bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P375: Vascular Age Versus Calendar Age as Surrogate for Atherosclerotic Burden and Cardiovascular Disease Risk
Authors: Peters Sanne A , Groenewegen Karlijn A , den Ruijter Hester M , Bots Michiel L
Published: July 2021

Background
Vascular age is the chronological age of an individual adjusted by their level of atherosclerosis. Vascular age can be used as understandable communication tool towards patients. It has been proposed that carotid intima-media thickness (CIMT) could be used to estimate the vascular age in individuals. The issue on how to best estimate vascular age remains an unanswered question and was evaluated in this study.

Methods
Data were used from the USE-IMT study collaboration, a global individual patient data meta-analysis including 14 population-based cohorts contributing data for 45 828 individuals. We used two methods to define vascular age. First, vascular age was the age at which a participant’s CIMT value would be at the 50th percentile of the age-and sex specific reference values of the healthy USE-IMT subpopulation (VA50). Second, vascular age was the age at which the estimated cardiovascular risk equals the risk of the observed CIMT value (VArisk).

Results
Mean (+/- standard deviation [SD]) chronological age, VA50, and VArisk were 58 (9), 63 (19), and 59 (7) years, respectively. VArisk was 0.24 yrs higher in women and 1.5 yrs higher in men than chronological age whereas VA50 was 4.4 yrs higher in women and 5.8 yrs higher in men than chronological age. After adjustment for traditional cardiovascular risk factors, a SD increase in VA50 and VArisk was associated with a 15% (95% confidence interval [CI]: 1.12; 1.19) and 22% (95% CI: 1.17; 1.28) higher risk of cardiovascular disease. For comparison, a SD increase in mean common CIMT increased the risk of cardiovascular disease with 15% (95% CI: 1.12; 1.19).

Conclusion
We presented two distinct measures a vascular age: VA50, and VArisk. VA50 is a straightforward translation of CIMT and is a measure of the age at which the average person would be expected to have a certain CIMT. In contrast, VArisk incorporates information about expected cardiovascular risk and is the chronological age of a person that conveys the same risk as the CIMT. VA50 and VArisk might provide a convenient transformation of CIMT to a scale that is more easily understood by patients and clinicians.
Abstract P403: Animal and Plant Protein and Change in Blood Pressure During 15 Years of Follow-up: The Zutphen Elderly Study
Authors: Tielemans Susanne M , Kromhout Daan , Altorf-van der Kuil Wieke , Geleijnse Johanna M
Published: July 2021

Introduction:
Data from randomized controlled trials and observational studies suggest that blood pressure (BP) is inversely related to dietary protein, especially plant protein. We examined whether intake of animal and plant protein were related to long-term changes in BP in a cohort of elderly men in the Netherlands.

Methods:
Analyses were based on data of 269 men participating in the Zutphen Elderly Study, who were examined in 1985, 1990, 1995 and 2000. Men did not use antihypertensive medication and were initially free of cardiovascular disease, diabetes mellitus and cancer. Diet was repeatedly assessed by trained dieticians using the cross-check dietary history method and BP was measured twice by trained research staff at every occasion. The associations of animal and plant protein (in tertiles) with 5-year BP change were obtained by a random intercept model, taking into account serial correlation and measurement error. Median values of tertiles (in en%) were 7.9, 9.7 and 12.8 for animal protein and 4.1, 4.9 and 6.0 for plant protein. Adjustments were made for age, measurement year, BMI, socioeconomic status, smoking, prescribed diet, alcohol intake, total energy intake and intake of carbohydrates, types of fat, minerals, dietary fibre and plant protein (in animal protein analysis) or animal protein (in plant protein analysis).

Results:
At baseline, men were 70±5 years old and BP was 147/84 mmHg. Mean intake was 10.2±2.7 en% for animal protein and 5.0±1.0 en% for plant protein. Animal protein was not associated with 5-year BP change (p>0.30). For plant protein intake, 5-year change in systolic BP was -3.30 mmHg (95% CI: [[Unable to Display Character: ‑]]6.39; [[Unable to Display Character: ‑]]0.20) and -2.56 mmHg (95% CI: -5.69; 0.57) in tertile 2 and tertile 3, respectively, compared to BP change in tertile 1. For diastolic BP, these changes were -1.61 mmHg (95% CI: [[Unable to Display Character: ‑]]3.34; 0.12) and -1.70 mmHg (95% CI: -3.45; 0.05), respectively.

Conclusion:
Plant protein, but not animal protein, was inversely associated with BP change during 15 years of follow-up in elderly men.
Abstract P406: N-3 Fatty Acids Measured in Saliva do not Reflect Short-term Changes in Intake but may be Associated with Medium or Long-term Intake
Authors: Baylin Ana , Campos Hannia , Marin Constanza , Vargas Luz Nayibe , Mora-Plaza Mercedes , Villamor Eduardo
Published: July 2021

Background:
N-3 fatty acids in blood are adequate biomarkers of intake compared to dietary questionnaires because they do not rely on memory or self-reported information, and are not subject to interviewer bias. However, obtaining blood samples is an invasive approach, particularly among children. Measuring fatty acids in saliva is a non-invasive alternative that has not been explored yet in detail in population studies.

Objective:
To evaluate if n-3 fatty acids measured in saliva would be adequate biomarkers of intake.

Methods:
We selected 60 families for a 4-week intervention trial among participants in the Bogotá School Children Cohort. They were randomly assigned to receive a month’s supply of either soybean oil (high in α-linolenic acid [ALA], n=30) or sunflower oil (low in ALA, n=30). We obtained saliva and finger-prick blood samples in the children at baseline and follow-up. Fatty acids were analyzed by gas liquid chromatography in saliva and blood. To measure short-term responsiveness, we compared means of ALA in saliva by intervention arm at follow-up. To assess validity, we compared n-3 fatty acids concentrations in saliva and blood at baseline with the use of Spearman correlation coefficients.

Results:
Mean (SD) age of study participants was 14.5 (1.5) years; 37% (22 of 60) were male. Treatment groups did not differ at baseline with regard to socio-demographic and anthropometric characteristics, or fatty acids levels. Children assigned to soybean oil had a non-statistically significantly higher mean (SD) ALA concentration in saliva at follow-up (0.62 [0.66]), compared to children assigned to sunflower oil (0.47 [0.44]; p=0.45). Follow-up concentrations of long-chain n-3 fatty acids (EPA and DHA) in saliva did not differ significantly between intervention arms. To assess validity, we compared saliva and blood fatty acids concentrations at baseline (n=60) and found significant correlations for ALA (r=0.44, p=0.0005), EPA (r=0.27, p=0.04), and DHA (r=0.34, p=0.008).

Conclusions:
N-3 fatty acids measured in saliva do not reflect accurately short-term changes in ALA intake. However, moderate correlations between n-3 fatty acids in saliva and blood suggest that measuring fatty acids in saliva may be a valid proxy for intake. It is possible that fatty acids in saliva may have a slower turnover than those in blood and could be better biomarkers for medium or long-term intake of n-3 fatty acids.
Abstract P409: Both Body Mass Index and Waist Circumference are Adversely Associated with Exposure to Trans-fatty Acids in Persons with Type 2 Diabetes
Authors: Schwenke Dawn , Foreyt John , Miller Edgar , Reeves Rebecca , Vitolins Mara , Oxidative Stress Subgroup of Look AHEAD I
Published: July 2021

Trans-fatty acids (TFA) increase cardiovascular disease risk and have been associated with the cardiovascular risk factors body mass index (BMI) and waist circumference (waist) in persons without diabetes. Whether TFA are associated with BMI and waist in persons with type 2 diabetes is unknown. We investigated the association between TFA exposure as indicated by plasma concentrations of 18-carbon TFA and BMI and waist. We studied persons randomized into Look AHEAD at two clinics (Baltimore, n=81; Houston, n=151) who participated in a substudy assessing physical activity and an ancillary study of oxidative stress and completed the Look AHEAD Food Frequency Questionnaire (LAFFQ). Look AHEAD is a multi-center controlled trial of lifestyle intervention for weight loss in overweight or obese adults (aged 45-76) with type 2 diabetes. Representation of women (57%) and minorities (18.1% black, 8.2% Hispanic, 3.9 % other race/ethnicity) was similar to Look AHEAD. Before intervention, weight, height, and waist were measured, BMI was calculated, nutrients were estimated from LAFFQ, and physical activity was determined by accelerometry. TFA, saturated (SFA) and cis-monounsaturated (c-MFA) fatty acids were measured before intervention in plasma collected between December 2002 and April 2004. TFA intake in subjects was high (median 2.4% of energy, interquartile range 1.9%, 3.0%). In models adjusted for age, sex, race/ethnicity, clinic, sampling time, physical activity, and plasma total fatty acid concentration, BMI (p=0.0004) and waist (p=0.0018) varied according to plasma TFA concentration. For lowest, middle, and highest tertiles of plasma TFA, BMI was (mean+SE) 33.0+0.9, 36.9+0.9, and 36.6+0.9 kg/m
2
, respectively, while waist was 108.4+1.9, 115.8+1.9, and 114.8+2.0 cm, respectively. These associations were not attenuated by sequential adjustment for plasma SFA and c-MFA concentrations and for dietary variables including TFA, total fat, SFA, oleic acid, protein and total calories. These results extend findings concerning TFA exposure and BMI and waist circumference to persons with type 2 diabetes and are consistent with the notion that reducing TFA exposure may reduce cardiovascular risk in persons with type 2 diabetes.
Abstract P440: Ethnic and Gender-specific Prevalence of Type 2 Diabetes Mellitus among Adults in the California Health Interview Survey 2009
Authors: Choi Sarah , Liu Michael , Palaniappan Latha , Wang Elsie , Wong Nathan
Published: July 2021

Background:
The ethnic and gender-specific prevalence of type 2 diabetes mellitus (DM) have not been adequately documented in past studies; in addition, Asians and Hispanics have been often treated as aggregates, making it difficult to examine subgroup differences.

Methods:
Using the California Health Interview Survey (CHIS) 2009 data, we identified the prevalence of DM and associated risk factors, stratified by gender, for the following ethnicities: Chinese, Filipino, South Asian, Japanese, Korean, Vietnamese, Cambodian, Mexican, Hispanic (Other), African American, and Caucasian (n=45,857, projected = 26.6 mil).

Results:
Among men, the age-adjusted prevalence of DM was highest in Filipinos (15.8%), Japanese (11.8%), and Mexicans (10.2%). Among women, African Americans (13.3%) and Other Hispanic (10.7%) had the highest DM prevalence. Significant gender difference was observed in Caucasians and Mexicans, where men had a higher DM prevalence than women. In multiple logistic regression adjusting for age and other clinical and lifestyle risk factors, among women, compared to Caucasians, an increased likelihood of DM was seen in Koreans (OR=4.72,
p
<0.01), Cambodian (OR=3.84,
p
<0.05), and Other Hispanic (OR=2.90,
p
<0.01) Among men, compared to Caucasians, DM was more likely in Filipinos (OR=6.99,
p
<0.01), South Asians (OR=4.69,
p
<0.01), and Mexicans (OR=2.82,
p
<0.01).

Conclusion:
Ethnic and gender differences in DM prevalence persist, even after adjusting for lifestyle and other risk factors. Racial/ethnic minority groups, particularly certain Asian subgroups, have the highest DM prevalence in California, despite risk factor adjustment. Different ethnic and gender- specific diabetes prevention approaches may be required.
Abstract 04: Fried Food Consumption and Genetic Predisposition to Obesity
Authors: Qi Qibin , Chu Audrey , Kang Jae , Jensen Majken , Curhan Gary , Louis Pasquale , De Vivo Immaculata , Chan Andrew , Choi Hyon , Tamimi Rulla , Ridker Paul , Hunter David , Willett Walter , Rimm Eric , Chasman Daniel , Hu Frank , Qi Lu
Published: July 2021

Background:
Fried food consumption has been associated with obesity; little is known about whether genetic background modifies this association.

Methods:
We analyzed interactions between a genetic risk score (GRS) based on 32 BMI-associated variants and fried food consumption on body mass index (BMI) and obesity in 9623 women from the Nurses’ Health Study (NHS) and 6379 men from the Health Professionals Follow-up Study (HPFS) and in a replication cohort of 21426 women from the Women’s Genome Health Study (WGHS).

Results:
An interaction between fried food consumption and the GRS on BMI was identified in both NHS and HPFS (P for interaction≤0.001). Among participants in the highest tertile of the GRS, the differences in BMI between individuals who consumed fried foods ≥4times/week and those consumed <1time/week amounted to 1.0 in women and 0.7 kg/m2 in men, whereas the corresponding differences were 0.5 and 0.4 kg/m2 in the lowest tertile of the GRS. The gene-diet interaction was replicated in the WGHS (P for interaction<0.001). Viewed differently, the genetic association with adiposity was strengthened with higher consumption of fried foods. In the combined three cohorts, the differences in BMI per 10 risk alleles were 1.2, 1.6, and 2.4 kg/m2 for fried food consumption<1, 1-3 and ≥4times/week (P for interaction<0.001) (Figure); and the odds ratios (95% CI) for obesity per 10 risk alleles were 1.60 (1.38-1.84), 2.13 (1.74-2.60) and 2.65 (2.08-3.39) across the three categories of consumption (P for interaction=0.002). In addition, we found that the individual variants in genes highly expressed or known to act in the central nervous system showed significant interactions, with the FTO variant showing the strongest result (P for interaction<0.001).

Conclusion:
Fried food consumption may interact with genetic background in relation to obesity, highlighting the particular importance of reducing fried food consumption in individuals genetically predisposed to obesity.
Abstract 06: Body Mass Index And The Risk Of All-cause Mortality Among Patients With Type 2 Diabetes
Authors: zhao wenhui , Katzmarzyk Peter , Horswell Ronald , Wang Yujie , Johnson Jolene , Heymsfield Steven , Cefalu William , Ryan Donna , Hu Gang
Published: July 2021

Background:
Several prospective studies have evaluated the association between body mass index (BMI) and the risk of all-cause mortality among diabetic patients; however, the results are controversial.

Aim:
To investigate the association of BMI levels with all-cause mortality among patients with type 2 diabetes in the Louisiana State University Hospital-based Longitudinal study (LSUHLS).

Methods:
We performed a prospective cohort study (2000-2009) of diabetic patients including 19,785 African Americans and 15,534 whites. Cox proportional hazards regression models were used to estimate the association of BMI levels at baseline, during follow-up and at last visit with the risk of all-cause mortality.

Results:
During a mean follow up of 8.7 years, 4,206 deaths were identified. The multivariable-adjusted (age, sex, smoking, income and type of insurance) hazard ratios (HRs) of all-cause mortality associated with BMI levels (<23, 23-24.9, 25-29.9, 30-34.9 [reference group], 35-39.9, and ≥40 kg/m
2
) at baseline were 2.53 (95% confidence interval [CI] 2.18-2.93), 1.76 (1.48-2.09), 1.23 (1.08-1.40), 1.00, 1.19 (1.02-1.38), and 1.22 (1.05-1.41) for African Americans, and 1.92 (1.63-2.27), 1.53 (1.28-1.82), 1.07 (0.95-1.21), 1.00, 1.07 (0.93-1.23), and 1.21 (1.06-1.39) for whites, respectively. When stratified by age, gender, smoking status or use of anti-diabetic drugs, a U-shaped association was still present. When we used an updated mean or last visit value of BMI, the U-shaped association of BMI with all-cause mortality risk did not change.

Conclusions:
The current study indicated a U-shaped association of BMI with all-cause mortality risk among African American and white patients with type 2 diabetes. A significantly increased risk of all-cause mortality was observed among African Americans with BMI<30 kg/m
2
and BMI ≥35 kg/m
2
, and among whites with BMI<25 kg/m
2
and BMI ≥40 kg/m
2
compared with patients with BMI 30-34.9 kg/m
2
.
Abstract 14: Examining the Predictive Power and the Impact of Incorporating Hemoglobin A1c into Existing Diabetes Risk Prediction Models among African American Adults in the Jackson Heart Study
Authors: Lacy Mary E , Wellenius Gregory , Eaton Charles B , Loucks Eric B , Correa Adolfo , Gjelsvik Annie , Wu Wen-Chih
Published: July 2021

Background:
In 2010, the American Diabetes Association (ADA) updated diagnostic criteria for diabetes to include hemoglobin A1c (A1c). However, the appropriateness of these criteria in African Americans (AAs) is unclear as A1c may not reflect glycemic control as accurately in AAs as in whites. Moreover, existing diabetes risk prediction models have been developed in populations composed primarily of whites. Objectives were to (1) examine the predictive power of existing diabetes risk prediction models in the Jackson Heart Study (JHS), a prospective cohort of 5,301 AA adults and (2) explore the impact of incorporating A1c into these models.

Methods:
We selected 3 widely-used diabetes risk prediction models and examined their ability to predict 5-year diabetes risk among 3,185 JHS participants free of diabetes at baseline and who returned for the 5 year follow-up visit. Incident diabetes was identified at follow-up based on current antidiabetic medications, fasting glucose ≥126 mg/dl or A1c ≥6.5%. We evaluated model performance using model discrimination (C-statistic) and reclassification (net reclassification index (NRI) and integrated discrimination improvement (IDI)). For each of the 3 models, model performance in JHS was evaluated using (1) covariates identified in the original published model and (2) published covariates plus A1c.

Results:
Of 3,185 participants (mean age 53.7; 64.0% female), 9.8% (n=311) developed diabetes over 5 years of follow-up. Each diabetes prediction model suffered a drop in predictive power when applied to JHS using ADA 2010 criteria (Table 1). The performance of all 3 models improved significantly with the addition of A1c, as evidenced by the increase in C-statistic and improvement in reclassification.

Conclusion:
Despite evidence that A1c may not accurately reflect glycemic control in AAs as well as in whites, adding A1c to existing diabetes risk prediction models developed in primarily white populations significantly improved 5-year predictive power of all 3 models among AAs in the JHS.
Abstract 16: Diabetes, Pre-diabetes, and Progression of Subclinical Myocardial Damage
Authors: Selvin Elizabeth , Lazo Mariana , Shen Lu , Rubin Jonathan , McEvoy John William (Bill) , Hoogeveen Ron C , Ballantyne Christie M , Coresh Josef
Published: July 2021

Background:
Persons with hyperglycemia even below the threshold for the diagnosis of diabetes are at increased risk for cardiovascular events. The relationships of pre-diabetes and undiagnosed diabetes with progression of subclinical myocardial damage are relatively uncharacterized.

Objective:
To characterize the associations of diabetes and pre-diabetes with 6-year progression of subclinical myocardial injury, as assessed by a novel highly sensitive assay for cardiac troponin T (hs-cTnT).

Methods:
We conducted a prospective analysis of hs-cTnT measured at two time points, 6 years apart, in 8446 participants of the community-based ARIC Study with hs-cTnT <14 ng/L and without a history of heart disease, stroke or heart failure at baseline (1990-92). We examined the associations of pre-diabetes and diabetes defined by HbA1c or fasting glucose with 6-year change in hs-cTnT after adjustment for traditional cardiovascular risk factors. Diagnosed diabetes was defined as self-reported physician diagnosis or medication use for diabetes. We used Poisson regression to evaluate the risk of progression of hs-cTnT from non-elevated (<14 ng/L) to elevated (≥14 ng/L) (“incident elevated hs-cTnT”) at 6 years of follow-up.

Results:
Baseline prevalence of elevated concentrations of hs-cTnT among persons with no diabetes (HbA1c<5.7%), prediabetes (HbA1c 5.7-6.4%), undiagnosed diabetes (≥6.5%), and diagnosed diabetes were 1.8%, 3.3%, 6.3% and 10.3%, respectively. Diagnosed diabetes, undiagnosed diabetes, and pre-diabetes were significantly associated with incident elevated hs-cTnT (Table). The associations of undiagnosed diabetes and pre-diabetes defined by diagnostic categories of HbA1c showed somewhat stronger associations compared to those clinical categories defined by fasting glucose.

Conclusions:
These results provide evidence for a progressive, deleterious effect of hyperglycemia on the myocardium, even below the threshold for a diagnosis of diabetes.
Abstract 17: Global diet quality among adults in 187 countries
Authors: Imamura Fumiaki , Khatibzadeh Shahab , Micha Renata , Fahimi Saman , Shi Peilin , Powles John W , Mozaffarian Dariush
Published: July 2021

Background:
Global quality and trends over time of dietary patterns, a priority for reducing chronic diseases, are unknown.

Methods:
We evaluated age- and sex-specific energy-adjusted consumption, derived from 325 national surveys covering 88.7% of the global adult population, of 17 key foods and nutrients in 187 countries in 1990 and 2010. Diet patterns were assessed by two distinct scales, one based on higher intakes of healthful items (higher intakes=higher scores), and the other on lower intakes of unhealthful items (lower intakes=higher scores), by country, age, sex, and national income.

Results:
In 2010, global diet patterns varied substantially (
Figure
). African and South Asian nations had low scores based on more healthful items, but high scores based on fewer unhealthful items. In contrast, Western countries had moderate scores based on healthful items and very poor scores based on unhealthful items. This distinction between more healthful items and fewer unhealthful items was largely masked if we aggregated the two pattern scores, which were weakly correlated (
r
=-0.08). By age and sex, women and older adults had higher scores based on either healthful or unhealthful items (
p
<0.05). Compared to low-income countries, high-income countries had higher scores based on more healthful items (+4.4 [95% uncertainty interval: 3.8, 5.0]), but substantially lower scores based on fewer unhealthful items (-28.1 [-27.3, -28.9]). From 1990 to 2010, most regions improved their diets based on more healthful items (global average=+2.2 [2.0, 2.4]), except for poorest nations; conversely, nearly all regions worsened their diets based on fewer unhealthful items (-2.5 [-2.8, -2.2]), with marked heterogeneity across global regions.

Conclusions:
Diet quality varies substantially worldwide, with important differences by higher intakes of healthier foods vs. lower intakes of unhealthy foods. The findings emphasize distinct, nation-specific policy priorities for increasing healthful and decreasing unhealthful foods.
Abstract 24: Prenatal Socioeconomic Position is Associated with Adipose Tissue DNA Methylation in Women and Not Men
Authors: Agha Golareh , Houseman Andres E , Kelsey Karl T , Eaton Charles B , Buka Stephen L , Loucks Eric B
Published: July 2021

RATIONALE:
Adiposity is a major cardiovascular risk factor, suggesting an important role for adipose tissue in development of cardiovascular outcomes. There is evidence that early life adversity has a lasting impact on the development of adiposity, particularly in women. In utero exposure to famine was related to adulthood adiposity in women but not men, and associations between early life socioeconomic adversity and adulthood adiposity is established in women but less so in men. There is interest in epigenetic mechanisms by which early life adversity may program risk for adiposity, and utilizing directly affected tissue such as adipose tissue is ideal for investigating such mechanisms.

Objective:
To determine whether prenatally-assessed socioeconomic index (SEI) is associated with adulthood genome-wide DNA methylation in blood and adipose tissue, and whether associations differ between men and women.

Methods:
Participants (aged 44-50 y) were from the New England Family Study birth cohort, born in Providence, RI. Of 400 participants assessed during 2010-2011, a representative subsample of 106 participants (68 women, 38 men) was selected for DNA methylation analyses. SEI was measured prenatally as a composite numerical score, using a weighted percentile of both parents’ educational attainment, occupation, and income relative to the US population. DNA methylation in subcutaneous adipose tissue and peripheral blood leukocytes was evaluated using the Infinium HumanMethylation450K BeadChip.

Results:
Prenatal SEI was associated with adipose tissue DNA methylation in women (permutation-based omnibus p-values <0.001), but not men or the pooled sample. Associations in women were not attenuated after adjustment for race, current smoking, or mother’s smoking during pregnancy. Prenatal SEI was not related to blood DNA methylation.

Conclusion:
Results provide mechanistic insight on the association between early life adversity and adulthood adiposity, which is seen mainly in women.
Abstract 28: HIV Infection Is Associated With Greater Risk of Carotid Artery Lesions Over Seven Years
Authors: Hanna David B , Post Wendy S , Deal Jennifer A , Hodis Howard N , Anastos Kathryn , Lazar Jason M , Palella Frank J , Tien Phyllis C , Witt Mallory D , Kaplan Robert C , Kingsley Lawrence A
Published: July 2021

Background:
We previously found that low CD4+ T-cell counts among HIV-infected (HIV+) women and men were associated with an increased prevalence of carotid artery lesions in a cross-sectional analysis. We now report on the association of HIV infection with
progression
of subclinical atherosclerosis in the same well-characterized population of HIV+ and HIV-uninfected (HIV-) women and men. We hypothesized that HIV infection would be associated with greater progression over seven years of follow-up.

Methods:
We examined data from a subset of participants without a history of coronary heart disease in the Women’s Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS) who underwent serial B-mode carotid artery ultrasound imaging between 2004 and 2012 (median follow-up: 7 years). We included individuals with at least two examinations during this period, with a median of 4 exams among women and 3 exams among men. We evaluated changes in common carotid artery intima-media thickness (cIMT, mm) and the development of carotid artery lesions (focal IMT >1.5 mm), defined as an
increased
number of lesions over the time period, based on regression models with generalized estimated equations to take into account clustering by individual, controlling for demographic factors and smoking status. Models combining women and men, as well as stratified by cohort, are presented.

Results:
We studied 1011 women (74% HIV+) and 811 men (65% HIV+). The median age was 41 years (IQR 35-47) in women and 49 (IQR 44-55) in men. The unadjusted mean cIMT increased during the period from 0.725 to 0.752 mm in women and from 0.757 to 0.790 mm in men. The prevalence of carotid artery lesions increased from 8% to 15% in women and from 25% to 34% in men during follow-up. In analyses controlling for sex, age, race/ethnicity, study site, and smoking status, progression of carotid artery lesions differed by HIV serostatus. HIV+ persons had a 1.9-fold higher adjusted risk of developing lesions during the follow-up period than HIV- persons (17% with increase in lesions among HIV+ vs. 10% in HIV-; 95% CI 1.29-2.72, p=0.001). This association persisted in models stratified by cohort (in women, adjusted relative risk 1.66, 95% CI 0.96-2.89, p=0.07; in men, 1.92, 95% CI 1.14-3.11, p=0.01), with no evidence of effect modification by cohort (p=0.58). We did not find significant differences in cIMT change over time by HIV serostatus, either in combined or cohort-specific analyses.

Conclusion:
HIV infection was associated with a greater increase in carotid artery lesions over a seven-year period in both women and men. HIV appears to play a role in focal cIMT thickening in atherosclerosis-prone carotid artery segments, but not a generalized increase in wall thickness in the common carotid artery.
Abstract 30: Body Mass Index Is Associated With Markers Of Inflammation And Liver Damage Among Healthy Adolescents
Authors: Jun Byong Nam , Nam Yoo Ju , Choi Dong Phil , Lee Ju-Mi , Kim Hyeon Chang
Published: July 2021

Objectives:
Obesity is the main cause of non-alcoholic fatty liver disease. Clinical studies reported that adolescent obesity is also associated with elevated levels of inflammatory markers and liver enzymes. However, it is unclear whether adolescents’ body mass index (BMI) within the normal range is associated with inflammatory marker or liver enzyme levels. Thus we investigated the association of BMI with C-reactive protein (CRP) and alanine aminotransferase (ALT) levels in healthy Korean adolescents.

Methods:
The JSHS Study is a prospective cohort study to investigate the risk factors for vascular change in early life. The current cross-sectional analysis enrolled 540 boys and 506 girls, aged 15-16 years old, who participated in the baseline examinations between 2007 and 2012. Baseline measurements included anthropometrics, physical examinations, questionnaires, and fasting blood analysis. Spearman correlation and linear regressions analyses were used to investigate the association of BMI with CRP and ALT. All statistical analyses were performed separately for males and females.

Results:
CRP levels were positively correlated with BMI in males (correlation coefficient r=0.175, p<0.001) and females (r=0.206, p<0.001). After adjustment for age, smoking and alcohol consumption, higher BMI was positively associated with increased CRP levels (β=0.157, p<0.001 for male; β=0.195, p<0.001 for female). But this association was attenuated (β=0.091, p=0.074 for male; β=0.085, p=0.091 for female), when the analysis was limited to adolescents with normal range of BMI (18.5 to 25.0 kg/m2).

ALT levels were positively correlated with BMI only in males (correlation coefficient r=0.337, p<0.001) but not in females (r=0.072, p=0.104). After adjustment for age, smoking and alcohol consumption, higher BMI was positively associated with increased ALT levels (β=0.436, p<0.001 for male; β=0.094, p=0.034 for female). But this association was significant only in males (β=0.190, p<0.001) not in females (β=0.074, p=0.143), when the analysis was limited to adolescents with normal range of BMI.

Conclusion:
Higher BMI was positively associated with increased levels of CRP and ALT among healthy Korean adolescents. The positive association between BMI and ALT levels was observed even in male adolescents with normal range of BMI.
Abstract 35: Transcriptome-wide Association Study of Circulating Lipid Levels
Authors: Chen Brian H , Schurmann Claudia , Peters Marjolein J , Pfeiffer Liliane , Schramm Katharina , Pilling Luke C , Joehanes Roby , Freeman Lita , Yaghootkar Hanieh , Esko Tonu , Cupples L. Adrienne , Grallert Harald , Johnson Andrew D , Kathiresan Sekar , Munson Peter J , Reischl Eva , Waldenberger Melanie , Ying Saixia , Melzer David , Ferrucci Luigi , Prokisch Holger , Herder Christian , Isaacs Aaron , Levy Daniel , Teumer Alexander
Published: July 2021

Genome-wide association studies have identified scores of DNA variants that are associated with circulating lipid levels. We conducted a transcriptome-wide association study (TWAS) of triglycerides (TG), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), and total cholesterol (TC) using whole blood derived RNA from 1,838 Framingham Heart Study participants using the Affymetrix GeneChip Human Exon 1.0 ST array. External replication was conducted in four separate population-based cohorts (SHIP-TREND, KORA F4, Rotterdam Study, InChianti) totaling 3,244 individuals assayed using the Illumina HumanHT-12 Expression BeadChip array. Individuals taking lipid-lowering medications were excluded from analysis. Models were adjusted for age, sex, blood cell counts, and technical covariates (e.g., batch). Using a stringent transcriptome-wide FDR of 0.05 in both discovery and replication results, there were 119 significant transcript associations for TG; 57 for HDL-C; 1 for LDL-C; and 3 for TC. Expression levels of HDC and CPA3 genes were the two strongest associations with all 4 lipid traits in both discovery and replication cohorts. Known lipid pathway gene MYLIP was inversely associated with triglycerides (replication P=6.4x10-45) and directly associated with HDL-C levels (replication P =3.5x10-26). ABCA1 was also directly associated with triglyceride levels (replication P =9.4x10-50). In summary, through TWAS we identified many known and novel genes whose expression levels in whole blood were associated with circulating lipid levels. We believe that TWAS may serve as a useful method for identifying novel therapeutic targets. However, further studies are needed to elucidate the role that these genes may play in regulating circulating lipid levels or mediating the effect of lipids on atherosclerotic cardiovascular diseases.
Abstract 38: HDL Cholesterol, Inflammation and Peripheral Arterial Disease in U.S. Adults
Authors: Kuang Lei , Wong Nathan.D
Published: July 2021

Introduction:
The protective relation of high density lipoprotein-cholesterol (HDL-C) with coronary heart disease may be weakened in the presence of inflammation; however, whether inflammation may attenuate any association of HDL-C with peripheral arterial disease (PAD) is unknown.

Hypothesis:
We hypothesized that inflammation measured by high-sensitivity C-reactive protein (hs-CRP) will attenuate any inverse association of HDL-C with PAD.

Methods:
We studied 6512 men and women aged ≥ 40 years who participated in the National Health and Nutrition Examination Survey (NHANES ) from 1999-2004 who had measures of ankle brachial index (positive for PAD defined as <0.9 or ≥1.5), lipids, high-sensitivity CRP (hs-CRP) and other risk factors. Groups were categorized by low (<40 mg/dL for men or <50 mg/dl or women), intermediate (40 or 50-59 mg/dL), and high (≥60 mg/dL) HDL-C, and low (<1 mg/L), normal (1-3), and high (3 mg/L) hs-CRP levels. We evaluated the odds ratio (ORs) for PAD by logistic regression adjusted for age, race, gender, low density lipoprotein-cholesterol, smoking, diabetes, body mass index, systolic blood pressure waist circumference and triglycerides.

Results:
Those with the highest hs-CRP levels had the highest prevalence of PAD (8.5-10.8%), regardless of level of HDL-C (figure 1). Using high HDL-C/low hs-CRP as the reference, the likelihood of PAD was significantly increased among those with normal and high hs-CRP within the intermediate HDL-C group: OR 4.7 (95%CI 1.6, 14.1) and OR 4.5 (95% CI 1.4,14.2) , respectively. Among those with normal and high hs-CRP within the low HDL-C group, the likelihood of PAD was also increased:OR 5.0 (95% CI 2.1,12,1) and OR 6.4 (95% CI 2.2,18.1), respectively.

Conclusion:
High hs-CRP is associated with higher likelihood of PAD across all ranges of HDL-C, but especially when HDL-C is normal or low. These results support the value of combined hs-CRP and HDL-C in risk stratification for PAD which should be validated by prospective studies.
Abstract 50: Adiposity is Associated with Genome-wide DNA Methylation in Adipose Tissue
Authors: Agha Golareh , Houseman Andres E , Kelsey Karl T , Eaton Charles B , Buka Stephen L , Loucks Eric B
Published: July 2021

Background:
Adiposity is a major risk factor for type 2 diabetes, dyslipidemia, and CVD, suggesting an important role for adipose tissue in development of these conditions. There is interest in epigenetic mechanisms by which genetic and environmental factors may contribute to adiposity, however studies of DNA methylation in relation to adiposity rarely focus on adipose tissue.

Objective:
To determine whether genome-wide DNA methylation profiles in blood and adipose tissue are associated with central fat, body fat distribution, and obesity in adulthood.

Methods:
Participants (aged 44-50 years) were from the New England Family Study birth cohort, born in Providence, RI . Of 400 participants assessed during 2010-2011, a representative subsample of 106 participants (68 women, 38 men) was selected for DNA methylation analyses. DNA methylation in subcutaneous adipose tissue and peripheral blood leukocytes was evaluated using the Infinium HumanMethylation450K BeadChip. Dual-energy x-ray absorptiometry scans assessed android fat mass, android:gynoid region fat ratio, and trunk:limb region fat ratio. BMI (kg/m
2
) was directly assessed.

Results:
Adipose tissue DNA methylation was associated with all four measures of adiposity, after adjusting for race, sex, smoking, and accounting for multiple testing (permutation-based omnibus p-values <0.001). Associations were similar in sex-specific analyses, and upon exclusion of single nucleotide polymorphisms. Investigation of top differentially-methylated genes revealed several that are biologically relevant to adiposity development, including
SOD3
,
AOC3
,
AQP7, TIMP4, ANGPT4,
and
ADAMTS4
. Blood DNA methylation was not related to adiposity.

Conclusion:
Adipose tissue DNA methylation was associated with directly-assessed measures of central fat and body fat distribution, as well as obesity, all of which are important determinants of cardiometabolic risk. Targeting the primary affected organ may be important for elucidating the epigenetic basis of adiposity.
Abstract 53: Biomarkers of Cardiovascular Stress and Left Ventricular Hypertrophic Patterns: Cross-sectional relations and prognostic significance
Authors: Xanthakis Vanessa , Stevenson Meredith , Vasan Ramachandran S
Published: July 2021

Background:
Cardiac stress biomarkers (growth differentiation factor 15 [GDF-15], soluble ST-2 [ST2], high-sensitivity troponin I [hsTnI]) and B-type natriuretic peptide [BNP]) are associated with incident heart failure (HF) and left ventricular mass (LVM). It is unclear if biomarker levels and their prognostic significance vary according to LV hypertrophy (LVH) pattern and extent. We hypothesized that concentric & eccentric LVH would be associated with highest biomarker levels; presence of both LVH and higher biomarker levels would indicate high HF risk.

Methods and Results:
We evaluated 2,425 Framingham Study participants free of HF (57% women, mean age 58 years) attending a routine examination, with available biomarker and echocardiographic measurements. We defined 4 LVH patterns: a.
normal
(normal LVM and Relative Wall Thickness [RWT]); b.
concentric remodeling
(normal LVM, elevated RWT); c.
eccentric hypertrophy
(elevated LVM, normal RWT); and d.
concentric hypertrophy
(elevated LVM and RWT). Adjusting for age & sex, biomarker levels (except BNP) increased sequentially across LVH patterns a-d (
Figure
). BNP levels were lowest in concentric remodeling and highest in eccentric LVH. In multivariable models, all biomarkers were associated with incident HF (106 cases, 12 yrs follow-up). We observed a significant interaction only between BNP and LVM (p=0.02). In stratified analyses, higher LVM was associated with incident HF in both BNP strata (Hazard Ratios [HR] per SD increase in LVM = 2.24 [<median BNP] and 1.35 [≥median BNP]; p<0.01 for both). However, higher BNP was associated with incident HF only in the stratum with LVM<median (HR = 2.09 per unit-increase in logBNP, p=0.003).

Conclusions:
In our large community-based sample, cardiac stress biomarker levels varied by LVH pattern. Contrary to our hypothesis, BNP levels were more strongly associated with HF in individuals with lesser degree of LVH.
Abstract 54: A Comparison of Blood Pressure-Lowering Treatment Decisions Based on Levels of Blood Pressure, Age, and Risk
Authors: Karmali Kunal N , Lloyd-Jones Donald M , van der Leeuw Joep , Goff David , Rahimi Kazem , Sundstrom Johan
Published: July 2021

Introduction:
The goal of primary prevention is to direct treatment to individuals who will derive greatest benefit. However, single risk factors such as blood pressure or age incompletely capture absolute risk and potential treatment benefit for the individual, thus providing a role for multivariable risk assessment. In this study, we aim to compare blood pressure treatment decisions based on levels of systolic blood pressure (SBP), age, or pretreatment risk.

Methods:
We used individual participant data from participants without cardiovascular disease in the Blood Pressure Lowering Treatment Trialists’ Collaboration, a prospective overview of randomized blood pressure trials. Three treatment strategies based on thresholds of SBP, age, or five-year Framingham risk estimates were compared by calculating expected number of cardiovascular events and net benefit using graphical methods and decision curve analyses. Strategies were compared as differences in the areas under the curves expressed as percentages of the maximum possible area, with bootstrap-obtained confidence intervals.

Results:
We analysed 16,419 individuals with 53,571 person-years of follow-up. At every level of number of individuals treated or number of events expected, the risk-based approach using the Framingham risk estimates appeared superior to SBP (risk minus SBP-based treatment decisions = -2.8% [95% CI -4.1% to -1.3%]) or age (risk minus age-based decisions -2.6% [95% CI -4.7% to -0.7%]) (Figure). For a treatment threshold based on expected absolute risk reduction, net benefit was maximized using Framingham risk estimates for a threshold of 1 to 4%, although the differences did not meet statistical significance.

Conclusions:
Blood pressure treatment decisions based on estimated absolute risk appear more efficient than age- or SBP-based treatment decisions, across a wide range of treatment thresholds. These results support prioritizing risk-based blood pressure treatment strategies in the primary prevention of cardiovascular events.
Abstract 57: Increased Fitness Attenuates the Risk for Developing Atrial Fibrillation in African-Americans
Authors: Faselis Charles , Kokkinos Peter , Kokkinos John Peter , Tsimploulis Apostolos , Kyritsi Fiorina , Pittaras Andreas , Doumas Michael , Moore Hans , Karasik Pamela , Fletcher Ross
Published: July 2021

Introduction:
Atrial fibrillation (AF) is associated with increased mortality risk. Some studies indicate that endurance training may increase the rate of progression to AF. However, others dispute this notion. Furthermore, fitness status and atrial fibrillation in African-Americans has not been investigated.

Methods:
From 1986 to 2011, a total of 4,401 African-Americans with normal sinus rhythm (mean age 56±11) underwent a routine exercise tolerance testing at Veterans Affairs Medical Centers Washington DC. During a mean follow-up period of 8.0±4.7 years 361 (8.2%) developed AF. To assess the role of fitness status in the development of AF, we formed the following four fitness categories based on peak workload achieved (metabolic equivalents; METs): Least-Fit: ≤ 5METs (≤20%; n=531); Low-Fit: 5.5-7.2 METs (20.1%-50%; n=1,367); Moderate-Fit:7.3-9.0 METs (50.1%-80%; n=1,775); and High-Fit: >9 METs (>80%; n=728). Cox proportional hazards models were applied after adjusting for age, BMI, race, gender, CV disease, CV medications, and cardiac risk factors. P-values <0.05 using two sided tests were considered statistically significant.

Results:
The association between exercise capacity and the risk for developing AF was inverse and graded. For every 1-MET increase in exercise capacity the AF-risk was 25% lower (HR=0.75; CI: 0.71-0.81; p<0.001). When compared to the Least-Fit category, the risk for developing AF was 36% lower (HR=0.64; CI: 0.48-0.83; p=0.001) in Low-Fit; 66% (HR=0.44; CI: 0.33-0.60; p<0.001) in Moderate-Fit; and 76% (HR=0.24; CI: 0.14-0.40; p<0.001) in High-Fit individuals.

Conclusions:
Aerobic fitness is inversely and independently associated with lower risk for developing AF.
Abstract 65: Exercise Mitigates Chronic Stress Effects on BMI Trajectories in Girls Aged 10 to 19: Longitudinal Findings from the NHLBI Growth and Health Study.
Authors: Puterman Eli , Prather Aric A , Epel Elissa E , Loharuka Sheila , Adler Nancy E , Laraia Barbara , Tomiyama A. Janet
Published: July 2021

Introduction:
Obesity is a leading cause of cardiovascular disease. Adolescence is a period when behavior changes consolidate, setting a trajectory towards obesity. Both poor health behaviors and psychological stress promote obesity. Studies have shown that ongoing stress is related to weight gain while maintaining physical activity mitigates obesity in children as they transition to adulthood. We hypothesized that during childhood, physical activity maintenance would moderate the relationship between chronic stress and BMI increase.

Methods:
The NHLBI Growth and Health Study enrolled 2,379 Black and White girls aged 9-10 and assessed them annually over ten years.
Perceived Stress
was measured in years 2, 4, 6, 8, and 10 with the well-validated Perceived Stress Scale, simplified for use in children. The
Physical Activity
Patterns Questionnaire assessed duration and frequency of activities in and out of school at years 1, 3, 5, and 7-10.
Body mass index
(BMI; kg/m2) was available all years. Covariates included pubertal timing, race, parental income and education, and nutrient intake. Repeated measurement allows prediction of trajectories of BMI with growth curve modeling, i.e. rate of BMI change over time.

Results:
On average, baseline BMI was 20.79 and increased 0.63 BMI units/year. Yet, BMI increase varied significantly as a function of stress and physical activity (p = .005). Even when reporting high stress, girls who maintained activity had lower BMI growth than girls who were fairly inactive between ages 10 and 19. An average of two units less in BMI was seen at age 19 in those highly stressed yet active versus highly stressed and less active - a likely clinically significant difference, as the girls in the latter category neared 30 kg/m2 (see Figure). The slowest increase in BMI between ages 10 and 19 was evidenced in girls more active and lower in stress.

Conclusion:
This study adds to a converging literature showing that physical activity is a modifiable behavior that can limit the harmful health effects of ongoing stress.