bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP045: The Ratio of Visceral and Subcutaneous Adipose Tissue Area was Positively Associated with Subclinical Atherosclerosis for Smoking Men
Authors: Lee Jung H , Kim Hyeon C , Shim Jee-Seon , Lee Myung H , Song Bo M , Suh Il
Published: July 2021

Introduction:
Several studies have examined the association between adipose tissue distribution and atherosclerosis. However, the effect of smoking on this association has not been evaluated yet.

Hypothesis:
We assessed the hypothesis that there is positive association between the ratio of visceral and subcutaneous adipose tissue areas and carotid intima media thickness (CIMT), and the association can be modified according to gender and smoking status in South Korea.

Methods:
A total of 1,606 middle-aged participants without cardiovascular disease were enrolled in this cross-sectional study from 2013 to 2015 in South Korea (568 men; 1,038 women). The CIMT of study participants was measured using B-mode ultrasonography at distal right common carotid artery, based on a predetermined protocol. We measured the abdominal adipose tissue distribution of study participants using computerized tomography. The area of adipose tissue at L4 vertebrae level was calculated, and the area of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were separated by abdominal wall. Then, we calculated the ratio of VAT and SAT (VAT/SAT) area. Other major cardiovascular risk factors were measured by standardized questionnaire, physical exam and fasting blood analysis. Smoking status of study participants was classified into three groups: current, former and never smokers. For evaluating the association between adipose tissue area and CIMT, we used multiple linear regressions. Separated analyses based on gender and smoking status were also performed.

Results:
Mean CIMT of study participants was 0.62 mm (SD, 0.12 mm), and mean VAF/SAF ratio of study participants was 0.62 (SD, 0.29). The prevalence of current smoker was 36.8% (209 of 568) for men, and 4.1% (42 of 1038) for women. In our multiple linear regression models, the VAT/SAT ratio showed statistically significant positive β-coefficient for total participants (β =8.62, p=0.008): showing significant for men (β =15.95, p=0.001) and not for women (β =3.15, p=0.377). When considering men only with respect to smoking status, the association between VAT/SAT ratio and CIMT was significant for current smokers (β=30.37, p<0.001), while it was not for never smokers (β=0.62, p=0.958) and former smokers (β=12.84, p=0.119). There was no significant interaction for gender and also for smoking status for men (p for interaction>0.05).

Conclusions:
In conclusion, the VAT/SAT ratio was positively associated with CIMT, and more preeminent positive association was observed for current men smokers than for never and former men smokers. The results of this study supported the need of smoking cessation to prevent atherosclerosis by adipose tissue distribution, especially for men.
Abstract P001: Life′s Simple 7 in Middle-age and Prognosis After Myocardial Infarction in Later Life
Authors: Mok Yejin , Sang Yingying , Ballew Shoshana H , Rebholz Casey M , Heiss Gerardo , Folsom Aaron , Coresh Josef , Matsushita Kunihiro
Published: July 2021

Background:
The AHA recommends focusing on seven traditional risk factors (Life’s Simple 7) for cardiovascular health promotion, primarily based on their impact on the risk of incident cardiovascular disease. However, the contribution of Life’s simple 7 in mid-life to prognosis after myocardial infarction (MI) in later life is unknown.

Methods:
In 13,500 participants from the Atherosclerosis Risk in Communities (ARIC) study (age 45-64 years) at Visit 1 (1987-1989), a 14-point score of Life’s simple 7 was constructed according to the status of each of seven factors (smoking, body mass index, physical activity, dietary quality, total cholesterol, blood pressure, and fasting glucose). We quantified the association between this score and adverse outcomes after validated incident hospitalized MI occurring during ARIC follow-up, using Cox proportional hazards models adjusting for age at MI, gender, race, and year of MI occurrence.

Results:
1,341 participants had a definite or probable hospitalized MI after the ARIC baseline visit (median elapsed time between baseline and MI occurrence, 24.4 years [IQR 17.5-25.4]). Of these, 807 (60%) had cardiovascular outcomes of interest after MI during a median follow-up of 3.0 years. Higher Life’s Simple 7 score (better cardiovascular health) in middle-age was associated with lower risk of adverse outcomes after MI in later life (Table). For example, individuals with Life’s Simple 7 score ≥10 had 50-80% lower risk of cardiovascular mortality, recurrent MI, and heart failure compared to those with score ≤3. The associations were largely consistent across years of MI occurrence and when we restricted the follow-up after MI to 1-3 years.

Conclusion:
A better AHA Life’s Simple 7 in middle-age was associated not only with lower incidence but also with a lower risk of adverse outcomes after MI in later life. Our findings suggest a secondary prevention benefit of striving for ideal CV health status in mid-life, further supporting AHA promotion of Life’s Simple 7.
Abstract P008: Abnormal Ankle-Brachial Index is Inversely Associated with Improved Cardiovascular Health
Authors: Singh Sarah , Pilkerton Courtney , Frisbee Stephanie
Published: July 2021

Background/Objective:
An abnormal ankle-brachial index (ABI) strongly correlates with higher mortality in patients with cardiovascular disease however, the inverse link has not been established for cardiovascular (CV) health. The American Heart Association (AHA) aims to improve CV health by 20% by 2020 and has thus proposed the use of CV health metrics (Life’s Simple 7 or LS7). This study examines the relationship of abnormally low ABI with CV health.

Methods:
We evaluated 5,308 men and women aged ≥40 years, without history of CVD or diabetes mellitus (DM), participating in NHANES from 1999-2004. Abnormally low ABI was defined as ABI< 1.00 which included borderline low [0.91-0.99] and low ABI [<=0.90]). LS7 was scored on a 0-14 point scale and calculated based on poor, intermediate and ideal categories of 7 health components: diet, BMI, smoking, physical activity, blood pressure, glucose and cholesterol. LS7 scores were categorized as inadequate (0-7points), average (8-11) and optimum (12-14) CV health. Ordinal logistic regression models identified associations between abnormal ABI and CV health, with adjustments for sex, age, race/ethnicity, socioeconomic status and hs-CRP.

Results:
The mean (95% CI) LS7 score was 7.4 (7.3-7.5), with the majority of the population (75.3%) clustered at the lower end of average CV health. Adjusted models demonstrated that, compared to those with inadequate CV health, those with average CV health experienced 28% lower odds of abnormal ABI (OR 0.72, 95% CI; 0.52-0.97). Further improving CV health from inadequate to optimum was associated with 78% lower odds of abnormal ABI (OR 0.22, 95% CI; 0.09-0.57). On examining individual components, only blood pressure was found to be significantly associated with lower odds of abnormal ABI. Those with intermediate, as compared to poor, blood pressure readings showed 32% lower odds of abnormal ABI (OR 0.68, 95% CI; 0.48-0.94) while those with ideal blood pressure showed a 61% lower odds of abnormal ABI (OR 0.39, 95% CI; 0.21-0.72).

Discussion/Conclusion:
Although those with average CV health experienced lower odds of abnormal ABI, improving CV health to optimum can significantly lower these odds. This suggests that optimizing cardiovascular health, particularly in those who have not yet been affected by CVD or DM, can significantly slow or prevent progression of systemic atherosclerosis.
Abstract P015: A Novel Healthy Blood Pressure Phenotype is Associated With Better Cardiovascular Health Benefits and Neuropsychological Performance in the Long Life Family Study
Authors: Marron Megan M , Boudreau Robert M , Christensen Kaare , Cosentino Stephanie , Feitosa Mary , Minster Ryan L , Schupf Nicol , Sebastiani Paola , Ukraintseva Svetlana , Wojczynski Mary K , Newman Anne B
Published: July 2021

Introduction:
We assessed the hypothesis that a novel healthy blood pressure phenotype is familial and sought to identify factors associated with this phenotype in the Long Life Family Study (LLFS).

Methods:
The LLFS is a unique multi-center, international study that recruited families demonstrating clustering for longevity. Families were recruited from four centers; three in the U.S.: Boston, New York, and Pittsburgh and one in Denmark. The pedigrees included two generations: 1) probands and their siblings and 2) offspring of participants in the proband generation. Offspring (n=2211, ages 32-88, mean age=60.5; 43% male) were classified as having healthy blood pressure if their age- and sex-adjusted systolic blood pressure z-score was between -1.5 and -0.5 (i.e., a systolic blood pressure lower than expected for their age and sex, but not “too low”). Offspring on anti-hypertensive medications were classified as not having healthy blood pressure. Families (n=419) were defined as having healthy blood pressure if ≥2 and ≥50% of their offspring met the healthy blood pressure phenotype.

Results:
There were 476 (22%) offspring who met the healthy blood pressure phenotype. These offspring tended to have a better health profile than remaining offspring. When examining families, only 44 (11%) families met the criteria for healthy blood pressure. Both offspring and probands from families with healthy blood pressure performed better on neuropsychological tests that place demands on complex attention and executive function than offspring and probands from remaining families. Among families with healthy blood pressure, a higher proportion of offspring met the American Heart Association ideal cardiovascular health definition compared to remaining families (11% versus 4%, respectively, p<0.0001; not including the diet component). There was also a larger proportion of probands (n=1164, ages 71-110, mean age=90.5; 45% male) who met the American Heart Association ideal cardiovascular health definition when compared to the U.S. prevalence for ≥6 components among those ages ≥60 (1% versus 0.1%, respectively).

Conclusion:
In this cohort of familial longevity, few families had a novel healthy blood pressure phenotype in multiple members. Families and individuals with healthy blood pressure performed better on neuropsychological tests that represent aspects of executive function and had a higher proportion with ideal cardiovascular health than the U.S. population. In summary, a novel healthy blood pressure phenotype was rarely familial in this cohort; however, when it was, it was associated with cognitive and cardiovascular health benefits. Blood pressure may be a key pathway for family longevity.
Abstract P023: Association of Sickle Cell Trait with Common Electrocardiographic Abnormalities in The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Douce Daniel , Soliman Elsayed Z , Naik Rakhi P , Hyacinth Hyacinth I , Cushman Mary , Winkler Cheryl A , Howard George , Zakai Neil A
Published: July 2021

Introduction:
Sickle cell disease (SCD) arises from an autosomal recessive mutation that leads to progressive vascular obstruction and early death. Sickle cell trait (SCT), the carrier status, is present in ~8% of African-Americans (AA) and is thought to be a benign condition, although evidence now suggests an association with worse cardiovascular and renal outcomes. Electrocardiogram (ECG) changes have been documented in SCD patients; however, similar studies in SCT individuals are lacking. We hypothesized that left ventricular hypertrophy (LVH), atrial fibrillation (AF) and QTc prolongation would be more common in SCT carriers than non-carriers.

Methods:
SCT was genotyped in 10,731 AA participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Baseline risk factors were recorded from 2003-7. LVH was determined using Sokolow-Lyon criteria for all participants, and Cornell criteria in those with 12 lead ECGs (n = 8,690). AF was based on both self-report and ECG criteria. We assessed the association of SCT with LVH, AF, and QTc using multivariable logistic regression adjusting for age, sex, income, education, self-reported history of stroke, myocardial Infarction, diabetes, hypertension, and chronic kidney disease.

Results:
Among AA participants with ECG data and genotyping, 787 of 10,553 were SCT carriers (7.5%). AF was present in 814 (7.8%), LVH in 1,556 (14.7%) and QTc prolongation in 357 (3.4%). SCT status was associated with AF with an adjusted OR of 1.36 (95% CI 1.05, 1.76). SCT was not associated with LVH by Cornell criteria or Sokolow-Lyon (OR 1.16; 95% CI 0.94, 1.42). There was a significant age (continuous) by SCT interaction (p=0.02) with SCT associated with increased risk of LVH in younger but not older individuals. When stratified by the mean age of the cohort (65 years), younger individuals with SCT had an OR of 1.50 (95% CI 1.14, 1.97) for LVH, an association not seen in older individuals (OR 0.86; 95% CI 0.63-1.18). QTc prolongation was not associated with SCT (OR 0.97, 95% CI 0.64-1.47).

Conclusions:
SCT was associated with increased prevalence of AF in all individuals and with LVH in younger but not older individuals and was not associated with QTc prolongation. These data suggest SCT is not benign, and for the first time report the association of SCT with common ECG abnormalities. The association with AF and LVH is concerning with respect to increased stroke risk, especially the increased prevalence of LVH seen at younger ages in SCT. These data raise the question of whether individuals with SCT need more intensive monitoring and/or hypertension control than the general population.
Abstract P046: Cardiometabolic Risk Liver Transplant Survivors
Authors: Salyer Jeanne , An Kyungeh , Siddiqui Shadab
Published: July 2021

Background:
Coronary heart disease (CHD) is an important cause of long-term mortality in liver transplant recipients (LTR). LTR are at increased risk for CHD-related mortality due to exposure to chronic immunosuppression contributing to cardiometabolic risk. Physical activity (PA) and nutrition are important lifestyle management tools used in clinical practice to reduce CHD risk, however, little is known about the long-term effects of these strategies in LTR.

Objective:
The aim of this study was to evaluate PA and diet and correlate findings with the atherogenic lipoprofile, obesity and 10-year risk of CHD.

Methods:
LTR (≥ 2 years post LT; stable immunosuppression) without documented CHD, diabetes, graft cirrhosis, physical limitations, and malignancy were included. PA was quantitated via International Physical Activity Questionnaire (IPAQ). Anthropometric assessment was used to obtain body mass index (BMI) and waist hip ratio (WHR). NMR Lipoprofile was used to obtain athrogenic lipoprotein concentration and size followed by generic lipid profile. Food preferences were evaluated via Olbrisch Eating Style Questionnaire and Diet History Questionnaire. CHD risk was assessed by Framingham Risk Score (FRS).

Results:
Of 122 subjects screened, 27 met entry criteria. Most were overweight (N=11) or obese (N=8) with mean BMI 28.5 kg/m
2
(
SD
=4.05; range=20.2-37.8) and mean WHR= 0.94 (SD=0.22; range=0.65-1.85). According to IPAQ, 20 patients (75%) were sedentary. Eating style and food preference choices suggested that 23 (85.2%) were unable to control portion sizes and 14 (51.9%) preferred sugar, fat, or starches in their diet. Fasting glucose was 98.8mg/dL (
SD
=14.2, range=78-133) suggesting 7 participants were “pre-diabetes” and 2 undiagnosed type 2 diabetes. Four reported smoking; of these, one was highly nicotine dependent. FRS was 7.15% (SD=6.15, ranged 7-23). While the calculated total cholesterol 166.44 (SD=34.15), HDL 55.19 (SD=15.31), LDL 84.56 (SD=26.58), and TG 143.44 (SD=76.29)(all in mg/dL) were within normal range, numbers and sizes of lipoprotein particles indicate that LTRs were at moderate risk of CHD: LDL-C 1221.48 (SD+447.31)>1000 nmol/L as reference), small LDL-P 799.81 (SD=489.95) >527nmol/L), LDL-size 20.89 (SD=1.12)>20.5nm, Large VLDL-P 2.93 (SD=4.35) >2.7 nmol/L, and VLDL size 51.07(SD=9.74) >46.6 nm. PA (more time sitting) was associated with higher BMI (r=.394, P<0.05) and WHR (r=.535, P<0.01) but not with particle number or density. PA (MET minutes/week) was associated with WHR (r=.535, p<0.01). Neither PA nor nutrition (Kcal/day) was associated with FRS.

Conclusion:
LTR are generally inactive and make poor dietary choices which are reflected by the obesity indices and characterized by the atherogenic lipoprofile.
Abstract P073: Co-morbidities and Cardiac Associated Mortality in Smokers
Authors: Kinney Gregory L , Young Kendra A , Pratte Katherine , Regan Elizabeth A , Duca Lindsey , Make Barry , Crapo James , Hokanson John ,   COPDGene Investigators
Published: July 2021

Background:
Chronic Obstructive Pulmonary Disease (COPD) is a complex syndrome involving all aspects of the lungs which is strongly associated with cigarette smoking. Parenchymal destruction and remodeling are disease processes involving inflammatory pathways likely to have systemic vascular effects outside of the lungs. Indeed cardiovascular disease (CVD) is a leading cause of mortality in people affected by COPD and many co-morbid conditions are also associated with the disease. We explored CVD mortality in smokers considering aspects of COPD as well as co-morbidities in the longitudinal follow-up of the COPDGene study.

Methods:
The COPDGene study includes baseline and longitudinal assessment of mortality for 8,157 participants with (3,604) and without COPD (4,553) all of whom reported >10 pack-years smoking exposure. Aspects of COPD including CT phenotyping and pulmonary function were combined using Principal Components Analysis (PCA), co-morbidities were combined using Latent Class Analysis (LCA) and cause specific mortality was assessed using study center reports, SSRI searches and single clinician adjudication. Cox Proportional Hazards models accounting for the effects of competing risks were used to assess the association between PCA factors and CVD mortality and PCA factors plus LCA classes and CVD mortality.

Results:
PCA analysis resulted in 5 factors describing emphysema, airway disease, gas trapping, BMI and its effect on CT measurement and hyperinflation and LCA analysis identified 7 classes of co-morbidities. CVD associated mortality occurred in 128 participants and competing causes of mortality occurred in 605. The PCA factor describing airway disease predicted CVD mortality in the PCA only model (HR 1.8, 95%C.I. 1.4-2.3,p<0.0001), as well as in the LCA model (HR 1.7, 95% C.I. 1.3-2.2, p<0.0001). LCA classes associated with CVD mortality include a class describing diabetes, high BP and high Cholesterol (HR 3.5, 95% C.I. 1.8-6.8, p=0.0003) and a class describing known CVD (HR 2.9, 95% C.I. 1.3-6.7, p=0.01).

Conclusions:
Co-morbidities of COPD represent independent predictors of CVD associated mortality in smokers accounting for pulmonary disease and competing mortality risks. Clustering of comorbidities using LCA is an approach that may be informative in complex diseases.
Abstract P083: Qualitative Evidence Supporting a New Model of Health Behavior Change for African American Men in a Faith-Based Community
Authors: Lee Sohye , Lindquist Ruth
Published: July 2021

Purpose:
Programs of behavior change with education targeting application to lifestyle habits may result in changes in risk-related behavior and improved cardiovascular disease (CVD) outcomes. The purpose of this abstract is to describe the changes, as evidenced in the qualitative analyses of transcripts of 14 sessions of a 6-month peer support group intervention to foster risk-related behavioral change, and in final program interviews.

Method:
African American men (N=8), aged 45-83 years, from one Baptist church in NE U.S. participated in a peer-led behavior change program targeting Life’s Simple 7 (get active, control cholesterol, eat better, manage blood pressure, lose weight, reduce blood sugar, stop smoking), over a 6-month period. Research staff monitored the hour-long peer intervention sessions by phone and recorded and transcribed the sessions. Qualitative analysis comprised thematic analyses of the textual content of the peer group sessions and transcripts of follow-up interviews to identify evidence in the text supporting the existence of shifting stages of change within the group over time. Self-reported stages of readiness to change related to the 7 CVD behavioral risk areas were also quantified using 7 contemplation ladders with rungs ranging from zero (“no thoughts of changing”) to 10 (“taking action to change”).

Results:
Over the course of the 6-month intervention, changes in group participants’ stages of change were evident. Six key themes emerged from the group sessions, including: (1) individuals’ resistance to change behaviors (weeks 1-2); (2) engagement through peer discussion of challenges and barriers (weeks 2-5); (3) awareness of physical benefits of change (weeks 2-24); (4) peer group cooperation for problem solving (weeks 3-24); (5) initiating health promotion inclusive of family and community (weeks 11-24); and (6) teaching others (weeks 18-24). The median difference in change in the contemplation ladders was <0; likely due to a ceiling effect due to the recruitment of motivated men who were ready to change. In the 6-month interviews, although men have changed behaviors positively over time, participants still reported challenges to changing and maintaining behaviors in different areas. This reveals that behaviors are continuing to evolve, and that in this shifting, behavior change is still an ongoing process as the men become more aware of their behaviors and increasingly view them in context of family and community.

Conclusions:
In this 6-month, intensive peer-led intervention, the micro-culture of the peer support group transformed from self-focused resistance to cohesion, then to other-oriented action. The data moved beyond Prochaska’s Stages of Change Model to break out and define a new paradigm of change that affected family and community and which will likely lead to longer term, continued changes and ongoing reinforcement.
Abstract P096: The Genetics Architecture of the Serum Metabolome
Authors: Wang Zhe , Yu Bing , De Vries Paul S , Feofanova Elena V , Yu Fuli , Gibbs Richard A , Morrison Alanna C , Boerwinkle Eric
Published: July 2021

Introduction:
The metabolome is a collection of small molecules in a biologic sample, and may serve as biomarkers or predictors of heart disease. Whole genome sequence analysis offers the opportunity to investigate rare and low-frequency annotated variants across the human genome. We used whole genome sequence analysis to characterize the genetic architecture of the serum metabolome.

Methods:
Whole genome sequencing and measurement (chromotagraphy and mass spectroscopy) of 245 serum metabolites were done in 1,458 European Americans and 1,679 African Americans from the Atherosclerosis Risk in Communities (ARIC) study, and these data were used to perform a trans-ethnic meta-analysis. Common variants (MAF>5%) were analyzed individually using an additive genetic model. Rare and low-frequency protein-altering variants (MAF≤5%) were aggregated by genes. In order to determine the contribution of regulatory and non-protein coding regions of the genome, we conducted aggregate tests across the entire genome using a 4kb sliding window as well as in predefined regulatory elements, which includs enhancers, promoter, and 3’ and 5’ untranslated region of a gene.

Results:
We identified 119 significant associations between genetic variants and metabolite levels (significance threshold p<2.0*10
-10
for single variants, p<2.9х10
-10
for aggregate tests), of which 49 were novel, including genes involved in known Mendelian conditions, protein biological processes, and disease related pathways. Six genes (
DMGDH, AGA, ACY1, PRODH,
DDC
and
CPS1
) causing rare inborn errors of metabolism were associated with amino acid levels in the general population. A predicated regulatory variant in the
AGA
gene, encoding a protein involved in asparagine generation, was associated with serum asparagine levels independent of any coding variants in this gene. Seven genes (
ABCC2, PKD2L1, SLC10A1, FDX1, CYP3A43, UGT2B15
and
SULT2A1
) related to lipid-related metabolite levels were identified, whose gene products are involved in secretion, channeling and transportation. Analysis of regulatory regions unraveled associations between three steroid lipids and a member of the cytochrome P450 family,
CYP3A43
. Five genes within the kinin-kallikrein pathway were identified to be related to small peptide levels, including
KLKB1
,
KNG1
,
F12
,
ACE and CPN1
. Variants in
CPN1
, which is known to bind to fibrinogen, were associated with DSGEGDFXAEGGGVR, a peptide which is produced during fibrinogen to fibrin conversion.

Conclusion:
This study outlines an approach to characterize the genetic architecture of the human serum metabolome and shows that sequence variants affect multiple human metabolites. Using the principle of Mendelian randomization, the next step is to determine whether any of these metabolites are in causal pathways to disease.
Abstract P107: Leucocyte Telomere Length and Cardiovascular Disease in the Jackson Heart Study
Authors: Mwasongwe Stanford , Raffield Laura , Gao Yan , Wilson James G , Aviv Abraham , Reiner Alexander P
Published: July 2021

Background:
In European descent populations, shorter leucocyte telomere length (LTL) has been associated with clinical and subclinical atherosclerosis, while longer LTL has been associated with greater left ventricular hypertrophy (LVH). We evaluated the relationship of LTL with subclinical indices of cardiovascular disease (CVD) (coronary artery calcification [CAC], abdominal aorta calcification [AAC], carotid intima media thickness [CIMT], left ventricular mass [LVM], and ankle-brachial index [ABI]) in African Americans (AAs). We also examined whether LTL is associated with CVD events and mortality.

Methods:
Analyses included participants of the Jackson Heart Study (JHS), a prospective cohort study of AAs, with LTL data (n=2,573) measured by Southern blot analysis in DNA from the baseline exam (2000-2004). Adjudicated CVD events (coronary heart disease [CHD], heart failure [HF] and stroke) and mortality were identified through December 2012. Relationships were assessed using linear, logistic regression models, or Tobit model (CAC and AAC due to left censoring) in STATA 14.

Results:
In an age and sex adjusted model, longer LTL was significantly associated with lower CAC (
P
=0.049, β=-0.535; 95% confidence interval [CI], -1.066,-0.003); this association was no longer significant after adjusting for body mass index, current smoking and other CVD risk factors. There were no significant associations between LTL and AAC, CIMT, or LVM. LTL was associated with higher ABI (
P
=0.017, β=0.023; 95% CI, 0.004, 0.042) when the highest was compared to the lowest LTL quartile in models adjusted for CVD risk factors. After a median follow-up of 9 years, longer LTL was associated with lower risk of incident ischemic stroke and total mortality in age and sex adjusted models, but these associations were no longer significant in models fully adjusted for CVD risk factors.

Conclusions:
In conclusion, among a community-based cohort of AAs, LTL was associated with increased ABI, indicative of increased risk of peripheral arterial disease, but there were no significant associations with other CVD indices and mortality after adjustment for established risk factors.
Abstract P124: Network Meta-analysis of the Effects of Breast Cancer Hormone Therapy on Changes in Lipid Profiles
Authors: Huang Hsin-Hui , Barinas-Mitchell Emma , Diergaarde Brenda , Chang Chung-Chou , Bertolet Marnie
Published: July 2021

Introduction:
Adjuvant hormone therapy prolongs survival of patients with early-stage hormone receptor-positive breast cancer (BC). For postmenopausal patients, aromatase inhibitors (AIs) have been shown to improve disease free survival compared to tamoxifen, but the impact on overall survival has been inconsistent. A meta-analysis showed higher risk of cardiovascular diseases (CVDs) for patients taking AIs. Deteriorating lipids induced by AIs may contribute to this result. This analysis aims to compare the effects of hormone therapeutic options on changes in lipids from published randomized clinical trials (RCTs).

Methods:
RCTs evaluating effects of adjuvant hormone therapy on lipids (total cholesterol, high-density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc), and/or triglycerides) in postmenopausal early-stage BC patients published in PubMed and Embase, prior to Jan. 31, 2016 were reviewed. Bayesian network meta-analysis was used to compare effects of placebo, selective estrogen receptor modulators (SERMs- tamoxifen and toremifene) and AIs (letrozole, anastrozole, and exemstane) on lipids across longitudinal time points. Heterogeneity was examined by meta-regressions adjusting for mean age, baseline lipid value, and prior tamoxifen use. An arm-based random effect model tested the consistency of the direct and indirect evidence of the drug effects.

Results:
We identified 17 articles from 13 RCTs for a total of 1,913 subjects. The Table summarizes the results, with statistically significant results bolded. Toremifene significantly improved all lipids and was the best choice regardless of covariate adjustment, while tamoxifen had weaker but significant LDLc lowering but opposite HDLc/triglyceride effects to toremifene. AIs generally had little effect on lipids.

Conclusions:
In general, AIs tend to have worse effects on lipids than SERMs, while only toremifene had beneficial effects on all lipid values. Patients on AIs with high risk of CVD should monitor their lipids.
Abstract P152: Cardiometabolic Risk Factors in Adolescent Blood Donors
Authors: Keeton James , Eason Stephen J , Sayers Merlyn , Ayers Colby , Gore Maria O
Published: July 2021

Objective:
Cardiometabolic risk factors have been extensively studied in adults, but to a lesser extent in adolescents. We assessed potential cardiometabolic risk factors in a large cohort of adolescent blood donors.

Methods:
Glycated hemoglobin (HbA
1c
), blood pressure (BP), and total cholesterol were measured in 10,756 blood donors aged 16-19 years at school blood drives conducted by Carter BloodCare, a large North Texas blood center. Borderline values were defined as HbA
1c
5.7-6.4%, BP (systolic/diastolic) 120-139/80-89 mm Hg, and total cholesterol 170-199 mg/dL. Elevated values were defined as HbA
1c
≥6.5%, BP ≥140/90, and total cholesterol ≥200 mg/dL. Subjects were classified into one of three subcohorts: (A) no borderline or elevated values (“healthy” subcohort); (B) one borderline value; (C) either two borderline values or one elevated value. The subcohorts were further stratified as shown in the Table.

Results:
Of the 10,756 blood donors, 35.2% had one borderline cardiometabolic risk factor, and 17.9% had either two borderline or one elevated risk factor. There were more girls than boys in the “healthy” subcohort (p<0.0001). Girls had a higher prevalence of borderline or elevated total cholesterol (p<0.0001), whereas boys had higher prevalence of borderline or elevated BP (p<0.0001). Other differences between subcohorts are summarized in the Table.

Conclusion:
More than half of adolescents in this study had at least one cardiometabolic risk factor that was either borderline or elevated. Blood donation programs can serve as highly efficient and cost-effective gateways for cardiometabolic risk screening in adolescents, with potential for the development of targeted interventions aimed at promoting healthy behaviors early in life, specifically among those at increased risk.
Abstract P168: Animal & Dairy Protein Intakes Associate With Increased Risk of Heart Failure in Men: The Kuopio Ischaemic Heart Disease Risk Factor Study
Authors: Virtanen Heli E , Voutilainen Sari , Koskinen Timo T , Mursu Jaakko , Tuomainen Tomi-Pekka , Virtanen Jyrki K
Published: July 2021

Introduction:
Different protein sources, such as processed red meat and fish have indicated distinct associations with risk of heart failure. Whether these distinct associations are partly due to the differences in proteins themselves remains unclear. Thus, we examined the associations of proteins from different food sources with risk of heart failure in Finnish male subjects.

Hypothesis:
We hypothesized that proteins from different dietary sources would have distinct associations with heart failure risk.

Methods:
The study included 2441 men aged 42-60 y at the baseline examinations in 1984-1989 in the Kuopio Ischaemic Heart Disease Risk Factor Study. Protein intakes at baseline were assessed with 4-d dietary records. Data on incident heart failure cases were obtained from national registers. The multivariable-adjusted risk of heart failure according to protein intake was estimated by Cox proportional hazard ratios. Multivariable analyses included age, examination year, education, income, family history of ischaemic heart disease, smoking, leisure-time physical activity, and intakes of alcohol, energy, fiber, and saturated, monounsaturated, polyunsaturated and trans fatty acids.

Results:
During the mean follow-up time of 22.2 y, 334 incident cases of heart failure occurred. Total protein (multivariable-adjusted extreme-quartile HR 1.45, 95% CI: 1.04-2.00, P-trend 0.01), animal protein (HR 1.56, 95% CI: 1.12-2.17, P-trend 0.01) and dairy protein (HR 1.53, 95% CI: 1.11-2.11, P-trend 0.01) intakes were associated with increased risk of heart failure. Especially protein from fermented dairy products associated with higher risk (HR 1.48, 95% CI: 1.08-2.02, P-trend 0.002). Adjustment for the potential effect mediators [body mass index and diseases or medications (coronary heart disease, hypertension, type 2 diabetes, lipid-lowering or heart medications) at baseline and during the follow-up] slightly attenuated the associations, but associations of animal, dairy and fermented dairy protein remained statistically significant. Plant protein intake had no association with heart failure risk (HR 1.00, 95% CI: 0.63-1.59, P-trend 0.82).

Conclusions:
Our data suggest that high intake of protein, especially from animal and dairy sources, may increase the risk of heart failure.
Abstract P188: The Pooled Cohort Equations Over-predict Risk in Women With Hypertensive Disorders of Pregnancy, Even After Refitting the Model
Authors: Dam Veerle , Onland-Moret N. C , Verschuren W. M , Boer Jolanda M , Moons Karel G , Boersma Eric , van der Schouw Yvonne T
Published: July 2021

Introduction:
The AHA guidelines for the Prevention of Cardiovascular Disease (CVD) in Women describe hypertensive disorders of pregnancy (HDP) as a failed stress test, which might unmask early CVD. An abundance of prediction models for CVD risk is available for the general population, but their validity in women with HDP is not established.

Hypothesis:
The prognostic performance of the Pooled Cohort Equations (PCE) is lower in women with HDP compared to women without HDP and recalibrating and refitting the model will improve the prognostic performance.

Methods:
Data were used from 27,339 women out of the MORGEN and PROSPECT cohorts; we excluded those who had never been pregnant. In total, 5,358 answered the question: ‘Did you suffer from high blood pressure during pregnancy?’ with ‘Yes’; and 15,266 with ‘No’. Outcome definition was equal to that in the original PCE model. MORGEN and PROSPECT were analyzed separately, because of differences in characteristics (e.g. MORGEN is younger and has more current smokers) and observed risks. First, we calculated the 10-year predicted risk and compared this with the observed risk. Subsequently, the model was updated in three steps: by recalibrating the mean linear predictor, by additionally updating the baseline hazard, and by refitting the full model. The performance of all models was quantified by calibration (calibration plot, expected:observed ratio) and discrimination (c-statistic).

Results:
The Table shows that the original model over-predicts risk in all women, but more in women without HDP. Calibration plots improved most after refitting, which is confirmed by the expected:observed ratio, although the model still over-predicts. Refitting only improved discrimination in women with HDP, but not in women without HDP.

Conclusion:
The PCE over-predicts risk in women with and without HDP, even after refitting the model. Discrimination is overall quite good, except for MORGEN women without HDP. Especially in women with HDP the model discrimination benefits from refitting.
Abstract P189: Age-related Differences in Antihypertensive Medication Adherence in Hispanics: A Cross-sectional Community Based Survey in New York City
Authors: Bandi Priti , Goldmann Emily , Parikh Nina S , Farsi Parisa , Boden-Albala Bernadette
Published: July 2021

Introduction:
U.S. Hispanics, particularly younger adults in this population, experience a disproportionate burden of uncontrolled hypertension. Little is known about predictors of antihypertensive medication adherence - a major determinant of hypertension control and cardiovascular disease - and differences between age groups in this fast-growing population.

Methods:
The study included 1,043 community dwelling Hispanic hypertensives residing in three Northern Manhattan neighborhoods. Age-stratified analyses assessed the prevalence and predictors of high medication adherence (score 8 on Morisky Medication Adherence Scale, MMAS-8) among younger (<60 years) and older (≥60 years) Hispanic adults.

Results:
Prevalence of high adherence was significantly lower in younger vs. older adults (24.5% [105 of 429] vs. 34.0% [209 of 614], p=0.001). In younger adults, heavy alcohol consumption, a longer duration of hypertension, and recent poor physical health were negatively associated with high adherence, but poor self-rated general health was positively associated with high adherence. In older adults, age, education level, knowledge of hypertension control, private insurance/Medicare vs. Medicaid and poor health-related activity limitations were negatively associated with high adherence.

Conclusion:
Equitable achievement of national hypertension control goals will require particular attention to suboptimal antihypertensive medication adherence found in this study and other samples of U.S. Hispanics, particularly in younger adults. Age differences in predictors of high adherence highlight the need to tailor efforts to the specific life stage of hypertensive individuals.
Abstract P196: Cardiovascular Health Across the Lifespan: The Development and Validation of a Synthetic Cardiovascular Cohort
Authors: Allen Norrina B , Ning Hongyan , Lloyd Jones Donald , Zhao Lihui , Siddique Juned
Published: July 2021

Introduction:
The burden of cardiovascular (CV) risk factors accumulates over the lifespan: however, little information on CV risk across the full lifespan is available. Synthetic cohorts offer the opportunity to understand CV health across the lifespan. In this study we developed and validated a synthetic cohort approach to examine CV risk factors from age 18-90 years of age.

Methods:
This study included African American and Caucasian participants from 7 cohorts in the Lifetime Risk Pooling Project. Individuals’ demographics (age, birth year, sex, race, SES), CV risk factors (smoking, total cholesterol, SBP, DBP, glucose, diabetes, lipid-lowering and antihypertensive meds) and outcomes (incident CVD and death) at each exam were included. To generate a complete set of values from age 18 to 90 for each participant, we multiply imputed the participant’s CV risk profile and outcome using the available exam records based on a joint multi-level imputation model. To validate our imputed values, we removed the observed CARDIA data with exam ages 18-30, MESA data with exam ages 50-59 and CHS data with exam ages 80-90. We then imputed the CV risk profile of these deleted values and compared imputed and observed values.

Results:
We included 41,387 participants (55% female, 30% African American, mean age 51 at baseline, avg follow-up time 20 yrs). In our validation sample, imputed CV risk factor levels were consistent with observed values at both younger and older ages (table) for BMI, SBP, DBP, glucose and total cholesterol. The prevalence of antihypertensive meds was 14.6% in the observed and 14.9% in the imputed data. Similar findings were shown for the prevalence of diabetes, current smoking, CVD events and death. Imputed prevalence of lipid-lowering meds was lower than observed rates (5% vs 12%).

Conclusions:
This synthetic cohort approach provides valid and unbiased estimates of CV risk factors across the lifespan. Future studies using this synthetic cohort can provide novel insights into the origins and accumulation of CVD.
Abstract P198: Racial Disparities in Cardiovascular Outcomes in REGARDS Persist After Using Inverse Probability Weighting to Account for Missing Data
Authors: Long D. Leann , Howard George , Judd Suzanne , Manly Jennifer , McClure Leslie , Safford Monika , Glymour M. Maria , Katz Ronit
Published: July 2021

Introduction:
When data are missing, analysts often choose to perform ‘complete case’ analysis, restricting statistical analysis to those participants with all necessary fields completed. However, this analysis is subject to selection bias if those participants excluded are somehow inherently different from those included. One approach to address the potential selection bias is inverse probability weighting, where participants with complete data are weighted to reflect the original population. We compare estimated racial disparities in hypertension and left ventricular hypertrophy using complete cases to those estimates from inverse probability weighted analysis.

Methods:
The REasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled 30,183 participants aged 45+ between 2003 and 2007 to study racial and geographic differences in stroke and cardiovascular health. When the second in-home visits were conducted, 18% (5542) of participants had died and 23% (7071) of participants had withdrawn. For the baseline population, the probabilities of being a complete case are estimated through logistic regression models using baseline characteristics. These predicted probabilities are inverted to create the weights used in statistical analysis, such that the complete participants are weighted to represent the enrolled population. Through logistic regression, we estimate the association between race and hypertension and left ventricular hypertrophy at the second in-home visit for complete data and compare these results to the results from inverse probability weighted analysis. All models are adjusted for sex, age and region.

Results:
The logistic models for dropout and death have low and moderate predictive abilities (c-statistics 0.602 and 0.811, respectively). For incident hypertension, the estimated odds ratio comparing blacks to whites differs little between the complete case (1.87 (1.66, 2.10)) and the weighted (1.83 (1.61, 2.09)) analysis. For left ventricular hypertrophy, the estimated odds ratio comparing blacks to whites changes little from the complete case analysis (1.54 (1.32, 1.79)) to the weighted analysis (1.45 (1.21, 1.74)).

Discussion:
Estimated racial inequalities in the odds of incident hypertension and left ventricular hypertrophy were similar in the complete case and inverse probability weighting analyses, indicating little evidence of selection bias in the estimation of racial inequalities for these outcomes.
Abstract P230: Metabolically Healthy Obesity and QT interval. The Polish Norwegian Study
Authors: Vaidean Georgeta , Manczuk Marta , Magnani Jared W
Published: July 2021

Introduction:
Obesity has been linked to increased risk of sudden cardiac death and ventricular arrhythmia. Whether the metabolically healthy obese phenotype is a benign condition, is debatable and few studies examined its ventricular repolarization profile.

Purpose:
To examine the association of metabolically healthy/unhealthy obesity phenotypes with prolonged corrected QT (QTc) interval in a large population-based study.

Methods:
Cross-sectional data from an ongoing cohort study in Poland. Data was collected using a standardized protocol. The QT intervals were obtained from digital standard 12-lead resting ECG and were corrected for heart rate by Bazett’s formula. Plasma lipids and glucose were measured in a fasting state. After excluding drugs known to affect the QT interval (antiarrhythmics, digoxin, antipsychotics), the analytic sample size was 11068 participants, ages 45 to 64 years. Based on the presence of obesity (BMI ge 30 kg/ m
2
) and metabolic syndrome (per the AHA/NHLBI harmonized definition), we defined four phenotypes: metabolically healthy non-obese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Multivariable linear and logistic regression models were used for analyses.

Results:
The prevalence of the 4 phenotypes was: MHNO: 51.34%, MUNO: 18.07%, MHO: 10.07%, MUO: 20.52%. The prevalence of an increased QTc interval (greater than >430ms in men/450ms in women) was 14.28%, and the prevalence of a highly prolonged QTc interval (greater than 450ms in men/470ms in women) was 5.2%. The age- and sex-adjusted mean QTc across the 4 phenotypes was: MHNO: 417.05ms (416.39- 417.71; MUNO: 418.82 ms (417.71-419.92); MHO: 420.46 ms (418.99 -421.93); MUO: 422.45 ms (421.41-423.49). The age- and sex adjusted odds (OR, 95% CI) of an increased QTc interval (greater than 430/450ms in men/women) were increased in MUNO (1.11, 0.96-1.29), MHO (1.44, 1.20-1.72) and MUO (1.47, 1.28-1.69), compared to MHNO phenotype. These estimates were minimally attenuated after additional adjustment for prevalent CVD, LVH on ECG, smoking, alcohol intake, physical activity and education: MUNO (1.10, 0.94-1.28), MHO (1.45, 1.21-1.73) and MUO (1.44, 1.26-1.66). We did not detect effect modification by sex. We obtained similar results in subgroup analyses restricted to those without diabetes and after excluding those with third degree atrioventricular blocks or conduction abnormalities with QRS>120ms.

Conclusion:
Both metabolically healthy- and non-healthy obese phenotypes had a higher likelihood of an increased/borderline QTc interval compared to the MHNO phenotype. Our study furthered our understanding of ventricular repolarization as reflected in the QTc interval, in the setting of different obesity phenotypes.