bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P252: The Effects of Sodium Reduction on Metabolism and Thirst
Authors: Juraschek Stephen P , Miller Edgar R , Chang Alexander , Anderson Cheryl , Hall John E , Appel Lawrence J
Published: July 2021

Background:
Recent studies challenge the traditional understanding of sodium physiology. Some animal studies suggest that high sodium intake may induce catabolism, leading to weight loss. Other studies suggest that high sodium intake might reduce, rather than increase, thirst.

Hypothesis:
Higher sodium intake increases thirst, fluid intake, and sodium excretion without altering energy intake or lowering weight.

Methods:
In the DASH-Sodium feeding study, adults with pre- or stage 1 hypertension without antihypertensive medications, were randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks (randomized crossover design). Participants were provided all meals, but could drink water freely. Throughout the trial, calorie intake was adjusted to keep weight constant. The three sodium levels (at 2100 kcal/d) were: low (1150 mg), medium (2300 mg), and high (3450 mg). Weight, energy intake, self-reported thirst, urine volume, plasma renin, serum aldosterone, urine osmolality, and urine sodium excretion were assessed at the end of each period.

Results:
Among 412 participants (57% women, 57% black, mean age 48 yrs), weight increased slightly with higher sodium on the control diet, but not the DASH diet; energy intake did not vary across sodium levels in both diets (
P
-trends > 0.34) (
Table
). In contrast, participants reported more thirst with high vs low sodium (both diets
P
-trends < 0.001) and potentially higher fluid intake (urine volume) during the control diet (1,566 vs 1,491 ml on high vs low sodium;
P
-trend = 0.07). On both diets, plasma renin and serum aldosterone were lower with higher sodium (each
P
-trend < 0.001). Likewise, both urine osmolality and sodium excretion were higher with higher sodium intake (all
P
-trends < 0.001).

Conclusions:
Higher sodium intake did not alter energy intake, but did increase thirst and sodium excretion. These findings are consistent with the traditional understanding of the physiology of excess dietary sodium intake.
Abstract P254: Is Obesity Associated With the Predicted 6-Month Mortality in Patients With Atrial Fibrillation and Acute Coronary Syndrome?
Authors: Chesler Roseann , Fung Daniel , Kamran Haroon , Cavusoglu Erdal , Mitchell Judith E
Published: July 2021

Introduction:
The blunting of the expected improvement in cardiovascular health over the past decade has been attributed in part to the substantial increase in the prevalence of obesity. Atrial fibrillation and heart failure are among the cardiovascular diseases with increasing incidence in the US. We sought to evaluate the effect of obesity on the predicted 6-month mortality in our patients with atrial fibrillation [AF] and acute coronary syndrome [ACS] utilizing the GRACE score [GS], a validated risk assessment model for predicting death within 6-months of hospital discharge.

Methods:
Eighty patients, 88% black, 54% female, mean age 68, +/-12, h/o AF admitted with ACS were included.

Results:
An extraordinarily high prevalence of DM and HTN [46% and 95% respectively] and obesity [46%] were noted. The mean weight: 87 Kg, +/- 23. The mean BMI was 31 kgm
2
, +/-10; median BMI 29 kgm
2
and 25% had a BMI of 35 kgm
2
or greater, (Chart). Seventy-five percent of the cohort had clinical or radiographic evidence of congestion. Ejection fraction: mean 45%, +/-17. B-type natriuretic peptide [BNP] level: mean 765 pg/ml. BNP was significantly and negatively related to obesity [BMI p= 0.0001; r=
-
0.422; weight p= 0.001; r=
-
.359]. This inverse relationship of BNP and obesity was most apparent when comparing the level of BNP in patients who were at or above the median BMI (29.3 kgm
2
), p= 0.001, (Fig). Although we found a significant direct association of the GS with age [p<0.001; r= .62], troponin [p=0.001; r= .74] and BNP [p= 0.018; r= .41], no independent significant relationship was apparent with obesity [weight p= 0.54; r= -.11, or BMI p= 0.11; r= -.28].

Conclusions:
In a traditionally high risk cohort with AF and ACS a high prevalence of obesity was recorded. Clinical or radiographic evidence of congestion was present in the majority. We found no significant link between obesity in this population and the GS—predictor of 6-month mortality. Can this be another cardiovascular paradox? Lengthier outcome studies of larger cohorts are warranted.
Abstract P265: Cancer Risk in Persons After a Diagnosis of Clinical Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Mok Yejin , Florido Roberta , Selvin Elizabeth , Prizment Anna , Joshu Corinne E , Platz Elizabeth A , Matsushita Kunihiro
Published: July 2021

Introduction:
With improved survival of patients with cardiovascular disease (CVD), the risks of non-CVD outcomes is of increasing interest. We investigated the risk of subsequent cancer in persons with clinical CVD compared to those without using a matched cohort study nested in the ARIC study.

Hypothesis:
Persons with CVD may have higher risk of cancer compared to those without.

Methods:
In ARIC participants (aged 45-64 years) without prevalent CVD or cancer at the study baseline (1987-1989), we first identified every participant who developed clinical CVD (myocardial infarction [MI], heart failure, or stroke as a combined outcome and separately) during follow-up (through 2012). For each of them, applying incidence density sampling, we selected up to two participants without clinical CVD matched on key confounders (age, sex, race, diabetes, hypertension, lipid-lowering therapy, and smoking). Then, we used the Cox proportional hazards regression to estimate the risk of total and site-specific cancer comparing CVD to no CVD further adjusting for conventional risk factors for CVD or cancer, socioeconomic status, insurance, and routine physical examination.

Results:
We followed 2,565 with CVD and 4,622 without CVD from the date of sampling for a total of 62,772 person-years (mean of 9 years). The hazard ratio [HR] for total cancer risk was 1.13 (95% confidence interval, 1.00-1.32) for participants with CVD compared to those without. None of the HRs for site-specific cancers were statistically significant. When individual CVD subtypes were analyzed separately, participants with MI and heart failure had 2.1- and 1.3- folds significantly higher risk of total cancer compared to those without, respectively. Participants with MI had significantly increased HR in major types of cancer such as prostate, lung, and breast, with adjusted HR ranging from 2.5 to 3.5.

Conclusion:
Persons with clinical CVD, especially MI, had a modestly increased risk of total cancer following that event compared to those without. Future studies are warranted to better understand its potential reasons.
Abstract P266: Prevalence and Risk Factors of Thyroid Dysfunction in Older Adults in the Community
Authors: Diab Nermin , Daya Natalie , Juraschek Stephen P , Martin Seth , McEvoy John W , Schultheiß Ulla T , Köttgen Anna , Selvin Elizabeth
Published: July 2021

Context:
Prevalence estimates and evidence informing treatment targets for thyroid dysfunction largely come from studies of middle-aged adults. There are limited data on the prevalence of thyroid dysfunction in older populations.

Objective:
To determine the prevalence of thyroid dysfunction and risk factors for abnormal thyroid tests in older adults.

Methods:
We conducted a cross-sectional analysis of data from participants aged 65 or older in the Atherosclerosis Risk in Communities (ARIC) study who attended visit 5 in 2011-2013. We measured serum concentrations of triiodothyronine (T3), free thyroxine (FT4), thyroid peroxidase antibody (Anti-TPO), and thyroid stimulating hormone (TSH) in 5,392 participants. We used multivariable linear and logistic regression to assess associations of demographic and clinical risk factors with thyroid hormone levels.

Results:
In this population of older adults (mean age 76; 56% women and 22% black), the prevalence of thyroid dysfunction was up to 25% when accounting for treated and untreated thyroid dysfunction categories. 15.6% reported use of medication for thyroid dysfunction. Among those not being treated, the prevalence of overt chemical hypothyroidism was 6.0% and subclinical hypothyroidism was 0.82%. Overt chemical hyperthyroidism and subclinical hyperthyroidism affected 0.26% and 0.78% of the population, respectively. Multivariable adjusted cardiovascular risk factor associations for TSH, FT4 and T3 levels are presented in
Table
. Men were less likely to be anti-TPO positive compared to women (OR=0.59, CI: 0.47,0.75, P<0.001).

Conclusions:
There is a high prevalence of thyroid dysfunction in this older, community-based population. Prevalence of thyroid dysfunction and thyroid hormone levels vary with sex, race, age group and multiple cardiovascular risk factors. Accounting for these associations in the clinical setting might prove useful in improving thyroid function assessment in this age group.
Abstract P270: Body Size Throughout the Life Course and Risk of Venous Thromboembolism
Authors: Hagan Kaitlin A , Harrington Laura B , Kim Jihye , Grodstein Francine , Kabrhel Christopher
Published: July 2021

Introduction:
Adult body mass index (BMI) is strongly associated with venous thromboembolism (VTE), however whether earlier-life adiposity or other measures of adult adiposity are associated with VTE risk remains unknown.

Hypothesis:
Since BMI is a strong risk factor for incident VTE, we hypothesized that early life body size as well as other measures of adult adiposity may also be positively associated with VTE risk.

Methods:
We evaluated associations of childhood somatotype, BMI at age 18, change in BMI since age 18, and measures of waist and hip circumference with incident VTE among 47,415 women age 40-67 years at baseline from the Nurses’ Health Study (NHS), 47,539 women age 29-48 years from the Nurses’ Health Study II (NHS II), and 32,707 men age 39-76 years from the Health Professionals Follow-Up Study (HPFS) without a prior VTE. We calculated multivariable-adjusted hazard ratios (HR) of VTE using Cox proportional hazards models.

Results:
Over ≥25 years of follow-up, there were 1,191 incident VTE cases in NHS, 763 cases in NHS II, and 1,350 cases in HPFS. Adult BMI was strongly associated with VTE in all three cohorts (HRs comparing ≥35 kg/m
2
vs. <22.5 kg/m
2
: NHS: 3.03 [95% CI: 2.58, 3.55], NHS II: 3.88 [95% CI: 3.36, 4.48], HPFS: 2.49 [95% CI: 1.83, 3.29]; all P
trend<
0.01). Waist circumference, hip circumference, and height were associated with greater VTE risk, even after adjusting for adult BMI (all P
trend<
0.01) (Table). Somatotype at ages 5 and 10, BMI at age 18, and change in BMI since age 18 were not significantly associated with VTE risk, after accounting for adult BMI.

Conclusions:
Adult BMI, waist circumference, hip circumference, and height were independently, positively associated with incident VTE risk. Early life body size was not significantly associated with VTE risk after accounting for adult BMI, indicating that BMI and adiposity are likely more important acutely that cumulatively over time in the etiology of VTE. Clinically, encouraging weight loss in adults
Abstract P286: Walking as a Source of Physical Activity for Cardiovascular Disease Prevention
Authors: Omura John D , Ussery Emily N , Loustalot Fleetwood , Fulton Janet E , Carlson Susan A
Published: July 2021

Introduction:
Increasing physical activity among adults at risk for or with cardiovascular disease (CVD) can help prevent and manage disease. Walking may present an opportunity for promoting physical activity among this high risk group. We hypothesized that in US adults the prevalence of self-reported walking would decrease with increasing CVD risk.

Methods:
Nationally representative data from the 2015 National Health Interview Survey Cancer Control Supplement (N=28,780) were analyzed. Analyses were repeated after excluding those needing assistance with walking (n=2,192). Walking was defined as engaging in at least one 10-minute bout of transportation or leisure walking in the past seven days. Prevalence estimates of walking (any, transportation, and leisure) are reported overall and by presence of risk factors (overweight or obesity and ≥1 of diabetes, high cholesterol, or hypertension) or CVD (myocardial infarction or stroke). Orthogonal polynomial contrasts were used to identify significant trends.

Results:
Overall, 64.9% (standard error, SE=0.5) of adults reported any walking (TABLE). This prevalence was highest among those with no CVD or risk factors (67.1%, SE=0.5), decreased with increasing number of risk factors (1 risk factor: 64.0%, SE=1.0; 2 risk factors: 60.3%, SE=1.3; 3 risk factors: 54.8%, SE=2.0), and the lowest was among those with CVD (51.9%, SE=1.7). Similar trends were observed for leisure and transportation walking. To ensure differences in prevalence of walking by risk factor or disease status was not due to functional limitations, repeated analyses that excluded those needing assistance with walking observed similar patterns.

Conclusions:
Prevalence of any and leisure walking decreased as the presence of CVD risk factors increased and was lowest among those with disease. Promoting walking, especially among adults at higher risk, may present an important opportunity for encouraging an active lifestyle for CVD prevention and management.
Abstract P311: Individual Characteristics of Resilience Are Associated With Lower-Than-Expected Neighborhood Rates of Cardiovascular Disease in African-Americans: Results From the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity Study
Authors: Topel Matthew L , Xu Junjun , Baltrus Peter , Vaccarino Viola , Mujahid Mahasin S , Quyyumi Arshed A , Taylor Herman A , Lewis Tene T
Published: July 2021

Background:
Excess rates of cardiovascular (CV) disease in African-Americans, relative to Whites, have been well-documented. However, factors promoting CV health in the face of high risk, i.e. CV resilience, are unknown and may identify novel areas for intervention in reducing racial health disparities.

Methods:
Using data obtained from the Georgia Hospital Association, we identified age-, sex-, and income-matched neighborhoods (census tracts) in Atlanta, GA, with higher-than-expected (“high risk") or lower-than-expected (“low risk") rates of CV morbidity and mortality for African-Americans from 2010-2014. African-Americans from low risk (N = 742) and high risk (N = 753) neighborhoods were surveyed. Several domains of psychosocial well-being and neighborhood quality were assessed as features of resilience, in addition to individual demographic, socioeconomic and medical history variables. Ordinal logistic regression was used to determine odds of resilient characteristics among individuals living in neighborhoods at low versus high risk.

Results:
After adjustment for age, sex, household income, education, marital status and occupation, African-Americans living in low compared to high risk neighborhoods reported better overall neighborhood quality (odds ratio [OR] 1.25; 95% confidence interval [CI] 1.01, 1.57), driven by better aesthetic quality (OR 1.42; CI 1.17, 1.73), more safety (OR 1.34; CI 1.10, 1.62), absence of violence (OR 1.42; CI 1.10, 1.83) and better access to healthy foods (OR 1.50; CI 1.24, 1.82). Additionally, individuals from low compared to high risk neighborhoods reported greater environmental mastery (OR 1.33; CI 1.03, 1.71), purpose in life (OR 1.22, CI 1.01, 1.48), optimism (OR 1.28; CI 1.05, 1.55) and resilient coping (OR 1.33; CI 1.04, 1.70), while also reporting less depressive symptoms (OR 0.78; CI 0.63, 0.98). There were no reported differences in CV risk factors or disease, religious practices, spirituality or experiences of discrimination between low and high risk neighborhoods.

Conclusions:
African-Americans living in neighborhoods at lower risk for CVD morbidity and mortality reported better neighborhood quality and psychosocial well-being than individuals from neighborhoods at higher risk. Neighborhood and personal psychosocial determinants of health may confer resilience to CVD in African-American individuals and communities.
Abstract P320: Optimism and Cardiovascular Health Among African Americans in the Jackson Heart Study
Authors: Sims Mario , Glover LáShauntá , Norwood Arnita , Jordan Christina , Min Yuan-I , Brewer LaPrincess , Kubzansky Laura
Published: July 2021

Introduction:
Compared to other racial and ethnic groups, African Americans experience greater negative psychosocial factors (depression, stress), which are related to increased risk of cardiovascular disease (CVD). Little research has examined the association of positive psychosocial factors (optimism) with cardiovascular health in this population. Using the Jackson Heart Study (JHS) data, we examined the association of optimism with the American Heart Association Life’s Simple 7
TM
(LS7), a measure of seven metrics that assesses a person’s cardiovascular health.

Hypothesis:
Higher levels of optimism are positively associated with individual LS7 metrics, and positively associated with the total LS7 score.

Methods:
We evaluated cross-sectional associations of optimism with each LS7 metric [cigarette smoking, physical activity, diet, body mass index (BMI), blood pressure, cholesterol, glucose] and with a composite LS7 score among 4,761 participants, 21-95 years old (women=3,070; men=1,691) enrolled in the JHS, a single-site, community-based cohort of African Americans residing in Jackson, MS. Optimism was measured in tertiles (low, moderate, high) to examine threshold effects. Each LS7 metric was classified as poor, intermediate, and ideal. LS7 metrics were also summed to create a total continuous score (0-13) categorized in tertiles (low, moderate, high). Multinomial logistic regression estimated the odds ratios (OR, 95% confidence interval-CI) of intermediate (vs. poor) and ideal (vs. poor) LS7 metric by levels of optimism. Multinomial regression also estimated the odds of moderate (vs. low) or high (vs. low) total LS7 score by optimism. Models adjusted for demographics, SES, and depressive symptoms.

Results:
Descriptive findings showed that participants who reported high optimism had ideal physical activity, nutrition, smoking, blood pressure, glucose and high total LS7 score (all p<0.01). After adjustment for age, sex, education, income, marital status, and insurance status, participants who reported high (vs. low) optimism had a 39% increased odds of having ideal (vs. poor) physical activity (OR 1.39; 95% CI 1.10-1.76) and a 33% increased odds of having ideal (vs. poor) smoking (OR 1.33; 95% CI 1.02-1.73). Participants who reported high (vs. low) optimism had a 34% greater odds of having a high (vs. low) total LS7 score (OR 1.34 95% CI 1.03-1.74) after full adjustment.

Conclusion:
Optimism is associated with ideal physical activity and ideal smoking, which is important for promoting cardiovascular health and reducing the risk of CVD among African Americans in this sample.
Abstract P326: Perceived Neighborhood Crime is Associated With Serum Cholesterol Levels Among Females, but Not Males: Santiago Longitudinal Study
Authors: Delker Erin M , Blanco Estela , East Patricia , Burrows Raquel , Delva Jorge , Gahagan Sheila
Published: July 2021

Introduction:
In a Chilean sample, adolescents’ CVD risk factors were associated with perceived neighborhood crime. To determine if this effect was sustained, we examined associations between adolescents’ perceived neighborhood crime and their serum cholesterol levels in young adulthood. Neighborhood stress has been cross-sectionally related to dyslipidemia in previous studies.

Hypothesis:
(1) Higher levels of perceived crime will be associated with higher low-density lipoprotein (LDL) cholesterol and lower high-density lipoprotein (HDL). (2) Sex will modify this association.

Methods:
Data were from adolescent (x =14 yrs) and young adult waves (x =22 yrs) of the Santiago Longitudinal Study (N=645). Perceived neighborhood crime was measured using three scale items about neighborhood drug use, muggings, burglaries and assaults. Crime was analyzed as a continuous and categorical variable. Fasting HDL and LDL cholesterol (mg/dL) were measured at 22 yrs. Associations between crime and HDL and LDL were analyzed by linear regression, adjusting for sex, age and SES. Effect modification by sex was tested with sex*crime interaction.

Results:
Participants were low-middle income and 55% female. Females perceived slightly more crime than males (F: x =9.1 M: x =8.8, p=0.30). There was a significant sex*crime interaction for HDL (p=0.03) and LDL (p=0.01). Among males, average HDL and LDL were 100±32 and 41±12; crime did not relate to either outcome. Among females, average HDL and LDL were 100±28 and 46±14; neighborhood crime was negatively associated with HDL and positively associated with LDL. For example, females reporting the most crime had, on average, 7.5 mm/dL lower HDL and 12.8 mm/dL higher LDL than females reporting the least amount of crime (Fig. 1).

Conclusions:
Perceived crime was prospectively associated with worse lipid profiles among females but not males. A sex-specific stress mechanism may be operating. Further study of the physiologic and behavioral mechanisms contributing to these findings is needed.
Abstract P327: Stress Overload and Methylation of Hypertension Related Genes
Authors: Brown Kristen M , Hui Qin , Crusto Cindy , Taylor Jacquelyn Y , Sun Yan V
Published: July 2021

Background:
Nearly 30% of U.S. adults are hypertensive with a high prevalence existing among Black Americans (42%). Exposure to psychosocial stress has been identified as a risk factor for hypertension and may explain part of the observed racial disparities. One pathway through which stress exposure may mechanistically alter biological functioning in a manner that affects risk of hypertension is via epigenetic modifications in hypertension-related genes, but this area remains understudied.

Aims and Hypothesis:
In the present study, we investigate the relationship between stress exposure and methylation of 25 genes that have been associated with blood pressure in Blacks in previous genetic research. We hypothesize that stress exposure is associated with DNA methylation of blood pressure related genes.

Methods:
We conducted an epigenetic association study using data from the ongoing InterGEN Study, a longitudinal investigation of the psychological, environmental, and genetic factors that contribute to hypertension risk in African American mothers (n=74) and their young children. Stress exposure was measured using the 24-item Stress Overload Scale (α=0.95), and a summary score was calculated by summing the Likert scale responses. Methylation was measured using the Illumina Infinium MethylationEPIC Beadchip, and M-values (i.e. log2 ratio of the intensities of methylated probe versus unmethylated probe) were calculated for association analysis. Linear regression was employed to assess the association between stress exposure and methylation in the a priori defined genes.

Results:
At p<0.05, we identified 45 methylation sites associated with stress overload. These sites represented 17 of the 25 investigated genes. The most statistically significant sites were related to the genes: insulin like growth factor binding protein 3 (
IGFBP3
), calcium voltage-gated channel subunit alpha1 H (
CACNA1H
), and solute carrier family 4 member 5 (
SLC4A5
) (p=0.001, p=0.002, and p=0.006, respectively).

Conclusion:
This study provides biological insight into DNA methylation as a mechanism whereby exposure to psychosocial stress affects risk of hypertension in Black women. Additional replication studies with a larger sample size and includes men are needed to validate and generalize the findings. Future research should further investigate the biological mediators between DNA methylation and hypertension manifestation.
Abstract P329: Prospective Association of Serum Uromodulin and Cardiovascular Disease in Chronic Kidney Transplant Receipents
Authors: Eaton Charles B , Steubl Dominik , Roberts Mary , Garimella Pranav , Shireman Theresa , Pasch Andreas , Ix Joe , Katherine Tuttle R , Ivanova Anastasia , Pfeffer Marc A , Bostom Andrew
Published: July 2021

Serum levels of the exclusively renal-derived glycoprotein, uromodulin, a putative tubular function index, were recently associated with the development of fatal and non-fatal cardiovascular disease [CVD] outcomes during longitudinal surveillance of two cohorts undergoing diagnostic coronary angiography (Leiherer A et al. Int J Cardiol. 2017; 231:6-12; Delgado GE et al. 2017; 28: 2201-10). Using a case-cohort design (total n=685; random subcohort n=433) from the completed FAVORIT trial of chronic, stable kidney transplant recipients [KTRs], we examined the association between baseline serum uromodulin (mean ± standard deviation [SD]: 67.8 ±39.7 ng/mL), and the development of CVD (myocardial infarction, CVD death, stroke, & major revascularization procedures, pooled, n=311 events), during a median 3.7 years of follow-up. Unadjusted, weighted Cox proportional hazards modeling, based upon the subcohort uromodulin level SD (±39.7), revealed that each SD higher was associated with a 23% decreased risk for CVD (hazards ratio [HR]= 0.77; 95% confidence interval [CI]=0.65-0.92). This association was attenuated after adjustment for age, sex, smoking status, graft type, prevalent diabetes & CVD, systolic blood pressure gt140, diastolic blood pressure lt 70, estimated glomerular filtration rate [eGFR] gt=45 mL/min per 1.73m
2
, & natural log urinary albumin/creatinine [UACR]: (HR=0.83; 95% CI=0.67-1.04). Comparing subcohort uromodulin [ng/mL] quartile ranges (Q1=5.6-39.1; Q2=39.2-58.8; Q3=58.9-82.9; Q4=83.0-309.6), with the lowest quartile as referent, unadjusted Cox models demonstrated that the risks for CVD were as follows: Q2 v. Q1 (HR=0.92; 95% CI=0.62-1.38); Q3 v. Q1 (HR=0.69; 95% CI= 0.46-1.03); Q4 v. Q1 (HR=0.56; 95% CI=0.37-0.85). Full adjustment yielded: Q2 v. Q1 (HR=1.16; 95% CI= 0.70-1.92); Q3 v. Q1 (HR= 0.77; 95% CI=0.44-1.37); Q4 v. Q1 (HR=0.76; 95% CI=0.44-1.31). Higher serum uromodulin, an ostensible indicator of better preserved tubular function, was associated with reduced risk for the development of CVD in a large cohort of chronic, stable KTRs, but this association did not persist upon adjustment for major CVD risk factors, eGFR, & UACR.
Abstract P344: Sleep Duration and Obesity: Impact of Demographics, Socioeconomic Status, Health Behaviors, and Health Status
Authors: Grandner Michael
Published: July 2021

Introduction:
Many studies have shown that sleep duration is associated with obesity. It is unclear, though, whether this relationship exists equally across groups and whether it depends on demographics, socioeconomics, or aspects of health.

Methods:
Nationally-representative data from the 2016 BRFSS was used. Obesity was calculated as BMI≥30. Sleep duration was categorized as very short (≤4), short (5-6), normal (7-8), and long (≥9). Covariates included demographics (age, sex, race/ethnicity, education, marital status), socioeconomics (education, income, employment, # children), health risk factors (smoking, heavy drinking, sedentary lifestyle, access to a doctor, foregoing medical care due to cost), and health status (physical health, mental health, health-related limitations). Weighted logistic regression examined 5 models (unadjusted, demographics, add socioeconomics, add health behaviors, add health status). Whether relationships depended on covariates were evaluated with interaction terms and followed up by stratified analyses.

Results:
See Table for associations between sleep duration and obesity across all 5 models. In all models, very short, short, and long sleep were all associated with obesity, with very short sleep carrying the greatest risk. Note that as the number of covariates increased, the analytic samples were smaller. Interaction terms for all variables were statistically significant (p<0.001). Very short and short sleep effects were strongest in the youngest adults. Relationships were stronger in women. Sedentary individuals, heavy drinkers, and smokers demonstrated a weaker relationship. Lack of care was associated with a stronger relationship.

Conclusions:
Both short and long sleep are associated with obesity, even after accounting for many covariates. However, this relationship depends on factors such as age, sex, race/ethnicity, socioeconomic status, and health. This will help towards understanding risk and targeting interventions.
Abstract P356: Prevalence of Left Ventricular Hypertrophy versus Atrial Fibrillation on Electrocardiogram in Stroke Patients
Authors: Tahir Hassan , Omar Mazen , Omar Bassam A , Awan G. Mustafa , Malozzi Christopher
Published: July 2021

Background:
While atrial fibrillation is a well established cause of stroke, a strong association has been previously postulated between left ventricular hypertrophy (LVH) and stroke. The prevalence and significance of LVH by electrocardiogram in stroke patients, however, is not clear.

Objectives:
To examine the prevalence of left ventricular hypertrophy by electrocardiographic (EKG) criteria, versus atrial fibrillation or flutter, in patients receiving an EKG for a diagnosis of stroke.

Methods:
An EKG database from a university cardiology noninvasive lab was examined for the diagnosis of stroke or CVA over a one year period. The EKGs were evaluated for the presence of LVH or atrial fibrillation/flutter. The results were analyzed using a categorical Chi square test.

Results:
There was a total of 14,798 EKGs performed over one year, 1,439 of which reported LVH (9.7%). There were 272 EKGs with a diagnosis of acute stroke or CVA (1.7% of total EKGs). Out of these, there were 174 EKGs in sinus rhythm without LVH (64%), 78 EKGs in sinus rhythm with LVH (29%, P < 0.05), and 20 EKGs in atrial fibrillation or atrial flutter (7.4%).

Discussion:
Stroke is major health problem associated with increased mortality and morbidity. Hypertension is a well established risk factor for stroke in addition to cardiovascular events, and when long-standing and uncontrolled, causes left ventricular hypertrophy on EKG. In our cohort nearly one third of patients with stroke were in sinus rhythm, but had left ventricular hypertrophy by EKG, a prevalence that was four time that of atrial fibrillation or atrial flutter, and three time the prevalence of LVH in the overall database. Therefore, LVH by EKG appears to predict an increased risk of stroke, and thereby need for aggressive work-up and risk factor modification. Further studies to examine blood pressure and other cardiovascular risk factors as correlates of LVH on EKG will help shed further light on this important observation.
Abstract P359: Non-Alcoholic Fatty Liver Disease Severity is Associated With Aortic Stiffness Independently From Adiposity and Cardiovascular Risk Factors
Authors: Harada Paulo , Bensenor Isabela M , Goulart Alessandra C , Mill Jose G , Lotufo Paulo A
Published: July 2021

Background:
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions closely related to adiposity, hypertension, diabetes, and dyslipidemia. NAFLD has been consistently associated with adverse-health cardiovascular outcomes and subclinical atherosclerosis markers. However, there are contradictory findings (most of them with few participants) of the relationship between NAFLD and aortic stiffness: ones describing as an independent association, others as an association mediated by traditional cardiovascular risk factors.

Hypothesis:
NAFLD presence and severity is associated independently with aortic stiffness.

Methods:
We addressed this question among civil servants aged 35 to 74 years, 54% of them, women, and free of cardiovascular disease during the baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The presence and severity of NAFLD were assessed by ultrasound hepatic attenuation validated with computerized tomography. Aortic stiffness was measured by the carotid-femoral pulse wave velocity (cf-PWV) by a non-invasive certified device (Complior SP). We applied ANOVA to compare the estimated cf-PWVs means and 95% Confidence according to NAFLD categories. These values were adjusted for age, sex, race, waist circumference, diabetes, dyslipidemia, high sensitivity C reactive protein, mean arterial pressure, and use of anti-hypertensive drugs.

Results:
Among 7,156 participants, 63.5% did not have NAFLD, 22.7% were classified as mild NAFLD, 11.7% as moderate, and 2.1% as severe. An overview of crude means from the absence of NAFLD to severe NAFLD there were slightly older individuals, a higher proportion of men, lower frequency of current smokers, and people with at least or hypertension or diabetes or dyslipidemia. In the fully adjusted analysis, the cf-PWV (m/s) values were similar among subjects with absence of NAFLD [9.27 (9.18 to 9.36)] compared with the presence of either grade of NAFLD [9.24 (9.15, 9.32)(p=0.285)]. However, there was a significant difference between cf-PWV for people without NAFLD [9.23 (9.15, 9.32)] compared with subjects with severe NAFLD [9.51 (9.31, 9.70). A significant high cf-PWV was significant thru NAFLD categories. (p-value for trend=0.045)]. There was no effect modification of this association across age strata, sex, race, waist circumference and body mass index strata, and presence of hypertension, diabetes, and dyslipidemia.

Conclusion:
In a population of individuals free of cardiovascular disease, NAFLD severity was associated with aortic stiffness regardless of adiposity and the traditional cardiometabolic risk factors.
Abstract P367: Association Between Resting Heart Rate and Progression of Valvular Calcification
Authors: Amoakwa Kojo , Fashanu Oluwaseun E , Tibuakuu Martin , Zhao Di , Guallar Eliseo , Whelton Seamus P , O’Neal Wesley T , Post Wendy S , Budoff Matthew J , Michos Erin D
Published: July 2021

Background:
Mitral annular calcification (MAC) and aortic valvular calcification (AVC) are progressive and linked to increased cardiovascular disease (CVD) morbidity and mortality. Few known modifiable risk factors associated with the progression of MAC and AVC exist. Resting heart rate (RHR) is an established independent risk factor for CVD. Due to the potential hemodynamic effects of RHR on development or progression of valve calcification, we assessed whether RHR is associated with the incidence and progression of MAC and AVC in a community-based cohort free of CVD and atrial fibrillation at baseline.

Methods:
We obtained RHR from baseline 12-lead electrocardiograms of 5,498 MESA cohort participants. We studied RHR as a continuous variable (per 1 SD increment) and also categorized at clinical cut points of < 60, 60 - 69, 70 - 79, and ≥ 80 bpm. MAC and AVC were quantified (using Agatston scoring) from cardiac computed tomography scans obtained at baseline and at follow-up examinations 2 or 3. We examined associations between RHR and incident MAC/AVC and annual change in MAC/AVC scores, after adjusting for demographics, CVD risk factors, physical activity, and atrioventricular nodal blocker medication use. We used progressively adjusted parametric survival models for incident MAC/AVC and linear regression models for annual change in MAC/AVC.

Results:
At baseline, participants had a mean age of 62±10 years and mean RHR of 63±10 bpm; 12.3% and 8.9% had prevalent AVC and MAC [Agatston Units (AU) >0], respectively. Over a median follow up time of 2.3 years, 4.1% and 4.5% developed incident AVC and MAC, respectively. Each 10 bpm higher RHR was significantly associated with incident MAC [Hazard Ratio 1.18 (95% CI 1.03-1.36)], but not incident AVC. However, RHR (per 10 bpm) was associated with AVC progression [β coeff 1.62 (0.45-2.80) AU/year], but not MAC progression. The association of RHR on annual change in AVC was modified by age and sex (p-interactions 0.006 and <0.02, respectively) but not race/ethnicity. Each 10 bpm higher RHR was significantly associated with AVC progression for age > 62 years [β coeff 2.94 (0.55, 5.34) AU/year] and male sex [3.49 (1.31, 5.67) AU/year]. The association between RHR and AVC progression was not significant for age ≤ 62 or female sex. Similar trends were seen using clinical cut-points for RHR.

Conclusion:
Higher RHR predicted incident MAC and AVC progression independent of traditional CVD risk factors. Future studies are needed to determine whether this association is causal and whether modification of RHR through lifestyle or pharmacologic interventions can reduce valvular calcium progression.
Abstract P368: Neighborhoods and Subclinical Cardiovascular Disease
Authors: Sponholtz Todd R , Vasan Ramachandran S
Published: July 2021

Background:
Research on the health impact of the built environment has focused on health behaviors such as diet and exercise, and conditions such as obesity and diabetes. Few studies have examined its influence on downstream outcomes such as cardiovascular disease. We investigated the proportional variance in the 10-year and 30-year Framingham risk score (FRS) attributable to neighborhoods in the Framingham Heart Study.

Methods:
Offspring- and Generation 3 cohort members’ homes at the time of exam 7 (Offspring, 1998-2001) or exam 1 (Generation 3, 2002-2005) were geocoded to 2000 Census block groups. We evaluated Framingham Offspring and Generation 3 cohort participants inhabiting private residences in block groups within Massachusetts containing the residences of 5 or more participants. Analyses of the 10-year FRS were further restricted to participants aged 30-74 at the time of the relevant exam and those of the 30-year FRS to participants 20-59 years old. Cardiovascular risk was determined on the bases of sex, age, systolic blood pressure, anti-hypertensive medication, smoking, diabetes, total cholesterol, and HDL. The outcomes were the standardized residuals of log-transformed FRS regressed on age and sex. We analyzed the percentage of variance of FRS explained at the block-group level and 95% confidence intervals using multilevel linear regression. An empty model was first used to estimate the total variance and the following factors were then added singly to evaluate their influence on the group-level FRS variance explained by education, body mass index, waist circumference, physical activity score, and depression (CES-D score ≥16). Analyses were repeated stratified by sex.

Results:
The analysis of 10-year FRS included a total of 2,882 participants in 188 census block groups. The block-group-level variance explained for this outcome was 1.77% (95% CI=0.69, 4.44). Upon the addition of BMI to the model, the variance explained dropped to 1.11% (95% CI=0.28%, 4.30%). None of the other covariates had a substantial impact. Among 1,363 women in 117 block groups, the block level group explained a total of 2.03% of the FRS variance at the block level group (95% CI=0.61, 6.56), which dropped to 0.64% (95% CI=0.03, 13.82) when BMI was added to the model. Results were somewhat stronger in analysis of the 30-year FRS. The group-level FRS variance explained by census blocks was 3.56% (95% CI=1.75, 7.12) among 2096 participants in 156 neighborhoods. Similar to the 10-year CVD risk score, the variance explained among women (959 in 97 block groups) was higher (6.06%, 95% CI=2.75, 12.83), but null among males.

Conclusions:
In this relatively homogenous suburban white population, census block groups explained a small percentage of the variance in CVD risk. The explained variance was higher among women (19% non-working vs. 5% of males), and largely explained by the clustering of obesity.
Abstract P373: Trends in Cardiovascular Risk Factors by Clinical Definitions of Prediabetes
Authors: Liu Caroline , Foti Kathryn , Selvin Elizabeth
Published: July 2021

Introduction:
There are five different definitions of prediabetes currently used in clinical practice. How cardiovascular risk may differ by these different definitions of prediabetes and whether trends in cardiovascular risk in persons with prediabetes have changed over time is largely uncharacterized.

Hypothesis:
We expect the prevalence of cardiovascular risk factors will vary by prediabetes definition and will be highest among those who meet clinical definitions with higher cutoff values. We hypothesize awareness, treatment and control of hypertension and hypercholesterolemia have increased over time among those with prediabetes.

Methods:
We analyzed data for adults ages ≥ 20 years from the 1999-2014 National Health and Nutrition Examination Survey (NHANES). We used calibrated HbA1c and FPG values to estimate prediabetes prevalence. We examined the prevalence and trends of hypertension and hypercholesterolemia among those who met each clinical definition of prediabetes, as well as awareness, treatment, and control.

Results:
The prevalence of prediabetes by each definitions remained stable across survey years. The prevalence, awareness, treatment, and control of hypertension and hypercholesterolemia by clinical definition modestly increased over time.

Conclusion:
The prevalence of hypertension and hypercholesterolemia was higher among individuals who met HbA1c-based definitions of prediabetes than other measures and was highest when more restrictive criteria for prediabetes were used. Awareness, treatment, and control of cardiovascular risk factors increased over time by any definition, but the high prevalence of cardiovascular risk factors highlights the need for improvement in risk factor management in people with prediabetes.
Abstract P375: Secular Trends in Validity of Troponin I Assays for Myocardial Infarction Classification Among Four US Communities: Findings From the ARIC Study
Authors: Loop Matthew S , Fine Jason P , Folsom Aaron R , Rosamond Wayne
Published: July 2021

Introduction:
The Atherosclerosis Risk In Communities (ARIC) study conducted community surveillance of hospitalized myocardial infarction (MI) from 1987 to 2014 among four US communities (Jackson MS, Forsyth County NC, Washington County MD, and Minneapolis MN). Surveillance of MI during the troponin era (1996 - ) has been complicated by increasing sensitivity of troponin I assays. It is unclear to what extent increased assay sensitivity has affected the validity of event classification. We hypothesized that among events that would have been classified as a definite/probable MI or a suspect/no MI regardless of cardiac biomarkers, the sensitivity and specificity of troponin I assays to identify abnormal enzyme levels (ARIC community surveillance criterion: 2x upper limit of normal) has changed over time in hospitals participating in ARIC community surveillance.

Methods and results:
From 33,995 community hospitalizations with suspicion of MI or coronary heart disease with a troponin I measurement that occurred between 1996 and 2014, 2,143 met ARIC criteria as MI cases (ARIC computer algorithm classification of definite or probable MI regardless of cardiac biomarker levels) and 9,909 we considered noncases (ARIC computer algorithm classification of no or suspect MI regardless of cardiac biomarker levels). In order to be an MI case, the event had to include an evolving diagnostic ECG. To be an noncase, the event had to include no chest pain and an equivocal or absent/uncodable ECG. We used survey-weighted logistic regression models to predict sensitivity and specificity from 1996 - 2014. The sensitivity of troponin I assay being abnormal was approximately 50% for most of the time period, with a potential increase to 70% after 2010. The specificity was approximately 90% in the late 1990s and early 2000s, but fell to 68% (95% confidence interval: 63% - 73%) by 2014. The median upper limit normal (ULN) for troponin I among all 33,995 hospitalizations dropped from 1.4 ng/mL in 1996 to 0.045 ng/mL in 2014.

Conclusions:
For most of the troponin era among the four ARIC communities, hospitalizations that were classified as an MI regardless of cardiac biomarker levels were equally likely to have or not have abnormal troponin I. In recent years, the likelihood that hospitalizations that were classified as no MI regardless of cardiac biomarker levels had normal troponin I decreased, potentially affecting the usefulness of troponin I measurements to separate hospitalized MIs from non-MIs in the context of community surveillance, particularly among hospitalizations with few other signs of MI. These shifts in assay validity were likely due in part to a decrease in ULN for troponin I in the four ARIC communities.
Abstract 17015: PGC-1alpha/Arhgap6 Axis Mediates Diabetic Vascular Dysfunction Through Diminution of Endothelial Glycolytic Flux
Authors: Ariyoshi Makoto , Aoyagi-Keller Mariko , Arany Zolt , Sawada Naoki
Published: July 2021

Introduction:
Aberrant angiogenesis in diabetes (DM) is caused by failure of local endothelial cells (ECs) to properly undergo VEGF-driven migration, and leads to a high propensity to develop critical limb ischemia. We recently showed that type 1 and 2 DM induce PGC-1α in ECs, which in turn strongly blocks EC migration and angiogenesis. Despite this therapeutic potential, PGC-1α may not be “druggable” due to the diverse distribution and functions in non-vascular tissues. Thus, understanding EC PGC-1α effectors is critical, which may involve bioenergetics since PGC-1α broadly induces mitochondrial OxPhos. Although ECs show high rate of glycolytic flux and synthesis of lactate, a burgeoning angiogenic mediator, this is blunted in DM via mechanisms still ill-defined. We hypothesized that a novel PGC-1α target in DM mediates blunted EC glycolysis and migration.

Methods and Results:
By leveraging NRF1/2-binding defective PGC-1α, we show that PGC-1α blocks glycolysis, through PPARgamma-driven Notch induction independent of mitochondrial activation, which fully accounts for PGC-1α inhibition of EC migration in DM. mRNA microarray identified ARHGAP6, a Rho-GAP and actin cytoskeletal modulator, as a DM-inducible main effector of PGC-1α axis to inhibit EC lactate synthesis and migration. Data suggest the causal role for ARHGAP6 in the reduced migration and glycolysis (Seahorse XF analyzer) of STZ-induced DM mouse ECs. Impaired migration of DM ECs and ECs overexpressing PPARgamma or ARHGAP6 was associated with decreased activity of Rac1 and rescued by addition of lactate. Reduced GTP-Rac1 in ECs overexpressing PGC-1α was restored by knockdown of ARHGAP6. Positive feedback loop between Rac1 and LDHA was demonstrated, suggesting a cytoskeletal-metabolic module to mediate EC migration and dysfunction.

Conclusions:
PGC-1α/ ARHGAP6 inhibition of EC glycolysis and lactate synthesis is a key mechanism of impaired EC migration in DM angiopathy. Our data provide important insights into the mechanistic link between EC actin cytoskeleton and bioenergetics mediated by ARHGAP6, and opportunities to restore diminished glycolysis in DM ECs by targeting PGC-1α axis component ARHGAP6 to develop safe and efficacious therapeutic since it is dispensable for health.