bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19: Stimulatory Effects of Fructose vs. Glucose on Brain Reward Activation and Hunger are Heightened in Obese Young Adults
Authors: Page Kathleen , Luo Shan , Huang Sandra , Romero Ana , Monterosso John
Published: July 2021

Increases in consumption of sugar-sweeteners are linked to obesity, diabetes and cardiovascular disease. Studies by our group and others suggest that the fructose component of sugar-sweeteners may act centrally to promote overeating behavior. Using functional magnetic resonance imaging (fMRI), we previously demonstrated that, unlike glucose, fructose ingestion failed to reduce neuronal activity in brain appetite and reward regions and failed to increase satiety in normal-weight adults. The objective of this study was to test the hypothesis that fructose compared to glucose ingestion would cause greater food-cue reactivity in brain reward areas and greater hunger, and that these differential effects would be heightened in obese compared to lean individuals. This study is part of a larger ongoing double-blinded, random-order crossover study on brain, hormone and appetitive responses to acute consumption of drinks containing 75 grams (300kcal) fructose or an equivalent dose of glucose. fMRI scans were performed using a 3-Tesla scanner on 13 participants, 5 obese (3 female,2 male; age 22±2, BMI 37±3.8) and 8 lean (3 female,5 male; age 21±2, BMI 22.8±1.7). Scanning was performed while participants viewed images of high-calorie food pictures and non-food items using a block design. Appetite scales were obtained before and 60 min after drink ingestion. Blood-oxygen level dependent (BOLD) sequences were used to measure brain responses to food and non-food cues after drink ingestion. Paired-t tests were performed to examine drink effects on BOLD responses to high-calorie food vs. non-food cues and hunger responses. Obese vs. lean comparison of drink effects were analyzed using independent samples T-tests. In the total group, fructose vs. glucose ingestion resulted in greater activation of the amygdala (9.1±4, p=.045) and the nucleus accumbens (11.4±6, p=.07), brain regions that mediate reward and pleasure. There were no significant differences in baseline hunger ratings between sessions. However, hunger ratings were significantly greater after consumption of fructose compared to glucose (1.9±0.6, p=.011). Body mass index (BMI) group interactions were seen with drink condition. Amygdala activation was significantly greater after fructose vs. glucose ingestion in the obese group (t(1,4)=4.406, p=0.01), but not the lean group (t(1,7)=0.754, p=0.48). Ratings of hunger tended to be higher after fructose vs. glucose ingestion in the obese compared to the lean group but the differences were not statistically significant with this sample size (p=0.15). In conclusion, these results demonstrate that acute consumption of fructose compared to glucose results in greater brain reward activation to high-calorie food cues and increased hunger. These disparate responses to fructose vs. glucose ingestion were heightened in obese individuals and may play a role in promoting overeating behavior.
Abstract 22: Influence of Smoking and Sex on Genetic Associations of Body Fat Distribution: The Giant (Genetic Investigation of ANthropometric Traits) Consortium
Authors: Young Kristin L , Hadley David , Justice Anne , Winkler Thomas , Graff Misa , Ngwa Julius , Czajkowski Jake , Ahluwalia Tarunveer S , Xue L. , Qi Quibin , Mahajan Anubha , Qi Lu , Franks Paul , Monda Keri , Heard-Costa Nancy L , Kilpeläinen Tuomas O , Loos Ruth , Borecki Ingrid , North Kari , Cupples L. Adrienne
Published: July 2021

Visceral fat and smoking are important risk factors for CVD and other long-term poor health outcomes. Central adiposity is frequently assessed in population studies using waist-to-hip ratio adjusted for BMI (WHRadjBMI). Genome-wide association studies (GWAS) have discovered loci that influence WHRadjBMI, sometimes with sex-specific effects. However, we do not know whether and how smoking behavior influences the association between genetic variants and WHRadjBMI. Our study investigates the influence of smoking and genetic variants on WHRadjBMI, with particular consideration for differential effects by sex.

Forty-one GIANT GWAS (108,397 participants) were used to investigate the influence of smoking on SNP WHRadjBMI associations using sex-stratified models considering SNP main effects adjusted for smoking status, and SNP main effects stratified by smoking status. Results from each study were meta-analyzed using an inverse-variance weighted fixed-effects model for men and women separately as well as combined.

A total of 19 SNPs reached genome-wide significance (p<5x10-8) having adjusted the SNP effect for smoking across strata (women, men, and combined), including 11 previously reported WHRadjBMI loci. For known WHRadjBMI loci, the influence of smoking varied by sex. In women, four known WHRadjBMI SNPs (TBX15, DNM3, RSPO3, and ADAMTS9) had a greater effect in smokers vs. nonsmokers (TBX15: β(SE) = 0.0506 (0.014), p = 3.84x10-4) vs. β(SE) = 0.0382 (0.0072), p = 1.14x10-7). Three of these (TBX15, DNM3, RSPO3) have been previously associated with tobacco use disorder (TUD). In men, three known WHRadjBMI loci (ADAMTS9, DNM3, ZNRF3) had a greater effect among smokers vs nonsmokers (ZNRF3: β(SE) = 0.0365 (0.0148), p = 1.37x10-2) vs β(SE) = 0.0192 (0.0088), p = 12.87x10-2). Eight of our 19 top SNPs have not been previously associated with WHRadjBMI (within 500 kb). Of these eight loci, distinct patterns of association by smoking and sex were again noted. In addition, one locus (ABCA1) has been previously associated with TUD.

In addition to identifying novel loci associated with body fat distribution, these findings underscore the importance of considering the effect of smoking when investigating the genetics of obesity related phenotypes and emphasize the need to consider sex separately when studying the effects of smoking on body fat distribution.
Abstract 25: Six-year Change in C-reactive Protein Levels and Risk of Incident Diabetes, Cardiovascular Events and Mortality
Authors: Parrinello Christina M , Lutsey Pamela L , Ballantyne Christie M , Folsom Aaron R , Pankow James S , Selvin Elizabeth
Published: July 2021

Background:
High levels of C-reactive protein (CRP) are associated with cardiovascular disease, diabetes and mortality. It is unclear whether changes in CRP or persistently high CRP are associated with these outcomes beyond the baseline measure.

Methods:
We conducted a prospective cohort analysis of 10,229 participants from the ARIC Study with two measurements of CRP six years apart (at visits 2 and 4, 1990-92 and 1996-98, respectively). CRP was categorized into two groups using a standard cut-point for defining high levels (≥3 vs. <3 mg/L). Six-year change in CRP was categorized as: persistently not high (<3 mg/L), decreasing (≥3 to <3 mg/L), increasing (<3 to ≥3 mg/L), and persistently high (≥3 mg/L). Cox proportional hazards models were used to assess the association between visit 2 CRP, visit 4 CRP and six-year change in CRP and each of the following outcomes from visit 4 through 2010: diabetes, coronary heart disease, ischemic stroke, heart failure and all-cause mortality. Models were adjusted for traditional risk factors at visit 2. Sensitivity analyses additionally adjusted for visit 4 covariates.

Results:
Persons with CRP ≥3 mg/L at visit 2 or 4 had higher risk of each outcome compared to those with CRP <3 mg/L (
Table
). We observed higher risk of all outcomes in persons with persistently high CRP, and of all outcomes except stroke in persons with increasing CRP, compared to those with CRP <3 mg/L at both visits (
Table
). Persons whose CRP decreased from high to <3 mg/L did not have significantly increased risk of cardiovascular outcomes or diabetes compared to those with CRP persistently <3 mg/L. Results were similar after adjusting for visit 4 covariates.

Conclusions:
Persons with sustained high levels of CRP or whose CRP increased to high levels had higher risk of diabetes, cardiovascular disease, and death, while those whose levels decreased from high to moderate or low were at lower risk. Multiple measures of CRP may better characterize inflammatory status and provide more comprehensive information regarding long-term risk.
Abstract 31: Prediction of coronary artery and abdominal aortic calcium in middle-aged adults using the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) risk score: the CARDIA study
Authors: Prendergast Christopher , Rana Jamal S , McMahan Alex , McGill Henry , Carr Jeff , Liu Kiang , Colangelo Laura , Loria Catherine , Lima Joao , Terry Greg , Gidding Samuel S
Published: July 2021

Background:
Risk scores to predict coronary and abdominal atherosclerosis have been developed from autopsy specimens from the right coronary artery and descending aorta and risk factors measured post-mortem in the Pathobiological Determinants of Atherosclerosis in Youth Study (PDAY), cohort aged 15-34 years. While the PDAY risk score predicts coronary artery calcium (CAC) up to 15 years before its assessment in Coronary Artery Risk Development in Young Adults (CARDIA), the clinical validity at 25 years follow up and of the abdominal score to predict abdominal aortic calcium (AAC) has not been tested.

Objectives:
To test the hypotheses: 1) PDAY risk scores at CARDIA baseline (cohort aged 18-30 years) predict CAC and abdominal aortic calcium (AAC) at year 25 better than PDAY risk scores measured at subsequent time points. 2) Change in risk over time will improve associations in Aim 1.

Methods:
The CARDIA study assessed CAC and AAC by computed tomography in young adults participating at year 25. The PDAY risk score was calculated from risk factors measured at the CARDIA examinations at years 0 (cohort aged 18-30 years), 5, 10, 15 and 25 (age 43-55 years).

Results:
Age and gender independent PDAY risk scores increased from CARDIA year 0 to year 25 (coronary from 1.80 to 4.95, abdomen from 1.88 to 3.18). Prevalence of any CAC was 28% and AAC was 53%. For a one point increase in risk score, baseline risk predicted CAC and AAC better than year 25 risk; change in risk improved the prediction further (Table). C-statistics for CAC prediction were higher at year 0 but similar at years 0 and 25 for AAC. Further analyses using PDAY scores calculated at 5 year intervals prior to the CT scan confirmed that CAC at baseline and AAC at year 5 had the highest Odds Ratios for a one point increase in score (AAC year 5 Odds Ratio 1.35 (1.30-1.41)).

Conclusions:
PDAY risk scores, applied to living adults in the CARDIA study, predicted CAC and AAC in 43-55 year old adults; including change in risk slightly improves model performance.
Abstract 33: Parity is Associated with Aortic Remodeling: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Aggarwal Shivani R , Bluemke David A , Hundley William G , Lima João A , Mittleman Murray A , Ouyang Pamela , Parikh Nisha I , Vaidya Dhanajay , Yeboah Joseph , Herrington David M
Published: July 2021

Introduction:
Several lines of evidence suggest that increased gravidity and/or parity is associated with increased risk for clinical cardiovascular events and left ventricular remodeling. However, the mechanism(s) that account for these associations remain unclear. Recent analyses from MESA indicate that parity is also associated with increased carotid stiffness; consistent with the hypothesis that extra-cellular matrix remodeling that occurs to facilitate child birth may also lead to adverse effects on arterial structure and function. To date there are few data on the effects of gravidity or parity on central aortic structure and function. To study this we examined the relationship between reproductive history and MRI-based measures of aortic dimensions in women enrolled MESA.

Methods:
Study subjects included 1908 women aged 45-84, from four race/ethnic groups who were free from cardiovascular disease. Women were classified as having 0 to ≥ 5 live births and 0 to ≥6 pregnancies. Minimum and maximum cross-sectional area and average diameter of the descending aorta at the level of the right pulmonary artery were measured using thoracic MRI. After exploratory data analysis and data cleaning, univariate and multivariable models were used to describe the relationship between number of pregnancies or live births and aortic dimensions, after adjustment for potential confounders including age, race-ethnicity, height, weight, smoking, diabetes, total and HDL cholesterol, SBP, use of anti-hypertensive medications and education as a proxy for socio-economic status.

Results:
Of 1908 participants, 41.1% were Caucasian, 31.1% African-American, 16.7% Hispanic and 11.1% Chinese-American. The mean (±SD) age was 61.1±10.0 years, 46% had HTN, and 19% had diabetes mellitus or impaired fasting glucose. In univariate analyses, minimum and maximum aortic area were 14 mm
2
larger and average diameter was 0.28 mm greater for each live birth (all p<0.001). In fully adjusted models the number of live births remained significantly associated with min and max area and average diameter (all p<0.005). Qualitatively similar results were seen using number of pregnancies.

Conclusions:
Increasing number of pregnancies and live births is associated with greater aortic remodeling. Further studies are needed to determine if specific physiologic effects of pregnancy are responsible for the apparent deleterious consequences on arterial remodeling and whether these changes translate into adverse cardiovascular outcomes.
Abstract 37: Lipoprotein Subclasses and Incident Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis
Authors: Mackey Rachel H , Mora Samia , Bertoni Alain G , Wassel Christina , Carnethon Mercedes , Sibley Christopher T , Goff David C
Published: July 2021

Lipoprotein changes often precede incident type 2 diabetes and may be diabetogenic, but effects of lipid-lowering medications, ethnicity and sex on these associations are unclear. In the Multi-Ethnic Study of Atherosclerosis, among 5636 men and women, ages 45-84, without baseline diabetes or CVD, 694 diabetes cases were identified during mean follow-up of 7.7 years. NMR spectroscopy was used to measure lipoprotein particle concentrations and size, including a calculated lipoprotein-related insulin resistance score (LP-IR), on baseline plasma. Analyses were stratified by baseline lipid-lowering medication (primarily statin) use, as “untreated” (n=4816) or “treated” (n=820), and by glucose <100 vs.100-125 mg/dl (impaired fasting glucose, IFG). Among treated and untreated participants, higher LP-IR, larger mean VLDL particle size, HOMA-IR and (log)insulin were associated with incident diabetes, adjusted for age, ethnicity and sex (HRs per SD >1.5, p<0.05). Associations of LP-IR and VLDL size with incident diabetes remained significant when additionally adjusted for HDL-C, (log) triglycerides, BMI, glucose, family history of diabetes, physical activity and alcohol use and among treated participants with IFG, and were similar by sex and race-ethnicity. In conclusion, lipoprotein particle measures, particularly LP-IR and VLDL size, were robustly associated with incident diabetes among both untreated and treated ethnically diverse adults.
Abstract 40: Integrative Genomics Analysis Reveals Novel Mechanisms For Plasma Lipid Regulation
Authors: Zhao Yuqi , Luk Helen , Mäkinen Ville-Petteri , Meng Qingying , Yang Xia
Published: July 2021

Dysregulation of plasma lipids, especially cholesterol levels, has been identified as a critical risk factor for various complex human diseases such as cardiovascular diseases and Alzheimer’s disease. Recent genome wide association studies (GWAS) have implicated a number of susceptibility loci for complex traits of lipid metabolism. However, these loci only explain a limited proportion (25-30%) of the genetic heritability and a comprehensive understanding of the underpinning regulatory mechanisms has not been achieved. To better understand the mechanisms and to identify potential novel regulators, in this study, we utilized an integrative genomics approach that leveraged multiple genetic and genomic datasets including 1) GWAS from Global Lipids Genetics Consortium (GLGC) for four lipid traits (high density lipoprotein cholesterol [HDLC], low density lipoprotein cholesterol [LDLC], triglycerides [TG], and total cholesterol [TC]), 2) expression quantitative trait loci(eQTLs) from genetics of gene expression studies of human tissues related to lipid metabolism(such as liver and adipose tissues), 3) knowledge-driven biological pathways, and 4) data-driven regulatory gene networks. The integration of these diverse data sources enabled tissue-specific investigations on whether the genetic variants associated with lipid traits from GWAS were concentrated on specific parts of gene regulatory networks, termed “subnetworks”, and whether novel key regulators of the lipid subnetworks could be identified based on data-driven network structures.We identified 17, 16, 18, and 14 subnetworks for HDLC, LDLC, TC, and TG, respectively. Among these, subnetworks associated with lipid metabolism, protein modification, response to external stimulus, receptor activity, and neurophysiological process were shared among the four lipid traits. Among the trait-specific subnetworks, those involved in glutathione metabolism, and taurine and hypotaurine metabolism were found to be HDLC-specific while cadherin-associated subnetworks were LDLC-specific. Finally, by utilizing the gene-gene relationships revealed by the network architecture, we detected key regulator genes, both known (e.g.APOE, APOA5,and ABCA1) and novel (e.g.NCAM1, and F2), in these lipid-associated subnetworks. Our results shed lights on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation.
Abstract 47: Genetically Elevated Low-Density Lipoprotein Cholesterol is Associated with Aortic Valve Calcification and Incident Aortic Stenosis
Authors: Thanassoulis George , Luk Kevin , Schulz Christina A , Engert James , Owens David , Do Ron , Hindy George , Rukh Gull , Dufresne Line ,   CHARGE Extracoronary Calcium Working Group, Rich Stephen S , Kathiresan Sekar , Orho-Melander Marju , Gudnason Vilmundur , O'Donnell Christopher J , Post Wendy S , Smith J G
Published: July 2021

Background:
Although plasma low density lipoprotein cholesterol (LDL-C) appears to be a causative factor in animal models of aortic valve (AV) disease, randomized trials with cholesterol lowering therapies in established disease have failed to reduce progression. We sought to evaluate whether life-long genetic elevations in LDL-C, high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) are associated with AV disease.

Methods:
Using 144 single nucleotide polymorphisms associated with LDL-C, HDL-C or TG in genomewide association studies (GWAS), we constructed three separate genetic risk scores (GRS). We estimated the association between each GRS and (1) the presence of AV calcium determined by computed tomography in 6942 participants of white European ancestry from the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) consortium using summary level GWAS data and; (2) incidence of aortic stenosis in 28,585 participants from the Malmo Diet and Cancer Study (MDCS) over a mean follow-up time of 15.8 years.

Results:
The LDL-C GRS, but not the HDL-C or the TG GRS, was associated with presence of AV calcium (OR per predicted mmol/L LDL-C, 1.38 95% CI 1.09-1.74; p=0.007). The LDL-C GRS was also associated with incident aortic stenosis (HR per mmol/L LDL-C, 3.04 (1.34-6.91, p=0.008). In sensitivity analyses excluding SNPs also associated with HDL-C or TG to reduce pleiotropy, the LDL-C GRS remained associated with AV calcium (OR per predicted mmol/L LDL-C 1.39 95% CI 1.04-1.90; p=0.03) and aortic stenosis (HR per mmol/L LDL-C 3.85, 95% CI 1.37-10.79, p=0.01). Further analyses to exclude residual pleiotropic effects of HDL-C and TG, did not materially change these findings.

Conclusions:
Genetic predisposition to increased LDL-C is associated with presence of AV calcium and incidence of aortic stenosis, providing novel supportive evidence that LDL-C is a causal factor for the development of AV disease. Earlier intervention to reduce LDL-C merits further investigation to prevent AV disease.
Abstract 58: Age-specific Exercise Capacity Threshold for All-cause Mortality Risk in Men
Authors: Kokkinos Peter , Myers Jonathan , Faselis Charles , Sui Xuemei , Zhang Jiajia , Blair Steven
Published: July 2021

Introduction:
Exercise capacity is inversely associated with mortality risk. However, there is no age-specific standardized exercise capacity threshold to guide clinical assessment of mortality risk.

Hypothesis:
We assessed the hypothesis that an age-specific standardized threshold can be defined based on maximal exercise capacity (METs) to assess mortality risk across age groups.

Methods:
Peak exercise capacity was assessed in 18,102 men (mean age: 58±11) at DC and Palo Alto CA VA Medical Centers. We stratified the cohort into four age-groups (<50; 50-59; 60-69; and ≥70 yrs of age). We applied Cox proportional hazards models with spline function of MET to define the MET level associated with no increase in mortality risk (hazard ratio (HR)=1.0). We formed five additional age-specific fitness categories based on METs achieved above and below this threshold (T1; n=3,705): T2=T1-2 METs (n=4,884); T3; T1->2 METs (n=1,692); T4=T1+2 METs (n=4,646); T5=T1+2-4 METs (n=1,874) and T6=T1+>4 METs (n=1,301).

Results:
The MET thresholds for the aforementioned age groups were identified as 8; 7; 6; and 5 METs, respectively. There were 5,103 deaths (median follow-up=10.8 yrs; 208,108 person-yrs). Cox proportional hazards analysis adjusted for age, cardiac risk factors, medications and muscle-wasting disease revealed 19% (HR=1.19; CI: 1.10-1.28) and 46% (HR=1.46; CI:1.33-1.60) higher all-cause mortality risk for those with exercise capacity 2 and >4 METs below the threshold, respectively. For those with an exercise capacity 2; 4 and >4 METs above the threshold, mortality risk was lower by 27% (HR= 0.73; CI:0.66-0.79), 35% (HR= 0.65; CI: 0.58-0.74), and 48% (HR=0.52; CI:0.45-0.62), respectively (p<0.001 for all comparisons). The trends for mortality risk were similar for each age category (Table).

Conclusions:
We identified an age-specific MET threshold for fitness-related clinical assessment of mortality risk in men.
Abstract 63: Higher Exercise Capacity Predicts Lower Levels of Inflammation in Both Men and Women with Coronary Artery Disease
Authors: Elajami Tarec K , Morteza Afsaneh , Avila Maria D. , Vetter Jennifer A , Welty Francine K
Published: July 2021

Introduction:
Metabolic equivalent (METS) estimates the amount of oxygen the body uses during physical activity and reflects cardiorespiratory fitness. Exercise capacity (measured in METS), peripheral white blood cell count (WBC) and microalbuminuria (urine microalbumin/creatinine ratio -MCR) are associated with cardiovascular morbidity and mortality. Monocytes are an initiating event in atherosclerosis and are a measure of inflammation as are WBC and MCR.

Hypothesis:
Higher exercise capacity is associated with lower levels of inflammation (WBC, monocyte count and MCR) in patients with coronary artery disease (CAD).

Methods:
291 subjects with stable CAD underwent graded exercise treadmill stress testing with calculation of METS. WBC, monocyte count and MCR were measured. Multivariate linear regression modeling was employed to identify predictors of inflammation for the total group and then stratified by gender and diabetes status.

Results:
METS was inversely correlated with and the best predictor of WBC, monocyte count and MCR for the total group and for men and women although age was slightly better than METS for WBC in men (see Table). When stratified by diabetes status, METS was inversely correlated with and the best predictor of monocyte count and MCR in non-diabetics whereas in diabetics, BMI was the best predictor. METS was significantly inversely correlated with WBC in diabetics and non-diabetics although age was slightly better in non-diabetics.

Conclusions:
Higher exercise capacity may have cardiovascular protective effects in patients with CAD through an anti-inflammatory effect as reflected in the lower levels of peripheral WBC, monocytes and microalbuminuria. Our findings suggest that exercise capacity could be a measure of chronic inflammation in patients with CAD and support the importance of exercise training in improving inflammation. The less pronounced effect of METS on monocyte count and MCR in diabetics could be due to other factors affecting inflammation in diabetics.
Abstract MP03: Associations Of 24-hour Blood Pressure Patterns With Cognitive Function In Healthy Older Adults
Authors: Conway Kyle , Forbang Nketi , Beben Tomasz , Criqui Michael , Ix Joachim , Rifkin Dena
Published: July 2021

Background:
Abnormal 24-hour ambulatory blood pressure monitoring (ABPM) patterns have been associated with diminished cognitive function in hypertensive and very elderly populations. The relationship between ABPM patterns in community-living older adults is unknown.

Methods:
We conducted a cross-sectional study in which ABPM, in-clinic blood pressure, and cognitive function measures were obtained in 354 community living older adults. We used multiple linear regression to examine the associations of in-clinic and ABPM with the Montreal Cognitive Assessment (MoCA [range 0-30 with lower levels indicating worse cognition]), adjusting for age, sex, race/ethnicity, education, and comorbid medical conditions.

Results:
The mean age was 72 years, 68% were female, and 13% were African American; 45% had a diagnosis of hypertension. In-clinic blood pressure measurements were not significantly associated with cognitive function after adjustment. In contrast, less nighttime systolic dipping percentage (Figure) and lower 24-hour average diastolic blood pressure obtained from the ABPM were both significantly associated with worse cognitive function. In the final model, each 1% less night-time dipping was associated with 0.25 points (0.1-0.9) lower MoCA score, whereas each 10 mmHg lower diastolic blood pressure was associated with 0.59 (0.14-1.05) points lower MoCA score.

Conclusions:
In community-living older persons, less nighttime systolic dipping and lower 24-hour diastolic blood pressure obtained by ABPM were associated with worse cognitive function whereas clinic based blood pressure measurements were not. Future studies should examine whether 24-hour diastolic blood pressure and nighttime systolic dipping may predict future risk for cognitive impairment.

(Legend: Dipping quartiles: Q1 -17.8% to 6.0%; Q2 6.1% to 11.0%; Q3 11.1% to 16.3%; Q4 16.4% to 34.2%)
Abstract MP10: Traditional Risk Factors for Atrial Fibrillation in Individuals with Normal Left Atrial Size: The Atherosclerosis Risk in Communities Study
Authors: Qureshi Waqas , Soliman Elsayed , Solomon Scott , Arking Dan , Shah Amil , Shah Deepak , Alonso Alvaro , Wagenknecht Lynne , Herrington David
Published: July 2021

Background:
Traditional risk factors for atrial fibrillation (AF) likely contribute to the pathogenesis of AF through their effects on left atrial (LA) enlargement. However, little is known about risk factors for AF in individuals with normal LA size.

Hypothesis:
We hypothesized that the risk factors for AF differ between individuals with normal and enlarged LA.

Methods:
LA diameter was measured by cardiac echocardiography in participants in the Atherosclerosis Risk in Communities (ARIC) study during 2011 - 13. AF was defined by ECGs and/or hospital discharge ICD-9 codes. Gender-specific cut points (3.9 cm for females and 4.1 cm for males were used to dichotomize the sample into normal and enlarged LA. Univariate and multivariate logistic regression models adjusting for age, gender, race, diabetes, hypertension, alcohol use (>1 drink/day), height, weight, coronary artery disease, heart failure, and exercise (>1 day per week) were used to evaluate risk factors for AF among ARIC participants with and without enlarged LA.

Results:
Of 5540 (mean age 75.6±5.2, women 58.6%) participants enlarged LA was present in 955 (16.2%). AF was prevalent in 3.9% of normal LA and 20% of enlarged LA participants. In multivariate analysis, alcohol use and exercise (>1 per week) were independently associated with AF in participants with normal sized LA (p<0.05)(table). Interaction terms of alcohol use, and exercise with LA size were statistically significant despite adjusting for age, gender, height, weight and race in the multivariate model. The population attributable risk of AF for alcohol use and lack of exercise were 5.5% and 6.4%, respectively.

`

Conclusion:
Many of the risk factors for AF are similar irrespective of the LA size. However, lack of exercise and alcohol drinking are associated with prevalent AF only in the normal sized LA group. More research is warranted to determine the potential benefits of interventions targeting these two modifiable risk factors in the setting of normal LA size.
Abstract MP11: Association of Sick Sinus Syndrome with Incident Cardiovascular Disease and Mortality: the Atherosclerosis Risk in Communities Study and Cardiovascular Health Study
Authors: Alonso Alvaro , Jensen Paul N , Lopez Faye L , Chen Lin Y , Psaty Bruce M , Folsom Aaron R , Heckbert Susan R
Published: July 2021

Background:
Sick sinus syndrome (SSS) is a disorder characterized by symptomatic dysfunction of the sinoatrial node. Despite being relatively frequent and a major indication for pacemaker implantation (PMI), the impact of SSS on the risk of other cardiovascular diseases (CVD) and mortality is unclear. Thus, we assessed whether SSS incidence was associated with mortality and CVD in two community-based studies.

Methods:
We included 19,893 men and women age 45 and older enrolled in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), without pacemaker and free of atrial fibrillation (AF) at baseline. Incident cases of SSS were adjudicated after review of medical charts from hospitalizations with a 427.81 ICD-9 code. Ascertainment of incident CVD (heart failure, myocardial infarction, stroke, AF, PMI) and mortality was done according to standard validated protocols. The association between SSS and the selected outcomes was assessed using age, sex, and race-standardized rates and multivariable Cox models adjusted for potential confounders.

Results:
During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence = 6 events per 10,000 person-years). Age, sex, and race-standardized rates for each of the outcomes in those with and without SSS are presented in the Table. Overall, individuals with SSS had higher rates of mortality and CVD. These differences were still present, though weakened, after adjustment for baseline cardiovascular risk factors (Table, Model 2). After additional adjustment for incident CVD (Model 3), SSS was no longer associated with higher mortality, myocardial infarction or stroke, but an association with heart failure, AF and PMI remained.

Conclusion:
Individuals who develop SSS are at increased risk of death and incident CVD. Their management should incorporate comprehensive cardiovascular prevention in addition to symptom relief. The mechanisms underlying these associations warrant further investigation.
Abstract MP17: Cumulative Risks for Hypertension In Middle-Aged White and African American Men and Women
Authors: Wilkins John T , Ning Hongyan , Intwala Sunny , Lloyd-Jones Donald M
Published: July 2021

Intro:
Despite the high prevalence of hypertension (HTN) and the disproportionate burden of HTN-related diseases in African Americans (AA), the long-term risks for incident HTN for AA men and women, compared with whites, are poorly described.

Methods:
We conducted an individual-level pooled analysis of participants from The Atherosclerosis Risk in Communities and The Framingham Offspring Studies with baseline prevalence and follow-up data on HTN and medication use. HTN was defined as elevated levels and/or medication use at ≥2 consecutive exams. We quantified the long-term risk for stage I (untreated BP≥140/90 mm Hg), stage II (untreated BP≥160/100 mm Hg) and ≥ Stage I HTN or blood pressure medication use separately, using competing risk models to assess incidence from index age 55 years (y) through age 70y to 85y, adjusted for baseline prevalence and competing risks of death. Analyses were stratified by race and sex.

Results:
There were 11,405 White and 2,886 AA participants (55% and 64% female, respectively) included in the analysis. At index age 55y, the mean (SD) BMIs in white and AA (men/women), respectively, were 27.8(4.1)/26.9(5.6) and 28.1(5)/31.3(6.7) kg/m2. African Americans had higher baseline prevalence and higher overall long-term risks for HTN than Whites. Through age 70y, AA women had risks as high as 82.1% (95% CI: 79.2, 85.0), and white men had risks of 61.4% (95% CI: 59.5, 63.3). The overall rate of incident HTN development (over follow-up time) appears similar across groups; differences in long-term risk are attributable to substantial disparities in the prevalence of HTN by age 55y in this sample.

Conclusions:
Cumulative risks for HTN are very high in all groups, particularly in AA women. The earlier onset of HTN at high rates in AA men and women underscores the necessity of aggressive primordial prevention efforts early in the life course to reduce the massive population burden of HTN and HTN-related diseases.
Abstract MP25: Is Surgical Menopause Associated With Future Cardiovascular Risk Factors Independent Of Antecedent Levels? The Cardia Study
Authors: Appiah Duke , Schreiner Pamela J , Bower Julie K , Sternfeld Barbara , Lewis Cora E , Wellons Melissa F
Published: July 2021

Objective:
The aim of this study was to compare changes in selected CVD risk factors prior to and after natural or surgical (hysterectomy with or without bilateral oophorectomy) menopause.

Methods:
Data were obtained from women aged 18 to 30 years at baseline without hysterectomy enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study and followed for 25 years. Piecewise linear mixed effects models were used to examine changes in waist circumference (WC) and HDL-cholesterol (HDL-c) from baseline to index visit (first visit after the date of natural or surgical menopause) and after index visit to the end of observation.

Results:
During follow up, 639 women reached natural menopause (NM), 304 reported hysterectomy with one or both ovaries conserved (HO) and 153 reported hysterectomy with bilateral oophorectomy (HBO). Baseline mean values of WC were 73.9, 76.4, 75.9 cm, p=0.005 for NM, HO, and HBO respectively while those for HDL-c were 57.6, 54.6, 54.2 mg/dL, p=0.001. After adjustment for race, education, field center, traditional CVD risk factors, lipid-lowering medication, age at and time since menopause, the mean values of WC at the index visit were 88.8, 92.4, 92.0 cm, p=0.001 for NM, HO, and HBO respectively while those for HDL-c were 61.5, 57.0, 57.8 mg/dL, p=0.006. Compared to women with natural menopause, surgically menopausal women (regardless of ovarian status) had higher annual rate of change for WC (0.74 vs. 0.63 cm, p=0.002) as well as lower rate of change for HDL-c (0.15 vs. 0.30 mg/dL, p=0.001) from baseline to index visit. No statistically significant differences in the annual rate of change after index visit to the end of follow up were observed between these two groups for either WC or HDL-c.

Conclusion:
While surgical menopause is commonly believed to worsen CVD risk, in this population-based sample, we found that women who undergo hysterectomy with or without bilateral oophorectomy had more adverse values for central adiposity and lipids at baseline compared to women with natural menopause. However, antecedent risk factor levels were strongly associated with postmenopausal levels in all women.
Abstract MP27: Effects of Healthy Lifestyle Behaviors on Lifetime Risk of Chronic Disease Mortality and Life Expectancy in Men and Women
Authors: Lee Chong-Do
Published: July 2021

The impact of healthy lifestyle behaviors on lifetime risk of chronic disease mortality and life expectancy in U.S. population remains less explored.

Purpose:
We investigated the combined effects of lifestyle factors on lifetime risk of chronic disease mortality and life expectancy in US men and women at 40 years of age.

Methods:
Lifetime risks of chronic disease mortality to 80 years of age were estimated for men and women, with death free of chronic diseases as a competing event. We followed 7848 men and women, aged 40 to 80 years, who participated in the Third National Health and Nutrition Examination Survey. All participants completed baseline lifestyle behavior questionnaires. A healthy lifestyle profile was defined as physically active, never smoking, and a healthy diet defined by the American Heart Association Strategic Committee. They were further categorized as having 0, 1, 2, or 3 combined healthy lifestyle factors.

Results:
During an average of 13.2 years of follow-up (103,851 person years), there were a total of 1645 chronic disease deaths (915 CVD, 546 cancer, 281 respiratory disease, 98 diabetes mellitus). The lifetime risks of chronic disease mortality (at 40 years of age) were 38.1% (95% CI: 35.7 to 40.5) and 30.7% (95% CI: 28.5 to 33.0) in men and women, respectively. Men and women who were physically active, never smoked, and had a healthy diet had a substantially lower lifetime risk of chronic disease mortality. The lifetime risks of chronic disease mortality across 0, 1, 2, and 3 combined healthy lifestyle factors were 47.2%, 33.0%, 21.2%, and 16.2%, respectively. After adjustment for multiple risk factors, men and women with all 3 healthy lifestyle factors had a 36% (95% CI: 28% to 42%) lower risk of chronic disease mortality compared with men and women with zero healthy lifestyle factors. Persons with 0 compared with 3 healthy lifestyle factors had a shorter life expectancy by 10 years (95% CI: 7.8 to 12.1 years). Approximately 30% (95% CI: 14% to 43%) of chronic disease deaths might have been avoided if men and women had maintained all 3 healthy lifestyle factors.

Conclusion:
Maintaining a healthy lifestyle is associated with lower risk of chronic disease mortality in men and women. Nationwide primordial and primary prevention efforts are needed to support the attainment of healthy lifestyles for the lifetime.
Abstract MP33: The Deaf Weight Wise Study: A Unique Clinical Trial of Health Behavior Modification with Deaf Adults
Authors: Barnett Steven , Sutter Erika , Pearson Thomas ,   Deaf Weight Wise Study Group
Published: July 2021

Introduction:
Deaf people who use American Sign Language (ASL) comprise linguistic and cultural minority populations without access to language-concordant health information and healthcare. Deaf ASL users are rarely included in health research or public health surveillance. Recent research with Deaf ASL users found a higher prevalence of obesity than in the general population. No randomized trials of lifestyle modification or weight reduction have ever been attempted with Deaf ASL users.

Methods:
We worked with the Rochester (NY) Deaf community to adapt a 16-week healthy lifestyle program previously shown to be effective with hearing people. We adapted the curriculum and research measures to be culturally and linguistically appropriate. We used a group intervention format recommended by our Deaf partners, and trained group leaders who were Deaf, ASL fluent and had backgrounds in counseling, public health, or healthcare. For this Deaf Weight Wise (DWW) trial, we recruited Deaf adults aged 40-70 with a BMI of 25-45 from community settings, and randomized participants to immediate intervention or intervention delayed 1 year. We will collect data from DWW trial participants over two years. We present analyses of data after 6 months here. Primary outcomes were changes in weight, BMI and scores on two standard measures: Dietary Risk Assessment (DRA) and Physical Activity Assessment (PAA). We used group by time repeated measures ANOVA to examine changes from baseline to 6 months for the immediate group and delayed group (no intervention yet).

Hypothesis:
The immediate intervention group would have greater reduction in weight and BMI as well as improvement in DRA and PAA scores six months after baseline compared with the delayed intervention group.

Results:
At baseline, the 104 participants’ mean age was 53.5 years; 68.3% (71 of 104) were female and 91.3% (95/104) were White. Randomization was successful based on baseline data. At 6 months, the immediate group weight changed -3.35kg (1.0 s.e.; p=.002) and BMI changed -1.35 (0.4 s.e.; p≤.0001) compared with the delayed group. Most of the immediate group (58.3%, 28/48) lost ≥ 5% of baseline weight versus 14.3% (8/56) of the delayed group (p≤.0001). Changes in mean DRA (p=.055) and moderate PAA (p=.054) scores numerically favored the immediate group.

Conclusions:
Deaf Weight Wise is the first randomized controlled trial of a healthy lifestyle program with Deaf ASL users. This culturally appropriate and language accessible behavioral intervention was feasible and highly effective with this underserved and rarely studied population.
Abstract MP43: The Population Impact and Cost-Effectiveness of Statins for Primary Prevention in Adults 75 and Older in the United States
Authors: Odden Michelle C , Coxson Pamela , Thekkethala Divya , Pletcher Mark , Bibbins-Domingo Kirsten
Published: July 2021

Introduction:
Several investigations have evaluated the cost effectiveness of a low density lipoprotein (LDL) cholesterol “threshold” treatment strategy compared with a “risk-based” strategy based on a person’s 10-year risk of coronary heart disease (CHD). No studies to date have focused on adults 75 years and older.

Methods:
Based on the Cardiovascular Disease Policy Model, a Markov model of the U.S. population, we forecasted the population impact of statin therapy over 10 years in adults aged 75-94 years. We compared two strategies for statin therapy in adults 75-94 years free of prevalent CHD and stroke: 1) treatment in anyone with LDL cholesterol >100 mg/dL in diabetics, and >130 mg/dL in non-diabetics, and 2) high intensity statins for persons with a 10-year CHD risk of >20% and low intensity statin for persons with a risk of 10-20%, independent of LDL cholesterol level. We assumed the use of low-cost statins ($4 per month), 100% adherence, 3% discounting/year, and costs from a healthcare perspective.

Results:
The threshold strategy would treat an additional 50 million elders and prevent 99,000 incident myocardial infarctions and 55,000 CHD deaths at a cost of $ 1.4 billion, whereas the risk-based strategy would treat 103 million and prevent 143,000 incident myocardial infarctions and 97,000 CHD deaths at a cost of $ 7.8 billion. The threshold strategy is more cost-effective than the risk-based strategy ($4,300 vs. $18,000 per quality-adjusted life year gained).

Conclusions:
A risk-based strategy prevents more events compared with a threshold strategy due to the large proportion of older adults who have high 10-year CHD risk scores, but is less efficient than a threshold strategy in adults 75 years and older.
Abstract MP53: Associations of Dietary Patterns and Cardiovascular Disease Risk Do Not Differ by Diabetes Status
Authors: Pearson Keith E , Voeks Jenifer H , Carson April P , Shikany James S , Safford Monika M , Fernandez Jose R , Judd Suzanne E
Published: July 2021

Introduction:
Adults with diabetes have been shown to have differences in reported diet compared to adults without diabetes. While diet is associated with cardiovascular disease (CVD) risk, few studies have examined whether dietary patterns may differentially affect CVD risk in adults with and without diabetes.

Objective:
We examined whether the relationship between diet and CVD risk differed between adults with and without diabetes who were free of CVD at baseline in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Methods:
REGARDS is a nation-wide, longitudinal study of 30, 239 black and white participants ages 45 and older. Previously, principal components analysis was utilized to derive dietary patterns for participants with usable Block98 food frequency questionnaire data (n=21,636). Diabetes was defined as self-reported medication use, fasting glucose ≥ 126 mg/dL, or non-fasting glucose ≥ 200 mg/dL. The final sample for this analysis included 2,701 participants with diabetes and 13,906 participants without diabetes. CVD events, including stroke and nonfatal or fatal myocardial infarction, were physician-adjudicated. Cox proportional hazards regression was used to assess the association of each dietary pattern (modeled in quintiles) with risk of CVD, stratified by diabetes status.

Results:
We observed 787 CVD events over an average follow up of 5.5 years. Greater adherence to the Southern dietary pattern (which loaded highly on fried foods, processed meats, and sugar-sweetened beverages) significantly increased risk of CVD in adults without diabetes (comparing Q5 to Q1: HR=1.54; 95% CI=1.16, 2.06) and the association trended similarly, though non-significant, in adults with diabetes (comparing Q5 to Q1: HR=1.32; 95% CI=0.76, 2.31). Adherence to the Plant-based pattern (which loaded heavily on fruits, vegetables, and legumes) showed a non-significant inverse association with CVD risk in both adults with diabetes (comparing Q5 to Q1: HR=0.77; 95% CI=0.49, 1.23) and adults without diabetes (comparing Q5 to Q1: HR=0.87; 95% CI=0.65, 1.17). After adjustment for age, race, gender, region, income, education, physical activity, smoking status, and total energy intake, there were no differences in the association of either dietary pattern and risk of CVD between adults with and without diabetes (p for interaction = 0.23 for Plant-based; p for interaction = 0.87 for Southern).

Conclusions:
While adults with and without diabetes may differ in reported dietary practices, our results suggest there are no differences in the associations of dietary patterns and CVD risk between the two groups - further demonstrating the importance of healthful dietary practices in the prevention of CVD regardless of diabetes status.