bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13853: Routine Follow Up Coronary Angiography versus Clinical Follow Up Only in Patients With Dyslipidemia Following Percutaneous Coronary Intervention With Drug-eluting Stents: 3-year Clinical Follow Up Results
Authors: Rha Seung Woon , Choi Byoung Geol , Choi Se Yeon , Byun Jae Kyeong , Na Jin Oh , Choi Cheol Ung , Lim Hong Euy , Kim Jin Won , Kim Eung Ju , Park Chang Gyu , Seo Hong Seog , Oh Dong Joo
Published: July 2021

Background:
It is unclear whether the routine follow up (FU) coronary angiography (CAG) regardless of patient’s symptoms after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) in patients (pts) with dyslipidemia is beneficial or not.

Methods:
The study population consisted of 554 consecutive dyslipidemia pts underwent PCI with unrestricted utilization of DESs from January 2004 to May 2011. Routine FU CAG was performed between 6 to 9 months following index PCI and was decided by individual physician’s discretion. Rests of the pts were clinically followed and ischemic driven events were captured. Clinical events including mortality, myocardial infarction and clinically driven PCI before 9 months were excluded in both groups. Cumulative clinical outcomes up to 3 years were compared between the Routine CAG group (n=329 pts) and the Clinical FU group (n= 225 pts). To adjust potential confounders, a propensity score matched (PSM) analysis was performed using the logistic regression model.

Results:
After PSM analysis, 2 propensity-matched groups (165 pairs, n = 330 pts, C-statistic=0.718) were generated and, the baseline characteristics of the two groups were balanced. At 3 years, the incidence of repeat revascularization and major adverse cardiac events (MACEs) was higher in the Routine CAG group than the control group (Table).

Conclusions:
Despite the expected beneficial effects, routine FU CAG following index PCI with DESs in dyslipidemia pts was associated with higher incidence of repeat PCI and MACE up to 3 years.
Abstract 14092: Reduction of Atherosclerosis in Gucy1a3 Deficient Mice
Authors: Segura Puimedon Maria , Mergia Evanthia , Al-Hasani Jaafar , Aherrahrou Redouane , Freyer Jennifer , de Wit Cor , Kösling Doris , Schunkert Heribert , Erdmann Jeanette , Aherrahrou Zouhair
Published: July 2021

Introduction:
GUCY1A3 encodes the α1 subunit of the soluble guanylate cyclase (sGC) and has been associated with CAD/MI by genome-wide association studies (GWAS) and in a rare extended family with MI. The α1 and the β1 subunit form the heterodimeric sGC, the nitric oxide (NO) receptor. NO plays an important role in the human cardiovascular system. The aim of our study is to define the role of GUCY1A3 in atherosclerosis using a mouse atherogenic model.

Methods:
Gucy1a3 KO mice were backcrossed on an Ldlr KO atherogenic background. Four groups were used, i.e. C57BL/6 (WT), Gucy1a3 KO, Ldlr KO and Gucy1a3-Ldlr double KO. All groups were fed high fat diet (HFD) or standard diet (SD) starting at the age of 12-14w and for 20 weeks. Blood pressure was studied at the end of the experiment in the HFD. At the start and end of the diet, lipid metabolism parameters (TC, HDLC, LDLC and TG) were analyzed. Plaque lesion size and collagen and macrophages content were studied. As smooth muscle cells play a key role in atherosclerosis, primary mouse aortic smooth muscle cells (maSMC) were isolated from WT and Gucy1a3 KO animals and subjected to proliferation and migration assays.

Results:
Blood pressure was studied in HFD animals, showing, as expected, an increase of systolic and diastolic blood pressure in double KO animals when compared to Ldlr KO animals. Regarding lipid levels, no differences were found in the double KO to Ldlr KO comparison under HFD, but a reduction in total cholesterol was found in double KO under SD. For atherosclerosis, a significant reduction in plaque area at the aortic root of double KO when compared to the Ldlr KO animals was demonstrated in both SD and HFD. The reduction was further confirmed in an additional independent experiment under SD. Similarly, a significant reduction of plaque lesion was found in the whole aorta of double KO when compared to the Ldlr KO under HFD. Moreover, a reduction in collagen content was found in double KO mice under HFD when compared to Ldlr KO animals. The migration and proliferation assays show a significant reduction in both migration and proliferation of the Gucy1a3 KO maSMC compared to WT.

Conclusions:
Our results point to an atherogenic role of Gucy1a3 in mice probably induced via smooth muscle migration and proliferation defects.
Abstract 14339: Nonalcoholic Fatty Liver Disease and the Risk of Clinical Cardiovascular Events: A Meta-Analysis
Authors: Mahfood Haddad Toufik , Hamdeh Shadi , Anantha Narayanan Mahesh , Kanmanthareddy Arun , Alla Venkata M
Published: July 2021

Background:
Numerous studies have assessed the association of Nonalcoholic fatty liver disease (NAFLD) withcardiovascular disease (CVD). However, results have been conflicting due to variability in definitionsof NAFLD and ascertainment of CVD, often combining clinical and surrogate endpoints. We therefore systematically reviewed published literature to assess the association between NAFLD and clinical cardiovascular events.

Methods:
We searched Medline, Cochrane, google scholar, CINAHL, and Web of Sciencedatabasesusing terms “nonalcoholic fatty liver disease”, “cardiovascular disease”, and their combinations to identify studies published through March 2015. Data from selected studies was extracted and meta-analysis was then performed using Random effects model following the PRISMA guidelines. Publication bias and heterogeneity wereassessed. The main outcome measure was Odds ratio (OR) with 95% CI. Clinical CVD was defined as symptomatic coronary artery disease, myocardial infarction, coronary or peripheral intervention, ischemic stroke, and symptomatic peripheral vascular disease.

Results:
A total of 7 studies with 14634 patients (NAFLD: 4204; controls: 10430) were included in the final analysis. 3 studies were cross- sectional reporting prevalence, while 4 studies were prospective cohort studies reporting incidence. Patients with NAFLD had a significantly higher risk of clinical CVD compared to controls [OR: 3.17; 95% CI: 1.89-5.30, P<0.01) (figure 1A). There was significant heterogeneity (I2=93%). Funnel plot and Begg’s test did not reveal significant publication bias. Separate analyses of the cohort and cross sectional studies and exclusion sensitivity analysis did not alter the findings (figure 1B).

Conclusion:
NAFLD is associated with a three fold increase in the risk of clinical CVD compared to controls without NAFLD. These results need to be conformed in large prospective studies.
Abstract 14575: Implantable Cardiac Defibrillator in the Setting of Tetralogy of Fallot: Long-Term Follow-Up of a French National Multicenter Retrospective Registry
Authors: Bouzeman Abdeslam , De Guillebon Maxime , Duthoit Guillaume , Ladouceur Magalie , Martins Raphael , Fauchier Laurent , Amet Denis , Defaye Pascal , Gourraud Jean-Baptiste , Sellal Jean-Marc , Mondoly Pierre , Lalombarda Fabien , Anselme Frederic , Koutbi Linda , Elbaz Nathalie , Halimi Franck , Messali Anne , Mathiron Amel , Thambo Jean-Benoit , Iserin Laurence , Combes Nicolas , Marijon Eloi
Published: July 2021

Background:
Tetralogy of Fallot (TOF) is the most frequent form of congenital heart disease managed by EP physicians for potential ICD. However, few studies have reported long-term outcomes of TOF patients with ICD.

Methods:
Between 2005 and 2014, all TOF patients with ICD in 17 French centers were enrolled in a specific evaluation aiming to determine characteristics at implantation as well as outcomes (overall mortality, appropriate ICD therapies, and device-related complications).

Results:
Overall 78 patients (45±13 years, 64% males) were enrolled. A majority of patients were implanted in the setting of secondary prevention (73%), whereas the remaining (27%) in primary prevention. Among the latest group, known risk factors for sudden cardiac death were: severe pulmonary regurgitation (30%,) prior palliative shunt (50%), syncope with unknown origin (25%), inducible ventricular tachycardia (45%), QRS duration ≥180ms (18%), non-sustained ventricular tachycardia (25%), and documented sustained supra ventricular tachycardia (45%).Overall, patients implanted in the setting of primary prevention presented with a mean of 3.1±1.4 risk factors. After a mean follow-up of 4.9±3.8 years, 35 patients (45%) experienced at least one appropriate therapy (25% in the primary prevention group compared to 53% in the secondary prevention group), giving annual-incidences of 6.9% (95%CI 0.14-13.7) and 21.3% (12.4-30.3) respectively (P=0,01). The mean time between ICD implantation and the first appropriate therapy was 2.2±3.2 years, without significant differences between primary and secondary prevention. Overall, ≥one ICD-related complication occurred in 30 patients (38%), including inappropriate shock (n=9), major pocket hematoma (n=1), lead dysfunction (n=12), infection (n=4), shoulder algodystrophia (n=2), device failure or dislodgement needing reintervention (n=2). Eventually, four patients were transplanted (5%), and six patients (8%) died during the course of follow-up.

Conclusions:
Considering relatively long-term follow-up, patients with TOF and ICDs experience high rates of appropriate ICD therapies, in both primary and secondary prevention. Major ICD-related complications remain, however, high.
Abstract 14731: Association of Longitudinal Changes in CRP, IL-6, and Fibrinogen Level With Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Bakhshi Hooman , Ostovaneh Mohammad R , Ambale Venkatesh Bharath , Allison Matthew , Herrington David , Cushman Mary , Szklo Moyses , Wu Colin O , Blaha Michael , Budoff Matthew , Tracy Russell , Bluemke David A , Lima João A
Published: July 2021

Background:
Inflammatory biomarkers have been used for cardiovascular disease (CVD) risk stratification. However, the relevance of longitudinal changes in levels of these biomarkers in relation to CVD is unclear.

Methods:
MESA is a population-based cohort consisting of 6814 participants free of symptomatic cardiovascular disease at baseline. We included all participants who had blood assayed for measurement of inflammatory biomarkers - C-reactive protein (CRP), Interleukin-6 (IL-6), and fibrinogen measured at baseline and follow-up 2-4 years later (n=1,362). Coronary heart disease (CHD) was assessed as any of myocardial infarction, resuscitated cardiac arrest, definite angina, probable angina (if followed by revascularization) and CHD death. CVD was considered a composite of CHD, stroke, stroke death, atherosclerotic death and CVD death. Cox proportional hazard regression analysis was used to assess the association of annual longitudinal changes in inflammatory biomarker level and time to first CHD and CVD event after adjustment for traditional risk factors and demographics.

Results:
The mean (SD) age was 61.6 (9.8) years and 55% were male. Over 8.6 median (IQR, 8.4-9.3) years of follow-up, there were 87 CHD and 121 CVD events. The median (IQR) CRP (mg/L), IL-6 (pg/ml) and fibrinogen (mg/dl) levels at baseline were 1.74(0.82-3.95) 1.11(0.71-1.72) and 332(292-382); and at follow-up were 1.4(0.69-3.03), 1.76(1.16-2.72) and 421(371-476). An increase in IL6 of 1 pg/mL/year was associated with a 26% increased risk of total CVD events independent of risk factors, while an increase of 1 mg/L/year of CRP was independently associated with a 7% and 6% increased risk of both CHD and CVD events respectively. There were no significant associations with changes in fibrinogen.

Conclusion:
Longitudinal increases in the inflammatory biomarkers CRP and IL6 are associated with higher risk of future cardiovascular events in a multi-ethnic population.
Abstract 15067: Incidence and Outcomes of Neonates With Congenital Heart Disease Complicated by Necrotizing Enterocolitis
Authors: Shamszad Pirouz , Morris Shaine A , Nandi Deipanjan , Costarino Andrew T , Marino Bradley S , Rossano Joseph W
Published: July 2021

Introduction:
The management of neonates with congenital heart disease (CHD) may be complicated by necrotizing enterocolitis (NEC), however, there is limited multicenter data describing the incidence and outcomes of NEC in the CHD population.

Objective:
We aimed to assess the incidence and risk factors for the development of NEC in neonates with major CHD and the impact on survival.

Methods:
A retrospective cohort study of neonates with CHD was performed for all index hospitalizations of neonates (<28 days) with major CHD between 2004 and 2014 using the Pediatric Health Information System database. The diagnosis of NEC was determined by the presence of ICD-9 code 777.5x. The incidence of NEC was determined as were risk factors for the development of NEC. Mortality was the primary outcome measure.

Results:
Of 38770 neonates with major CHD, 1448 (3.6%) were diagnosed with NEC. The rate of NEC varied between 0-8% by hospital and was not associated with hospital volume (p=0.4). Among neonates with a single, major CHD diagnosis, the rate of NEC was 6% in hypoplastic left heart syndrome (HLHS), 6% in truncus arteriosus (TA) , 4% in tetralogy of Fallot (TOF), 3% in aortic arch obstruction (AO), and 2% in transposition of the great arteries (TGA); these diagnoses accounted for 47% of all NEC. Prematurity and chromosomal anomalies were independently associated with the diagnosis of NEC (p≤0.01 for both). Unadjusted mortality among neonates with NEC was 24% compared to 12% in neonates without NEC (OR 2.4, 95%CI 2.1-2.7). When evaluating changes in adjusted mortality associated with NEC by CHD diagnosis, TOF mortality increased from 8% to 16% (p<.01), TGA increased from 5% to 21% (p<0.01), AO increased from 6% to 20% (p<0.01), HLHS increased from 22% to 28% (p=.07), and TA decreased from 13% to 12% (p=0.7). Median LOS was higher in neonates with NEC than without NEC (54d [IQR 31-93] vs. 18d [IQR 9-34], p<0.01) as was median hospital charge ($600k [IQR 310k-1.1m] vs. $220k [IQR 100k-430k], p<0.01).

Conclusions:
The incidence of NEC among neonates with major CHD is highest in HLHS and TA. NEC is associated with significantly higher hospital mortality, LOS, and charges. Determining modifiable factors associated with NEC may allow for interventions to reduce morbidity in this population.
Abstract 15205: Atheroprotective Effect of the AFFITOPE®-based Anti-PCSK9 Vaccine (AT04A) in APOE*3Leiden.CETP Mice
Authors: Galabova Gergana , Juno Claudia , Mairhofer Andreas , van der Hoorn José W , Pieterman Elsbet J , Pouwer Marianne , Jukema J. W , Princen Hans M , Schneeberger Achim , Staffler Guenther
Published: July 2021

Background:
Elevated low density lipoprotein cholesterol (LDLc) is one of the major risk factors for premature cardiovascular diseases (CVD). Thus, therapeutic approaches aim at reducing LDLc. PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) has been shown to be a key regulator of the LDLR-mediated cholesterol clearance pathway. Many preclinical and clinical studies confirm the LDLc-lowering effect of PCSK9 inhibition, and emphasize PCSK9 as a potential novel target for the treatment of CVD.

Aim:
Proof of concept study for AFFITOPE®-based (AT04A) anti-PCSK9 immunization in the APOE*3Leiden.CETP mouse model and its safety aspects.

Methods:
AT04A vaccine was administered subcutaneously in APOE*3Leiden.CETP mice. Control and vaccine treated mice were fed Western-type diet for 18 weeks. Antibody titers and concentration, and their affinity towards PCSK9, as well as plasma lipids were monitored throughout the whole study by ELISA, Biacore® and FPLC, respectively. Moreover, body weight (BW), food intake (FI) and liver enzymes (ALT and AST) were measured. The progression of atherosclerotic lesion development was evaluated by histological analysis of serial cross-sections from the aortic sinus.

Results:
AT04A vaccine induced antibodies (mean titers up to ODmax/2=12,000 and mean concentration up to 250 μg/mL), which significantly reduced the plasma total cholesterol (TC) (-53%, P<0.001) and triglycerides (TG) (-46%, P<0.001), contained in the apoB-containing lipoproteins, in comparison to the control. Moreover, immunization neither altered FI or BW, nor plasma liver enzymes concentration. Furthermore, anti-PCSK9 immunization resulted in a higher percentage of undiseased aortic segments (+119%, p=0.026), decreased segments with severe lesions (-64%, p=0.051) and a decrease in atherosclerotic lesion area (-64%, P=0.004) as compared to the control.

Conclusions and Outcome:
AT04A vaccine is highly immunogenic and atheroprotective in APOE*3Leiden.CETP mice. The induced antibodies are able to decrease significantly plasma lipids and atherosclerotic lesions progression in the aorta. A phase I clinical study with AT04A and with a second vaccine candidate AT06A is scheduled for Q3/2015.
Abstract 15492: Spontaneous Coronary Artery Dissection: Characterizing Presentation, Management, and Outcomes at a Large Referral Cardiovascular Center
Authors: Shivapour Daniel M , Erwin Phillip , Gornik Heather L , Kim Esther S
Published: July 2021

Introduction:
Non-atherosclerotic spontaneous coronary artery dissection (SCAD) primarily affects women and may be associated with arteriopathies such as fibromuscular dysplasia (FMD). We aimed to describe patient characteristics, management, and outcome of SCAD at a large referral center.

Methods:
We queried our institutional cardiac cath database for SCAD diagnoses from 2000-2014. The electronic medical record was also queried for consecutive SCAD patients seen in a specialty arteriopathy clinic from 2010-2015. Details regarding presentation, treatment, and outcome of SCAD were collected. Trends in management over two time periods (2000-2009, 2010-2015) were compared.

Results:
There were 96 SCAD events in 75 patients (16 patients had one recurrence, one had three events, and one had four distinct events). Mean age at presentation was 47 years, 83% were female, and 84% presented with ACS. The LAD was the most commonly affected vessel (54%). Most SCAD events were treated medically (52%). Of 41 events treated with PCI, 19 were complicated by hematoma extension. Four PCI patients required subsequent CABG. Imaging of other arterial beds increased over time, with 2/3 patients receiving vascular ultrasound to evaluate for renal or carotid FMD in the more recent time period (Table). Of those evaluated for FMD, 45% had imaging findings compatible with multifocal FMD. Significant carotid tortuosity was present in 38%, with four demonstrating a classic “S surve” appearance recently shown to be a variant presentation of FMD. All patients survived to index hospitalization discharge, however, 24% of patients had at least one recurrence.

Conclusions:
SCAD affects predominantly young females and often manifests as ACS. Findings of FMD or carotid tortuosity are frequent and recognition of SCAD as a potential manifestation of FMD is increasing in our institution. In support of other reports, recurrence of SCAD is not rare and PCI attempts are complicated nearly half of the time.
Abstract 15584: Mitotimer Protein Reveals Remarkable Macro and Micro Heterogeneity in the Heart; A Novel Tool for Determining Mitochondrial Turnover in the Heart
Authors: Stotland Aleksandr , Ramil Jennifer , Gottlieb Roberta A
Published: July 2021

In order to study mitochondrial turnover at the level of a single mitochondrion, our laboratory has developed the MitoTimer protein. Timer is a mutant of DsRed fluorescent protein developed by Terskikh et al. The Timer protein transitions from green fluorescence to a more stable red conformation as it matures over a span of 48 h. Furthermore, the protein is very stable under physiological conditions, insensitive to variations in ionic strength, and changes in pH between 7.0 and 8.0. Notably, Timer maturation from green to red is significantly slowed in deoxygenated buffer, suggesting that molecular oxygen plays a part in fluorophore maturation. We created a construct that fused the Timer protein cDNA with the inner mitochondrial membrane signal sequence and placed it under the control of the cardiac-restricted α-myosin heavy chain promoter. This construct was used to create the α-MHC MitoTimer mice. Surprisingly, initial analysis of the hearts from these mice demonstrated a high degree of heterogeneity in the ratio of red-to-green fluorescence of MitoTimer in cardiac tissue, revealing regions of high and low oxygen tension. Further, individual mitochondria within cardiomyocytes display a higher red-to-green fluorescence relative to fluorescence of the other mitochondria in the cell, implying a block in import of newly synthesized MitoTimer caused by the lack of a high membrane potential, indicative of older, dysfunctional mitochondria. These mitochondria can be isolated and sorted from the heart by flow cytometry for further analysis. Initial studies suggest that these mice represent an elegant tool for the investigation of mitochondrial turnover in the heart.
Abstract 17277: Apixaban Use in Patients With Atrial Fibrillation With Bioprosthetic Valves: Insights From ARISTOTLE
Authors: Pokorney Sean D , Rao Meena P , Wojdyla Daniel M , Gersh Bernard J , Lopes Renato D , Lewis Basil S , Hanna Michael , Avezum Alvaro , Wallentin Lars , Alexander John H , Granger Christopher B
Published: July 2021

Background:
The package insert for apixaban recommends against its use for stroke prevention in patients with atrial fibrillation (AF) with prosthetic heart valves. There are no published data on the use of apixaban in patients with AF with bioprosthetic valves. This analysis provides preliminary exploratory data on the safety and efficacy of apixaban in these patients.

Methods:
The ARISTOTLE trial randomized patients with AF to apixaban versus warfarin, and patients with a history of bioprosthetic valve replacement were eligible for inclusion in the trial. In this secondary analysis, baseline characteristics of patients with bioprosthetic valves were compared between apixaban and warfarin patients using Wilcoxon tests for continuous variables and chi-square tests for categorical variables. Unadjusted endpoints were compared between randomized treatments using a Cox regression model. With data collection on these valve patients ongoing, this interim report represents 82 of 260 patients with a history of valve surgery from ARISTOTLE.

Results:
Among 82 patients with bioprosthetic valves, 41 patients each were in the apixaban and warfarin arms. The patients had a median age of 78 years (vs. 70 years in overall trial), 18% had prior stroke (vs. 19% in overall trial), and 41% had concomitant aspirin use (vs. 31% in overall trial). Other than a higher rate of hypertension in the warfarin arm (98% vs. 81%, p=0.03), there were no statistically significant differences in baseline characteristics between the two groups. There were few events in patients with bioprosthetic valves. There were 2 stroke events, and there were no statistically significant differences between the apixaban and warfarin groups for major bleeding, stroke/systemic embolism, all-cause death, or cardiovascular death (Table).

Conclusions:
Among the small number of patients in ARISTOTLE with bioprosthetic valves, there were few events with similar event rates in both the apixaban and warfarin groups.
Abstract 008: Casual and 24-hour Urinary Sodium-to-potassium Ratio and Intakes of Sodium and Potassium Among Men and Women From Multi-ethnic General Populations: The Intersalt Study
Authors: Iwahori Toshiyuki , Miura Katsuyuki , Ueshima Hirotsugu , Chan Queenie , Arima Hisatomi , Dyer Alan R , Elliott Paul , Stamler Jeremiah
Published: July 2021

Background:
Urinary sodium-to-potassium ratio may be more strongly related to blood pressure and cardiovascular disease than either urinary sodium or potassium alone. The casual urine sodium-to-potassium ratio is readily obtained, can provide prompt on-site feedback, and with repeated measurements may provide useful individual estimates of 24-hour urinary sodium-to-potassium ratio. The World Health Organization (WHO) has recently published guidelines for sodium and potassium intakes, but no generally accepted guideline prevails for favorable sodium-to-potassium ratio.

Objective:
Our primary aim was to compare the level of urinary Na/K ratio with the current recommended levels of Na and K intakes suggested in WHO guidelines.

Methods:
INTERSALT is an international study on associations of multiple urinary variables, with blood pressure (BP), based on standardized data on 24-hour and casual urinary electrolyte excretion in 10,065 individuals from 52 population samples in 32 countries. The associations between casual urinary sodium-to-potassium ratio and 24-hour urinary sodium and potassium excretion of individuals were assessed by correlation and stratification analysis.

Results:
Mean 24-hour sodium and potassium excretions were 156.0 mmol/24h and 55.2 mmol/24h; mean 24-hour urinary sodium-to-potassium ratio was 3.24. Pearson-r correlation coefficients of casual urinary sodium-to-potassium ratio with 24-hour sodium and potassium excretions were 0.42 and -0.34, respectively, and these were 0.57 and -0.48 for 24-hour urinary sodium-to-potassium ratio. The proportion of participants with estimated sodium chloride intake below the WHO recommended guideline of 85 mmol/day was 61.1% for those with casual urinary sodium-to-potassium ratio less than 1, and 96.3% where the 24-hour ratio was less than 1. For potassium, the proportion of people with potassium intake more than the WHO recommended guideline of 90 mmol/day was 21.3% where the casual urinary sodium-to-potassium ratio was less than 1 and 28.6% for the 24-hour urinary sodium-to-potassium ratio.

Conclusions:
Casual urinary sodium-to-potassium ratio less than 1 may be a useful indicator of adherence to the World Health Organization recommended levels of sodium intake, and to a lesser extent potassium intake in diverse different populations.
Abstract 027: Life-course Cardiovascular Risk Mobility in the International Childhood Cardiovascular Cohort (i3C) Consortium
Authors: Pollock Benjamin D , Hu Tian , Raitakari Olli T , Burns Trudy L , Sinaiko Alan R , Magnussen Costan G , Urbina Elaine M , Woo Jessica G , Steinberger Julia , Juonala Markus , Venn Alison , Daniels Stephen R , Dwyer Terry , Jacobs David R , Bazzano Lydia A
Published: July 2021

Background:
We previously adapted a methodology from literature on socioeconomic mobility (the “American Dream”) to develop an analogous concept of Cardiovascular (CV) Risk Mobility (CRM: movement across CV risk rankings during aging) in the Bogalusa Heart Study (BHS). We found high mobility, such that childhood CV risk burden tracks into adulthood, but not so strongly that a low CV-risk stratum in adulthood is unreachable. Because geopolitical, ethnic, and healthcare differences may affect mobility in life course CV health, we sought to further test CRM using an international consortium.

Methods:
We used prospective data from n=20,685 children followed into adulthood (inverse probability weighted, n=6,029 with adult follow-up) from the 1970s-2010s in three of the i3C Consortium cohorts: BHS, the Young Finns Study (YFS), and the Muscatine Study. During childhood (age 5-18 yr), participants were percentile-ranked by their CV risk factor burden using an age- and sex-adjusted sum of z-scores from total cholesterol, systolic blood pressure, BMI, and triglycerides. During adult follow-up (age 40-55 yr), participants were percentile-ranked using the Framingham score. The rank-rank slope (β) from the regression of adult/child percentile rankings forms the measure of CRM.

Results:
Patterns of CRM were similar to BHS in both YFS [β=.15 (95% CI: .12, .18) at age 10] and Muscatine [β=.14 (95% CI: .09, .19) at age 10]. Pooled results of age/rank interaction were significant (
p
=0.005), indicating a pattern of lower CRM (more tracking) earlier in childhood. The pooled β=.15 (95% CI: .14, .16)], meaning that a child ranked 10 percentiles better was only 1.5 percentiles better as an adult.

Conclusions:
Populations in the developed world track, yet exhibit large mobility in CV risk. Children are readily able to move from both high to low and low to high CV risk strata over the life course. The earlier children develop a high CV risk factor burden relative to their peers, the lower their mobility, or opportunity to “catch up,” into adulthood.
Abstract 044: Cardiorespiratory Fitness May Explain a Proportion of Observed Racial Disparity in Incident Chronic Kidney Disease over 30 Years: Results From the CARDIA Study
Authors: Paluch Amanda E , Pool Lindsay , Isakova Tamara , Wolf Myles , Mehta Rupal , Peralta Carmen , Lewis Cora E , Schreiner Pamela , Sidney Stephen , Carnethon Mercedes
Published: July 2021

Introduction:
Racial and ethnic minorities are at higher risk for Chronic Kidney Disease (CKD). Higher levels of cardiorespiratory fitness (CRF) can reduce the risk of a rapid decline in estimated glomerular filtration rate (eGFR) and incidence of CKD. Little is known regarding how CRF contributes to racial disparities in CKD. Hypotheses: We hypothesized that: 1) baseline CRF is inversely associated with the risk of incident CKD after adjustment for covariates and 2) differences in baseline CRF account for a proportion of the disparity in incident CKD between blacks and whites.

Methods:
A total of 4328 young adults without CKD (age 24.8±3.6 years, 52.8% (n=2285) women, 51.9% (n=2247 black) completed a maximal graded treadmill test at baseline. We calculated eGFR using the CKD-EPI formula (baseline eGFR: 102.1±17.9 and 92.3±14.1 mL/minute/1.73 m
2
for blacks and whites, respectively). We defined CKD status as eGFR of <60 mL/minute/1.73 m
2
during 10, 15, 20, 25, and 30 year follow-up assessments. Multivariable Cox models examined hazard ratios (HR) and 95% confidence intervals (CI) for incidence of CKD. Models adjusted for baseline race, sex, age, field center, alcohol intake, smoking status, healthy eating index, eGFR, maximal educational attainment, and time-varying BMI, diabetes, and hypertension. The percent reduction in parameter estimates determined the excess risk explained according to CRF.

Results:
During the 30 years of follow-up, 84 blacks and 43 whites developed CKD. Every 1-minute lower treadmill duration associated with 12% higher rate of CKD (HR=1.12 (1.01-1.22)). Blacks were 1.89 times more likely to develop CKD compared to whites (HR=1.89 (1.23-2.91)). This was reduced to 1.75 (1.13-2.70) with CRF added to the model. This corresponds to a β reduction of 14.3% for race according to CRF.

Conclusion:
Both low fitness during young adulthood and black race are associated with higher incidence of CKD later in life. Fitness is a modifiable factor that could be targeted to address a portion of the disparity gap in CKD.
Abstract 045: Leisure Time Physical Activity is Associated With Higher Coronary Artery Calcium Density: The Multi-Ethnic Study of Atherosclerosis
Authors: Thomas Isac C , Allison Matthew , Forbang Nketi , Takemoto Michelle , Michos Erin , McClelland Robyn , Budoff Matthew , Criqui Michael
Published: July 2021

Introduction:
Leisure-time physical activity (LTPA) has favorable effects on many risk factors for cardiovascular disease (CVD). Paradoxically, LTPA has also been associated with
higher
amounts of coronary artery calcium (CAC) in athletes. Recently, a higher
density
of CAC was shown to significantly mitigate the risk of CVD associated with a given volume of CAC. The effects of LTPA and non-LTPA on the density and volume components of CAC among individuals with calcified coronary atherosclerosis are unknown.

Methods:
We evaluated 3,398 participants from the Multi-Ethnic Study of Atherosclerosis with prevalent CAC (50% of cohort). CAC was assessed via cardiac computed tomography, while physical activity was assessed via questionnaire and categorized by quintiles of moderate and vigorous LTPA (e.g. exercise) and non-LTPA (e.g. work). Multiple linear regression with mutual adjustment for LTPA, non-LTPA, demographics, and CVD risk factors was performed.

Results:
Mean age of the sample was 66 years, 58% were male, 44% were Caucasian, 24% were African-American, 20% were Hispanic, and 12% were Chinese-American. Compared to the lower four quintiles, LTPA above the threshold of 2567 MET-minutes/week (quintile 5) was associated with 0.057 (0.008, 0.105)
higher
CAC density-units after full adjustment. LTPA at any level was not associated with CAC volume. Conversely, non-LTPA was associated with both
lower
CAC density and
higher
CAC volume in a stepwise fashion, with the highest quintile meeting statistical significance for both (see Table).

Conclusions:
The highest quintile of LTPA was associated with higher CAC density but not higher CAC volume, suggesting a possible explanation for high CAC scores in athletes with favorable CVD risk factor profiles. Non-LTPA was associated with a less favorable CAC composition after adjustment for LTPA, an unexpected finding that merits further investigation.
Abstract MP03: Plasma Sphingolipids and Risks of Heart Failure and Atrial Fibrillation in Older Adults: The Cardiovascular Health Study
Authors: Lemaitre Rozenn N , Jensen Paul N , McKnight Barbara , Hoofnagle Andrew , King Irena B , Heckbert Susan R , Sotoodehnia Nona , Mozaffarian Dariush , Psaty Bruce M
Published: July 2021

Introduction:
Ceramides and sphingomyelins (sphingolipids) are circulating lipids involved in multiple physiological pathways relevant to heart failure (HF) and atrial fibrillation (AF), including apoptosis, oxidative stress, and inflammation. Experimental studies suggest that sphingolipids with different saturated fatty acids exhibit different biological activities, but their relationships with HF and AF are unknown.

Hypothesis:
Higher levels of plasma ceramide and sphingomyelin that contain the fatty acid 16:0 are associated with higher risks of HF and AF; and higher levels of ceramides and sphingomyelins that contain the fatty acid 20:0, 22:0 or 24:0 are associated with lower risks.

Methods:
We measured sphingolipids in the Cardiovascular Health Study (CHS) in plasma samples from 1994-95 (N=4026) or from 1992-93 (N=586). We assessed the separate associations of the levels of 8 sphingolipids with risks of incident HF and incident AF using Cox regression. A p-value threshold of 0.006 was used to account for multiple testing.

Results:
Among 4,612 participants, 1179 incident HF and 1198 incident AF occurred during >40,000 person-years of follow-up. In adjusted analyses, higher levels of Cer-16 (ceramide with 16:0) and SM-16 (sphingomyelin with 16:0) were associated with higher risk of incident HF, but not with risk of incident AF (Table). In contrast, higher levels of Cer-20, Cer-22 and Cer-24 were each associated with lower risk of AF, but not with risk of HF. Higher levels of SM-20, SM-22, and SM-24 tended to be associated with lower risks of AF and HF, with only the association of SM-20 with AF significant.

Conclusions:
Plasma levels of ceramide and sphingomyelin with 16:0 show different associations with HF and AF than species with 20:0, 22:0 or 24:0. Associations of Cer-16 and SM-16 specifically with higher risk of HF may be due to a role of apoptosis in HF. The novel findings that Cer-20, Cer-22, and Cer-24 are associated with lower risk of AF warrant further examination of the role of these sphingolipids in protecting from AF.
Abstract MP31: State-Level Impact of Low Physical Activity on All-Cause Disease Burden
Authors: Sur Patrick , Afshin Ashkan
Published: July 2021

Introduction:
While a consensus for the beneficial effects of physical activity exists, the optimal level of exercise and its effect on the disease burden across all states of the United States has not been evaluated.

Objective:
To systematically quantify the attributable burden to physical inactivity in all states of the United States by age, sex, year, and cause.

Methods:
We obtained data on categorical prevalence of domain-specific and total physical activity levels from nationally or subnationally representative surveys. Risk-outcome effect sizes of total physical activity were gathered from a meta-analysis of prospective cohort studies. The optimal level of physical activity was determined based on the activity levels associated with lowest risk of mortality in prospective observational studies. A comparative risk assessment analysis then quantified the proportion of death and disability attributable to low physical activity. The variation of physical activity levels and its associated burden was further evaluated across each state of the United States.

Results:
In 2016, physical inactivity accounted for 87 (95% UI: 122.6- 44.5) thousand DALYs in the United States (84.4% from CVD, 9.1% from DM, and 6.5% from cancers), with 59% of DALYs coming from men and 41% in women. Only 5 states (WY, ME, MT, AK, VT) demonstrated mean total physical activity levels above our suggested physical activity level of 3500 MET-mins per week. The highest burden attributable to physical activity was seen in Mississippi, while the lowest was seen in Colorado (955 & 458 DALYs per 100,000, respectively).

Conclusion:
Our findings suggest that population inventions to increase physical activity at the population level could save hundreds of thousands of life years across the United States.
Abstract MP34: Tai Chi Exercise is More Effective Than Brisk Walking in Reducing Cardiovascular Disease Risk Factors
Authors: Chan Aileen W , Leung Doris Y , Chair SY , Sit Janet W , Taylor-Piliae Ruth E
Published: July 2021

Background:
Physical inactivity is one of the major modifiable lifestyle risk factors associated with cardiovascular disease (CVD). Tai Chi (TC) is safe and popular among older adults; yet direct comparisons between TC and brisk walking (BW) on reducing CVD risk factors are lacking.

Methods:
A total of 246 adults (mean age=64.4±9.8 years, 45.5% men) with hypertension and two other CVD risk factors (i.e., smoker, diabetic, dyslipidemia, or overweight) were randomly assigned to either TC (n=82), BW (n=82), or control (C, n=82) groups. The TC and BW groups had 150 minutes/week, moderate-intensity physical activity for three months; with home-based practice encouraged for another six months. The primary outcome was blood pressure (BP). Secondary outcomes were: fasting blood sugar (FBS), HbA1c, total cholesterol, triglycerides, high and low density lipoprotein, body mass index (BMI), waist circumference and perceived stress. Data were collected at baseline, post-intervention at 3-month, 6-month and 9-month follow-up assessments. Generalized estimating equations models compared changes in the outcomes over time between groups.

Results:
At baseline, average BP=141/81, smokers=11%, diabetics=58%, dyslipidemia=61%, average BMI=26; with no significant differences between groups. TC significantly lowered BP (systolic -13.33 mmHg; diastolic -6.45 mmHg), FBS (-0.72 mmol/L), HbA1c (-0.39%), and perceived stress (-3.22 score) at 9-months, compared to C group. Pairwise comparisons indicated significantly greater reductions in SBP (p<0.001), DBP (p=0.049), FBS (p=0.001), HbA1c (p=0.002), and perceived stress (p=0.027) in TC group, compared to BW group. No significant changes in other CVD risk indicators over time between groups were observed.

Conclusion:
TC was better than BW in reducing several CVD risk factors, and can be recommended as a viable exercise to build a healthier life free of CVD.
Abstract P006: Cardiovascular Disease Risk Factor Burden is Associated With Hearing Loss in Young Men: The Hispanic Community Health Study/Study of Latinos
Authors: Baiduc Rachael R , Bogle Brittany , Gonzalez Franklyn , Dinces Elizabeth , Lee David J , Daviglus Martha , Dhar Sumitrajit , Cai Jianwen
Published: July 2021

Introduction:
Over 30 million Americans suffer from hearing loss (HL). Studies suggest that established cardiovascular disease (CVD) risk factors may contribute to the pathophysiology of the inner ear. However, the aggregate effect of CVD risk factors on hearing is not well understood.

Hypothesis:
We hypothesized that high CVD risk burden is associated with worse hearing.

Methods:
We assessed younger (ages 18-34) and older (ages 55-64) Hispanic Community Health Study / Study of Latinos participants who underwent audiometry in 2008-11. After excluding those with conductive pathology and asymmetric HL, we randomly chose one ear for analysis. Puretone thresholds were obtained at 0.5-8 kHz; puretone average (PTA) was calculated using thresholds at 0.5, 1, 2, and 4 kHz. Low CVD risk burden was defined as having all of: blood pressure (BP) <120/<80 mmHg; total cholesterol <180 mg/dL; not currently smoking; and not having prevalent diabetes. High CVD risk burden was defined as ≥ 2 of: diabetes; currently smoking; BP >160/>100 mmHg (or antihypertensive use); and total cholesterol >240 mg/dL (or statin use). By age group and sex, we estimated hearing thresholds per frequency with linear regression models adjusted for noise exposure. Least squares estimates were calculated using strata-specific means of covariates. Estimates were compared via t-tests. Data were weighted for all analyses and accounted for clustering.

Results:
Among younger and older individuals in the target population (51.9% female), 28.8% had low and 5.5% had high CVD risk. Younger men with high CVD risk had worse PTA than young men with low risk (7.7 dB HL [7.0-8.4] vs. 10.5 dB HL [8.4-12.5],
p
=0.02), and had significantly worse thresholds at 1,3,4,6 kHz than those with low risk (
Figure
). There was no difference in PTA or thresholds at any frequency by CVD risk burden in young women, older men, or older women.

Conclusions:
CVD risk burden is associated with HL among young men, but not young women or older adults. CVD risk burden may be useful for identifying young men at risk for HL.
Abstract P070: Risk of All-cause Mortality in Women versus Men With Type 2 Diabetes: A Systematic Review and Meta-analysis
Authors: Xu Jiaying , Xu Guodong , Duan Donghui , Zhao Jinshun , Zhang Lina , Han Liyuan
Published: July 2021

Introduction:
Previous studies have shown sex differences in the all cause mortality rate associated with type 2 diabetes.

Hypothesis:
We did a meta-analysis to provide reliable and comprehensive estimates of type 2 diabetes on risk of all-cause mortality in women versus men.

Methods:
We systematically searched PubMed, Embase, and Web of science for studies published from their starting dates to October 10, 2017. Studies were selected only if they reported sex-specific estimates of the standardized mortality ratio (SMR) or hazard ratios associated with type 2 diabetes for all-cause mortality. We used random effects meta-analyses with inverse-variance weighting to obtain sex-specific SMRs and their pooled ratio (women to men) for all-cause mortality. Study quality was assessed using the Newcastle–Ottawa scale.

Results:
Data from 30 studies including 2,307,694 individuals and 252,491 deaths occurred were included. The pooled women-to-men ratio of the SMR for all-cause mortality was 1·14 (95% CI 1.09-1.19, p<0.001; I
2
=81.6%). Compared with healthy counterparts, the pooled SMR for all-cause mortality in patients with T2D was 2.30(95%CI 1.97-2.68) in women, and 1.94(95%CI 1.73-2.18) in men, respectively. Sensitivity analysis with omission of one study at a time did not change the results of this meta-analysis.

Conclusions:
Women with type 2 diabetes have a roughly 14% greater excess risk of all-cause mortality compared with men counterparts. This meta-analysis was registered at the International Prospective Register of Systematic Reviews (Prospero) (
http://www.crd.york.ac.uk/PROSPERO
; registration number: CRD42017074187).

Figure 1
.Pooled women-to-men ratios of SMRs for all-cause mortality, comparing people with type 2 diabetes versus healthy counterparts.
Abstract P071: Association of Baseline Depressive Symptoms With 6-Year Incidence of Diabetes in the Hispanic Community Health Study/Study of Latinos
Authors: O'Brien Matthew J , Carnethon Mercedes R , Penedo Frank J , Tabb Karen M , Wassertheil-Smoller Sylvia , Schneiderman Neil , Khambaty Tasneem , Llabre Maria M , Perera Marisa J , Sotres-Alvarez Daniela , Gallo Linda C , Perreira Krista M , Daviglus Martha
Published: July 2021

Background:
Among Hispanics/Latinos, there is substantial heterogeneity in the prevalence of depressive symptoms and diabetes by background. This study aimed to examine the association between depressive symptoms and incident diabetes among Hispanic/Latino adults of diverse backgrounds.

Methods:
The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a prospective, community-based study of 16,415 self-identified Hispanic/Latino adults aged 18-74 years at Visit 1 (2008-2011) and 10,914 who have also completed the Visit 2 examination by August 2017. This analysis includes 8,804 participants who were free from diabetes at baseline and attended both Visits. Baseline depressive symptoms were assessed using the CES-D 10-item depression scale and divided into quartiles. Incident diabetes was defined by fasting glucose ≥126mg/dL, 2-hour postload glucose 140-199mg/dL, HbA1c ≥6.5%, or self-report. Accounting for HCHS/SOL complex survey design, we used Poisson regression models to estimate diabetes incidence density ratios (Table).

Results:
Baseline BMI was associated with both depressive symptoms and incident diabetes. Overall, 876 participants developed diabetes. In analyses stratified by Hispanic/Latino background, the association between baseline depressive symptoms and incident diabetes was significant for South Americans, Central Americans, and Mexicans. No significant associations between depressive symptoms and diabetes were seen among Hispanics/Latinos of Dominican, Cuban, or Puerto Rican backgrounds.

Conclusions:
These findings suggest that the association between depressive symptoms and incident diabetes in Hispanics/Latinos may differ by their background, with South and Central Americans at the highest risk. This difference may be partly explained by variation in participants’ understanding of CES-D questions by Hispanic/Latino background. Future research is needed to understand these novel findings fully and explore their implications for practice and policy.
Abstract P127: Gene-Lifestyle Interactions Detect Novel Blood Pressure Loci
Authors: Osazuwa-Peters Oyomoare L , Schwander Karen L , Sung Yun J , de las Fuentes Lisa , Rao Dabeeru C
Published: July 2021

Introduction:
Gene-lifestyle interaction effects (GxE more generally) on blood pressure (BP), a promising approach for novel loci discovery, is being actively pursued in the CHARGE Gene-Lifestyle Interactions Working Group using individual lifestyle domains, such as smoking status.

Objectives:
To explore the potential utility of a “lifestyle index” (aggregating multiple lifestyle domains) for identifying novel BP loci in a GxE context, we performed genome-wide interaction analysis with two lifestyle index variables.

Methods:
For each of 6,257 subjects (19 – 80 years, 46.9% male) in the Framingham Heart Study SHARe dataset, lifestyle index was defined as the sum of risk scores for four lifestyle factors: smoking status (0 = Never, 1 = Former, 2 = Current), alcohol intake (0 = Moderate, 1 = Never, 2 = Heavy), physical activity (0 = Active, 1= Inactive), and educational level (0=College degree, 1 = Some college, and 2 = No college). We examined GxE for systolic BP using the quantitative index (ranging from 0 to 7) and a binary form of the index (≥ vs < the median), while adjusting for sex, age, and kinship. Promising loci were identified using a 2 df joint test of main and interaction effects at α = 5 x 10
-6
.

Results:
Sixteen promising single nucleotide polymorphisms (SNPs) representing 8 loci were found when using the quantitative lifestyle index, and 43 SNPs representing 4 loci when using the binary lifestyle index (Table 1), with only one locus common to both indices. Of the 11 unique loci detected, 3 are within 500 kb of known BP loci and 6 are in or near a gene with a known function.

Conclusions:
We demonstrate that a composite of multiple lifestyle factors can enhance novel discovery.