bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 042: Accelerometer-measured Light Physical Activity is Heart Healthy in Older Women: The OPACH Study
Authors: LaCroix Andrea Z , Bellettiere John , Rillamas-Sun Eileen , Evenson Kelly R , Di Chongzhi , Buchner David M , Stefanick Marcia L , Lee I-Min , Lewis Cora E , LaMonte Michael J
Published: July 2021

Background:
The longstanding, prevailing paradigm in physical activity (PA) research and US PA guidelines is that moderate to vigorous physical activity (MVPA) for at least 150 minutes/week, preferably in increments of at least 10 minutes, is needed to prevent cardiovascular disease (CVD) in adults. Because light physical activity (LPA; 1.1-<3 metabolic equivalents (METs)) is poorly measured by self-report, we know little about its association with CVD.

Methods:
Women’s Health Initiative participants in the OPACH Study (n=5861, mean age=78.5±6.7, 33.5% Black, 17.6% Hispanic) without a history of myocardial infarction or stroke wore accelerometers for up to 7 days and were followed for incident CVD for up to 4 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for CVD and coronary heart disease (CHD) across awake wear time adjusted quartiles of MVPA and LPA. Fully adjusted models accounted for age, race-ethnicity, smoking, education, body mass index, systolic blood pressure, co-morbidity score, physical function, and self-rated health. We then examined the LPA association with CVD/CHD after adjustment for MVPA.

Results:
Higher levels of both LPA and MVPA were associated with reduced risks of CVD and CHD after adjusting for covariates (Table; p-trend <0.05, all). Women with the highest vs. lowest levels of MVPA had markedly reduced risks of CVD (31%) and CHD (50%). Women in the highest vs. lowest quartiles of LPA had 22% reduced risks of CVD and 39% reduced risks of CHD even after adjustment for many indicators of health status and CVD risk factors. The LPA association with CVD persisted after adjustment for MVPA (highest vs. lowest LPA quartile HR: 0.81 for CVD, p-trend=0.01; 0.74 for CHD, p-trend=0.04).

Conclusions:
LPA is associated with reduced risks of incident CVD and CHD in older women independent of health status indicators, CVD risk factors, and MVPA. Increasing levels of LPA is an achievable behavioral intervention for improving heart health in older women.
Abstract 043: Leisure-Time Physical Activity in Adulthood and Region of Interest (ROI) Brain Volumes: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)
Authors: Palta Priya , Sharrett A R , Evenson Kelly R , Jack Clifford R , Lutsey Pamela L , Wagenknecht Lynne E , Mosley Thomas H , Heiss Gerardo
Published: July 2021

Introduction:
Several studies report late-life physical activity (PA) to be associated with less brain atrophy. Associations of PA and subclinical brain markers evaluated at older ages may be subject to reverse causality due to comorbidity, age-related changes in lifestyle, or incipient cognitive impairment. Therefore, we aimed to compare late-life cross-sectional estimates of PA and ROI brain volumes to those using prospective PA measures from mid- to late-life.

Methods:
Participants (n=1549, mean age: 75, 39% male, 20% Black) with repeat assessments of PA from visit 1 (1987-1989) and a brain magnetic resonance imaging (MRI) in 2011-2013 were included. Total volume of PA in metabolic equivalent-min/week was estimated using the Baecke Physical Activity Questionnaire and classified as no, low, middle or high at each visit. Based on visit 1 and 3 (1993-1995) PA assessments, a subset of participants (n=663) were further categorized as habitually inactive or having habitually low, middle, or high PA in mid-life. Brain MRI using 3D-1.5T equipment quantified ROI volumes following a standardized protocol. Weighted linear regression adjusted for intracranial volume, demographics, select cardiovascular risk factors and ApoE4 estimated the standardized difference in ROI volumes.

Results:
Compared to no PA, high PA was associated with larger ROI brain volumes cross-sectionally in late-life (Table). High mid-life PA was only modestly associated with larger frontal cortical and deep gray matter volumes in late-life (Table). Habitually high PA in mid-life was not associated with less atrophy across brain regions in late-life.

Conclusions:
Our results do not support a causal interpretation of the cross-sectional associations between PA and brain volumes reported in late-life. Drawing on long-term population-based data, this study provides novel information on the associations of PA across life epochs with brain health, which can inform translational and intervention efforts to reduce age-related cognitive impairment.
Abstract 048: Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women
Authors: Tobias Deirdre K , Lawler Patrick R , Harada Paulo H , Demler Olga V , Ridker Paul M , Manson JoAnn E , Cheng Susan , Mora Samia
Published: July 2021

Introduction:
Recent metabolomics studies have identified circulating levels of branched-chain amino acids (BCAAs; isoleucine, leucine, valine) as strong predictors of type 2 diabetes (T2D). Whether BCAAs are implicated in cardiovascular disease (CVD) risk has not been established.

Hypothesis:
We hypothesized that higher baseline levels of plasma BCAAs are associated with an elevated risk of incident CVD events, and evaluated whether this relationship was dependent on an intermediate diagnosis of T2D.

Methods:
Participants enrolled in the Women’s Health Study prospective cohort were eligible if they did not report CVD or cancer prior to baseline blood collection (N=27,172, mean baseline age=54.7 years). Plasma BCAA metabolites were measured via proton NMR spectroscopy, ln-transformed, and standardized for analysis. We used multivariable Cox proportional regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) per standard deviation (SD) of total and individual BCAAs with incident CVD (myocardial infarction [MI], stroke, coronary revascularization).

Results:
1,917 confirmed CVD events occurred over follow-up (mean 18.6 years). In models adjusted for age, body mass index, smoking status, diet quality, physical activity, and other established CVD risk factors, total BCAAs were positively associated with CVD (per SD, HR=1.13, CI=1.08 to 1.19), comparable in magnitude to the association of LDL cholesterol with CVD (per SD, HR=1.15, CI=1.09 to 1.21). In particular, BCAAs were associated with coronary events (MI: HR=1.21, CI=1.10 to 1.33; revascularization: HR=1.15, CI=1.07 to 1.23), but not with stroke (HR=1.07, CI=0.98 to 1.15). The BCAA-CVD relationship was notably greater (p-interaction=0.008) among participants who developed T2D prior to a CVD event (HR=1.25, CI=1.13 to 1.39), vs. women without T2D (HR=1.07, CI=1.01 to 1.13). Isoleucine, leucine, and valine were each associated with CVD (p<0.05). Further adjusting for biomarkers of potential intermediates, HbA1c, lipids, and a lipoprotein-based insulin resistance score entirely eliminated the associations of BCAAs with CVD.

Conclusions:
Circulating plasma BCAAs were positively associated with long-term incident CVD in a cohort of US women, in particular among women who developed T2D prior to a CVD event. Impaired BCAA metabolism may represent a shared pathway of insulin resistance that links the risks of T2D and CVD.
Abstract 049: Mitochondrial DNA Copy Number and Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Zhao Di , Guallar Eliseo , Longchamps Ryan , Castellani Christina , Hong Yunsoo , Alonso Alvaro , Pankratz Nathan , Lane John , Arking Dan
Published: July 2021

Background:
Atrial fibrillation (AF) is the most common clinical arrhythmia. Molecular studies suggest that mitochondrial dysfunction is associated with increased risk of AF through reduced production of adenosine triphosphate and increased production of reactive oxidative species. Mitochondrial DNA copy number (mtDNA CN), a marker of mitochondrial function, has been found to be associated with sudden cardiac death and cardiovascular disease (CVD) in ARIC. However, the association between mtDNA CN and incident AF in the general population is unknown.

Objective:
To examine the prospective association between mtDNA CN and the risk of incident AF.

Methods:
Cohort study of 10,764 ARIC participants without AF at baseline (1987-89) and followed through December 31, 2014. AF were identified through electrocardiograms, review of hospital discharge codes, and death certificates. DNA samples were isolated from buffy coat. mtDNA CN was calculated from probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms (SNP) Array and standardized using the residual method. Cox proportional hazards models adjusted for demographics and CVD risk factors were used to estimate hazard ratios (HR) for AF comparing the four lowest quintiles of mtDNA CN to the highest quintile.

Results:
The mean (SD) age was 57.4 (6.0) years. During 21 years of median follow-up, 1,946 participants developed AF. In fully-adjusted models, the HRs (95% CI) for AF comparing quintiles 1 - 4 to quintile 5 of mtDNA CN were 1.17 (1.00, 1.37), 1.17 (0.99, 1.37), 0.92 (0.78, 1.10) and 1.05 (0.89, 1.24), respectively (p-trend 0.044; Figure). The HR for AF comparing 10
th
vs 90
th
percentile of mtDNA-CN was 1.16 (1.04, 1.30).

Conclusions:
mtDNA CN was inversely associated with the risk of AF independent of traditional CVD risk factors. Decline in mitochondrial function may be a novel mechanism underlying biological changes that increase the risk of AF in the general population. mtDNA CN may provide potential for novel AF prevention strategies.
Abstract 051: Genome-wide Association Study Identifies 12 Loci for Habitual Consumption of Bitter and Sweet Beverages
Authors: Zhong Victor W , Sanchez-Roige Sandra , Kraft Peter , Van Dam Rob M , Chasman Daniel I , Cornelis Marilyn C
Published: July 2021

Introduction:
Widely consumed beverages (e.g., soft drinks, coffee, tea) are critical sources of energy, added sugar and phytochemicals and are associated with obesity and chronic disease. Taste perception and preferences are highly heritable and strong determinants of food and beverage choice. We aimed to identify novel loci underlying habitual bitter and sweet beverage intake.

Methods:
We performed a genome-wide association study (GWAS) of self-reported bitter and sweet beverage intake in participants of European ancestry in the UK Biobank. Diet was assessed via multiple 24-h diet recalls (n=84703, subset) or questionnaire (n=335909, all). Bitter beverage intake was the sum of coffee, tea and grapefruit juice. Sweet beverage intake was the sum of artificially and sugar sweetened beverages and other fruit juice. Multivariable linear regression under an additive genetic model was applied. GW-significant (P < 5х10
-8
) SNPs were followed-up for replication in independent studies of European ancestry.

Results:
Multiple SNPs spanning 11 loci were associated with bitter beverage intake (P <5х10
-8
, Table 1), and at least 5 of them reflected the caffeine content of coffee and tea. Multiple SNPs in the obesity candidate gene
FTO
were associated with sweet beverage intake (P <5х10
-8
). The effect size per allele ranged from 0.02 to 0.2 cup per day. Loci in/near
AHR, CYP1A2,
and
FTO
were associated with both bitter and sweet beverage intake but in opposite directions. Replication efforts are ongoing. So far, associations at all loci, except 1q25.2 and 2q36.2, were replicated (P range: 0.04 to 1.8x10
-8
) in independent studies (n=17322) which provided 80% power for replicating 8 of these 12 loci at P=0.05.

Conclusions:
Loci linked to caffeine metabolism and obesity predisposition rather than taste are major determinants of beverage intake. These and other identified loci have been linked to chronic disease and risk factors, suggesting causal or pleiotropic effects. Our findings have potential public health and methodological implications.
Abstract 056: Serum Metabolomic Profile of the Dietary Approaches to Stop Hypertension (DASH) Dietary Pattern
Authors: Rebholz Casey M , Lichtenstein Alice H , Zheng Zihe , Appel Lawrence J , Coresh Josef
Published: July 2021

Introduction:
The DASH dietary pattern emphasizes vegetables, fruits, and low-fat dairy products and is associated with improved cardiometabolic outcomes. No biomarkers exist for assessing adherence to this dietary pattern. The objective of the study was to use metabolomics to identify serum compounds associated with the DASH diet.

Methods:
We conducted untargeted metabolomic profiling in stored serum specimens collected from participants at the end of an 8-week multi-center, randomized, controlled feeding study (N=218) comparing the DASH diet to a diet typical of intake in the U.S. (control). Multivariable linear regression was used to compare the association of individual log-transformed metabolites between the two diets after adjusting for age, sex, race, education, body mass index, and hypertension. Partial least squares-discriminant analysis was used to identify a composite of compounds that discriminate between the DASH and control diets. The area under the curve was calculated as the cumulative ability to distinguish between diets.

Results:
Serum levels of 97 known metabolites were significantly different among participants randomized to the DASH diet compared to the control diet at the Bonferroni threshold (p<6.11x10
-5
;
Figure
). The majority of these 97 metabolites were lipids (n=64; 66.0%), followed by amino acids (n=15), xenobiotics including food components (n=10), cofactors and vitamins (n=6), carbohydrate (n=1), and nucleotide (n=1). The ten most influential metabolites for discriminating between the DASH and control diets were: N-methylproline, stachydrine, tryptophan betaine, theobromine, 7-methylurate, chiro-inositol, 3-methylxanthine, methyl glucopyranoside, β-cryptoxanthin, and 7-methylxanthine (C statistic=0.986).

Conclusion:
An untargeted metabolomic platform identified a broad array of serum metabolites that differed between the DASH and control dietary patterns. The composite of top ten metabolites may be used to assess adherence to the DASH dietary pattern.
Abstract 057: Estimating the Benefits of the Proposed FDA Sodium Reformulation Policy on Cardiovascular Disease, Disparities and Economic Costs
Authors: Pearson-Stuttard Jonathan , Kypridemos Chris , Collins Brendan , Huang Yue , Bandosz Piotr , Whitsel Laurie , Capewell Simon , Mozaffarian Dariush , Wilde Parke , O'Flaherty Martin , Micha Renata
Published: July 2021

Background:
Sodium consumption is a leading modifiable risk factor for CVD mortality and morbidity in the US. In 2016, the US Food and Drug Administration (FDA), following recent effective examples in several other countries, proposed voluntary sodium targets for industry to reduce sodium in processed foods.

Aim:
We aimed to estimate the potential CVD, equity and economic impacts of implementing this policy.

Methods:
We used the validated US IMPACT Food Policy microsimulation model to estimate the CVD cases averted, quality-adjusted life-years (QALYs) gained and cost-effectiveness from 2017-2036 of the FDA sodium reformulation policy in US adults (30+ years). Model inputs included national demographics and sodium intakes from NHANES, FDA short- and long-term sodium reformulation targets, sodium effects on blood pressure and of blood pressure on CVD from meta-analyses, government costs to administer and monitor the policy and industry reformulation costs, and validated healthcare and productivity costs. We modelled 3 scenarios:

a) Optimal, 100% compliance of 10-year reformulation targets

b) Modest, 50% compliance of 10-year reformulation targets

c) Pessimistic, 100% compliance of 2-year reformulation targets with no further progress

Costs were inflated to 2017 US dollars and outputs were discounted annually by 3%. We took a societal perspective for this analysis. Rigorous probabilistic sensitivity analyses were conducted.

Results:
The optimal scenario achieving the 10-year sodium reduction targets could prevent ~ 450,000 CVD cases (95% Uncertainty Interval: 240,000-740,000), gain 2.1 million QALYs (1.7m-2.4m), and produce $41billion ($14bn-$81bn) cost-savings from 2017-2036. The modest and pessimistic scenarios were also cost-saving, with both health gains and savings about one half and one quarter, respectively, of the optimal scenario.

Relative disparities between non-Hispanic white and non-Hispanic black populations would be reduced in all scenarios. The pessimistic scenario yielded the largest reduction in absolute disparities (70,000 CVD cases (33,000-120,000) prevented in non-Hispanic blacks vs. 13,000 (0-54,000) in non-Hispanic whites). The optimal scenario would prevent approximately 4.6% (130,000 cases (65,0000-220,000)) of all CVD cases in non-Hispanic blacks compared to 1.5% (220,000 cases (120,000-360,000)) in non-Hispanic whites. Despite a smaller population, total net savings would be over 50% larger in non-Hispanic blacks than non-Hispanic whites ($19bn vs $12bn) in the optimal scenario.

Conclusions:
Implementing and even partly achieving the FDA sodium reduction targets could generate substantial health gains and net cost savings. Crucially, this policy could also reduce CVD disparities between non-Hispanic black and non-Hispanic white populations.
Abstract MP06: Circulating Fatty Acids in the De Novo Lipogenesis Pathway and Total and Cause-Specific Mortality Among Older Adults: The Cardiovascular Health Study
Authors: Lai Heidi T , de Oliveira Otto Marcia C , Wu Jason H , Lee Yujin , Song Xiaoling , King Irena B , Psaty Bruce M , Lemaitre Rozenn N , McKnight Barbara , Siscovick David S , Mozaffarian Dariush
Published: July 2021

De novo lipogenesis (DNL) is a crucial metabolic pathway that convert excess carbohydrates to fatty acids (FA) for energy and storage. Both DNL and the synthesized FA have biologic effects that may affect cardiometabolic risk. Yet, the association between DNL FA and mortality and CVD are not well-established in older adults, especially using serial biomarkers which objectively allow more accurate estimates of long-term FA exposure, as well as changes over time. We investigated the longitudinal association between serial levels of circulating DNL FA and total mortality, cause-specific mortality, and total CVD among 3,869 older U.S. adults (mean age 75 y) free of prevalent CVD at baseline. Levels of plasma phospholipid palmitic (16:0), palmitoleic (16:1n-7), stearic (18:0), and oleic acid (18:1n-9) were quantified at baseline, year 6, and year 13. Outcomes were centrally adjudicated using multiple sources. Risk was assessed in multivariable-adjusted Cox models with time-varying FA and covariates. During 46,974 person-years, 3,227 deaths (including 1,131 from CVD, 2,096 from non-CVD causes) and 1,754 incident total CVD events occurred. After multivariable-adjustment, cumulative levels of 16:0, 16:1n-7 and 18:1n-9 were each positively, while 18:0 was inversely, associated with total mortality (
Table
). Associations were generally similar for CVD vs. non-CVD mortality, and vs. total incident CVD (not shown). Among non-CVD deaths, associations for dementia and pulmonary deaths were generally similar to total mortality; while only 16:0 and 18:1n-9 were positively associated with cancer mortality. Higher long-term levels of circulating 16:0, 16:1n-7 and 18:1n-9 were positively, while 18:0 was inversely, associated with total mortality in older adults. Novel findings highlight the potential relevance of DNL later in life, and the need for further experimental research and interventions on the relevant underlying physiology and long-term health effects of DNL FA. Findings for FA changes over time to be presented.
Abstract MP59: The Association Between Acute Mental Stress and Abnormal P-wave Axis
Authors: Almuwaqqat Zakaria , O'Neal Wesley T , Hammadah Muhammad , Sandesara Pratik , Kaseer Belal , Amin Matthew , Tahhan Ayman S , Gafeer Mohamad M , Abdelhadi Naser , Obideen Malik , Al Mheid Ibhar , Alkhoder Ayman , Bremner Douglas , Kutner Michael , Soliman Elsayed Z , Shah Amit J , Quyyumi Arshed A , Vaccarino Viola
Published: July 2021

Background:
Exposure to psychological stress has been associated with the development of sustained arrhythmias. Acute changes in atrial electrophysiology may serve as intermediate phenotypes for stress-induced arrhythmia. The relationship between atrial electrical changes and stress related changes in heart rate and myocardial ischemia is unknown. We sought to study the effect of altered atrial electrophysiology and stress related rise in HR and myocardial ischemia in females and males.

Methods:
We examined if acute mental stress was associated with abnormal P-wave axis development in 359 patients (mean age=56 ± 9.9 years; 62% men; 43% white) with stable coronary heart disease and normal baseline P-wave axis (between 0° and 75°) who underwent mental stress testing (speech task). We computed the percentage of patients who had abnormal P-wave axis during stress and recovery. Sex-stratified analyses were performed. A multivariable logistic regression model was used to determine if mental stress ischemia independent predictors of abnormal P-wave axis development.

Results:
A total of 46 (13%) patients developed abnormal P-wave axis during either stress or recovery (stress: n=43, 12%; recovery: n=12, 3%). A rise in heart rate during mental stress was associated with an increased risk of abnormal P-wave axis development (per 5-unit increase: OR=1.37, 95%CI=1.03, 1.30). Mental stress-induced myocardial ischemia was associated with increased risk of abnormal P-wave axis in women (OR=5.2, 95%CI=1.7, 15.6) and not in men (OR=0.1, 95%CI=0.01, 1.01), p-interaction=0.004). Interactions were not detected for other characteristics.

Conclusion:
Acute mental stress results in the development of abnormal P-wave axis, and this phenomenon is related to increases in heart rate and, among women, mental stress-induced ischemia. Our data suggest that acute psychological stress can promote adverse transient electrical changes in the atria.
Abstract MP62: Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels
Authors: Wang Zhe , Chen Han , Chasman Daniel I , Liu Ching-Ti , Noordam Raymond , Boerwinkle Eric , Morrison Alanna C ,   CHARGE Gene-Lifestyle Interactions Working Group
Published: July 2021

Introduction:
Alcohol intake modifies plasma lipid levels and such effects may be modulated by genetic variants. We use emerging statistical methods that extend well-established common variant approaches to characterize the role of aggregated rare and low-frequency variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels.

Methods:
Up to 247,870 exonic variants on the Illumina HumanExome BeadChip and fasting plasma triglycerides (TG), and high- and low-density lipoprotein cholesterol (HDL-c and LDL-c) were measured in 46,443 European Americans from 4 studies (the Atherosclerosis Risk in Communities (ARIC) study, the Framingham Heart Study, the Netherlands Epidemiology of Obesity Study and the Women’s Genome Health Study) of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.

Using the gene-based rareGE method, we conducted exome-wide gene-environment (GxE) tests with genetic main effects estimated as fixed and random effects, and a joint analysis of genetic main and GxE interaction effects. Rare and low-frequency (minor allele frequency ≤ 5%) functional variants, (i.e. frameshift, nonsynonymous, stop/gain, stop/loss, and splicing) were aggregated by genes. Two dichotomous self-reported alcohol consumption variables, current drinker (at least 1 drink per week, yes/no) and regular drinker (at least 2 drinks per week, yes/no) were considered. A sample size weighted Z-test (weighted Stouffer’s method) was used to meta-analyze study-specific
p
-values. Exome-wide significance level was set at
p
< 3.7*10
-6
(0.05/13368 genes), using a Bonferroni procedure to correct for multiple testing.

Results:
We identified 24 gene-lipid associations at 13 known lipid loci (within 500kb) harboring rare and low-frequency variants through the joint analysis. In ARIC, numerous genes (
PCSK9, LPL, LIPG, ANGPTL4, APOB, APOC3-A5
) remained significant after conditioning on common index single nucleotide polymorphisms (SNPs), suggesting an independent role for rare variants at loci highlighted by previous genome-wide association studies. However, no significant gene-alcohol interactions were observed with rare and low-frequency variants on TG, HDL-c or LDL-c.

Conclusion:
This study applied new statistical approaches to investigate the role of rare and low-frequency variants in gene-alcohol consumption interactions on lipid levels. Results show promise for other larger scale studies analyzing rare variant GxE interactions.
Abstract P016: Physical Activity as Key Risk Factors for Incident Dementiain a Thai Population: Health Checks Ubon Ratchathani (HCUR) Study
Authors: Chamnan Parinya , Boongird Prasert , Laptikultham Somsak , Nitiyanont Wannee , Aekplakorn Wichai ,   HCUR Investigators
Published: July 2021

Introduction:
There is little evidence to describe risk factors for dementia in a Thai general population.

Hypothesis:
This study was aimed to examine factors associated with the risk of developing dementia in a Thai general population in Ubon Ratchathani.

Methods:
Data on 761,935 men and women participating in the Health Check Ubon Ratchathani (HCUR) Project in 2006-7 were merged with diagnostic information from hospital’s electronic medical records in the following 5 years (2006-2012). Using a retrospective cohort study design, we examined the incidence of physician-diagnosed dementia over 5 years. Factors independently associated with the risk of developing dementia were examined using multivariate cox proportional hazard regression.

Results:
Over a total time at risk of 4,407,201 person-years, 519 individuals developed dementia, the incidence rate of dementia was 0.12 (95%CI 0.11-0.13) per 1,000 person-years. Factors independently associated with the risk of developing dementia in multivariate cox regression included increasing age, diabetes and lack of physical exercise. The risk of dementia rose by 9% for every one year of age older (Hazard ratio (HR) of 1.09 (1.08-1.09), p<0.001). Diabetes increased the risk of dementia by almost 2 times (HR 1.67 (1.26-2.23), p<0.05). Compared to no physical exercise, regular physical exercise of 3-5 days/week and >5 days/week reduced the risk of dementia by 36% and 57% (HR 0.64 (0.52-0.78) and 0.43 (0.28-0.67) respectively). These associations remained significant after controlling for sex, hypertension, systolic blood pressure, smoking, body mass index, waist circumference, high salt diet and alcohol drinking.

Discussion:
In this Thai general population, the incidence of dementia was modest and its independent risk factors included increasing age, diabetes and lack of physical exercise. Regular physical exercise may counter balance aging process, the main drive of dementia. The more physical exercise you do, the lower risk of dementia.
Abstract P124: Neighborhood Density of Hispanic/Latinos and Left Ventricular Structure: ECHO-SOL and SOL-CASAS
Authors: Ponce Sonia , Allison Matthew A , Carlson Jordan A , Perreira Krista M , Loop Matthew S , Gonzalez Franklyn , Isasi Carmen , Hurwitz Barry E , Penedo Frank J , Kansal Mayank M , Daviglus Martha L , Talavera Gregory A , Rodriguez Carlos J , Gallo Linda G
Published: July 2021

Introduction:
Heart failure represents a significant public health problem because of increasing prevalence and lack of effective medical treatment. Hispanic/Latinos have a high burden of cardio-metabolic comorbidities and adverse socioeconomic conditions that place them at risk for heart failure. However, some literature indicates that among Hispanics/Latinos, residing in areas with high Hispanic/Latino ethnic density is associated with better health outcomes. There is a paucity of data on the effect of Hispanic/Latino ethnic density and risk markers for heart failure. Therefore, we evaluated the association between Hispanic/Latino ethnic concentration and several echocardiographic measures of left ventricular structure and function.

Methods:
Data on baseline characteristics from the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL), echocardiographic measures of cardiac structure and function (ECHO-SOL), and neighborhood Hispanic/Latino ethnic density (San Diego SOL-CASAS) were analyzed. Hispanic/Latino ethnic density was calculated for each person based on an 800-m buffer around their home. Hispanic/Latino ethnic density was then calculated using data from the 2010 Census as the percent of Hispanic/Latinos divided by the total population at the Census block level and calculating an average value for all Census blocks that overlapped with the participant's address. Multivariable linear regression analysis adjusting for personal demographics and cardiovascular risk factors was conducted.

Results:
A total of 350 participants with data from all three databases were included in the analysis. The mean age was 55±7 years, 69% were female, and 26%, 38%, and 43% had diabetes, hypertension, and dyslipidemia, respectively. Thirty-six percent had less than high school education, and 58% were low income. In models adjusting for age, sex, education level, income, acculturation, and cardiovascular risk factors, a 1-percent higher Hispanic/Latino ethnic density was associated with lower left ventricular mass (0.47, p-value = 0.02). Other echocardiographic measures of cardiac structure and function were not significantly related to Hispanic/Latino ethnic density.

Conclusion:
Higher Hispanic/Latino ethnic density was associated with lower LVM independent of personal SES and common cardiovascular risk factors. These findings suggest that Hispanic/Latinos residing in areas with higher Hispanic/Latino ethnic density might have a lower risk of future HF. However, further research to understand the specific factors that mediate the observed associations are necessary.
Abstract P126: Sex Interacts With Chromosome 6p24 on Coronary Artery Calcium but Not Chromosome 9p21
Authors: Lutz Sharon M , DeMeo Dawn , Budoff Matthew , Hokanson John E
Published: July 2021

Introduction:
Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis. CAC has been shown to strongly correlate with the amount of atherosclerotic plaque and predicts future coronary disease events and mortality. CAC is a complex heritable trait and levels differ by sex. We investigated the interaction between sex and genome wide association study (GWAS) signals on chromosome 6p24 and 9p21 on Coronary Artery Calcium (CAC) in the COPDGene study.

Hypothesis:
We assessed the hypothesis that sex would interact with the GWAS signals on CAC.

Methods:
The COPDGene is a study of 10,192 current and former smokers with at least 10 pack-years of smoking history. CAC was measured using high dose, inspiration chest CT scans, following an established protocol in 8,739 individuals (6,150 non-Hispanic Whites (NHW) and 2,589 African Americans (AA)). We considered sex by SNP interactions on CAC for our previously identified GWAS signals on chromosome 6p24 and chromosome 9p21 using R software adjusting for genetic ancestry using principal components as well as recognized risk factors (age, pack-years of smoking history, BMI, diabetes, high blood pressure, high cholesterol, and steroid use). We used the log transformation of CAC plus 1 as the quantitative phenotype.

Results:
There was a significant interaction between sex and chromosome 6p24
PHACTR1
[rs9349379] (p=0.023) on CAC among NHW subjects in the COPDGene study. There was a genome-wide significant association for rs9349379 with CAC among male NHW subjects [p-value= 1.21E-8] but not among female NHW subjects [p-value= 0.02]. Overall there was no genome-wide significant association for rs9349379 with CAC among all NHW subjects [p-value= 6.39E-7]. There was no significant interaction between sex and chromosome 9p21
CDKN2B-AS1
[rs10757272] (p-value=0.25) on CAC among NHW COPDGene subjects. Among AA subjects in the COPDGene study, there was not a significant interaction between sex and rs9349379 [
PHACTR1
] (p-value=0.48) or sex and rs10757272 [
CDKN2B-AS1
] (p-value=0.21) on CAC.

Conclusions:
There was a SNP by sex interaction on CAC for chromosome 6p24 with a genome wide significant signal for NHW men but not for NHW women. The chromosome 9p21 signal for CAC did not significantly differ by sex. This study demonstrates the importance of considering gene by sex interactions in genome wide association studies of cardiovascular disease risk.
Abstract P179: Lifetime Variation in the Impact of Cardiovascular Risk Factors on CVD Outcomes and Mortality: Lifetime Risk Pooling Project
Authors: Allen Norrina B , Ning Hongyan , Zhao Lihui , Wilkins John , Lloyd-Jones Donald
Published: July 2021

Introduction:
Prior studies have suggested that there are age-specific differences in the association of traditional cardiovascular risk factors (RFs) with cardiovascular disease (CVD) and mortality later in life, but few have directly tested this.

Hypothesis:
We hypothesized that elevated RF levels at younger ages are more strongly associated with CVD and mortality.

Methods:
We used a synthetic cohort including black and white participants (ppts) of CARDIA, MESA, Framingham, Jackson Heart, ARIC and CHS. RF levels included SBP, BMI, total cholesterol and glucose from ages 20. Outcomes included CVD incidence and total mortality. We implemented a Cox proportional hazards model with time-varying coefficients adjusted for age, sex, race, cohort, smoking status and time-varying effects for other risk factors.

Results:
We included 41,387 ppts (55% female, 30% black). Hazard ratios (HR) per standard deviation in risk factor levels at every 5 years of age are shown in the figure. Effects of SBP and BMI varied significantly by age, with early adulthood levels imparting the greatest relative hazards for CVD incidence and mortality. Ignoring time-dependent differences, the mean effect for every 1 SD higher SBP would be a hazard ratio (HR) of 1.3 for CVD and HR 1.2 for mortality (as shown by the dashed lines). However, association of SBP with outcomes varied by age, with the largest HR (~1.5) early in adulthood (ages 20-50), decreasing below 1.3 by age 70. Similarly, early adult levels of total cholesterol were associated with higher HRs for CVD; however its association with mortality did not differ by age. Higher glucose levels were significantly associated with CVD and mortality, with consistent associations across the lifespan.

Conclusions:
Strength of associations of RFs on CVD incidence and mortality are not consistent across the lifespan and vary by RFs and outcomes. These patterns and their differences may provide insights into vulnerable age periods when elevated RF levels impart a proportionally greater risk for future CVD and death.
Abstract P180: Ambulatory Blood Pressure Monitoring Phenotypes in Adults With and Without Chronic Kidney Disease Taking Antihypertensive Medication: The Jackson Heart Study
Authors: Mwasongwe Stanford , Tanner Rikki M , Pugliese Daniel , Young Bessie , Abdalla Marwah , Musani Solomon K , Gutierrezi Orlando , Correa Adolfo , Shimbo Daichi , Muntner Paul
Published: July 2021

Background:
Ambulatory blood pressure monitoring (ABPM) can detect hypertension phenotypes associated with increased risk for chronic kidney disease (CKD) progression. There is a high prevalence of these phenotypes in the general population; however, it is unclear whether they are more common among African Americans (AAs) with versus without CKD.

Methods:
We examined the prevalence of daytime, nocturnal, white-coat, masked, and sustained hypertension and a non-dipping BP pattern among AAs participating in the Jackson Heart Study. Analyses were restricted to 561 participants taking antihypertensive medication with a complete ABPM recording at baseline (2000-2004). CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m
2
or the presence of kidney damage indicated by the presence of albumin-creatinine ratio ≥30 mg/g. We used log binomial regression models in a multivariable adjusted model to calculate the association between CKD and ABPM phenotypes.

Results:
The mean age of participants included in the current analysis was 62 years, 72% were female, and 26% had CKD. Daytime, nocturnal, masked, and sustained hypertension and non-dipping were more common, while white-coat hypertension was less common, among participants with versus without CKD (Table 1). The prevalence of sustained hypertension was 1.46-fold (CI 1.03-2.06) greater among those with CKD compare to those without after multivariable adjustment.

Conclusions:
In a large community-based study of AAs, ABPM phenotypes were common among adults with CKD. Sustained hypertension was statistically significantly higher in those with versus without CKD.
Abstract P183: 20-year Secular Trend of Cardiovascular Disease Comorbidities in the United States, 1997-2016
Authors: Sun Dianjianyi , Zhou Tao , Li Xiang , Heianza Yoriko , Shang Xiaoyun , Qi Lu
Published: July 2021

Background:
Cardiovascular disease (CVD) has been the number one cause of death and disability in the US and globally for decades, and its comorbidity complicates the management of CVD. However, little is known about the secular trend of CVD comorbidities in national representative populations in the last 20 years.

Methods:
Prevalence of CVD and nine major chronic comorbidities was estimated using data from 1,324,214 adults aged 18 years and older in the National Health Interview Survey (NHIS) from 1997 through 2016, with age-standardized to the U.S. population in the year 2000.

Results:
CVD prevalence in the US adult population significantly declined in the past twenty years (from 6.6% in 1997 to 5.9% in 2016, P
trend
<0.01in Figure a). And such trend was shown in women and whites (P
trend
<0.01), but not in men and blacks (P
trend
>0.05). We ranked the nine major chronic comorbidities (high to low) in the CVD patients (Figure b.), including (1) hypertension, (2) respiratory conditions, (3) nervous system conditions, (4) digestive conditions, (5) diabetes, (6) cancer, (7) genitourinary conditions, (8) circulatory conditions, and (9) endocrine/nutritional/metabolic conditions. From 1997 to 2016, the prevalence of CVD comorbidities including hypertension (38.8% to 50.2%), digestive conditions (17.0% to 27.1%), diabetes (10.0% to 19.2%), cancer (9.4% to 12.8%), and genitourinary conditions (4.1% to 5.2%) continuingly increased (all P
trend
<0.01), while respiratory conditions declined (35.9% to 27.6%, P
trend
<0.01). Similar trends of CVD comorbidities were observed among subgroups stratified by gender or by race.

Conclusions:
CVD prevalence in the U.S. adults have declined significantly in the past two decades, but rates of CVD comorbidities including hypertension, digestive conditions, diabetes, cancer, and genitourinary conditions increased substantially.
Abstract P186: Plasma Ceramides Are Associated With HIV Treatment and Increased Risk of Carotid Artery Plaque in Two Prospective HIV Cohorts
Authors: Zhao Wei , Hua Simin , Clish Clary B , Deik Amy , Hanna David B , Haberlen Sabina A , Shah Sanjiv J , Post Wendy S , Hodis Howard N , Landay Alan L , Anastos Kathryn , Kaplan Robert C , Qi Qibin
Published: July 2021

Introduction:
Ceramides, a family of bioactive sphingolipids on plasma membrane, have been implicated in inflammation, immune response, and HIV infection. Recent studies have related plasma ceramides with cardiovascular diseases (CVD), but data are sparse in HIV infected people who have excess CVD risk.

Methods:
We profiled baseline plasma ceramides C16:0, C22:0, C24:0 and C24:1 in 737 participants aged 35-55 years (520 HIV+, 217 HIV-) from two prospective cohorts (Women’s Interagency HIV Study and Multicenter AIDS Cohort Study) and examined their associations with the risk of incident carotid artery plaque (CAP), assessed by B-mode carotid artery ultrasound imaging over a 7-year period. Plasma levels of ceramides were inverse-normal transformed. We used robust variance estimates from Poisson regression to estimate risk ratios (RRs) on CAP per standard deviation increment in ceramides. We also compared ceramide levels by HIV infection status and antiretroviral therapy (ART) use.

Results:
Over a 7-year follow-up, 112 individuals developed CAP (90 HIV+, 22 HIV-). After multivariate adjustment, ceramides C16:0 (RR=1.40 [95% CI: 1.09-1.79];
P
<0.001) and C24:1 (RR=1.32 [1.06-1.65];
P
<0.001), but not ceramides C22:0 or C24:0, were significantly associated with increased risk of CAP in all participants. Ceramides C16:0 showed stronger association with CAP in HIV+ people compared to HIV- people (
Figure
), but there was no significant effect modification by HIV infection status (
P
for interaction>0.05). Compared to HIV- group, plasma ceramides C16:0, C22:0 and C24:1 were significantly (
P
<0.001) higher in HIV+ group. Further analyses in HIV+ group showed that ceramides were significantly (
P
< 0.001) higher in people using ART than those not using ART.

Conclusions:
This study reported that elevated plasma ceramides, especially C16:0, are increased with ART use and associated with HIV-related atherosclerosis. Our data suggest that ceramides might be an intermediate link between HIV infection and CVD risk.
Abstract P188: Differences in Statin Utilization for Persons Living With HIV (PLWH) and Uninfected Controls in the HIV Electronic Comprehensive Cohort of CVD Complications (HIVE-4CVD)
Authors: Riestenberg Robert , Furman Andrew , Pawlowski Anna , Schneider Daniel , Achenbach Chad J , Lloyd-Jones Donald M , Feinstein Matthew J
Published: July 2021

Background:
Real-world clinical data on statin use and intensity among PLWH are sparse. We hypothesized that significant differences exist regarding statin utilization and dosing as well as on-statin total cholesterol (TC) lowering for PLWH compared with uninfected controls.

Methods:
HIVE-4CVD is an electronic data repository of 5,041 PLWH and 10,082 uninfected controls frequency matched on age, sex, race, zip code, and clinic location receiving care at Northwestern Medicine from 1/1/2000 to 5/17/2017. Medication administration records, prescription data, and validated natural language extraction algorithms were used to extract statin utilization information. Statins were categorized by generic name and intensity (high, moderate, and low). Lipid values were analyzed and categorized as before or after statin initiation. We compared statin utilization for PLWH vs. controls and used multivariable-adjusted regression models to compare changes in TC levels after statin initiation for PLWH vs. controls.

Results:
Among people on statins, PLWH were more likely than controls to have ever taken pravastatin (34.8% vs. 12.3%, p < 0.001) and atorvastatin (72.2% vs. 65.6%, p = 0.002), and less likely to have ever taken simvastatin (14.2% vs. 39.5%, p < 0.001). PLWH on statins were more likely to have their intensity reduced (14.6% vs. 11.2%, p = 0.034); this pattern was more apparent when analyses were restricted to patients on high-intensity statins (63.6% vs. 36.4%, p = 0.030). Although PLWH had borderline significantly less TC reduction after statin initiation than controls (-22.9 mg/dL vs. -28.5 mg/dL, p = 0.058; Figure 1), this association was attenuated after adjustment for age, sex, race, and pre-statin TC level (4.2 mg/dL greater TC lowering for controls than PLWH; p = 0.16).

Conclusions:
Significant differences exist in type and intensity of statin utilized for PLWH compared with uninfected controls. Studies of patient and provider knowledge and preferences are needed to understand reasons underlying these differences.
Abstract P190: Triggering of Coronary Heart Disease by Infection Type: The Atherosclerosis Risk in Communities Study
Authors: Cowan Logan , Lutsey Pamela , Pankow Jim , Matsushita Kunihiro , Ishigami Junichi , Lakshminarayan Kamakshi
Published: July 2021

Introduction:
Acute infections are known triggers of coronary heart disease (CHD). It is unclear how the strength of the association varies by infection type.

Hypothesis:
We hypothesized that all acute infections increase CHD risk but the level of increased risk varies by infection type.

Methods:
Incident CHD (myocardial infarction and fatal CHD) cases were identified and adjudicated in the ARIC cohort. ARIC participants were linked to Medicare claims data. We used ICD-9 codes to identify 4 infection types based on infection frequency: cellulitis, pneumonia, urinary tract infections (UTI), and bloodstream infections. We used a case-crossover design and conditional logistic regression to compare infections among CHD cases 90 days before the event with two corresponding control periods 1 year and 2 years prior. The Wald test was used to assess differences between infection types.

Results:
A total of 1,312 CHD cases were identified. Among cases, 43 had cellulitis, 102 had pneumonia, 116 had a UTI, and 28 had a bloodstream infection within 90 days of the CHD event. All infection types were associated with higher CHD risk within 90 days of the infection; (odds ratios and 95% Cis) (cellulitis = 1.41 (0.93, 2.15), pneumonia = 5.60 (3.72, 8.43), UTI = 2.62 (1.92, 3.57), bloodstream infections = 4.77 (2.34, 9.71)) although cellulitis was not statistically significant (Figure). The association between infection and CHD was significantly stronger for pneumonia, UTI, and bloodstream infections compared to cellulitis (p<0.05). Pneumonia and bloodstream infections were stronger CHD triggers compared to UTI but only pneumonia reached statistical significance (p<0.05).

Conclusions:
Patients with pneumonia or bloodstream infections may be at particularly elevated CHD risk. Clinical trials of CHD preventive therapies during and immediately following infection to reduce the otherwise elevated CHD risk are needed. Healthcare providers should consider CHD risk during and immediately after infection and optimize preventive therapies.