bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P115: Cardiorespiratory Fitness Level is Associated with Metabolic Risk in an Asymptomatic Population
Authors: Oni Ebenezer T , Blaha Michael J , Martin Seth S , Agatston Arthur S , Blumenthal Roger S , Carvalho Jose A , Conceiçao Raquel D , Meneghelo Romeu S , Santos Raul D , Nasir Khurram
Published: July 2021

Background:
Cardiorespiratory fitness (CRF) is a measure of habitual physical activity level of an individual. We evaluate the association between CRF and measures of metabolic risk: Fatty Liver Index (FLI) and Lipid Accumulation Product (LAP).

Methods:
This study evaluated 3,154 asymptomatic Brazilian subjects (43±10 years, 80% males) who had metabolic equivalent (METS) measured during routine health screen between November 2008 and July 2010. Both FLI and LAP were calculated from standardized algorithms.

Results:
The prevalence of METS attained were classified into 3; category 1: METS ≤ 12 (44%, n=1,377), category 2 METS >12 & <14 (33%, n=1050) and category 3: METS ≥ 14 (23%, n=727). There was a steady decrease in both median FLI and LAP with higher CRF categories, Figure 1. A logistic regression analysis showed that higher fitness level was associated with lower LAP and FLI levels, see table 1.

Conclusions:
Higher CRF level is associated with reduced cardiometabolic risk among asymptomatic individuals. This re-emphasis the importance of promoting increasing fitness level to improve health.
Abstract P127: Gender and Fitness Status Influence Age-related Decline in Peak Heart Rate Achievement: Insight From the FIT Cohort
Authors: Ahmed Haitham , Zhao Di , Guallar Eliseo , Blaha Michael J , Brawner Clinton A , Keteyian Steven J , Al-Mallah Mouaz H , Michos Erin D
Published: July 2021

Background:
The declines in peak heart rate (HR) and fitness level with age are related; however, whether this association differs based on gender is not well appreciated. In a large cross-sectional cohort of women and men referred for a clinically indicated exercise treadmill test (ETT), we set out to determine whether the decrease in peak HR by age varied by gender (and fitness) in the Henry Ford Exercise Testing (FIT) project.

Methods:
We analyzed data on 38,196 apparently-healthy patients aged 18-96 [mean age 51 ± 12 yrs, 25% black, 48% women] who completed an ETT. Those with history of coronary heart disease, congestive heart failure, diabetes on medications, atrial fibrillation or flutter, or taking AV nodal blocking medications were excluded. Being “fit” was defined as achieving ≥ the median MET level for each sex/age-decile group. Peak HR vs age was plotted, and regression lines were used to determine the intercept and slope for each group.

Results:
Men had higher peak HR than women but with a greater decline over time; the respective intercepts and slopes for peak HR estimates were 202.9 and 0.90 for men and 197.3 and 0.80 for women, (p-interaction = 0.023). Fit people also started out with higher peak HR but approached unfit people at higher age groups; respective intercept and slope by fitness status were 203.0 and 0.87 for fit and 194.7 and 0.83 for unfit (p-interaction <0.001). Separate regression lines were generated for categories of fit men/unfit men, fit women/unfit women (
Figure
). Fit and unfit men had similar declines in peak HR with increasing age (slope=0.92); whereas fit women (slope=0.81) had a slightly greater decline in peak HR with increasing age than unfit women (slope=0.73). However, peak absolute HR for fit people still remains higher than for unfit people even into elderly ages.

Conclusion:
In this cross-sectional cohort of patients referred for a clinical ETT, we found that the age-related decline in peak HR is influenced by both gender and fitness status.
Abstract P141: Usual Impact of Vegetable and Red Meat Intake on Urinary Nitrate
Authors: Wu Tianying , Sonoda Samantha , Ollberding Nicholas
Published: July 2021

The purpose of this study is twofold: 1) compare the effectiveness of non-quantitative food frequency questionnaire (NFFQ) to one-time or multiple 24-hr recalls on assessing the associations of vegetable and meat intakes with urinary nitrate; 2) to determine the associations of vegetable and meat intakes with urinary nitrate. Nitrate-related metabolic pathways have emerged as a fascinating topic because promising benefits of using nitrate supplement on several cardiovascular related outcomes in animal and small-scaled human intervention studies. In the past, most people consider that processed meat is the main source of nitrate exposure and nitrate is harmful. In fact, the major exogenous nitrate exposure comes from vegetables. Thus, we seek to untangle the mystery vegetable-nitrate and meat-nitrate associations in a large observational study. We conduct a cross-sectional analysis using the National Health and Nutrition Examination Survey (NHANES) during 2005-2006, among 7,683 participants. Urinary nitrate was measured, NFFQ and two-time 24-hr recalls were collected among these participants. We have found a positive association between vegetable intakes and urinary nitrate and an inverse association between red meat and processed meat intakes and urinary nitrate by using either non-quantitative NFFQ or averaged two-time 24-hr recalls. The magnitudes of the results were stronger when using NFFQ. Further, using NFFQ, we found that urinary nitrate intake increased by 26%, and decreased by 16% when comparing persons with the highest to the lowest quintile of vegetable intake and red and processed meat intake, respectively. Lastly, we found that the results from the 24-hr recall collected a few days after urine collection (but not the 24-hr recall on the day of urine collection) are consistent with NFFQ results. The trend of vegetable-urinary nitrate and red meat-urinary nitrate associations from NFFQ and averaged 24-hr recalls were consistent with our previous published findings using plasma nitrate measurement in the Health Professionals Follow-up Study, where only semi-quantitative FFQ (SFFQ) was administered. In summary, we conclude that dietary assessment with NFFQ,SFFQ, or average 24-hr recalls will yield similar results when evaluating red meat-circulating nitrate or vegetable-circulating nitrate associations. Measurement of circulating nitrate using either urine or plasma will yield similar results. Understanding how usual vegetable and red meat intake influences circulating nitrate in observational studies will provide valuable information for studying nitrate related pathways in the etiology of chronic disease and for designing long-term dietary intervention studies targeting circulating nitrate.
Abstract P152: Parent-child Associations for Changes in Diet and Physical Activity Across Two Decades in Modernizing China
Authors: Dong Fei , Howard Annie-Green , Herring Amy , Thompson Amanda , Popkin Barry , Zhang Bing , Gordon-Larsen Penny
Published: July 2021

Introduction:
While the household context is important for lifestyle interventions to reduce cardiometabolic disease, few studies have examined parent-child associations for diet and physical activity (PA) changes over time in a rapidly urbanizing country with burgeoning cardiometabolic disease rates.

Hypotheses:
We tested the hypotheses that although changes in diet and PA are associated in parents and their children, the magnitude of this association will decline over time and changes in these behaviors over time differ in adults versus children.

Methods:
We studied dietary and PA behaviors in parent-child pairs (children aged 7-17y) using longitudinal data from the China Health and Nutrition Survey (survey years: 1991, 1993, 1997, 2000, 2004, 2006, and 2009). Sample size varied at each year and on average there were 1,692 mother-child and 1,594 father-child pairs across all visits. Three-day 24-hour recall diet data were collected to generate percentage of total energy from animal-source foods (ASF), eating away from home, and snacking. Seven day PA recall across domains of PA included screen-based activity hours per week, and metabolic equivalent hours (MET-hrs) per week from commuting and leisure-time sports. Spearman partial correlation was used to test parent-child association, adjusting for child’s age and household sociodemographics. We used the Kruskal-Wallis test to examine differences of these behaviors across years. All models were stratified by child’s sex and parent’s sex.

Results:
We found statistically significant positive parent-child correlations for all dietary variables (correlation coefficients ranged from 0.49 to 0.89 across all years and all parent-child combinations, p<0.01), with stronger mother-child compared to father-child correlation. Whereas, parent-child associations for PA were weaker in magnitude. Coefficients ranged from 0.1 to 0.34 for screen-based hours, 0.08 to 0.17 for commuting, and 0.07 to 0.16 for leisure-time sports (p<0.05). Associations for commuting and leisure-time sports became non-significant at later years. Children and adults experienced statistically significant increases in the percentage of energy from ASF, eating away from home, and snacking, as well as in screen-based hours over time. Parents experienced a decrease in commuting MET-hrs over two decades (p<0.05), whereas children had minimal change. Leisure-time sports MET-hrs increased in children, and decreased in adults over time (p<0.05).

Conclusions:
Parent-child associations were comparatively stronger for diet than for PA. We observed an increase in energy from ASF, eating away from home, and snacking in parents and children over time, increases in PA in children and declines in adults. Our findings support household-based health behavior intervention strategies, particularly around diet-related behaviors.
Abstract P172: Postural Hand Tremor and Incident Hypertension in Young-to-middle Aged Adults: The Bogalusa Heart Study
Authors: Hu Tian , Guralnik Jack , Gustat Jeanette , Harville Emily , Webber Larry , Chen Wei , He Jiang , Whelton Paul K , Bazzano Lydia
Published: July 2021

Introduction:
Increased sympathetic nervous activity is a feature of postural hand tremor and increases blood pressure. Beta-blocker therapy is effective in managing postural hand tremor and hypertension. However, the relationship between postural hand tremor and hypertension has not been examined in a population-based cohort study.

Methods:
We prospectively examined the association between postural hand tremor and incident hypertension in a community-based cohort of 715 (184 Black, 531 White) American adults without hypertension and not using medications to control tremor (e.g., beta-blockers). At a baseline examination in 2000-2002, postural hand tremor was measured by having participants in a darkened room use their outstretched arms to point a laser beam for 8 seconds at a sheet of Polaroid film 8 feet away. Hand tremor was characterized by the width of the circular diameter that encompassed all laser beam exposures and enumeration of exposure dots in the contained area. Both hands were assessed sequentially. Incident hypertension was defined as new elevation of blood pressure (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg, based on an average of six readings over two visits), or self-report of hypertension, or antihypertensive medication use.

Results:
During a median follow-up of 6.4 years, 198 (69 Black and 129 White) participants developed hypertension. Tremor measurements (by quartile) were positively associated with incident hypertension after adjustment for demographics, lifestyle and metabolic risk factors at baseline. There was significant interaction by race (P: 0.01). Among Whites, tremor was positively associated with incident hypertension (Hazard ratio highest vs. lowest quartile: 2.35 [95% CI: 1.35 - 4.09], P - linear trend: 0.007 for the dot numeration method; and 3.02 [95% CI: 1.69 - 5.38], P - linear trend: 0.002 for the circular method). Among Blacks, tremor was not associated with hypertension risk.

Conclusions:
In this community-based cohort, postural hand tremor was strongly associated with the risk of incident hypertension among Whites, and merits further study as a potential indicator of risk for hypertension.
Abstract P173: Improvements in Adherence to Antihypertensive Medication Among Medicare Beneficiaries Initiating Treatment Between 2007 and 2012
Authors: Tajeu Gabriel S , Kent Shia T , Shimbo Daichi , Krousel-Wood Marie , Kronish Ian M , Bress Adam P , Huang Lei , Muntner Paul
Published: July 2021

Introduction:
Low antihypertensive medication adherence has been reported, leading to recommendations for interventions to improve adherence. We evaluated trends in low medication adherence and discontinuation among Medicare beneficiaries initiating antihypertensive medication from 2007 to 2012.

Hypothesis:
Low antihypertensive medication adherence has decreased over time.

Methods:
We analyzed data on beneficiaries with ≥ 2 diagnoses for hypertension (ICD-9, 401.xx) in the Medicare 5% random sample initiating antihypertensive medication. Initiation was defined by a pharmacy claim for antihypertensive medication with no claims within the previous 365 days. Beneficiaries were required to have full Medicare fee-for-service coverage (Parts A, B and D) for the 365 days prior to and following the date of initiation. Low adherence was defined as having a proportion of days covered <80% during the 365 day following initiation. Discontinuation was defined as having no days of supply or fills during the final 73 days in the year following initiation.

Results:
Between 2007-2012, 44,147 Medicare beneficiaries initiated antihypertensive medication. In the overall sample, low adherence decreased from 36.4% in 2007 to 31.7% in 2012 (p<0.001) (Table). After multivariable adjustment, the relative risk (RR) of low adherence for beneficiaries initiating treatment in 2012 compared with those initiating treatment in 2007 was 0.84 (95% CI 0.79-0.89). Throughout the study period, low adherence was more common in beneficiaries that were black (RR 1.41; 95% CI 1.35-1.48), Hispanic (RR 1.40; 95% CI 1.30-1.50), had low income (RR 1.19; 95% CI 1.08-1.32), depression (RR 1.06; 95% CI 1.01-1.12), or a serious fall injury following antihypertensive medication initiation (RR 1.34; 95% CI 1.23-1.47). Discontinuation did not decrease over time.

Conclusion:
Low adherence to antihypertensive medication among Medicare beneficiaries has decreased over time. Higher rates of low adherence remain for blacks compared with whites.
Abstract P175: Hypertension Burden in Luxembourg: Geographic Variations and Individual Risk Factors From the 2013-15 European Health Examination Survey
Authors: Ruiz-Castell Maria , Kandala Ngianga-Bakwin , Kuemmerle Andrea , Barré Jessica , Schritz Anna , Delagardelle Charles , Schmit Jean-Claude , Stranges Saverio
Published: July 2021

Introduction:
Hypertension is a modifiable risk factor for cardiovascular disease, the latter still representing the main cause of death in Luxembourg. The aim of this study was to estimate the current prevalence of hypertension, associated risk factors, and its geographic variations in the Grand Duchy of Luxembourg.

Methods:
Cross-sectional, population-based data on 1,508 randomly selected residents of Luxembourg, aged 25 to 64, were collected as part of the European Health Examination Survey (EHES-LUX) between 2013 and 2015. Hypertension was defined as systolic/diastolic blood pressure of ≥140/90 mmHg, self-report of a physician diagnosis or on anti-hypertensive medication. Standard and Bayesian regressions were used to examine associations between hypertension and covariates. We mapped hypertension‘s geographic distribution by using a Bayesian geo-additive mixed model adjusted by health-related behaviours, socioeconomic characteristics, body mass index, depressive symptoms and general health status.

Results:
31% (471 of 1508) of Luxembourg residents were hypertensive, and half of them were unaware of their condition. Among those who were aware of their condition, nearly 50% (121 of 261) were not adequately controlled. In men, the likelihood of being hypertensive was: lower in those being more physically active (>3h/week) (odds ratio [OR] and 95% credible region [CR]: 0.60[0.37, 0.92]) and consuming alcohol daily (0.33 [0.10, 0.83]), and higher in those with a low health perception (1.63 [1.01, 2.69]). In women, the likelihood of being hypertensive was higher in those experiencing depressive symptoms (1.83[1.27, 2.68]). There was a clear variation in hypertension prevalence across cantons and municipalities, with a North to South gradient: the highest odds ratio was observed in the South-West region of the country (1.21 [0.94, 1.57]), one of the most industrialized regions in Luxembourg. We observed a significant positive spatial effect in this region at 90% nominal level.

Conclusions:
In Luxembourg, the vast majority of people with hypertension are either unaware of their condition or not adequately controlled, which constitutes a major public health issue. There are geographic differences in hypertension prevalence in Luxembourg, which is remarkable given the size of the country. It is therefore necessary to consider the role of individual and regional (canton and commune level) risk factors in hypertension prevalence, as well as public health initiatives to control and promote awareness about this condition in order to reduce its burden in Luxembourg.
Abstract P187: Blood Pressure Control in Adults with Autistic Spectrum Disorders in a Large Integrated Medical Care Program is Better Than in a Demographically Matched Comparison Group
Authors: Sidney Stephen , Zerbo Ousseny , Sorel Michael E , Qian Yinge , Rich Steve , Young Joseph D , Croen Lisa A
Published: July 2021

Background:
The prevalence of autism spectrum disorders (ASD) has been increasing, with a recent CDC estimate of 1 of 68 children. As this cohort ages, millions of individuals will advance into adulthood with this diagnosis. A recent report from Kaiser Permanente Northern California (KPNC), an integrated medical care program serving about 3.5 million members, showed that adults with ASD have a higher prevalence of hypertension (HTN), than a comparable group not known to have ASD (non-ASD). We are unaware of data regarding HTN control in persons with ASD.

Hypothesis:
HTN control rates will be lower in ASD than in non-ASD KPNC members because of communication difficulties associated with ASD.

Methods:
We identified 1,507 KPNC members, age >18 years, with ASD (ICD-9-CM codes 299.0, 299.8. 299.9) during the time period, 1/1/2008-12/31/2012, of which 218 had HTN (2 outpatient diagnoses of HTN, or 1 outpatient diagnosis of HTN with a prescription for anti-hypertensive medication within 12 months of HTN identification). For each ASD patient, we identified 5 comparison KPNC non-ASD members with HTN, matched for age, sex, race, and year of HTN identification (n=1,090). We determined all primary care outpatient blood pressures (BP) recorded within 12 months after HTN identification and used the final BP obtained for analysis. We excluded 14 members with no BPs (1 ASD, 13 controls) and 39 members, age >65 years (8 ASD, 31 controls). HTN control was defined as systolic BP <140 and diastolic BP <90 mm Hg. BP control rates were age-adjusted using weighting derived from the 2000 U.S. census.

Results:
The mean age was 43.6 years for ASD and 43.9 for controls (p=0.74). The HTN control rate was higher for ASD (84.2%; age-adjusted 84.9%) than for controls (73.5%, age-adjusted 71.7%) (p=0.001). Members with ASD had more BP measurements (mean 6.0, standard deviation [s.d.] 6.2) than controls (mean 4.8, s.d. 4.4) (p=0.0008).

Conclusion:
HTN was better controlled in adults with ASD than in non-ASD adults, possibly related to more frequent measurement of BP.
Abstract P205: Neighborhood Socioeconomic Status and Long-term Incidence of Cancer After Myocardial Infarction
Authors: Gerber Yariv , Goldbourt Uri , Hasin Tal , Cohen Gali , Keinan-Boker Lital
Published: July 2021

Background:
Higher cancer incidence rates in patients with cardiovascular disease compared with the general population were recently documented in several European and North American settings. While different mechanisms were proposed to account for the association, the possibility of differential detection cannot be ruled out. We evaluated cancer incidence and case-fatality according to neighborhood socioeconomic status (NSES) in a cohort of myocardial infarction (MI) survivors.

Methods:
Patients aged ≤65 years admitted to hospital in central Israel with first MI in 1992-1993 were followed up for cancer (via the National Cancer Registry) and death (via the Population Registry) through 2011. NSES was estimated at baseline through a composite census-derived index (measured on a 1-20 scale) developed by the Israel Central Bureau of Statistics, along with other socio-demographic and clinical variables. Fine and Gray subdistribution hazard regression models were used to assess the hazard ratio (HR) for cancer associated with NSES, with death considered a competing event; Cox models were then used to assess the association with case fatality among incident cancer cases.

Results:
Among 1380 cancer-free patients at baseline (mean age, 54 years; 81% men), 230 developed cancer during a mean (SD) follow-up of 14 (6) years. The age-adjusted HR for cancer was 1.24 (95% CI: 1.08-1.41) per 1 SD increase in NSES. Further adjustment for individual SES measures and clinical variables (including smoking) did not weaken the association (HR=1.26, 95% CI: 1.09-1.46). Conversely, among patients diagnosed with cancer, NSES was associated with reduced mortality risk (age-adjusted HR=0.78, 95% CI: 0.65-0.93; multivariable-adjusted HR=0.80, 95% CI: 0.64-0.99).

Conclusions:
Residing in an affluent neighborhood was associated with higher incidence and lower case fatality rate of cancer post-MI, which, to some extent, may reflect detection bias due to increased medical surveillance.
Abstract P212: Health-related Quality of Life and Leukocyte Telomere Length Among Adults in the United States: Findings From the National Health and Nutrition Examination Survey, 2001-2002
Authors: Khan Rumana J , Gebreab Samson , Crespo Pia , Gaye Amadou , Xu Ruihua , Davis Sharon
Published: July 2021

Background:
Health-related quality of life (HRQOL) is defined as perceived physical and mental health over time. Lower HRQOL has previously been shown to be associated with elevated adverse health events and mortality. Leukocyte telomere length (LTL), which is a biomarker of aging at the cellular level, has also been associated with age-related diseases and mortality. However, the association of HRQOL with LTL in the general population is poorly understood.

Objective:
We examined the relationship between different measures of HRQOL and LTL by ethnicity among a nationally representative sample of US adults using the data of the National Health and Nutrition Examination Survey (NHANES, 2001-2002).

Method:
HRQOL were assessed through a brief set of survey-based questions that asked participants about their self-rated general health and the number of recent days when the person was physically unwell, mentally unwell, or limited in usual activities. Telomere length was assessed using the quantitative polymerase chain reaction method of telomere length relative to standard reference DNA. Multiple linear regression was used to estimate the relationship, where we sequentially controlled for demographic (age, sex, education, marital status), health risk indicator (cancer, hypertension, diabetes, obesity, heart failure) and health behavior (smoking, physical activity, and alcohol intake) variables. Log transformed value of LTL was used for regression modeling and all the analyses were estimated with adjustment for sample weights for the genetic sub-sample and design effects.

Results:
The current study included 2090 White, 788 Mexican American, and 669 African American participants with mean age of 46.89 (Standard Error, SE=0.56), 37.57 (SE=0.73) and 41.99 (SE=0.74) years respectively. After controlling for demographic factors, health risk indicators, and health behaviors, recent days of unwell physical health was associated with shorter telomere length for Whites (beta=-0.005, 95% Confidence Interval, 95% CI=-0.01 to -0.001, p value 0.03). Among African Americans, those who perceived their general health condition as “good” had shorter telomere length compared to those who perceived general health status as “excellent” (beta=-0.02, 95% CI=-0.03 to -0.01, p value 0.001). Mental health related quality of life showed no significant association with LTL in any race. For Mexican Americans none of the HRQOL measures had any association with LTL.

Conclusion:
Lower physical HRQOL and lower general HRQOL were associated with shorter LTL or faster cellular aging for Whites and African Americans in our study. The results endorse the value of assessing HRQOL,specially in relation to to physical and general health, and the importance of using this measure for evaluating age and disease related consequences.
Abstract P228: Abdominal Lean Muscle Mass is Associated with the Density, but Not the Volume, of Coronary Arterial Calcium and Abdominal Aortic Calcium
Authors: Crawford Margaret A , Allison Matthew A , Criqui Michael H , Larsen Britta A
Published: July 2021

Introduction:
Higher volume of coronary arterial calcium (CAC) and abdominal aortic calcium (AAC) are predictive of incident CVD, while higher density of CAC and AAC are associated with lower risk. The purpose of the present study was to determine the associations of abdominal lean muscle mass (ALMM) with CAC volume, CAC density, AAC volume, and AAC density.

Hypothesis:
We hypothesized that abdominal muscle mass would be negatively associated with CAC and AAC volume but positively associated with CAC and AAC density.

Methods:
The current study analyzed data from the Multi-Ethnic Study of Atherosclerosis (MESA) in those participants who underwent abdominal computed tomography (CT) to assess for AAC, which was also analyzed for volumes of fat (visceral and subcutaneous) and ALMM (psoas, rectus abdominis, obliques, and paraspinus). CAC and AAC were scored separately, for density and for volume.

Results:
Analyses were restricted to participants who had non-zero CAC or AAC volumes. The sample sizes for the CAC analyses and AAC analyses were 963 and 1283 subjects, respectively. For the CAC analyses, 39.4% (379 of 963) were female and the mean age was 66.4 years. Mean ± SD CAC volume was 218.52 ± 344.19 (range 2.34- 3244.77 mm
3
) ; Mean ± SD CAC density was 2.70 ± .72 (range 0.83- 4.0 Hu category units). Mean ± SD AAC volume was 1402.33 ± 1888 (range 4.68- 15822.2 mm
3
); mean ± SD AAC density was 3.02 ± .63 (range 0.83- 4.0 Hu category units). In multivariable linear regression models that controlled for age, race, gender, CVD risk factors, visceral fat, and liver and kidney markers, both CAC and AAC density were found to be significantly associated with abdominal lean muscle mass. For every 100 cm
2
increase of ALMM, CAC density decreased by .35 Hu category units (p < .05). For every 100 cm
2
increase of ALMM, AAC density decreased by .26 Hu category units (p < .05). Conversely, CAC and AAC volume were not significantly associated with abdominal lean muscle mass in final models.

Conclusion:
Higher levels of ALMM were associated with lower CAC and AAC density, but not volume. Contrary to expectation, we found an inverse association of ALMM with CAC and AAC density, independent of relevant CVD risk factors.
Abstract P248: Objectively Measured Physical Activity and Sedentary Behavior Change During a Lifestyle Intervention in Overweight Adults: Does Season Matter?
Authors: Rockette-Wagner Bonny , Kriska Andrea M , Ma Qianheng , Sereika Susan M , Imes Christopher C , Kline Christopher , Burke Lora
Published: July 2021

Introduction:
Lifestyle interventions, with physical activity (PA) as a key component, are important to reducing cardiometabolic disease risk. In our work in both efficacy and effectiveness clinical trials, we have shown that season has a significant impact on subjectively determined moderate-vigorous (MV) PA levels, both at baseline and during the intervention. However, the effect of season in these lifestyle interventions has not yet been examined utilizing objective measurements of PA so that time spent in all PA intensities and sedentary behavior(SB) can be quantified.

Hypothesis:
Our hypothesis is that PA would increase and SB would decrease due to the intervention but that season would have an additional effect on both.

Methods:
We enrolled 150 overweight/obese adults (51.1±10.2 y; 79% Caucasian; 91% female) in a 12-month lifestyle intervention for weight loss that provided regular feedback to participants on diet and PA goal achievement. Six cohorts were recruited from 2012-2014. The PA goal was to achieve and maintain 150 minutes/week of MVPA. ActiGraph GT3x accelerometers, worn on the waist, were used to assess average daily step counts and time spent in PA and SB. Accelerometer recordings with 10 hours/day of wear time on ≥4 days were considered a valid assessment of typical PA and SB. Changes in activity variables at 6 months and 12 months were examined using linear mixed models. We also examined the season (winter, spring, summer, or autumn) when the intervention was implemented and if this affected changes in PA and SB.

Results:
Baseline accelerometer data were valid for 149 participants. Mean (SD) baseline values were 6132 (1873) steps counts/day, 11 (11) MVPA min/day, 245 (64) light intensity (L)PA min/day, 635 (85) SB min/day. Season was significantly related to step counts, LPA, MVPA, and SB with significantly lower PA and higher SB in the winter (p<0.05). Changes in LPA and SB were not significant over the entire follow-up (p>0.05). When adjusted (for monitor wear time/day and season) mean (SD) increases in step counts from baseline were 1128 (208) and 742(209) steps/day at 6 and 12 months, respectively (both p<0.0001). For MVPA adjusted mean (SD) increases from baseline were 7(1) and 6(1) min/day at 6 and 12 months, respectively (both p<0.0001).

Conclusions:
Relevant improvements in steps counts and MVPA were recorded at 6 and 12 months. This was true even after controlling for the effect of differences in the season of implementation. When considering the effect of lifestyle interventions on activity, future studies should consider the effect of seasonal changes on PA levels.
Abstract P251: Triggers of Temptations and Urges Do Not Change During a 12-Month Behavioral Intervention for Weight Loss
Authors: Burke Lora E , Shiffman Saul , Siewiorek Daniel , Smailagic Asim , Kriska Andrea , Ewing Linda I , Zheng Yaguang , Mancino Juliet , Rathbun Stephen L
Published: July 2021

Introduction:
Ecological momentary assessment (EMA) assesses individuals’ behaviors and moods as they occur in their natural environment. We examined self-reported triggers of temptations/urges to eat and compared percent of times each trigger was reported as the top trigger in the 1st 6 mos. vs. the 2nd 6 mos. of a standard behavioral weight loss intervention.

Hypothesis:
The distribution of self-reported triggers of urges/temptations changes over time.

Methods:
We provided participants a smartphone app programmed to permit them to self-initiate completing EMA and report temptations/urges in real time. Questions included:
What were the triggers for the temptation/urge? What was the top trigger?
Only data from subjects reporting ≥ one urge/temptation were included in the analysis. For each trigger, generalized estimating equations were used to fit logistic regression models to test the hypothesis that proportion of urges/temptations including that trigger did not change between the 1st and 2
nd
6 mos. of EMA surveillance.

Results:
The sample (
N
= 139) was 90.6% female, 82.7% White, 50.9±10.10 years of age with a BMI of 34.2±4.6 kg/m2. There were 3175 reported episodes of temptation/urges. During both 6-mo.periods, sight/smell of food was the most frequently reported trigger occurring in 34.8% of temptations/urges in the first 6 mos., increasing to 35.52% in the second 6-mos. This was followed by stress, hunger/thirst, and habit during both 6-mo. periods. There were no significant differences in the frequency or type of triggers over time, except for “out of nowhere”, which occurred less often in the second period (6.98% vs. 5.42%, p = .02). The triggers are plotted in order of most to least frequent for both periods in the figure below.

Conclusions:
Fewer temptations/urges were reported in the second 6 mos., which likely is attributed to a decrease in compliance by participants to EMA protocols. The sight/smell of food remained the most frequently reported trigger, which is a concern in an environment that is very food centric.
Abstract P257: Between-pedigree Genome-wide Linkage Screen Identifies a Locus on Chromosome 9 Influencing Coronary Artery Calcification in the Family Heart Study
Authors: Hicks James E , Province Michael A
Published: July 2021

Coronary artery calcification (CAC) is the buildup of calcium deposits in the arteries leading to the heart, and is an indicator of atherosclerosis. CAC is known to have a genetic component. To identify the genes underlying CAC, a genome-wide linkage screen was performed in the Family Heart Study.

There are two established loci influencing CAC identified by genome-wide association scans, at chromosome 9p21 and 6p24. However, there may be rare variants on haplotypes in the population that influence CAC. These would not be able to be identified by genome-wide association scans, but linkage scans could detect them.

From the study, 2,687 individuals of European descent from 508 pedigrees with CAC scores were genotyped on the Illumina Human 1M-DuoV3 single nucleotide polymorphisms (SNP) array. CAC scores were determined by cardiac CT scan and adjusted for age, sex, and principal components before analysis.

Using 484,358 common SNPs (minor allele frequency greater than 5%), common ancestry across the genome was determined for all pairs of individuals in the study. A segment of the genome was considered to be inherited from a common ancestor (identical-by-descent, IBD) if it contained more than 1,000 matching SNP genotypes over a length of at least one megabase.

To test the influence of IBD at a locus on CAC, a linear mixed effects model was fit, including random effects to account for covariance due to relatedness and IBD states at each locus. All pedigrees were considered jointly in the model. Statistical significance was determined by comparing this model to one without IBD covariance via the likelihood ratio test. This model was evaluated approximately every megabase across all 22 pairs of autosomes. Since IBD states are determined solely by dense genotype data, IBD can be detected both within and between pedigrees in the study. This allows the inclusion covariance due to IBD in individuals in different pedigrees. If there is a haplotype shared across pedigrees, power to detect linkage is increased.

CAC was found to have a narrow-sense heritability of 37.4% in this sample. Significant evidence of linkage was encountered at rs13293430 (chromosome 9, 31,050,747bp, LOD=3.042). When considering IBD between pedigrees, 914 pairs of individuals from different pedigrees were IBD at this position. This locus is near DDX58. Mutations in DDX58 cause Singleton-Merton syndrome, a disease characterized by calcification of blood vessels, making it an intriguing candidate gene for influence on CAC.
Abstract P259: Genetic Risk Score, Lifestyle Cardiovascular Risk Score, and Myocardial Infarction in Hispanics
Authors: Sotos-Prieto Mercedes , Baylin Ana , Campos Hannia , Qi Lu , Mattei Josiemer
Published: July 2021

Background:
A genetic risk score (GRS) and a lifestyle cardiovascular risk score (LCRS) have been independently associated with myocardial infarction (MI) in Hispanics. However, it is unknown if there is an interaction or a joint association between these scores.

Objectives:
To assess the interactive and joint associations between a GRS and a LCRS, as well as each individual lifestyle risk factor on the likelihood of MI.

Methods:
Data included 1534 Costa Rican adults with nonfatal acute MI and 1534 without MI participating in a case-control study. The GRS was calculated by summing the number of the top three MI-associated risk alleles. The LCRS was calculated using the estimated coefficients as weights for each lifestyle risk factors (diet, physical activity, smoking, waist:hip ratio, low or high alcohol intake, and low socioeconomic status). Conditional logistic regression was used to calculate odds ratios (OR), adjusting for age, sex, and area of residence (matching condition), and to test for interaction and joint association.

Results:
The multivariable OR for MI was 1.14 (95% CI 1.07, 1.22) per GRS unit and 2.72 (2.33, 3.91) per LCRS unit. Participants in the highest tertile of the GRS and highest tertile of the LCRS had higher odds of MI (5.43 [3.80, 7.76]) compared to those in the lowest category. A significant joint association was detected (p <0.0001), while the interaction term was non-significant (p=0.44). Similar results were found for the joint association between GRS and each individual lifestyle component: joint odds for highest risk category vs. lowest was 2.16 (1.53, 3.04) for diet, 1.85 (1.33, 2.59) for physical activity, 3.31 (2.45, 4.48) for smoking, 1.32 (0.92, 1.89) for alcohol, 2.84 (1.82, 4.42) for waist:hip ratio, and 1.86 (1.29, 2.69) for socioeconomic status.

Conclusion:
Although lifestyle risk factors and genetics contribute independently and in combination to the odds of MI, lifestyle risk factors were stronger among Costa Ricans. Efforts to improve lifestyle behaviors in this population, regardless of genetic susceptibility, may help prevent MI and related heart conditions.
Abstract P260: Large-scale Meta-analysis of Diverse Ancestry Genome-wide Association Studies to Identify Pharmacogenomic Interactions of Sulfonylureas and ECG Phenotypes
Authors: Floyd James S , Sitlani Colleen , Avery Christy L , Whitsel Eric A , Lange Leslie , Smith Albert V , Evans Daniel S , Li Xiahui , Trompet Stella , Noordam Raymond , Stricker Bruno ,   CHARGE Pharmacogenomics Working Group
Published: July 2021

Introduction:
Sulfonylureas are a commonly-used class of diabetes medication that can prolong the QT-interval, which is a leading cause of drug withdrawals from the market given the possible risk of life-threatening arrhythmias. Previously, we conducted a meta-analysis of genome-wide association studies of sulfonylurea-genetic interactions on QT interval among 9 European-ancestry (EA) cohorts using cross-sectional data, with null results. To improve our power to identify novel drug-gene interactions, we have included repeated measures of medication use and QT interval and expanded our study to include several additional cohorts, including African-American (AA) and Hispanic-ancestry (HA) cohorts with a high prevalence of sulfonylurea use. To identify potentially differential effects on cardiac depolarization and repolarization, we have also added two phenotypes - the JT and QRS intervals, which together comprise the QT interval.

Hypothesis:
The use of repeated measures and expansion of our meta-analysis to include diverse ancestry populations will allow us to identify novel pharmacogenomic interactions for sulfonylureas on the ECG phenotypes QT, JT, and QRS.

Methods:
Cohorts with unrelated individuals used generalized estimating equations to estimate interactions; cohorts with related individuals used mixed effect models clustered on family. For each ECG phenotype (QT, JT, QRS), we conducted ancestry-specific (EA, AA, HA) inverse variance weighted meta-analyses using standard errors based on the t-distribution to correct for small sample inflation in the test statistic. Ancestry-specific summary estimates were combined using MANTRA, an analytic method that accounts for differences in local linkage disequilibrium between ethnic groups.

Results:
Our study included 65,997 participants from 21 cohorts, including 4,020 (6%) sulfonylurea users, a substantial increase from the 26,986 participants and 846 sulfonylureas users in the previous meta-analysis. Preliminary ancestry-specific meta-analyses have identified genome-wide significant associations (P < 5х10–8) for each ECG phenotype, and analyses with MANTRA are in progress.

Conclusions:
In the setting of the largest collection of pharmacogenomic studies to date, we used repeated measurements and leveraged diverse ancestry populations to identify new pharmacogenomic loci for ECG traits associated with cardiovascular risk.
Abstract P279: Major Dietary Risk Factors for Cardiometabolic Disease: Current Evidence for Causal Effects and Effect Sizes From the Global Burden of Diseases (GBD) 2015 Study
Authors: Shulkin Masha L , Micha Renata , Rao Mayuree , Singh Gitanjali M , Mozaffarian Dariush
Published: July 2021

Background:
Dietary habits are major contributors to cardiometabolic diseases. Estimating the impact of diet on these conditions requires identification and quantification of evidence for causal effects.

Objectives:
To comprehensively evaluate the current evidence and quantify the effects of major dietary factors on CHD, stroke, and diabetes as part of the Global Burden of Diseases (GBD) 2015 study.

Methods:
We assessed probable or convincing evidence for causal effects based on Bradford-Hill, World Health Organization, and WCRF/AICR criteria. We searched PubMed through April 2015 to identify systematic reviews and meta-analyses of well-designed observational studies and clinical trials. Meta-analyses were evaluated and selected based on design, number of studies and events, definition of dietary exposure and disease outcomes, length of follow-up, statistical methods, evidence of bias, and control for confounders. Effect sizes and uncertainty were quantified per standardized units. We focused on dose-response meta-analyses. When necessary, original data were extracted from individual studies within each meta-analysis to perform de novo dose-response meta-analyses using generalized least squares for trend estimation.

Results:
We identified 11 dietary factors with probable or convincing evidence for causal effects on CHD, 4 on stroke, and 7 on diabetes. (
Table
). Examples of other factors not yet meeting probable or convincing evidence for causal effects included coffee and tea (consistent dose-response, yet plausible biology not well-established), eggs, and dietary cholesterol.

Conclusion:
This evaluation provides the best current evidence-based quantitative estimates of effects of major dietary factors on CHD, stroke, and diabetes. These findings enable quantitative estimation of disease burdens of suboptimal diet in the US and globally, and also inform policy planning and priorities.
Abstract P305: Obesity is Associated with Differentiated Methylation in Glucose Tolerance-related Genes in Adolescents
Authors: He Fan , Berg Arthur , Imamura Kawasawa Yuka , Salzberg Anna C , Bixler Edward O , Vgontzas Alexandros N , Liao Duanping
Published: July 2021

Background:
Childhood obesity is related to increased cardiometabolic risk in adulthood. Insulin resistance is an established underlying mechanism between obesity and CVD risk. However, the role of epigenetic profiles in this mechanistic link is less investigated, especially in adolescents.

Hypothesis:
We assessed the hypothesis that obesity is associated with differentiated methylation profiles in genes related to glucose tolerance and its downstream functions in adolescents.

Methods:
We used data from a sample of 116 adolescents from the population-based Penn State Child Cohort follow-up exam (N=421). Among which, 22 were obese (BMI percentile ≥ 95) and 94 were normal weight (BMI percentile < 85). Peripheral leukocytes DNA was extracted and subject to enhanced reduced representation bisulfite sequencing. The high-throughput assay provided single nucleotide resolution of DNA methylation in CpG sites and surrounding regions. The R package methylKit was used in the post-processing and analysis. Bases with < 10x coverage were excluded in the assay, resulting in a total of 634,418 methylation sites with a minimum of 10 samples per group. Logistic regression was used in the differential methylation calculation. We decided
a priori
to choose the sites with ≥ 25% difference in methylation with a q value <0.01 for the enrichment analysis. We used Ingenuity Pathway Analysis (IPA) to perform gene-set enrichment analysis for downstream function and effects on the differentially methylated genes.

Results:
The mean (SD) age of the study sample was 16.3 (2.2) years. The sample consisted of 52% male and 79% white. No significant difference was observed between obese and normal weight groups with respect to demographic characteristics. We identified a total of 2349 bases with statistically significant (q<0.01) differentiated methylation with a difference of 25% or more. IPA revealed 38 sites related to glucose tolerance function, and this function is significantly enriched (p=1.51E-4). Highlighting some individual genes, obese adolescents showed 26.4% higher methylation at a site on the insulin (INS) gene compared to normal weight adolescents, and a site on the gastric inhibitory polypeptide receptor (GIPR) gene had 47.3% differential methylation. Other major significantly differentially methylated glucose tolerance-related genes included interleukin 6 (IL6), and tumor necrosis factor (TNF), and low density lipoprotein receptor (LDLR) genes.

Conclusion:
Obesity in adolescents is significantly associated with substantially differentiated methylation in glucose tolerance-related genes. It indicated that obesity is related to alternations in the epigenetic profiles related to impaired glucose tolerance, and potentially through which associated with elevated risk of its downstream diseases, such as diabetes and CVD.
Abstract P309: Vulnerabilities to Health Disparities and Statin Use in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: Schroff Praful , Gamboa Christopher M , Durant Raegan W , Oikeh Asikhame , Richman Joshua S , Safford Monika M
Published: July 2021

Introduction:
Statins reduce the incidence of major cardiovascular disease events, but many individuals do not receive them. The AHRQ National Healthcare Disparities Report identifies several vulnerable populations, but few studies have examined statin use from the perspective of the presence of multiple vulnerabilities in the same individual.

Hypothesis:
A greater number of vulnerabilities is associated with lower statin use.

Methods:
This study used data from the REGARDS study, which included 30,239 adults of age 45 and older recruited between 2003 and 2007 from the 48 contiguous US states. Baseline data included a 45-minute telephone interview and an in-home visit. Vulnerabilities included older age, black race, being a woman, rural/small city residence, area level poverty, Southeastern residence, and lack of health insurance. Prevalence ratios were estimated from Poisson models and adjusted for factors influencing health services utilization (education, awareness of hyperlipidemia, medication adherence, cigarette smoking, depressive symptoms, obesity, high-density lipoprotein cholesterol, physical functioning and Adult Treatment Panel III Framingham Risk Group).

Results:
The study sample included 18,047 individuals of mean age 65.8 years with indications for statin therapy; 41.7% were black, 50.8% were women, 8.7% lived in a rural area/small city, 25.2% lived in areas with >25% of residents living below the Federal poverty line, 55.0% lived in the Southeastern states and 6% did not have health insurance. Older age, being black, being a woman, area level poverty, and health insurance were significantly associated with lower statin use. Statin use decreased as the number of vulnerabilities increased.

Conclusions:
A greater burden of healthcare disparity vulnerabilities was associated with a graded pattern of lower statin use. Individuals with multiple vulnerabilities have the greatest risk of under treatment and should be targeted for intervention.