bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP19: Glycemic Load is Associated with Increased Odds of Cognitive Impairment in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Cohort
Authors: Pearson Keith , Wadley Virginia , Gower Barbara , Shikany James , Chandler-Laney Paula , Howard George , McClure Leslie , Unverzagt Fred , Judd Suzanne
Published: July 2021

Introduction:
Carbohydrate quality and quantity have been associated with several chronic diseases, but few studies have investigated associations with cognitive impairment. The objective of this study was to test the hypothesis that higher glycemic load (GL), glycemic index (GI), and available carbohydrate intakes are associated with higher odds of incident cognitive impairment in a large, prospective cohort.

Methods:
This analysis utilized the REGARDS study, a national cohort of 30,239 black and white participants (age > 45 yr). Dietary intake was assessed by the Block98 food frequency questionnaire, from which values for GL, GI, and available carbohydrate (total carbohydrate minus dietary fiber) were estimated. Incident cognitive impairment was defined as shifting from an intact cognitive status (a score >4) at the first cognitive assessment to an impaired cognitive status (a score ≤4) at the most recent cognitive assessment, measured by the Six-Item Screener. Logistic regression was used to evaluate the odds of incident cognitive impairment by quintile of GL, GI, and available carbohydrate.

Results:
This analysis included 16,755 participants free of stroke and cognitive impairment at baseline. A total of 1,513 cases of incident cognitive impairment were observed over a mean follow-up of 7.5 years. After adjustment for sociodemographic variables and cognitive risk factors, participants in the highest quintile of glycemic load had 42% higher odds of incident cognitive impairment compared to those in the lowest quintile (Q5 vs Q1: OR=1.42; 95% CI: 1.06, 1.89; p for trend: 0.02). Similarly, participants in the highest quintile of available carbohydrate had 42% higher odds of incident cognitive impairment (Q5 vs Q1: OR=1.42; 95% CI: 1.05, 1.91; p for trend: 0.04). No significant associations were observed with glycemic index (See Table 1).

Conclusion:
Consuming a dietary pattern lower in available carbohydrate and glycemic load may aid in the preservation of cognitive function in older ages.
Abstract MP23: Carbohydrate Quality and Quantity and Risk of Coronary Heart Disease Among US Women
Authors: AlEssa Hala B , Cohen Randy , Adebamowo Sally N , Malik Vasanti S , Rimm Eric B , Manson JoAnn E , Willett Walter C , Hu Frank B
Published: July 2021

Background:
Poor carbohydrate quality has been associated with increased risk of coronary heart disease (CHD), however the association between the novel carbohydrate to fiber ratio and CHD is unknown.

Objective:
To prospectively examine the relationship between various carbohydrate quality measures, including the carbohydrate to fiber ratios, and incident CHD in US women.

Methods:
Dietary and lifestyle behavior data were prospectively collected (1984-2012) in 71,639 women of the Nurses’ Health Study at baseline and every 2-4 years. Participants were free of diabetes, cancer or cardiovascular disease at baseline. Cox regression was used to assess the relationship between carbohydrate quality measures and incident CHD.

Results:
After 24 years (1,905,240 person-years) of follow-up, we identified 3,267 cases of incident CHD. After adjusting for age, BMI, lifestyle and dietary variables, carbohydrate (RR=1.01, 95% CI: 0.89-1.14, P-trend=0.76), starch (RR=1.11, 95% CI: 0.97 - 1.27, P-trend=0.13) and total fiber intake (RR=0.89, 95% CI: 0.77 - 1.01, P-trend=0.23) were not associated with incident CHD, comparing extreme quintiles of intake. Cereal fiber intake was associated with reduced risk of CHD (RR=0.76, 95% CI: 0.67 - 0.85, P-trend < 0.0001), comparing extreme quintiles of intake, but fruit and vegetable fiber were not associated with incident CHD. In fully adjusted models, the carbohydrate to total fiber (RR=1.08, 95%CI: 0.96 - 1.22, P-trend=0.27) and the starch to total fiber ratios (RR=0.95, 95% CI: 0.84 - 1.08, P-trend=0.80) were not associated with incident CHD, but the carbohydrate to cereal fiber and the starch to cereal fiber ratios were associated with increased risk of CHD (RR=1.19, 95% CI: 1.06 -1.33, P-trend=0.002, and RR=1.23, 95% CI: 1.09-1.39, P-trend <0.0001, respectively), comparing extreme quintiles of intake.

Conclusion:
Dietary cereal fiber appears to be an important component of carbohydrate quality. The carbohydrate to cereal fiber and the starch to cereal fiber ratios, but not the carbohydrate to total fiber ratio, were associated with an increased risk of CHD.
Abstract MP29: Kidney Function, Bone-mineral Metabolism Markers, and Peripheral Artery Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Yang Chao , Kwak Lucia , Ballew Shoshana , Jaar Bernard , Folsom Aaron , Heiss Gerardo , Selvin Elizabeth , Lutsey Pamela , Coresh Josef , Matsushita Kunihiro
Published: July 2021

Introduction:
Impaired kidney function is a known risk factor for lower-extremity peripheral artery disease (PAD). Whether novel markers of kidney filtration like cystatin C and beta-2-microglobulin (B2M) differ in their associations with PAD risk compared to creatinine-based estimated glomerular filtration rate (eGFRcr) is unclear. Also, bone-mineral metabolism (BMM) disorders are commonly complicated with impaired kidney function, but it is not known whether BMM markers influenced by kidney function are associated with PAD.

Hypothesis:
Novel filtration markers are more strongly associated with PAD risk than eGFRcr, and BMM markers are associated with PAD risk beyond kidney function.

Methods:
Using data from 13215 ARIC Study participants free of clinical history of PAD at baseline (1990-1992), we applied Cox proportional hazards model to quantify the associations of biomarkers and eGFR equations incorporating these biomarkers (cystatin C, B2M, eGFRcr, and eGFR based on cystatin C and cr [eGFRcr-cys]) with PAD risk. We also evaluated whether BMM markers (fibroblast growth factor 23, parathyroid hormone, calcium and phosphorus) were associated with PAD after adjustment for eGFR. PAD was defined as hospitalizations with ICD-9 code of 440.2x and 440.3.

Results:
During a median follow-up of 21 years, 587 participants had at least one hospitalization with a discharge code for PAD. The novel markers cystatin C and B2M showed stronger associations with PAD compared to eGFRcr (Table). When examining BMM markers, only elevated phosphorus level was associated with PAD risk and the association remained significant after adjustment for eGFRcr-cys (Table).

Conclusions:
The novel filtration markers cystatin C and B2M are stronger in their association with PAD compared to eGFRcr. Moreover, higher phosphorus level was related to future PAD risk beyond kidney function. Our results suggest novel filtration markers may improve PAD risk assessment, and there is a possible role for phosphorus metabolism in the pathophysiology of PAD.
Abstract MP30: Metabolomic Profiles Associated with Aging in Women
Authors: Rexrode Kathryn M , Balasubramanian Raji , Paynter Nina , Manson JoAnn , Chen Jiu-Chiuan , Vitolins Mara , Albert Christine , Clish Clary
Published: July 2021

Background:
Aging is a complex process that results from metabolic activities such as those that generate reactive oxygen species. Metabolomic profiling, an emerging technology, may shed light on metabolites associated with aging and identify key changes associated with premature aging.

Methods:
A total of 370 metabolites were profiled using liquid chromatography tandem mass spectroscopy (LC-MS) in plasma from 1153 healthy, control subjects in the Women’s Health Initiative. Metabolite levels were log-transformed and standardized, and each considered individually in statistical models. Linear regression models were created with the metabolite as the outcome and age as the primary exposure: <60 (referent), 60-<65, 65-<70, 70-<75, and 75 years and older. Models were adjusted for matching factors in the primary study (race, time period, hysterectomy status, and then additionally for body mass index, medications (antihypertensives, anti-diabetic drugs, aspirin and statins), and creatinine. The likelihood ratio test was used to compare models with age to model without age, with adjustment for false discovery rate (FDR). Significant results were defined as FDR adjusted p<0.05.

Results:
The median age of the women was 68 years (interquartile range 62-72). After multivariate adjustment, thirty-nine metabolites were significantly associated with age >75, including 12 acylcarnitines, 11 free fatty acids, 9 fatty acid derivatives, 2 amino acids, and 5 additional metabolites. Of these, octadecenoyl-L-carnitine (C18:1) had the strongest age association, with levels 0.70 SD (95% CI: 0.48-0.92) higher on average among women
>
75 years compared to women <60 years of age (referent). C22:0 sphingomyelin (SM), threonine and C24:0 SM were negatively associate with age; levels of these metabolites were on average 0.41 to 0.44 SD lower among the women 75 years and older when compared to the youngest women (linear trend FDR-p value <0.05 for all of these metabolites).

Conclusions:
Multiple metabolites involved in mitochondrial fatty acid oxidation, as well as several associated with insulin resistance, have a strong relationship with age, even after adjusting for multiple age-associated factors.
Abstract MP32: Long Term Prediction of Incident Heart Failure in African Americans - The Atherosclerosis Risk in Communities Study
Authors: Azeem Amir , Musani Solomon K , Beard Walter L , Mosley Thomas H , Butler Kenneth R , Fox Ervin R
Published: July 2021

Background:
Heart failure (HF) affects a large number of Americans with an estimated lifetime risk of over 20% among individuals over the age of 40 years. Heart failure is associated with significant morbidity, mortality and health care cost. Epidemiological data suggests that HF disproportionately affects African Americans. Existing risk prediction models may not accurately predict the risk of incident HF in this population limiting the implementation of screening and preventive strategies. We sought to examine the predictors of incident heart failure in a community-based African American cohort.

Methods:
The study population consisted of 2244 African American participants from the Jackson cohort of the Atherosclerosis Risk in Communities (ARIC) study. Participants with prevalent HF and missing data at the baseline were excluded. Cox proportional regression with backward elimination was used to assess the association of risk markers with first clinical HF event as follows: Model 1 - standard cardiovascular risk factors (age, gender, body mass index [BMI], systolic blood pressure, use of anti-hypertensive medication, diabetes status, current smoking, total cholesterol-HDL ratio [TC:HDL], logarithmically transformed-triglyceride); Model 2 - significant standard risk factors and biomarkers (logarithmically transformed-brain natriuretic peptide [BNP], logarithmically transformed-troponin, logarithmically transformed-albumin-creatinine ratio); Model 3 - significant standard risk factors and subclinical disease markers (estimated glomerular filtration rate [eGFR], ankle-brachial index, forced expiratory volume in one second [FEV1], forced vital capacity, left ventricular ejection fraction < 50%, left ventricular mass indexed to height2.7); Model 4 - significant standard risk factors, significant biomarkers, and significant subclinical disease markers.

Results:
The mean age and BMI were 58 years and 30 kg/m2 respectively. During a median follow-up of 18.1 years (maximum 19.8), there were 268 incident HF events. Triglyceride from Model 1, Troponin and Albumin-Creatinine ratio from Model 2, and eGFR from Model 3 were eliminated. In the final model, diabetes status (Hazard Ratio [95% Confidence Interval]: 1.76 [1.07, 2.89]), use of anti-hypertensive medication (2.38 [1.40, 4.06]), TC:HDL (1.34 [1.18, 1.52]) and BNP (1.28 [1.14, 1.44]) were significant predictors of incident HF. Higher FEV1 was associated with reduced risk of HF in this study (0.29 [0.11, 0.76]).

Conclusion:
In this community-dwelling African American population, diabetes status, use of anti-hypertensive medication, TC:HDL ratio, BNP and FEV1 were independent predictors of incident HF. This information may be useful to identify and target high risk individuals for aggressive preventive interventions.
Abstract MP43: Electrocardiographic and Blood Pressure Effects of Energy Drinks and Panax Ginseng in Healthy Volunteers: A Randomized Clinical Trial
Authors: Shah Sachin A , Nguyen Tinh An (April) , Occiano Andrew , Chan Amanda , Sky Joseph C , Bhattacharyya Mouchumi , O’Dell Kate M , Shek Allen , Nguyen Nancy N
Published: July 2021

Introduction:
Energy drink usage has been linked to emergency room visits and deaths. Cardiovascular and neurological adverse effects are among the most frequently reported, warranting further exploration of risk factors and cardiovascular outcomes.

Hypothesis:
We assessed the hypothesis that energy drinks and panax ginseng may contribute to significant electrocardiographic and blood pressure changes in healthy individuals.

Methods:
This was a randomized, double blinded, placebo controlled, crossover study where young healthy volunteers consumed 3 different study drinks on different days. The interventions included 32 ounces of an energy drink, control drink with 800 mg of panax ginseng or a matching placebo drink, all of which were consumed over a 45 minute period. Primary endpoints of interest were QTc interval and systolic blood pressure. Secondary endpoints included QT interval, PR interval, QRS duration, heart rate, and diastolic blood pressure. All endpoints were assessed at baseline, 1, 2, 3.5, and 5.5 hours post-study drink administration.

Results:
Twenty seven volunteers completed the study. A significant increase in QTc interval 2 hours post energy drink consumption was evident when compared to placebo (3.37±10.7 msec and -3.19±11.8 msec respectively; p=0.030). Similarly, systolic blood pressure 2 hours post energy drink consumption increased when compared to placebo (2.00±6.37 mmHg and -2.67±5.83 mmHg respectively; p=0.014). The PR interval significantly reduced over a 2 hour period post energy drink use in a clinically non-meaningful manner. Heart rate at 2 hours was not significantly higher in the energy drink group. The QT interval, QRS interval and diastolic blood pressure were not impacted at any time across groups.

Conclusions:
In conclusion, certain energy drinks consumed at a high volume can significantly increase the QTc interval and systolic blood pressure by over 6 msec and 4 mmHg respectively. Panax ginseng does not have a significant impact on ECG or blood pressure parameters. Future studies are warranted to delineate the electrophysiological and hemodynamic risks of certain energy drinks consumed at different concentrations and durations.
Abstract MP47: Associations Between Novel Biomarkers and Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Tang Weihong , Yao Lu , Hoogeveen Ron C , Alonso Alvaro , Couper David J , Maclehose Richard , Lutsey Pamela L , Steenson Carol C , Hunter David W , Lederle Frank A , Folsom Aaron A
Published: July 2021

Introduction:
Abdominal aortic aneurysms (AAA) are an important manifestation of vascular disease in older age and rupture of an AAA is associated with high mortality. Traditional atherosclerotic disease risk factors contribute to the etiology of AAA. Biomarkers for novel etiopathogenic mechanisms, including extracellular matrix remodeling and inflammation, have been assessed primarily in cross-sectional studies of AAA. The objective of this study was to prospectively assess the association between biomarkers for these novel mechanisms and clinical AAA during 24 years of follow-up in the ARIC study, a large, community-based cohort.

Methods:
Clinical AAAs were ascertained from baseline in 1987-1989 (45-64 years of age) to 2011 through hospital discharge codes, death codes, and Medicare outpatient claims. Over a maximum 24 years of follow-up, a total of 554 AAAs (85.3% whites) were identified. Using a nested case-cohort design, novel biomarkers, including MMP3, MMP9, IL6, IL1-beta, N-terminal propeptide of Type III procollagen (PIIINP), and osteopontin, were measured at baseline (90% of sample) or Visit 2 (1990-1992, 10% of sample) in all AAAs and a random sample of 747 participants who were selected from baseline and matched with AAAs by age (≤55 and >55), race, and gender. The association of the biomarkers with the risk of future AAA was estimated using multivariable Cox proportional hazard models with weighting to adjust for the varying sampling fractions of cases and controls across strata.

Results:
MMP9, IL6, PIIINP, and osteopontin were significantly associated with future risk of AAA after adjusting for age, gender, race and field center (Table). The associations for PIIINP and osteopontin were no longer significant after further adjusting for other traditional risk factors for AAA.

Conclusions:
Blood concentrations of MMP9, IL6, and osteopontin measured in middle-age were risk markers for incident AAA. These results highlight the role of inflammation and extracellular remodeling in the development of AAA.
Abstract MP60: Coronary Artery Calcium and Dementia Risk in the Multi-Ethnic Study of Atherosclerosis
Authors: Fujiyoshi Akira , Jacobs David R , Fitzpatrick Annette L , Alonso Alvaro , Duprez Daniel A , Sharrett A. Richey , Blaha Michael J , Luchsinger José A , Rapp Stephen R , Seeman Teresa
Published: July 2021

Introduction:
Vascular risk factors (VRFs) predict incident dementia. Coronary artery calcium (CAC), capturing cumulative VRFs exposure, may predict dementia beyond VRFs.

Hypothesis:
In a community-based sample, baseline CAC is associated with incident dementia independent of VRFs assessed at baseline and APOE
-ε
4 genotype.

Methods:
Among 6,814 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), aged 45-84 years at baseline (2000-2002), we first identified candidate cases for incident all-cause dementia using hospital and death certificate ICD codes. For the analyses, we limited to cases whose diagnosis was validated using following criteria: 1) verifiable medical records available, 2) unlikely alternative diagnosis (e.g. delirium), and 3) written dementia diagnosis. Baseline CAC was categorized according to Agatston score (0, > 0 to <50, 50 to <100, 100 to <400, and ≥400). Cox models were used to obtain hazard ratios (HRs) adjusted for demographics, VRFs, APOE
-ε
4, and incident stroke prior to dementia diagnosis.

Results:
We had complete data on 6,295 individuals for analysis with a mean follow-up of 11.1 years (208 validated cases). Crude rates of dementia were greater with higher baseline CAC categories. Adjusted HR of dementia per one higher CAC category was 1.14 (95%CI 1.03, 1.26) (see Table). The associations were similar when excluding interim incident coronary heart disease, or cardiovascular diseases, or using a model that accounted for competing risk of death with no dementia diagnosis.

Conclusion:
Higher CAC score measured at baseline was independently and significantly associated with increased risk of dementia. This finding is consistent with an important role for vascular injury in development of dementia.
Abstract MP65: Masked Hypertension is Associated with Cardiovascular Disease Events in African Americans: The Jackson Heart Study
Authors: Booth John N , Diaz Keith M , Seals Samantha , Sims Mario , Ravenell Joseph , Muntner Paul , Shimbo Daichi
Published: July 2021

Introduction:
Masked hypertension has been associated with increased cardiovascular disease (CVD) risk in Europeans and Asians.

Hypothesis:
Determine the association of masked hypertension with CVD events and all-cause mortality in African Americans (AA).

Methods:
The Jackson Heart Study, an exclusively AA population-based, prospective cohort study, was restricted to participants with clinic systolic/diastolic blood pressure (SBP/DBP) < 140/90 mmHg and valid ambulatory blood pressure monitoring (ABPM) at the baseline exam in 2000-2004 (n=738). Masked daytime hypertension was defined as mean ambulatory daytime (10am-8pm) SBP ≥ 135 mmHg or DBP ≥ 85 mmHg. Masked nocturnal hypertension was defined as mean ambulatory nighttime (12am-6am) SBP ≥ 120 mmHg or DBP ≥ 70 mmHg. Using all ABPM measurements, masked 24-hour hypertension was defined as mean SBP ≥ 130 mmHg or DBP ≥ 80 mmHg. CVD events (nonfatal/fatal stroke, nonfatal myocardial infarction or fatal coronary heart disease) and all-cause mortality were identified and adjudicated through December 31, 2011.

Results:
Any masked hypertension (masked daytime, nocturnal or 24-hour hypertension) was present in 52.2% of participants; 28.2% had masked daytime hypertension, 48.2% had masked nocturnal hypertension and 31.7% had masked 24-hour hypertension. There were 51 CVD events and 44 deaths over a median follow up of 8.2 and 8.5 years, respectively. The CVD rate (95% CI) per 1,000 person years in participants with and without any masked hypertension were 13.5 (9.9-18.4) and 3.9 (2.2-7.1), respectively (Table). The multivariable adjusted hazard ratio (95% CI) between any masked hypertension and CVD was 2.49 (1.26-4.93). CVD rates for those with and without masked daytime, nocturnal and 24-hour hypertension, and the hazard ratios for CVD associated with masked daytime, nocturnal and 24-hour hypertension, were similar. Masked hypertension was not associated with all-cause mortality.

Conclusion:
Masked hypertension is common and associated with increased CVD risk in AAs.
Abstract MP78: Effects of Regular Endurance Exercise on GlycA: Results Across Four Exercise Training Studies
Authors: Sarzynski Mark A , Church Timothy S , Hagberg James M , Landers-Ramos Rian , Leon Arthur S , Rao Dabeeru C , Seip Richard L , Skinner James S , Thompson Paul D , Wilund Kenneth R , Bouchard Claude
Published: July 2021

Objective:
Our goal was to examine the effects of regular endurance exercise on plasma GlycA levels, a novel NMR-derived biomarker of systemic inflammation.

Methods:
We examined NMR-derived plasma GlycA levels before and after 5-6 months of exercise training in 1,194 adults from four studies: APOE (N=104), DREW (N=298), GERS (N=78), HERITAGE (N=714). We used unadjusted and adjusted general linear models to evaluate changes in GlycA with regular exercise across sex-specific quartiles of baseline GlycA in all studies combined.

Results:
At baseline, the combined participants (69% white, 66% female) were an average of 42.5 (15.4) years old with a mean BMI of 28.1 (5.8) kg/m
2
. Exercise training resulted in a decrease in GlycA of 5.6 (42.0) μmol/L (P<0.0001) across all studies. In the unadjusted model, only the fourth quartile of baseline GlycA showed a mean decrease in GlycA with exercise training, while a linear decrease across Q2 to Q4 was observed in the adjusted model (
Figure 1
). In both models, Q4 showed the greatest decrease in GlycA.

Conclusions:
Regular exercise tended to decrease GlycA levels across four diverse, standardized exercise training studies. Our results suggest that the individuals at highest risk appear to benefit the most from regular exercise in terms of GlycA.

Figure 1. Mean change in GlycA after exercise training by baseline GlycA quartile in four exercise studies combined
.

P<0.0001 for trend in both the unadjusted and adjusted analyses. Unadjusted analysis included three dummy variables representing the four study groups. Adjusted analyses included age, sex, race, baseline BMI, baseline VO
2
max, baseline GlycA quartile, and three study group dummy variables as covariates. Sex-specific baseline GlycA quartiles in combined group (M/F): Q1: <282/<317; Q2: 283-323/317-356; Q3: 324-370/318-395; Q4: >370/>395
Abstract MP82: The Effect of Nicotinic Acetylcholine Receptor Genes CHRNA3/5 on Thoracic Aortic Calcium is Mediated by Smoking
Authors: Lutz Sharon M , Cho Michael , Kinney Greg , Young Kendra , Pratte Katherine , Duca Lindsey , Foreman Marilyn , Beaty Terri , Silverman Ed , Budoff Matthew , Hokanson John
Published: July 2021

Introduction:
Coronary artery calcium (CAC) and thoracic aortic calcium (TAC), markers of subclinical atherosclerosis, have been shown to strongly correlate with the amount of atheromatous plaque and subsequently predict future coronary disease events and mortality. CAC and TAC are complex heritable traits with both genetic and environmental risk factors such as cigarette smoking. We investigated the role of smoking, a key environmental risk factor, as a mediator of the genetic risk of subclinical atherosclerosis in the COPDGene study.

Hypothesis:
We hypothesized that smoking will mediate a portion of the genome-wide significant SNPs with subclinical atherosclerosis as measured by TAC and CAC.

Methods:
We performed genome wide genotyping of common and rare variants in COPDGene, a study of 10,192 current and former smokers with at least 10 pack-years of smoking history. CAC and TAC were measured using high dose, inspiration chest CT scans, following an established protocol in 8,739 individuals (6,150 non-Hispanic Whites and 2,589 African Americans). Mediation analysis, using the significant SNPs from the GWA of common and rare variants, was performed using R software adjusting for genetic ancestry using principal components as well as recognized risk factors (age, gender, BMI, diabetes, high blood pressure, steroid use, high cholesterol, and presence of a coronary stent). We used the log transformation of CAC plus 1 and the log transformation of TAC plus 1 as the quantitative phenotypes.

Results:
There were 3 SNPs on chromosome 15q25 [CHRNA5/3] achieving genome-wide significance with TAC in non-Hispanic Whites, with the most significant result being rs951266 (p= 3.074e-8). We previously replicated 9 SNPs on chromosome 9 [CDKN2B-AS1] reaching genome-wide significance with CAC in non-Hispanic Whites. In African Americans, no genome-wide significant associations were identified. Given these findings, we tested for mediation of these genetic signals by pack-years of smoking among non-Hispanic Whites in the COPDGene study. Pack-years of smoking history was a significant mediator of CHRNA5/3 [rs951266] on TAC (p <0.001, 13% indirect effect), while smoking was not a significant mediator of CDKN2B-AS13 on CAC (p =0.58).

Conclusions:
The nicotinic acetylcholine receptor genes on chromosome 15 (CHRNA5/3) were significantly associated with thoracic aortic calcium in this cohort of heavy smokers. Cigarette smoking mediates this genetic risk for subclinical atherosclerosis and may offer an avenue for intervening on the genetic susceptibility to coronary artery disease.
Abstract MP86: Hemodynamic and Metabolomic Change From Lifestyle Driven Weight Loss in Obese Adolescents
Authors: Zachariah Justin P , Newburger Jane W , Mitchell Gary F
Published: July 2021

Background:
While bariatric surgery is known to induce hemodynamic and metabolic pathway alterations, lifestyle-driven weight loss in obese adolescents are not well characterized with respect to hemodynamic and metabolomic effects. We studied aortic function and urine metabolomics changes in obese adolescent volunteers attending weight loss summer camps.

Methods:
Adolescents (n=45, 71% girls, mean age 15±1 year) attending long-standing weight loss camps over 3 summers volunteered to have weight, long term diet and activity history, and vascular tonometry after overnight fast at camp entry and exit. A subset (n=32) also gave urine entry and exit urine samples for metabolomic analysis (Metabolon, Durham NC). Camp administrators followed pre-existing protocols encouraging campers toward 5 hours or more of structured activity and free play as well as nutritionist-designed meal plan restricted to age-sex specific calorie goals. Paired students T-tests were used to assess changes in anthropometrics and hemodynamics. Osmolality-adjusted metabolomic changes were analyzed using principal components analysis; paired T-test with multiple comparison adjustment by Storey-Tibshirani false discovery rate thresholding; and Random Forest decision tree ensembles with selection of the top 30 biochemicals in variable importance gleaned from the Mean Decrease Accuracy metric, which randomly permutes a given chemical and reassesses predictive accuracy throughout the tree ensembles, and then grouped into pathway categories.

Results:
Median camp length was 6 weeks (25%,75% IQR 5,7). Campers on average lost body 11±4% of body weight (99±20 to 88±17 kilograms, p<0.0001). Supine systolic blood pressure declined from 115±11 to 111±12 mmHg (p<0.01), diastolic blood pressure from 57±8 to 52±7 mmHg (p<0.0001), and heart rate from 73±10 to 62±11 beats per minute (p<0.0001). Carotid femoral pulse wave velocity decreased from 5.4±0.7 to 5.1±0.6 meters per second (p<0.0001). This change in arterial stiffness was not dependent on changes in heart rate nor distending pressure. Augmentation index did not significantly change from 17±11% to 16±9% (p=0.5). On urine metabolomic analysis, altered biochemical pathways included lipid metabolism, bile acids, and carbohydrate excretion.

Conclusions:
Diet and activity driven weight loss in excess weight adolescents is associated with salutary hemodynamic improvement and specific metabolic alterations, paralleling findings after bariatric surgery. More investigation into the mechanisms of lifestyle driven weight loss is warranted.
Abstract MP99: Cerebral Small Vessel Disease and the Epigenetic Clock: The Atherosclerosis Risk in Communities Study
Authors: Raina Abhay , Zhao Xiaoping , Bressler Jan , Gottesman Rebecca F , Grove Megan L , Guan Weihua , Pankow James S , Boerwinkle Eric , Mosley Thomas H , Fornage Myriam
Published: July 2021

Cerebral small vessel disease (SVD) is one of the most common degenerative vessel disorders of the aging brain. White matter hyperintensities (WMH) on magnetic resonance imaging (MRI) are viewed as typical markers of SVD and are associated with an increased risk of stroke, dementia, and death. Advancing age is the strongest predictor of WMH prevalence and severity. Recent studies have developed a novel biomarker of aging, termed “epigenetic clock”, based on DNA methylation levels at specific sites across the genome, which are strongly correlated with chronological age. The deviation of the DNA methylation (DNAm)-predicted age from the chronological age, defined as “age acceleration”, is used as an index of an individual’s rate of aging. Here, we estimated blood DNAm age in African-Americans from the Atherosclerosis Risk in Communities (ARIC) study using two methodologies, and examined the cross-sectional association between WMH on MRI and measures of accelerated epigenetic aging.

We hypothesized that DNAm age acceleration, defined as the residual value from the regression of the predicted DNAm age onto chronological age, is associated with greater WMH burden independently of chronological age and other known risk factors, including sex, body mass index, systolic blood pressure, hypertension, diabetes, and current smoking.

DNA methylation was measured using the Illumina HM450 array on genomic DNA extracted from blood samples of African-American participants of the ARIC study. We estimated DNAm age using two published algorithms in 713 individuals aged 51-73 with both DNAm and brain MRI data. Linear regression models were used to estimate the association of the natural log-transformed WMH burden with each measure of age acceleration adjusting for covariates.

Age acceleration was significantly associated with WMH burden and results were similar for both estimates of DNAm age. Each unit increase in WMH burden (on the log scale) was associated with a 1.2 and 1.3 year increase in DNAm age after accounting for chronological age and other known risk factors (P=0.01 and 0.004). Further adjustment for blood cell composition did not meaningfully change these results.

In this population-based study of middle-aged to older African-American adults, we report evidence of an association between accelerated epigenetic aging of blood and increased WMH burden, independent of known risk factors, including chronologic age. Additional studies are ongoing to clarify whether DNAm age is simply a marker of the rate of aging or reflects biological mechanisms implicated in the aging of the cerebral white matter.
Abstract P003: Comparison of Ideal Cardiovascular Health Status Across National Representative Cohorts: A Systematic Review
Authors: Younus Adnan , Malik Rehan , Ahmad Rameez , Ali Shozab , Aziz Muhammad , Bukhari Syed MS. , Ogunmoroti Oluseye , Osondu Chukwuemeka , Younus Muhammad Amir , Roberson Lara , Latif Muhammad A. , Humayun Choudhry , Veledar Emir , Nasir Khurram
Published: July 2021

Introduction:
In 2010, the American Heart Association set 2020 national goals for promoting cardiovascular health (CVH), emphasizing measurement of reproducible health behaviors and health factors and attaining ideal CVH status. In recent years, significant emphasis has been placed on adopting these metrics globally to monitor strategies to improve CVH. In this study, we synthesize available data to compare distribution of CVH metric metrics detailed in national representative cohorts a focus on presence of ideal CVH (ICVH).

Method:
A MEDLINE database search was conducted using relevant free text terms such as “life’s simple 7”, “AHA 2020”, “American Heart Association 2020” and “Ideal cardiovascular health”. Ideal CVH was defined as 6-7 ideal factors; conversely poor ICVH was considered as 0-1 ideal factors.

Results:
The pooled data comprised of 7 cross-national cohorts with a total of 152289 participants from India, United States, China, Spain, Korea, Luxembourg and Republic of Srpska. Significant variations in individual ideal CVH metrics were noted. Across population cohorts, diet metric consistently appeared suboptimal apart from Korea in which 55% participants reported ideal diet status. Overall majority population in each of the 7 cross-national cohorts lied in the range having 2-5 ideal CV health metrics (79-88%). A very small percentage of each population had 0-1 METRICS, with Spain, USA and Republic of Srpska having the highest percentage (18%) of reported poor ICVH. On the other hand, only representative cohorts from China and Korea reported ideal CVH status in more than 10% population.

Conclusion:
Overall suboptimal proportion of national representative cohorts have reported ideal CVH status. Significant efforts are needed to streamline current policies for enhancing CVH and sharpening focus interventions that will yield the greatest sustainable improvement in population CVH status.
Abstract P016: Metabolites of Glutamate Metabolism are Associated with Incident Cardiovascular Events in the Predimed (“Prevencion Con Dieta Mediterranea”) Trial
Authors: Zheng Yan , Hu Frank B , Ruiz-Canela Miguel , Clish Clary , Dennis Courtney , Salas-Salvado Jordi , Hruby Adela , Liang Liming , Toledo Estefania , Corella Dolores , Ros Emilio , Fitó Montserrat , Gómez-Gracia Enrique , Arós Fernando , Fiol Miquel , Lapetra José , Serra-Majem Lluis , Estruch Ramón , Martínez-González Miguel A
Published: July 2021

Background:
Glutamate metabolism may play a role in the pathophysiology of cardiometabolic disorders. However, there is limited evidence on the association between glutamate-related metabolites and, moreover, changes in these metabolites, and risk of cardiovascular disease (CVD).

Methods and Results:
Plasma levels of glutamate and glutamine were measured at baseline and 1-year follow-up in a case-cohort study including 980 participants (mean age: 67 years; 46% male) from the PREDIMED randomized trial, which assessed a Mediterranean diet intervention in the primary prevention of CVD. During median 4.8 years of follow-up, there were 229 incident CVD events (non-fatal stroke, non-fatal myocardial infarction, or CVD death). In fully-adjusted models, per 1-SD, baseline glutamate was associated with 43% (95% CI: 16-76%) and 81% (39-137%) increased risk of composite CVD and stroke alone, respectively, and baseline glutamine-to-glutamate ratio with 25% (6-40%) and 44% (25-58%) decreased risk of composite CVD and stroke alone, respectively. Associations appeared linear for stroke (both Plinear trend≤0.005). Among participants with high baseline glutamate, the interventions lowered CVD risk by 37% compared to the control diet; the intervention effects were not significant when baseline glutamate was low (Pinteraction=0.02). No significant effect of the intervention on year-1 changes in metabolites was observed, and no effect of changes themselves on CVD risk was apparent.

Conclusions:
Baseline glutamate was associated with increased CVD risk, particularly stroke, and glutamine-to-glutamate ratio was associated with decreased risk. Participants with high glutamate levels may obtain greater benefits from the Mediterranean diet than those with low levels.
Abstract P034: Hypertension in a Pediatric Cardiology Practice
Authors: Sexson Tejtel Sara K , Cephus Constance , Seery Thomas , Suh America , Moodie Douglas
Published: July 2021

Background:
Hypertension (HTN) is becoming a more recognized problem in pediatrics in general, though the prevalence is not changing despite the increasing prevalence of obesity.(1) The prevalence of borderline high and high blood pressure in children and adolescents appears to have plateaued at 11-12%. (1) Annual blood pressure measurement in patients being seen in pediatric practices has long been recommended. Our goal is to evaluate whether or not patients with HTN seen in a pediatric cardiology practice were appropriately diagnosed with HTN.

Methods:
A retrospective analysis of patients seen in the Texas Children’s Hospital Pediatric Cardiology outpatient clinics between 2005 and 2015 was performed. All blood pressure measurements, heights, weights, and BMI obtained at the same clinic visit were obtained from the electronic medical record. Patients with missing data were excluded from the analysis

The data was analyzed using SAS with calculations performed of means, standard deviations and interquartile ranges. Chi-squre and t-tests were used to compare means.

Results:
A total of 57,670 patients (53% male, mean age 8.7 +/- 8.3) were seen in clinic. The average BMI was 19 (range 0 to 95). There were a total of 125,750 visits, with a average number of visits 3.9 (range 1-64). 33,765 patients had blood pressure measurements in the pre-HTN or HTN range and 9,149 patients had Stage 2 HTN measured at the time of clinic visit. Most children (35,220, 61%) had only one visit and were therefore unable to truly be diagnosed with HTN. Of the remaining 22,450 patients, 3,751 (15%) patients had hypertensive blood pressure measurements on at least three occasions and 977 (26%) of those were diagnosed with HTN. The diagnosis of HTN was made in younger patients (p<0.001). Of those with the diagnosis of HTN, 691 (70%) were on antihypertensive medication. Younger patients were more likely to be treated for HTN than not, 10.3 +/- 11.7 years and 16.2 +/- 16.4 years respectively (p<0.001). Additionally proportionally females were more likely to be diagnosed with (p<0.001) and treated for HTN (p<0.001) than males.

Conclusions:
HTN is a common problem in pediatrics. In a pediatric cardiology practice, many patients have HTN that is undiagnosed. If HTN is diagnosed it is frequently either untreated or inadequately treated. While evaluation of blood pressure is being performed and documented in most patients adequate diagnosis and treatment is lacking.
Abstract P035: Association Between Caregiver and Child Metabolic Risk Factors: Hispanic Community Health Study/Study of Latino (SOL) Youth
Authors: Carnethon Mercedes R , Bangdiwala Srikant I , Talavera A. , Perreira Krista , Reina Samantha , Daviglus Marha L , Ayala Guadalupe X , Delamater Alan M , Pulgaron Elizabeth R , Isasi Carmen R
Published: July 2021

Background:
There is limited prior research on the association of metabolic risk factors between youth and their caregivers within Latino families despite the high burden of obesity and the young age of onset of metabolic disorders.

Hypothesis:
Obesity and metabolic risk factors are correlated between youth and their caregivers.

Methods:
SOL Youth is a cross-sectional ancillary study of boys and girls ages 8 to 16 years old whose parents/caregivers participated in the HCHS/SOL. We studied 728 boys, 738 girls and 1,020 caregivers (86% women) who completed a clinical examination. Body mass index (BMI), waist circumference, systolic and diastolic blood pressure, fasting glucose, hemoglobin A1c (HbA1c) and lipids (total-, HDL-, and LDL- cholesterol and triglycerides) were measured. Obesity was determined as
>
95
th
age- and gender- specific percentile of BMI in youth and BMI
>
30 kg/m
2
in adults. We used weighted logistic regression to determine the odds of obesity in youth when caregivers were obese and we tested the association of each individual risk factor in caregivers with the same risk factor among youth using weighted linear regression. All models were adjusted for field center, youth age and ancestry and adult age, gender and education levels.

Results:
On average, boys and girls were 12 years old and caregivers were 41 years old. When caregivers were obese (vs. normal weight), girls and boys were 1.5 (95% CI: 0.92, 2.43) and 3.9 (95% CI: 2.44, 6.29) times more likely to be obese, respectively. Among girls, measures of adiposity, HbA1c, SBP and lipids (except triglycerides) were each positively associated with those same measures among caregivers (Table). Among boys, all measures except glucose and HbA1c were positively associated with caregiver measures.

Conclusions:
There were notable differences by gender in the odds of obesity among youth when a caregiver was also obese. Strong correlations between caregiver and youth metabolic risk factors underscore the need for family based interventions.
Abstract P037: School Lunch is Associated with Increased Cardiovascular Risk Among Middle-school Children
Authors: de Visser Rosa S , Sylvester Rachel , Jiang Qingmei , Kline-Rogers Eva , DuRussel-Weston Jean , Eagle Kim A , Jackson Elizabeth A
Published: July 2021

Introduction:
Millions of children consume school lunches daily. Children from low-income families are eligible for free or reduced-price school meals. While studies show improvement in the nutritional quality of school lunches, the effect of school lunch or lunch brought from home on cardiovascular risk factors among children is unknown.

Hypothesis:
We hypothesized that frequently consuming school lunch is associated with increased cardiovascular risk factors when compared with lunch brought from home.

Methods:
All 15,742 sixth graders enrolled in Project Healthy Schools, a school-based wellness intervention, were included in this cross-sectional study (2004-2015). We examined 10,169 behavioral surveys and 1,845 physiological screenings. We compared self-reported diet, physical activity (PA), sedentary behaviors and physiologic parameters (height, weight, blood pressure (BP) and heart rate) in 2 groups, children who reported eating school lunch daily and those who eat home-prepared lunch daily. The groups were further stratified by socioeconomic status (SES); low SES (<$35,000) or high SES (>$50,000) based on the median household income of the school region. Students in the middle SES range ($35,000-$50,000) were excluded from analysis (n=4230).

Results:
School lunch students were associated with less healthy behaviors (PA, diet [fruit/vegetable servings, meat and sugary beverage intake], and sedentary activities) and physiologic measures (percent of overweight/obesity, systolic BP and recovery heart rate) compared with students bringing lunch from home in low and high SES groups (Table 1).

Conclusions:
In this large cohort of children, we observed frequent school lunch consumption, even after adjustment for SES, was associated with less healthy behaviors and physiologic parameters. Further research is warranted to determine whether healthier school lunches would improve cardiovascular health characteristics and health behaviors in middle-school students.
Abstract P048: Effects of Aerobic Exercise on Oxidative Stress in the Kidneys of Type2 Diabetic Rats
Authors: Ito Daisuke , Cao Pengyu , Kakihana Takaaki , Sato Emiko , Muroya Yoshikazu , Ogawa Yoshiko , Hu Gaizun , Ishii Tadashi , Ito Osamu , Kohzuki Masahiro , Kiyomoto Hideyasu
Published: July 2021

Objective:
Aerobic exercise is known to have multiple beneficial effects including renal protection in type 2 diabetes mellitus and obesity. However, the mechanisms regulating these actions of aerobic exercise remain unclear. The present study evaluated the effects of chronic aerobic exercise on early stage of diabetic nephropathy focusing on renal oxidative stress and nitric oxide (NO), using Zucker diabetic fatty (ZDF) rats as an animal model of obese type 2 diabetes.

Methods:
Male ZDF rats (6 weeks old) underwent forced treadmill exercise for 8 weeks (Ex-ZDF). Sedentary ZDF (Sed-ZDF) and Zucker lean (Sed-ZL) rats served as controls. After the last exercise session, all rats were subjected to an intra-peritoneal glucose tolerance test.

Result:
Exercise ameliorated hyperglycemia with increased insulin secretion, and raised the values of homeostasis model assessment for β-cell function (HOMA-β) in ZDF rats. Exercise also reduced albumin excretion and normalized creatinine clearance in ZDF rats. Endothelial (e) and neuronal (n) NO synthase (NOS) protein expression, and NOS activity in the kidneys of Sed-ZDF rats were lower compared with Sed-ZL rats, while both NOS expression and NOS activity were upregulated by exercise in ZDF rats. Although there was no significant difference in plasma levels of adiponectin between the groups, plasma levels of leptin were significantly higher in the Ex-ZDF group compared with the Sed-ZL and Sed-ZDF groups. Exercise decreased plasma and urinary thiobarbituric acid-reactive substances (TBARS) as an index of lipid peroxidation in ZDF rats. Additionally, renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and expression of p47phox protein were significantly higher in the kidneys of the Sed-ZDF group compared with the Sed-ZL group, and there was no significant difference between the Ex-ZDF and Sed-ZL groups. Immunoblots for Nox4, Nox2, namely gp91phox and p22phox protein were undetected in the kidneys of the Sed-ZDF and Ex-ZDF group as well as the Sed-ZL group. In addition, expression of nitrotyrosine as an index of peroxynitrite (ONOO–) formation was significantly lower in the kidneys of the Sed-ZDF group compared with the Sed-ZL group, and was significantly higher in the Ex-ZDF group compared with the Sed-ZDF group. Further, morphometric evidence of renal damage was alleviated in response to exercise.

Conclusion:
Upregulated NOS activity and NOS protein, and ameliorated NADPH oxidase activity and p47phox protein in the kidneys may be potential mechanisms by which chronic aerobic exercise can reduced early diabetic nephropathy in ZDF rats. Chronic aerobic exercise does have beneficial effects and may be a novel therapeutic approach for preventing the development of renal dysfunction in patients with type 2 diabetes mellitus and obesity.