bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P348: The Effects of High Saturated Fat Intake on LDL and HDL Subclasses in Individuals with Atherogenic Dyslipidemia
Authors: Chiu Sally , Krauss Ronald M
Published: July 2021

Previous observations in normolipidemic individuals have indicated that the increase in LDL cholesterol (C) resulting from substitution of dietary saturated fat for carbohydrate or unsaturated fat is primarily due to higher plasma levels of large cholesterol-enriched LDL particles, with minimal effects on smaller LDL, as well as apolipoprotein (apo) B and total-C/HDL-C ratio. In the present study, we tested whether similar effects of saturated fat are observed in individuals with atherogenic dyslipidemia characterized by a preponderance of small LDL particles (LDL phenotype B). Fifty-three phenotype B participants consumed a baseline diet (55% carbohydrate, 15% protein, 30% fat, 8% saturated fat) for 3 weeks, after which they were randomized to either a moderate carbohydrate, high saturated fat diet (HSF; 39% carbohydrate, 25% protein, 36% fat, 18% saturated fat) or a moderate carbohydrate, low saturated fat diet (LSF; 37% carbohydrate, 25% protein, 37% fat, 9% saturated fat) for 3 weeks. The difference in saturated fat was derived primarily from dairy sources. Plasma lipids and lipoproteins were measured after the baseline and randomized diets. Compared to the LSF diet, participants who consumed the HSF diet had a greater percent increase in total-C (p<0.0001), LDL-C (p=0.0002), total-C/HDL-C ratio (p=0.0004) and apoB (p<0.0001) from the baseline diet, with no significant differences in HDL-C or apoAI. The HSF group had a greater percent increase in medium (p=0.05) and small (p=0.02) LDL particle concentrations from baseline compared to the LSF group, with no differences in large and very small LDL. There were also no significant differences in large and small HDL subclasses. The activities of both hepatic lipase (p=0.05) and cholesteryl ester transfer protein (p=0.04) were increased in the HSF group compared to the LSF group. Because medium and small LDL particles have been found to be more highly associated with CVD risk than larger LDL particles, the present results, in conjunction with our previous findings, suggest that adverse effects of very high saturated fat intake on CVD risk may be greater in phenotype B individuals than in those with normal lipoprotein profiles.
Abstract P392: Utilization of Electronic Medical Records to Identify Risk Factors for Abdominal Aortic Aneurysm
Authors: Smelser Diane T , Tromp Gerardus , Elmore James R , Kuivaniemi S. H , Franklin David P , Carey David J
Published: July 2021

Introduction:
Electronic medical records (EMR) contain a wealth of phenotypic information with high potential to replace costly traditional epidemiological methods for purposes such as determining disease risk factors. EMRs designed for clinical and billing applications frequently do not meet the standardization and quality of data essential for biomedical research.

Hypothesis:
Using abdominal aortic aneurysm (AAA) as a model, we assessed the hypothesis that utilizing EMR in a retrospective study is comparable to traditional epidemiologic methods for risk factor assessment of a complex disease.

Methods:
The Geisinger Health System is the main health provider serving a highly stable population in central and northeastern Pennsylvania. Clinical and diagnostic data from January 2004 to December 2009 were extracted from the Geisinger EMR. The study population consisted of cases diagnosed with AAA (
n
=964) and controls without AAA from the Geisinger MyCode
®
biobanking repository (
n
=14,555). The de-identified dataset was cleaned and formatted for research purposes. Data were analyzed unmatched, then cases were matched to controls on the confounders of sex, age, body mass index and smoking status. Matching was performed randomly, by propensity score and by group-frequency procedures. Bootstrap replication procedures (with and without replacement) confirmed the reproducibility of the results.

Results:
We replicated the direction and magnitude of several risk factors commonly noted in traditional epidemiologic AAA studies. Type 2 diabetes was associated with a decreased risk (OR=0.61, 95%CI 0.40–0.93). Peripheral artery disease (OR=2.94, 95%CI 1.81–4.78), kidney disease (OR=2.78, 95%CI 1.68–4.61), coronary occlusive disease (OR=2.64, 95%CI 1.79–3.88), cranial artery occlusive disease (OR=4.82, 95%CI 2.84–8.16), and pulmonary disease (OR=2.14, 95%CI 1.44–3.20) were all associated with an increased risk of AAA. In our population, the diagnosis of benign neoplasms was significantly inversely associated with AAA, a novel finding (OR=0.55, 95%CI 0.38–0.80). Pulse pressure was the most significant measure of hypertension associated with AAA (OR of 1.25 per 10 mmHg).

Conclusions:
This study demonstrated that EMR data can be feasibly used to assess risk factors and identify new associations. These findings could serve to enhance the current AAA screening guidelines to more efficiently target patients and increase screening utilization.
Abstract P402: Cardiovascular Diseases and Cancer: Is it Possible a Unique Prevention?
Authors: Palmieri Luigi , Donfrancesco Chiara , Rossi Silvia , Pannozzo Fabio , Busco Susanna , De Sanctis Caiola Patrizia , Capocaccia Riccardo , Giampaoli Simona
Published: July 2021

Background:
Cardiovascular diseases (CVD) and cancer together cause more than 70% of all deaths. Both the pathologies are caused by the interaction of environmental, behavioral and genetic risk factors. For some recognized CVD risk factors (e.g. smoking and obesity) recent studies found a relation also with several cancers. It’s rare to find studies including both CVD and cancer, fatal and non fatal events.

Aim:
To pool data from CVD longitudinal study and cancer register to investigate possible common risk factors and verify if cardiovascular favourable risk profile is protective also for cancer in order to implement common preventive strategies at population and individual level.

Methods:
Men and women (ages 20–75 years) data from the Italian Progetto CUORE cohorts and from the Cancer Register implemented in the area of Latina, were pooled. Risk factors were measured and collected using the same standardized procedures and methodologies: body mass index (BMI), diabetes, metabolic syndrome (MS) (ATP-III definition), total and HDL cholesterol, triglycerides, systolic and diastolic blood pressure, smoking habit, alcohol consumption, educational level. In women, menopausal status and parity were included. Follow-up was conducted until December 2004 for both CVD and cancer, fatal and non fatal events. All Cox regression Hazard Ratios (HR) were adjusted by age, gender, educational level, and study.

Results:
In 9752 persons (5153 women and 4599 men without cardiovascular events and cancer at baseline) 628 cancer events in men and 531 in women, 504 cardiovascular events in men and 274 in women were identified during a median f-u of 18 years. Smoking resulted significantly associated with cancer risk, also when adjusted by BMI, alcohol, and MS in men (current smokers HR=1.74). In women, MS was positively associated with cancer risk, but not significantly. Persons with favorable risk profile (no smoking, BMI<25 kg/m
2
, Total Cholesterol<200 mg/dl, Blood Pressure<120/80 mmHg, no diabetes) resulted at low risk for all cause, CVD and cancer mortality.

Conclusions:
There are important common risk factors for cardiovascular diseases and cancers. People with favourable risk profile live longer and cost less to the Heath System. This could be a first step to identify and implement common preventive actions at population and individual level in order to reduce both cardiovascular and cancer diseases.
Abstract 001: Quantity and Variety in Fruit and Vegetable Intake and Risk of Coronary Heart Disease
Authors: Bhupathiraju Shilpa N , Wedick Nicole M , Pan An , Manson JoAnn E , Rexrode Kathryn M , Willett Walter C , Rimm Eric B , Hu Frank B
Published: July 2021

Epidemiological data have consistently documented a protective effect of fruit and vegetable intake on risk of coronary heart disease (CHD). Consequently, dietary guidelines recommend increasing fruit and vegetable intake and, most recently, have also suggested increasing variety. Our objective was to examine the independent roles of quantity and variety in fruit and vegetable intake in relation to incident CHD. We prospectively observed 71,157 women from the Nurses’ Health Study (NHS, 1984-2008) and 39,752 men from the Health Professionals Follow-up Study (HPFS, 1986-2008) who were free of diabetes, cardiovascular diseases, and cancer at baseline. We documented 2585 incident CHD cases in women during 24 years of follow-up and 3408 cases in men during 22 years of follow-up. Diet was assessed using a standardized and validated questionnaire and updated every 4 years. Variety was defined as the number of unique fruits and vegetables consumed at least once per week. To account for minor differences in the number of fruit and vegetable items administered at each follow-up cycle, we standardized our variety score to 30 (11 for fruit score and 19 for vegetable score). Potatoes, soy, or other legumes were not included in our analyses. Because the AHA does not consider fruit juice to be equivalent to whole fruit, fruit juice was also not included in our analyses. Quantity (servings/day) and variety in fruit and vegetable intake were correlated (r=0.68, P<0.0001). We, therefore, regressed variety on quantity to assess their independent effects on CHD risk. In multivariable analyses, after adjusting for dietary and non-dietary covariates, those in the highest fifth of fruit and vegetable intake (median intake=7.80 servings/day) had a 13% lower risk (95% CI, 0.79 to 0.95) of CHD compared to those in the lowest fifth (median intake=2.14 servings/day). Conversely, quantity-adjusted variety was not associated with CHD risk (RR for highest fifth compared to lowest fifth=1.04, 95% CI, 0.92 to 1.19). Further, within each category of quantity, higher variety was not associated with CHD risk. Our data suggest that absolute quantity, rather than variety, in fruit and vegetable intake is associated with a significantly lower risk of CHD. Future work should examine the role of variety in reducing biological markers of inflammation and endothelial dysfunction. Meanwhile, policy efforts should continue to focus on increasing overall fruit and vegetable intake.
Abstract 018: Egg Consumption and Risk of Cardiovascular Disease: Findings from Three Large Prospective US Cohort Studies of Men and Women
Authors: Sands Amanda L , Tobias Deirdre K , Stampfer Meir J , Willett Walter C , Hu Frank B
Published: July 2021

Background:
Limiting dietary cholesterol intake is widely recommended for prevention of cardiovascular disease (CVD). Eggs are a major source of dietary cholesterol, but they also contain a variety of other nutrients. Several recent studies have examined egg intake and CVD with conflicting findings.

Objective:
To prospectively evaluate the association between egg intake and CVD risk in three large cohorts.

Methods:
Women and men from the Nurses’ Health Study (1980-2010; N=84,537), Nurses’ Health Study II (1991-2010; N=92,588), and Health Professionals Follow-up Study (1986-2010; N=42,815) were included if they were free of CVD and cancer at baseline. Egg intake was assessed every 4 years via validated food frequency questionnaire and evaluated in the following categories for frequency of consuming 1 egg: <1/month (reference), 1-3/month, 1/week, 2-4/week, 5-6/week, 1+/day. Incident coronary heart disease (CHD) (nonfatal myocardial infarction (MI) and fatal coronary disease) and stroke cases were ascertained via self-report and confirmed with review of medical records. Relative risks (HR) and 95% confidence intervals (CI) for CVD risk across categories of egg intake were estimated using multivariate Cox proportional hazards models, adjusted for age, race, smoking, physical activity, BMI, family history of CVD, alcohol, red and processed meat, whole milk, and other dietary covariates. Individual cohort estimates were combined using fixed effects meta-analysis.

Results:
We identified 5,838 incident cases of CHD (nonfatal MI and fatal CHD) and 6,030 stroke cases. Consumption of up to 1+eggs/day was not significantly associated with risk of incident total CVD (CHD and stroke) after adjustment for several diet and lifestyle factors (HR (CI) by category: <1/month: 1(reference); 1-3/month: 0.95(0.88, 1.02); 1/week: 0.85(0.79, 0.91); 2-4/week: 0.88(0.81, 0.96); 5-6/week: 0.96(0.84, 1.09); 1+/day: 0.99 (0.87, 1.13) (p-trend=0.77). When incident stroke and CHD were evaluated individually, egg intake was not associated with either endpoint (p-trend=0.09 for CHD and 0.52 for stroke).

Conclusions:
After controlling for lifestyle and dietary factors, egg intake (up to 1+/day) was not associated with increased risk of CVD in three prospective cohorts of men and women.
Abstract 022: Cystatin C Strengthens the Association of Kidney Function with Mortality and End-Stage Renal Disease
Authors: Shlipak Michael G , Matsushita Kunihiro , Ärnlöv Johan , Inker Lesley A , Katz Ronit , Polkinghorne Kevan , Rothenbacher Dietrich , Sarnak Mark J , Astor Brad C , Coresh Josef , Levey Andrew S , Gansevoort Ron T
Published: July 2021

Background:
Adding cystatin C to serum creatinine improves accuracy of estimated glomerular filtration rate (eGFR), but the impact on detection, staging and prognosis of chronic kidney disease (CKD) across diverse populations has not been determined.

Methods:
Meta-analyses including 11 general population cohorts (N=90,750 participants) and 5 CKD cohorts (N=2,960) with standardized serum creatinine and cystatin C at baseline. We compared associations of baseline GFR estimated by CKD-EPI equations using creatinine (eGFR
cr
) vs. cystatin C (eGFR
cys
) with mortality (13,202 deaths from 15 cohorts) and incident end-stage renal disease (ESRD) (1,654 cases from 7 cohorts) during mean follow-up of 7.7 years and studied prognostic consequences of reclassification.

Results:
In the general population cohorts, mean eGFRs were 85 ml/min/1.73m
2
for both equations but prevalence of eGFR<60 ml/min/1.73m
2
was higher for eGFR
cys
vs. eGFR
cr
(13.7% vs. 9.7% [12,403 vs. 8,833 of 90,750]). Across all eGFR
cr
categories (≥90, 60-89, 45-59, 30-44, 15-29, and <15 ml/min/1.73m
2
), upward and downward reclassification by eGFR
cys
was associated with lower and higher risk, respectively; net reclassification improvement for eGFR
cys
compared with eGFR
cr
was 0.23 (0.18-0.28) for mortality and 0.10 (0.00-0.21) for ESRD. Among participants with eGFR
cr
45-59 ml/min/1.73m
2
(N=6,358), ~40% were reclassified to higher eGFR
cys
categories and had lower risks of mortality (adjusted hazard ratio 0.66; 95% CI 0.57-0.77) and ESRD (0.20; 0.08-0.53) compared to those who were not reclassified. Among participants with eGFR
cr
60-89 ml/min/1.73m
2
(N=43,630), ~13% were reclassified to lower eGFR
cys
categories and had higher risk for mortality (1.57; 1.39-1.78) and ESRD (2.66; 1.52-4.67) compared to no reclassification. The results for CKD cohorts were largely similar.

Conclusions:
Cystatin C strengthens the association of eGFR with risk across diverse populations providing a potentially useful adjunct to eGFR
cr
for detection and staging of CKD.
Abstract 025: Urine Angiotensinogen and Salt-Sensitivity of Blood Pressure: The GenSalt Study
Authors: Rebholz Casey M , Chen Jing , Zhao Qi , Gu Dongfeng , Chen Jichun , Li Jianxin , Cao Jie , Navar Luis G , Hamm L. L , He Jiang
Published: July 2021

Urine excretion of angiotensinogen (AGT) has been proposed as a biomarker of intrarenal renin-angiotensin system activity, and therefore as a proxy for blood pressure regulation and sodium homeostasis. The association between urine levels of AGT and blood pressure response to dietary sodium intake has not been previously examined in the general population. We assessed the hypothesis that there is a direct relationship between urine levels of AGT and salt-sensitivity of blood pressure among participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) replication study. A 7-day low-sodium intervention, followed by a 7-day high-sodium intervention was carried out among 698 GenSalt-replication study participants from rural areas of north China. Absolute urine AGT excretion (μg/24 hours) and AGT-to-creatinine ratio (AGT/Cr, μg/g) were estimated at baseline for a random sample of 100 study participants. Nine blood pressure measurements were obtained at baseline and on the last three days of each intervention period. The absolute and percent changes in mean blood pressure from low-sodium to high-sodium intervention were used to assess salt-sensitivity. Median AGT and AGT/Cr were significantly (both p=0.01) reduced during the low-sodium intervention (AGT: 7.16 μg/24 hours, AGT/Cr: 8.36 μg/g) and increased during the high-sodium intervention (AGT: 8.84 μg/24 hours, AGT/Cr: 10.92 μg/g) compared to baseline (AGT: 8.28 μg/24 hours, AGT/Cr: 9.40 μg/g). Log-transformed AGT and AGT/Cr ratio at baseline was significantly and positively associated with blood pressure at baseline and at the end of each intervention. For example, one standard deviation higher log-transformed AGT/Cr ratio (1.2 μg/g) was associated with a 4.0 mm Hg (95% confidence interval: 1.3, 6.7) higher systolic blood pressure level at the end of the high-sodium intervention (p=0.004). One standard deviation higher log-transformed AGT/Cr ratio was associated with 1.58-times increased odds of high salt-sensitivity (≥5% change) of blood pressure (95% confidence interval: 1.00, 2.50; p=0.049). Log-transformed AGT/Cr ratio at baseline was positively associated with absolute and percent systolic blood pressure change from low- to high-sodium interventions (absolute: r=0.23, p=0.02; percent: r=0.20, p=0.047). In conclusion, elevated levels of urine AGT are associated with sodium-sensitivity of blood pressure. Augmentation of renal-angiotensin system activity may play an important role in the development of salt-sensitive hypertension.
Abstract 032: Associations between Middle-age Risk Factors and Future Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Tang Weihong , Alonso Alvaro , Lutsey Pamela L , Lederle Frank A , Yao Lu , Folsom Aaron R
Published: July 2021

Introduction:
Abdominal aortic aneurysm (AAA) is an important manifestation of vascular disease in older age and rupture of an AAA is a life threatening condition. Traditional atherosclerotic disease risk factors, particularly male sex, smoking and hypertension, are known to contribute to the etiology of AAA. However, epidemiologic studies of AAA have often been cross-sectional, and few have employed a prospective cohort design, especially with long follow-up. The objective of this study was to prospectively assess the association between atherosclerotic disease risk factors and hospitalized AAA in 15,722 participants (68% whites) of the ARIC study, a large, community-based cohort.

Methods:
Risk factors were measured at baseline at 45-64 year of age. Clinical AAAs were ascertained through hospital discharge diagnoses or death certificates. Over 15 years of follow-up, a total of 265 AAAs (85.3% whites) were identified, including repair procedures, AAA rupture or dissection, and incidental detection. Multivariable Cox proportional hazard models were used to estimate the association of risk factors with the risk of future AAA.

Results:
Consistent with the literature from prospective studies, we identified age, male gender, white race, smoking, height, total and HDL cholesterols, triglycerides, white blood cell count, and hypertension as risk factors for AAA (Table). In addition, LDL-C, fibrinogen, and peripheral artery disease that were previously reported only in cross-sectional case-control studies were also strongly associated with AAA (Table). Body mass index, diabetes, and alcohol consumption were not associated with AAA occurrence.

Conclusions:
Several lifestyle and clinical variables measured in middle-age were strong risk factors for future AAA during a long follow-up.
Abstract 052: Genome-wide Methylation Study of Body Mass Index (BMI) in African American Adults: Preliminary Data from the ARIC Study
Authors: Demerath Ellen W , Guan Weihua , Pankow James S , Grove Megan L , North Kari E , Fornage Myriam , Bressler Jan , Mosley Thomas H , Boerwinkle Eric A
Published: July 2021

Background and Objective:
DNA methylation patterns are influenced by environmental factors, alter gene expression, and can point to genomic regions affected by behavioral and lifestyle factors, such as obesity. However, analytic strategies for high dimensional methylation data are still evolving. Here we present preliminary analyses examining cross-sectional associations between DNA methylation level and BMI in African-American adults enrolled in the Atherosclerosis Risk in Communities (ARIC) study.

Methods:
BMI was measured at the same study visit as the DNA sample used for analysis. We used the Illumina Infinium HumanMethylation450 BeadChip to measure average methylation levels (beta values) in bisulfite-converted peripheral blood DNA obtained from participants from the Jackson, MS and Forsyth County, NC field centers. After excluding outlier samples and CpG sites using quality control filters, a model adjusting BMI (continuous) for batch (plate) and a model additionally adjusting for a small set of potential confounders (age, sex, center, smoking) were tested, with average beta value as the dependent variable. Robust standard errors were used for statistical testing and Bonferroni-corrected p value for significance was p<1 x 10
-7
.

Results:
A total of 2,873 individuals and 473,788 CpG sites entered the analysis. In the minimally-adjusted analysis, there were over 300 regions distributed across all 22 autosomes with at least one significant association between BMI and CpG methylation. Adjusting for confounders sharply reduced the evidence for association to a total of approximately 20 regions on 11 autosomes.

Conclusion:
Use of the 450K methylation BeadChip in large epidemiologic cohorts has potential to help identify genes that are transcriptionally altered by common behavioral factors such as obesity, leading to improved understanding of related diseases. However, whereas genetic associations with disease are generally unconfounded by demographic and other covariate factors, methylation associations can be strongly affected by selection of covariates as well as other analytic choices.
Abstract 057: Towards an Optimal Exercise Strategy for Reversing Low Cardiorespiratory Fitness: Distinct Effects of Exercise Volume and Intensity
Authors: Giovannetti Sara , Clarke John , Ko Gifferd , Shalev-Goldman Einat , Trevor O’Neill , Lam Miu , Ross Robert
Published: July 2021

Although a majority of adults increase cardiorespiratory fitness (CRF; VO2 peak) in response to an increase in daily physical activity, the optimal exercise strategy for reversing low CRF is unknown. We performed a randomized, controlled trial designed to study the separate effects of habitual exercise differing in dose (energy expenditure, kcal/session) and intensity (relative to VO2max) on CRF. We randomly assigned sedentary, abdominally obese men and women to one of the following 4 conditions: 1) No-exercise control (C), 2) Low volume, low intensity exercise (LVLI: 180 [[female symbol]] and 300 [[male symbol]] kcal @ 50% VO2 peak), 3) High volume, low intensity exercise (HVLI: 360 [[female symbol]] and 600 [[male symbol]] kcal @ 50% VO2 peak), 4) High volume, high intensity (HVHI: 360 [[female symbol]] and 600 [[male symbol]] kcal @ 75% VO2 peak). All participants were required to exercise under supervision 5 times per week for 24 weeks. Adherence to exercise averaged 95% across groups. Exercise dose and intensity achieved was not different from that prescribed regardless of group. The minutes exercised per session were 30±7 in LVLI, 51±16 in HVLI and 36±11 in HVHI. A marked variability in CRF response to exercise was observed independent of group (Figure). Compared to controls, CRF increased within all exercise conditions (P<0.05). However, the CRF increase within the HVHI group (0.61±0.30L/min) was greater than both the HVLI (0.42±0.32L/min) and LVLI (0.26±0.28L/min) groups (P<0.05). Thus, despite matching exercise volume within the HVHI and HVLI groups, exercise at 75% of VO2peak was associated with a marked increase in CRF by compared to exercise at 50%. Given that the time required to achieve the energy expenditure within the HVHI group was 30% less than the HVLI group (36 vs 51 min), these findings have important implications for allied health professionals seeking options for prescribing exercise to improve a major risk factor for morbidity and mortality, cardiorespiratory fitness.
Abstract MP18: Examination of Genetic Associations with Individual Lipoprotein Subfraction Measures, Aggregated Across Multiple SNPs, in Four Ethnic Groups within the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Frazier-Wood Alexis C
Published: July 2021

Introduction:
A large GWAS conducted in individuals of European descent identified several genetic markers (SNPs), subsequently validated as being associated with fasting lipoprotein measures (Chasman et al, 2009,
PloS Genetics
). We examined the reported associations separately in the Caucasian- African-, Hispanic- and Chinese- American MESA participants.

Hypothesis:
Genetic variants associated with lipoproteins in Caucasians will not be associated across all ethnic groups.

Methods:
Lipoproteins were determined by nuclear magnetic resonance spectroscopy in 4406 individuals after exclusions for lipid lowering medications and diabetes. 52 SNPs were genotyped using the Affymetrix 6.0 array or imputed using HapMap. SNPs were excluded for significant deviation from Hardy-Weinberg Equilibrium expectations (P < 1*10
-5
), imputation quality < 0.5, or minor allele frequency < 0.01. 112 SNP-phenotype associations were conducted using linear models, with SNP as the predictor, and age, sex, data collection site, smoking status, and ancestry-specific principal components of ancestry as covariates. As SNPs associated with each trait were located on different chromosomes, we assumed independence and Fisher’s test was used to combine P-values for each trait, to trait-specific aggregate Q-values (corrected using false discovery rate, Table 1).

Results:
Association (Q<.01) or suggestive association (.01<Q<.05) was seen for all but one of the 17 traits in the Caucasian group. In Hispanic-Americans, 14/17 of these traits showed association, or suggestively so. There were no associations in the African-American and Chinese-American groups.

Conclusions:
Aggregate P-values within a trait suggest that overall, different SNPs associate with lipoprotein measures in different ethnicities. Due to the limitations of ethnicity-specific sample size and allele frequencies, we are currently employing weights in a formal test for empirical differences in strength of association between the ethnicities.
Abstract MP20: Dietary Quality and Mortality among Myocardial Infarction Survivors
Authors: Li Shanshan , Chiuve Stephanie E , Flint Alan , Pai Jennifer , Forman John , Hu Frank B , Willett Walter C , Mukamal Kenneth J , Rimm Eric
Published: July 2021

Background:
Despite the increase in the prevalence of non-fatal Myocardial Infarction (MI) in the United States, evidence based recommendations for diet post-MI are limited and established primarily from studies of short duration.

Objective:
Using data from the Nurses’ Health Study and the Health Professional Follow-Up Study, we assessed dietary quality, measured by the recently developed Alternative Healthy Eating Index 2010 (AHEI2010), to evaluate diet post-MI and changes in diet from pre- to post-MI in relation to all-cause and cardiovascular mortality.

Method and Results:
We included 2,258 women and 1,840 men who were free of cardiovascular disease, stroke or cancer at the time of enrollment (1976 for women and 1986 for men), and survived a first MI during the follow up through 2008. Individuals were free of stroke at the time of initial MI onset, provided both pre-MI exposure information and at least one post-MI food frequency questionnaire (FFQ). During follow-up, we confirmed 682 all cause and 336 cardiovascular deaths for women, and 451 all cause and 222 cardiovascular deaths for men. The median survival time after initial MI was 8.7 years for women and 9.0 years for men. The Alternative Healthy Eating Index 2010 (AHEI2010) was developed based on a comprehensive review of the relevant literature to determine foods and nutrients most consistently associated with lower chronic disease risk and has the following 11 components: vegetables, fruits, nuts and legumes, red meat and processed meats, sugar-sweetened beverages, alcohol, polyunsaturated fat (no EPA or DHA), trans fat, omega-3 fat (EPA and DHA), whole grains and sodium intake. We used Cox proportional hazards models with time since initial MI onset as the underlying time scale and adjusted for medication use, medical history, and lifestyles factors. After pooling the results from both cohorts, the adjusted HR was 0.76 (95%CI: 0.60-0.96) for all-cause mortality and 0.74 (95%CI: 0.51-1.05) for cardiovascular mortality, between the highest and lowest quintile of the AHEI2010. A greater increase in AHEI2010 score from the pre- to post-MI period comparing Q5 (highest increase) vs. Q1 (lowest increase), was significantly associated with lower all-cause mortality (pooled HR= 0.71, 95%CI: 0.55-0.90) and cardiovascular mortality (pooled HR= 0.59, 95%CI: 0.41- 0.86).

Conclusions:
Our results suggest that post-MI patients who consume a higher quality diet, which has been associated with lower risk of CHD in primary prevention, have lower all-cause mortality. The current dietary recommendations for secondary prevention among MI patients need to be updated to reflect current scientific knowledge and to offer comprehensive advice on overall healthy diet quality.
Abstract MP32: Epigenome-Wide DNA Methylation Profiling in a CVD Cohort: The ARIC Study
Authors: Pankow James S , Demerath Ellen W , Guan Weihua , Fornage Myriam , Mosley Thomas H , Bressler Jan
Published: July 2021

DNA methylation is mitotically heritable modification in chromatin structure that impacts transcriptional control of genes and cellular function. Recent technological advances provide opportunities to systematically interrogate variation in DNA methylation across the genome in large epidemiologic studies. However, unlike inherited changes to the genetic sequence, variation in site-specific methylation varies by tissue, stage of development, disease state, and may be affected by gender, aging and exposure to environmental factors. As a result, there is likely a greater threat of confounding in epigenome-wide methylation studies compared to genome-wide association studies of SNPs. The Illumina Infinium HumanMethylation450 BeadChip was used to measure DNA methylation in peripheral blood obtained from African American participants from the Jackson, Mississippi and Forsyth County, North Carolina field centers of the Atherosclerosis Risk in Communities (ARIC) Study, a population-based cohort of middle-aged men and women. After excluding outlier samples and CpG sites using quality control filters, we analyzed 473,687 sites in 2873 subjects who were between 47-71 years of age at the time of DNA collection. We used linear regression with robust standard errors to examine cross-sectional associations of demographic factors with the beta value, an estimate of the average methylation level at each locus, and applied a Bonferroni correction to account for multiple testing. In univariate analysis, 91% of sites on the X chromosome and 10% of sites on the autosomes exhibited statistically significant gender differences in methylation level (p<1x10-7). Average methylation was higher in women than men for most of the significant sites (63% and 89% on the X chromosome and autosomes, respectively). Percent European ancestry estimated from ancestry informative markers was significantly associated with methylation level at 4% of sites. Age was also significantly associated with methylation at 4% of sites; average methylation was lower in older subjects compared to younger subjects for the majority (58%) of these sites. As we begin to implement epigenome-wide studies of DNA methylation and CVD outcomes, these results indicate that such studies will require careful consideration of adjustment techniques to avoid confounding by gender, age, and other covariates.
Abstract MP46: Dietary Pattern and Risk of Sudden Cardiac Death in Post-Menopausal Women
Authors: Bertoia Monica L , Triche Elizabeth W , Michaud Dominique S , Baylin Ana , Hogan Joseph W , Neuhouser Marian L , Tinker Lesley F , Van Horn Linda , Waring Molly E , Li Wenjun , Shikany James M , Eaton Charles B
Published: July 2021

Background:
The Mediterranean Diet and Dietary Approaches to Stop Hypertension (DASH) diet are characterized by higher intake of fruits, vegetables, whole grains, and unsaturated fatty acids. All of these foods/nutrients may affect cholesterol, inflammation, the development of atherosclerosis, and therefore risk of sudden cardiac death (SCD). Furthermore, the DASH diet is known to lower blood pressure and hypertension is a major risk factor for SCD.

Objective:
To examine the association between the Mediterranean and DASH dietary patterns and risk of SCD in women.

Methods:
Post-menopausal women enrolled in the Women’s Health Initiative observational study (n
=
93,676) completed a food frequency questionnaire at enrollment and at year three. Women enrolled at 40 clinical sites across the U.S. between 1993 and 1998, and were followed for an average of 10.5 years. We scored their diets according to how closely reported diet resembled each dietary pattern. SCD was defined as death occurring within one hour of symptom onset. We estimated risk of SCD according to quintile of dietary pattern score using hazard models with time-varying exposures.

Results:
A higher Mediterranean diet score was associated with a lower risk of SCD: women in the highest quintile, or who came closest to following the Mediterranean dietary pattern, had a HR of 0.62 (95% CI 0.41-0.93) compared to women in the lowest quintile, after adjustment for age, total energy, race, income, smoking, and physical activity (Table). After adjusting for other traditional coronary heart disease risk factors which are potential mediators, the association remained statistically significant: HR 0.65 (95% CI 0.43-0.99). A higher DASH diet score was not associated with reduced risk of SCD. However, sodium intake, a crucial component of the DASH dietary pattern, was not well-characterized by the FFQ.

Conclusions:
The Mediterranean dietary pattern may be associated with a lower risk of SCD in post-menopausal women, however there was no indication of a dose-response relationship.
Abstract MP47: The Epidemiology of Sick Sinus Syndrome: The Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study
Authors: Jensen Paul N , Heckbert Susan R , Gronroos Noelle N , Chen Lin Y , Folsom Aaron R , Alonso Alvaro , deFilippi Christopher
Published: July 2021

Objectives.
Little is known about the epidemiology of sick sinus syndrome (SSS). The goals of this study were to determine the age and sex-specific incidence of SSS in white and black participants in the Atherosclerosis Risk In Communities (ARIC) study and the Cardiovascular Health Study (CHS), and to investigate associations of CV risk factors with incident SSS.

Methods.
From among ARIC (n=15,792) and CHS (n=5,888) participants, we included those who at baseline were free of prevalent atrial fibrillation and pacemaker, had a heart rate of ≥50bpm unless using beta blockers, and reported white or black race. Potential incident SSS cases were identified by ICD9 hospital discharge diagnosis code 427.81 and validated by medical record review. Incidence rates of SSS were calculated for each age-sex-race category. Age, sex, race, and clinic adjusted Cox models were used to assess associations of risk factors with incident SSS; estimates were combined across cohorts using fixed-effects meta-analysis.

Results.
At baseline, the average age of included participants (n=19,146) was 60 years. Traditional CV risk factors were more prevalent among blacks. During 324,505 person years of follow-up (mean 17 years), 291 incident SSS cases were identified, 246 in whites and 45 in blacks. Incidence estimates and associations with CV risk factors were similar in ARIC and CHS. SSS incidence increased with age (Table), and blacks had a 44% lower risk of SSS than whites (age, sex, and clinic adjusted HR: 0.56, 95%CI: 0.27, 1.20). In multivariate models, incident SSS was associated with greater BMI, height, NT-proBNP, cystatin C, and QRS interval, with lower heart rate and HDL cholesterol, and with prevalent hypertension, diabetes, right bundle branch block, CHD, and HF.

Conclusions.
The incidence of hospitalized SSS increased with age, and was lower for blacks than whites. Several modifiable CV risk factors were associated with incident hospitalized SSS.
Abstract MP49: Socioeconomic Status and Metabolic Syndrome Components in Prepubescent Colombian Children
Authors: Mueller Noel T , Pereira Mark A , Buitrago-Lopez Adriana , Rodriguez Diana C , Duran Alvaro E , Ruiz Alvaro J , Rueda-Clausen Christian F , Villa-Roel Cristina
Published: July 2021

The association between socioeconomic status (SES) and cardiometabolic risk has been extensively described in developed societies. However, this topic has received little attention in children from developing populations undergoing nutritional transition. Using data from a population-based cross-sectional study of 1,260 children, aged 6-10 y, in Bucaramanga (Colombia), we examined the association between SES and prevalence of metabolic syndrome components (MetS) components. SES was defined according to classification of neighborhood public service fees. High mean blood pressure (≥ 90
th
%ile) was determined using sex-, age-, and height-adjusted cut points. For the remaining MetS components we defined internal age- and sex-specific cut points as follows: fasting triglycerides ≥ 90
th
%ile; HDL ≤ 10
th
%ile; insulin resistance (HOMA-IR) ≥ 90
th
%ile; and waist circumference ≥ 90
th
%ile. Odds ratios (ORs) and 95% confidence intervals (CIs) for each MetS component were calculated across SES before (
Model 1
) and after adjustment for measures of early-life nutrition (
Model 2
) and lifestyle factors (
Model 3
)(
Table
). Colombian children from households in high-SES neighborhoods had higher odds of central obesity and insulin resistance, but lower odds of high triglycerides and low HDL cholesterol than their low-SES counterparts (
Table
). ORs for high blood pressure were null. These results suggest that, in low-SES children from nutritionally transitioning populations, blood lipids may emerge as early cardiometabolic risk factors in the absence of central obesity and insulin resistance. These findings highlight the importance of evaluating MetS components individually in prepubescent children. Research is needed to confirm these associations and to understand the cultural and lifestyle factors that may differentiate cardiometabolic risk across SES in children of developing countries.
Abstract MP53: Racial Disparities in Predicted Cardiovascular Risk among Young Men and Women in the National Longitudinal Study of Adolescent Health (Add Health) Study
Authors: Alonso Alvaro , Everson-Rose Susan A , Clark Cari J
Published: July 2021

Background:
We used data from a nationally representative sample of young adults to examine sex-specific disparities in global cardiovascular risk across racial/ethnic groups, which have not previously been examined.

Methods:
Data were from National Longitudinal Study of Adolescent Health subjects who participated in wave 4 (2007-08) and who had valid weights and non-missing data (7270 women; 6499 men). Age, race/ethnicity, educational attainment, and cardiovascular disease (CVD) risk factors (body mass index, smoking status, diabetes, systolic blood pressure, and use of antihypertensive medication) were collected via an in-home exam. We calculated the 30-Year risk for hard CVD endpoints (coronary death, myocardial infarction, stroke) using a Framingham-based prediction model including data on age, sex, and CVD risk factors. Gender-specific differences in 30-year risk of CVD by race were calculated with weighted age- and education-adjusted linear models. Interactions between race/ethnicity and education were tested.

Results:
Mean age was 28.9 ± 1.7 years; participants were 69% non-Hispanic white (NHW), 15% non-Hispanic black (NHB), 12% Hispanic (HIS), 3% Asian/Pacific-Islander (API), 1% Native American (NA). Average 30-year risk of CVD was 10.3 ± 7.4% in men and 4.3 ± 4.1% in women. Compared to NHW men, NA and NHB had higher (p-values<0.05) and HIS and API had similar (p-values>0.05) 30-year risk of CVD. API and HIS women had lower risk and NHB and NA women had higher risk (all p-values<=0.05), compared to NHW women. A significant race/ethnicity by education interaction was observed (p-value=0.01), with racial/ethnic differences in women greatly reduced at the highest education level (Figure).

Conclusion:
Disparities in global CVD risk were observed for young men and women, though mostly attenuated among women with higher education level. Strategies to reduce disparities in CVD should start early in life, consider gender differences, and focus on educationally disadvantaged groups.
Abstract MP63: Fat Quality Estimated by Computed Tomography and Associations with Incident Cardiovascular Disease and All Cause Mortality
Authors: Rosenquist Klara J , Massaro Joseph M , Krieger Bernard E , Murabito Joanne M , Hoffmann Udo , Fox Caroline S
Published: July 2021

Background:
Computed tomography (CT) attenuation of abdominal fat as measured by Hounsfield units (HU) is associated with the composition of fat such as adipocyte size, vascularity, and fibrosis and has been associated with varying degrees of cardiometabolic risk. The objective of this study was to determine if fat quality, evaluated by CT attenuation of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), is prospectively associated with incident cardiovascular disease (CVD) and all cause mortality outcomes independent of absolute VAT and SAT volumes.

Methods:
Participants were drawn from offspring and third-generation cohorts from the multidetector computed tomography sub-study of the Framingham Heart Study (n=3324, 48% women, mean age of 51 years). SAT and VAT volumes were acquired by manually outlining the abdominal muscular wall separating the visceral from the subcutaneous fat depot. The average HU of each depot were recorded. Cardiovascular risk factors were measured using standard definitions. The outcomes of interest were incident CVD, all cause mortality, non-cardiovascular deaths and cancer deaths. Information on cause of death was obtained from death certificates, medical records and family members. Cox proportional hazard models were used to determine the association between VAT and SAT HU and the outcomes of interest. We adjusted for standard CVD risk factor covariates, secondarily for BMI, and then for VAT or SAT volumes.

Results:
There were a total of 111 incident CVD events, 85 deaths including 69 non-cardiovascular deaths and 45 cancer deaths in up to 23,047 person-years of follow-up. A one standard deviation (SD) increment in VAT attenuation was associated with a multivariable adjusted hazard ratio (HR) for all cause mortality of 1.40 (95% CI 1.12-1.75, p=0.003), which was strengthened after additional adjustment for BMI (HR 1.53, 95% CI 1.21-1.93, p<0.001) and VAT volume (HR 1.99, 95% CI 1.47-2.69, p<0.001). Non-cardiovascular death accounted for the majority of this trend and remained significant in all three models, including after adjustment for VAT volume (HR 1.97, 95% CI 1.42-2.75, p<0.001). More specifically VAT HU was associated with cancer deaths (HR 1.96, 95% CI 1.29-2.98, p=0.001). Conversely, we observed no association between VAT HU and incident CVD in the multivariable model (HR 0.83, 95% CI (0.67, 1.04) p=0.11) or after additional adjustment for BMI or VAT volume. Similar results were found for SAT HU.

Conclusions:
CT attenuation of both VAT and SAT is associated with all-cause mortality, non-cardiovascular death and cancer death. These associations highlight how indirect indices of fat quality can potentially add to our understanding of the complications of obesity.
Abstract MP67: The Association Between Habitual Dietary Sodium and Soluble Cell Adhesion Molecules Among Middle-Aged Male Twins
Authors: Eufinger Silvia C , Goldberg Jack , Ziegler Thomas R , McClellan William M , Manatunga Amita K , Vaccarino Viola
Published: July 2021

Introduction:
Habitual dietary sodium intake is associated with coronary flow reserve, a measure of microvascular function. We investigated the role of habitual dietary sodium in the expression of soluble cell adhesion molecules; these molecules are markers of endothelial dysfunction that are thought to contribute to the development of atherosclerosis.

Hypothesis:
Habitual dietary sodium is directly associated with soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) concentration.

Methods:
We recruited 475 predominantly healthy middle-aged male twins, including 214 monozygotic and dizygotic twin pairs and 47 unpaired twins, from the Vietnam Era Twin Registry. The twins had no previous history of coronary heart disease. Food intake was assessed using the Willett food-frequency questionnaire. We estimated habitual daily sodium consumption over the previous year from reported food intake. We measured sVCAM-1 and sICAM-1 concentration in blood using commercially available ELISA kits. We also obtained information on demographic characteristics and traditional CVD risk factors, including blood pressure. Mixed-effect regression analysis was used to examine individual-level effects and robust regression analysis was used to examine within-pair differences.

Results:
The twins’ mean age was 53.4 years (SD = 3.1), and 96% (455 out of 475) were white. An increase in dietary sodium of 1,000 mg/d was associated with a 12.2% higher sVCAM-1 concentration (95% CI: 3.1, 21.2;
P
= 0.009) after adjustment for total energy intake, various nutritional factors, demographic characteristics, and traditional CVD risk factors. For sICAM-1, the adjusted individual-level effect was only 3.1% and did not achieve statistical significance (
P
= 0.39). Across quintiles of sodium consumption, sVCAM-1 concentration was directly associated with dietary sodium (
P
for trend = 0.002) with the top quintile (sodium >1,505 mg/d) having a 22.9% higher sVCAM-1 concentration than the bottom quintile (sodium <742 mg/d) after controlling for potential confounders. This association persisted within twin pairs (
P
= 0.03), yet differed by zygosity (
P
interaction = 0.01). Among dizygotic pairs, a 1,000 mg/d within-pair difference in dietary sodium was associated with a 17.3% higher sVCAM-1 concentration in the twin with higher dietary sodium than in the co-twin with lower dietary sodium (
P
= 0.005) after adjustment for potential confounders. Among monozygotic pairs, however, the within-pair difference was only 5.0% per 1,000 mg/d of sodium intake and did not reach statistical significance (
P
= 0.25).

Conclusions:
Habitual dietary sodium is directly associated with sVCAM-1 concentration, a marker of abnormal endothelial function, independent of traditional CVD risk factors. However, shared genetic factors may mediate this association.