after excluding these chronic disease patients. Conclusion: Diabetic persons with ADL, IADL, and FL disabilities had a greater risk of CVD mortality. The American Heart Association should establish exercise and dietary guidelines for diabetic persons with physical disabilities.
Abstract P186: Obstructive Sleep Apnea and Risk of Chronic Kidney Disease in the ARIC Sleep Heart Health Study
Authors: Kelsie M Full, Chandra Jackson, Casey M Rebholz, Kunihiro Matsushita, Pamela L Lutsey
Journal: Circulation (2020)

Background: Obstructive sleep apnea (OSA) is a prevalent sleep disorder and may be associated with the development of chronic kidney disease (CKD) through hypoxia, inflammation, and oxidative stress. However, the prospective relationship between OSA and incident CKD remains unknown. In this study, we leveraged in-home polysomnography (PSG) data from a large community-based cohort of adults to examine the association between OSA and risk of incident CKD in late-midlife. Methods: Participants in the Atherosclerosis Risk in Communities (ARIC) study (N=1,525; mean age=62.5 ± 5.4 years, 52.4% female) completed in-home PSG assessments as part of the Sleep Heart Health Study. OSA severity was defined according to apnea-hypopnea index (AHI) (events/hour): normal &lt;5.0, mild 5.0-14.9, moderate 15.0-29.9, and severe ≥30.0. Incident CKD was defined according to estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1.73 m 2 and at least 25% decline in eGFR from baseline, CKD-related hospitalization or death, or end-stage renal disease. Cox proportional hazards regression was used to estimate OSA severity with risk of incident CKD. Models were adjusted for demographics, health behaviors, BMI, and other markers of cardiometabolic conditions. Results: Among 1,525 participants, a total of 461 CKD events occurred over an average of 19 years of follow-up. After adjustment for demographics and health behaviors, severe OSA (AHI ≥30.0) was associated with increased risk of CKD (Hazard Ratio (HR): 1.51; 95% Confidence Interval (CI): 1.08, 2.10). This association was attenuated after additional adjustment for BMI (HR; 1.07, CI: 0.75, 1.52). Conclusions: Overall, OSA was linked to greater CKD risk. The association was attenuated after adjusting for obesity, a risk factor for both conditions. Due the high prevalence of OSA and CKD in the US adult population, more investigation is needed. Figure 1. Estimated probability of years free of Chronic Kidney Disease (CKD) by obstructive sleep apnea (OSA) severity in the ARIC Sleep Heart Health Study: