bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P255: Genetic Variation in Chromosome 8p23 is Associated With Sedentary Behavior in Humans
Authors: Rankinen Tuomo , Sarzynski Mark A , Sternfeld Barbara , Sidney Steve , Bouchard Claude
Published: July 2021

Sedentary behavior, usually quantified as sitting time, has been shown to be associated with several adverse health outcomes, even among individuals who meet the current recommendations for physical activity. Both twin and family studies have shown that sedentary behavior aggregates in families and is a heritable trait. However, little is known about genes and DNA sequence variants that contribute to propensity to be sedentary. The purpose of our study was to conduct a genome-wide association study to identify genomic regions and DNA sequence variants associated with sedentary time. A total of 67,530 Caucasians (56% female, mean age 62.1 years [SD 12.5]) from the Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) cohort were used for the discovery analyses. Other RPGEH ethnicities (African-Americans: N=2,500; East Asians: N=6,300; Hispanics: N=8,800) were used for replication studies. Information on daily sitting time outside of work was obtained by a questionnaire. A custom panel of 657,184 autosomal single nucleotide polymorphisms (SNPs) was genotyped using Affymetrix platform. Associations between sedentary time (dichotomized; cases 3 hours or more, controls less than 3 hours per day) and the SNPs were tested with PLINK logistic model using age, sex, BMI and admixture principal components as covariates. The strongest evidence of association was detected on chromosome 8p23.1. A total of 24 SNPs within a 1.34 Mb region were associated with sedentary time at genome-wide significance level (p<5x10
-8
), with SNP rs11774552 showing the peak association (OR=0.924, p= 1.7x10
-12
). Sex-specific analyses confirmed that the associations were present both in men and women. The same SNPs were not associated with sedentary time in other ethnicities. However, SNP rs28754712, which is located in the immediate vicinity (+456 bp) of rs11774552, showed a significant association with sedentary time (OR=0.795, p=1.2x10
-3
) in African-Americans. In summary, our results provide the first evidence of genomic region and DNA sequence variants associated with sedentary behavior in humans. If confirmed in additional replication studies, these findings will advance our understanding of biological mechanisms contributing to propensity to be sedentary.
Abstract P264: Healthy dietary interventions and Lipoprotein (a) plasma levels: Results from the Omni Heart Trial
Authors: Haring Bernhard , Wyler von Ballmoos Moritz C , Appel Lawrence J , Sacks Frank M
Published: July 2021

Background:
Increased lipoprotein (a) [Lp(a)] levels are associated with atherosclerotic cardiovascular disease. Plasma Lp(a) levels are mainly genetically determined by race with levels higher in blacks compared to whites. Dietary interventions have been reported to alter Lp(a) but evidence is sparse. No study has evaluated the effect of macronutrient composition on Lp(a) concentration and racial differences.

Objective:
To compare three healthy, DASH-style dietary interventions differing in macronutrient content on the effect on Lp(a) concentrations in blacks and whites.

Design:
Secondary analysis of a randomized, 3-period feeding study including 152 (88 blacks/64 whites) individuals. Participants were given DASH-type healthy diets rich in carbohydrates [Carb], in protein [Prot] or in unsaturated fat [Unsat Fat] for 6 weeks each. Plasma Lp(a) concentration was assessed at baseline and after each intervention.

Results:
At baseline, median Lp(a) plasma level was 18 mg/dl overall, 9 mg/dl in whites and 28.5mg/dl in blacks. The Unsat Fat diet lowered Lp(a) by 1.2mg/dl (95% CI, -0.3,-2.2; p= 0.015) compared with the Carb diet, and by 2.7 mg/dl (95% CI, -1.7,-3.7; p<0.001) compared with the Prot diet (Table). The effects on Lp(a) of the controlled diets tended to be greater in blacks than whites, especially the reduction in Lp(a) on the Unsat compared to the Prot diet (-3.7 in blacks vs. -1.0 mg/dl in whites, P=0.008). On self-selected diet (prior to feeding) or intervention diets, blacks had higher mean Lp(a) than did whites.

Conclusions:
Compared to diets rich in carbohydrate or protein, a DASH-type diet high in unsaturated fat lowered Lp(a). These changes were greater in blacks compared to whites. Our results highlight a potential means to reduce racial disparities in CVD.

Table: Differences in Lp(a) concentration (mg/dl) between study diets by ethnicity
Abstract P266: Change in the Association Between Serum Lipids and Coronary Heart Disease among Middle-Aged Adults: Observational Data from the Pre- and Post-Statin Era.
Authors: Colantonio Lisandro D , Bittner Vera , Levitan Emily B , Kent Shia , Safford Monika M , Muntner Paul
Published: July 2021

Dyslipidemia is a major risk factor for coronary heart disease (CHD) and is usually treated with statins. Few observational studies have examined associations between lipids and CHD in the era of widespread statin use. The objective of the current analysis was to contrast the association between serum lipids and incident coronary heart disease (CHD) among middle-aged adults before and after statin use became widespread.

Methods:
We analyzed data from 14,590 Atherosclerosis Risk In Communities (ARIC) study participants who were recruited in 1987-1989 (pre-statins), and 13,196 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants (9,578 not taking statins) who were recruited in 2003-2007 (post-statins). Our analysis was restricted to participants 45 to 64 years of age without a history of CHD at baseline. Total and HDL cholesterol (HDL-C) and fasting triglycerides (TG) were measured at baseline and used to calculate LDL-C, non-HDL-C, total-to-HDL-C ratio and total-to-TG ratio. Each lipid parameter was categorized into four levels based on REGARDS quartile cut-points.

Results:
In ARIC, participants with higher LDL-C were more likely to have diabetes and use antihypertensive medication, whereas these CHD risk factors were progressively less common at higher LDL-C in REGARDS participants not taking statins. Over a maximum 7 years of follow up, 513 and 278 incident CHD events occurred among ARIC and REGARDS participants, respectively. After multivariable adjustment, higher categories of each lipid marker (lower categories of HDL-C) were associated with a higher hazard ratio (HR) for CHD among ARIC participants, but not among REGARDS participants not taking statins (figure). No association between lipid markers and CHD was observed among REGARDS participants taking statins.

DISCUSION:
The current analysis suggests that the widespread preferential use of statins among high risk individuals may have obscured the association between lipids and incident CHD.
Abstract P267: Cardiorespiratory Fitness Does not Attenuate the Association Between Adiposity and Blood Lipids in Children and Adolescents: Project HeartBeat! (1991-1995)
Authors: Folorunso Olakunle A , Shay Christina M , Ding Kai , Sisson Susan B , Magzamen Sheryl L , Day R S , Hallman D M , Labarthe Darwin R
Published: July 2021

Background:
Higher levels of adiposity are associated with unfavorable blood lipid levels in pediatric populations. However, little is known about the extent to which cardiorespiratory fitness attenuates this association.

Methods:
Participants ages 8-16 years (n=256) with valid measures of blood lipids, cardiorespiratory fitness (CRF) and adiposity were examined from Project Heartbeat!, a longitudinal study of cardiovascular risk factors among children and adolescents. CRF was assessed by maximum oxygen uptake: VO
2max
(mL/kg/min) measured during treadmill testing and adiposity was assessed by percent body fat (PBF) estimated using sex-specific formulas incorporating bioelectric impedance and six-site skinfold measures. Fasting blood lipids included total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). Linear regression was used to quantify cross-sectional associations between CRF and adiposity with blood lipids by sex and pubertal status (Tanner stage 1 vs. 2-5).

Results:
When examined individually, higher PBF and lower VO
2max
were associated with more favorable levels of blood lipids in pre-pubertal boys, however, the associations were not consistent across all sex/puberty groups (Table 1). In multivariate models where both VO
2max
and PBF were included, PBF remained significant for all blood lipids in pre-pubertal boys but only with TC and LDL-C in pre-pubertal girls. Among pubertal participants, only TG remained significantly associated with PBF when similarly accounting for VO
2max
.

Conclusions:
Prior to the onset of puberty, higher adiposity is independently associated with more favorable levels of TG and HDL-C in boys and TC and LDL-C in girls even after accounting for CRF. During puberty, the majority of these associations are greatly attenuated, which further highlights the complexities associated with examining correlates of blood lipids in developing children.
Abstract P269: Fasting HDL-C Partially Explains the Association of Postprandial Triglycerides and Coronary Artery Disease Detected by Computed Tomography Angiography
Authors: Staniak Henrique L , Filho Wilson , Miname Marcio , Benseñor Isabela , Lotufo Paulo , Sharovsky Rodolfo , Rochitte Carlos Eduardo , Bittencourt Marcio , Santos Raul
Published: July 2021

Background:
Postprandial triglycerides (TG) are associated with severe coronary artery disease (CAD), though the underlying mechanisms remain unclear. In this study, we have investigated the effect of clinical and laboratory parameters on the association between postprandial TG and CAD detected by coronary computed tomographic angiography (CTA).

Methods:
We enrolled 130 patients without previous diagnosis of CAD, (85 with CAD detected by CTA and 45 without); who underwent an oral fat tolerance test. We studied the postprandial lipemia measuring TG from time 0h, 2h, 4h and 6h to analyze the TG change over time. We used a longitudinal multivariable linear mixed effects model with the log of the TG (lnTG) as the primary outcome due to non normal distribution of TG. To evaluate the effect of the other parameters on the longitudinal changes in the TG, each variable has been individually included in the model to evaluate for changes in the lnTG over time.

Results:
Patients with CAD were older (56.5 ± 6.8 vs 50.4 ± 7.1 years, p<0.001), predominantly male (68.2% vs. 37.8%, p< 0.001) and had lower fasting HDL-C (49 ± 14 vs. 54 ± 12 mg/dL, p=0.015). The majority of individuals with CAD had non-obstructive atherosclerosis (65.6%). The patients with CAD had similar fasting lnTG (2.08 ± 0.20 vs. 2.02 ± 0.18, p=0.069)and increase in lnTG from 0 to 4 hours (p=0.54), but a significantly slower clearance of postprandial lnTG change from 4h to 6h (p=0.040) compared to patients without CAD. Interestingly, although age, gender, fasting glucose, and abdominal circumference did not influence those findings, after the inclusion of fasting HDL-C in the model, the change in the lnTG clearance after 4 hours did not reach statistical significance (Table 1).

Conclusion:
Patients with CAD had an impaired postprandial metabolism, due to a delayed TG clearance. This association was partially explained by the lower fasting HDL-C. Thus, the contribution of postprandial TG metabolism to the development of CAD, may be partially, related to the low fasting HDL-C concentrations.
Abstract P272: Cumulative Risk for Hypercholesterolemia In Middle-Aged White and African American Men and Women
Authors: Wilkins John , Ning Hongyan , Intwala Sunny , Lloyd-Jones Donald M
Published: July 2021

Introduction:
The long-term risks for incident hypercholesterolemia (HC) have not been quantified by sex in AA men and women.

Methods:
We conducted an individual-level pooled analysis of participants from The Atherosclerosis Risk in Communities and The Framingham Offspring Studies with baseline prevalence and follow-up data on HC and lipid-lowering medications. Hypercholesterolemia was defined as a total cholesterol level > 240mg/dL or the use of lipid-lowering medications on ≥2 consecutive examinations. We quantified the long-term risk for HC using competing risk models to assess incidence from age 55 years (y) though 70y to 85y, adjusted for baseline prevalence and competing risks of death. Analyses were stratified by race and sex.

Results:
There were 11,341 White and 2,828 AA participants (55% and 63% female, respectively) included in the analysis. At an index age of 55y the mean (SD) BMIs in White and AA (men/women) respectively were: 27.8(4.1)/26.9 (5.6) and 28.1(5)/31.3(6.7)Kg/m2. Baseline prevalence rates of HC were not substantially different across race and sex groups. White women had the highest risks for the development of HC, with long-term risks as high has 63% through age 80y. AA men had the lowest risks for hypercholesterolemia through at 70y.

Conclusions:
The burden of HC is substantial across all race groups, with the highest risks found in white women. Aggressive surveillance and early preventive efforts against HC are needed across all race and sex groups.
Abstract P281: A Novel Mutation in Adiponectin Receptor 1 Contributes to Cardiac Hypertrophy and Cardiometabolic Dysregulation
Authors: Kang Soojeong , Dhandapany Perundurai S. , Kunnoth Sreejith , Muthusami Uthiralingam , Thangaraj Kumarasamy , Hajjar Roger , Rathinavel Andiappan , Lebeche Djamel
Published: July 2021

Adiponectin, an adipocyte-derived cytokine, is known to influence cardiac remodeling and to suppress pathological cardiac growth and diabetes-induced disorders. Disruption of adiponectin or its receptor AdipoR1 has significant effects on cardiomyocyte hypertrophy and myocardial metabolism signal transduction. We recently identified a novel mutation in the AdipoR1 gene among 126 hypertrophic cardiomyopathy patients, including two family members with diabetes. Our screening identified a G>A transition at 146th position that replaced the amino acid valine (GUG) into methionine (AUG) (V146M). The consequences of this mutation on cardiac function and metabolism are not known. Here, using adenoviral gene delivery system, we found that Ad.V146M increased cell size, protein synthesis, induced expression of hypertrophic gene markers and increased serine phosphorylation of insulin receptor substrate 1 (IRS1) compared to control Ad.βGal or wild type AdipoR1 (Ad.AR1) in cultured cardiomyocytes. We also discovered that p38 and mTOR were activated by AdipoR1 mutant, but not wild-type. Pharmacological inhibition of p38 (SB203580) and mTOR (rapamycin) reversed the Ad.V146M-induced hypertrophic responses. Adiponectin is also known to promote the uptake and oxidation of fatty acid and glucose through AR1 in cultured myocytes. Recent studies suggest that p38 acts as an essential mediator in regulating adiponectin-induced glucose uptake and fatty acid oxidation in C2C12 myocytes, and the serine phosphorylation of IRS1 at S636/639 is known to be mediated by mTOR pathway. AdipoR1 mutant significantly deceased glucose uptake, facilitated palmitate uptake and repressed insulin responses. Interestingly, inhibition of p38 and mTOR pathways significantly attenuated the effects of Ad.V146M on the expression of genes involved in lipid oxidation (peroxisome proliferator-activated receptor α, PPARα; carnitine palmitoyltransferase 1, CPT1) or glucose utilization (phosphofructokinase, muscle, PFK-M), respectively. Intriguingly, these findings were confirmed in vivo in cardiac-specific transgenic mice overexpressing AdipoR1 mutant. Taken together, these results suggest that a mutation in the AdipoR1 may contribute to the development of cardiomyopathy via alterations in mTOR/p38 pathways and cardiac metabolism.
Abstract P282: Depressive Symptoms Are Associated with Worsening of Arterial Stiffness With Mental Stress
Authors: Pimple Pratik M , Shah Amit J , Rooks Cherie , Bremner J. Douglas , Ibeanu Ijeoma , Karohl Cristina , D’Marco Luis , Raggi Paolo , Vaccarino Viola
Published: July 2021

Introduction:
Arterial stiffness is an important marker of cardiovascular risk which worsens with acute mental stress. Psychological conditions, particularly depression, have been linked to recurrent cardiac events and death, but the mechanisms are unclear. We examined whether depressive symptoms, anxiety and anger worsen arterial stiffness induced by mental stress.

Methods:
In 81 subjects with a history of MI in the previous 6 months, we used the SphygmoCor® Pulse Wave Velocity system at rest and 60 minutes after a standardized psychological stress (via speech task) and after a conventional physical (exercise or pharmacological) stress test. The central augmentation index (CAIx) was derived by pulse wave analysis software and the difference between CAIx after each stress condition and the respective resting phase was calculated. Depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II), state and trait anxiety with the State-Trait Anxiety Inventory (STAI), and state and trait anger with the State-Trait Anger Expression Inventory (STAXI-II). Linear regression models were used to model the association between change in CAIx with each stress (dependent variable) and BDI total score, anxiety and anger subscales as individual predictors, adjusting for potential confounding factors.

Results:
Forty-one subjects were ≤ 50 years of age, 41 were female and 46 were non-white. Systolic and diastolic blood pressure and heart rate significantly increased in response to mental stress (48 ± 23 and 30 ± 13 (mmHg), and 28 ± 18 (bpm); p<0.001 for each), but this increase was not related to psychosocial risk factors. None of the psychosocial risk factors were associated with baseline/resting phase CAix. In unadjusted analysis, BDI total score, trait anger and trait anxiety were all significantly associated with an increase in CAIx with mental stress. After adjustment for demographic factors, CAD risk factors, CAD severity, and hemodynamic changes induced by mental stress, each 1-point increase in the BDI total score was associated with 0.34 units increase in mental stress-induced change in CAIx (95% CI: 0.10 - 0.57, p=0.005). The association did not persist for trait anger and anxiety, however. None of the psychological factors were related to changes in CAIx induced by physical stress.

Conclusion:
Higher depressive, but not anxiety or anger symptoms are associated with an increase in arterial stiffness during mental stress. This finding may provide a mechanistic link for the association between depression and adverse cardiovascular outcomes.
Abstract P299: Narrowing Of Retinal Arterioles Is Associated With Increased Risk Of Incident Microalbuminuria
Authors: Hirayama Atsushi , Kawasaki Ryo , Konta Tsuneo , Watanabe Tetsu , Shibata Yoko , Fukao Akira , Kubota Isao
Published: July 2021

Microalbuminuria is known as an independent risk factor of cardiovascular diseases. Retinal vessel caliber size is also linked to increased risk of stroke and coronary heart disease. Although there are shared anatomical and physiological characteristics between renal and retinal microvasculature, longitudinal study between renal and retinal microvasculature to illustrate temporal association is scarce.

To determine whether retinal vessel caliber size at baseline associated with incidence of microalbuminuria in a general Japanese population study of the Takahata study.

We conducted a community-based longitudinal cohort study, the Takahata study (Yamagata, Japan). In 2004-6, 711 individuals without microalbuminuria were identified at baseline examination. Microalbuminuria was defined as the urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Retinal vessel caliber was determined using semi-automatic software (IVAN, Wisconsin University) as the central retinal artery and vein equivalent (CRAE and CRVE). We analyzed the association between baseline retinal vessel calibers and cumulative incidence of microalubuminuria using multivariate logistic regression model adjusting for age, sex, body mass index, systolic and diastolic blood pressure, Hemoglobin (Hb) A1c, UACR at baseline, and smoking.

During follow-up period (mean, 6.7 years±0.6), 45 subjects (6.3%) developed microalbuminuria. In univariate logistic regression analysis, Age (per 1 years increase, Odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.01-1.09), HbA1c (per 1% increase, OR: 2.08, 95%CI: 1.28-3.36), UACR at baseline (per 1 mg/g increase, OR: 1.11, 95%CI: 1.06-1.16) were associated with increased risk of developing microalbuminuria. In multivariate logistic regression analysis, HbA1c (OR: 1.86, 95%CI: 1.07-3.24), UACR at baseline (OR: 1.09, 95%CI: 1.04-1.15), and CRAE (per 1SD decrease, OR: 1.45, 95%CI: 1.00-2.12) were significantly associated with increased risk of incident microalbuminuria.

In conclusion, narrowing of retinal artery seems to be precedent to the incidence of microalbuminuria in this adult population-based cohort.
Abstract P308: Lower Neighborhood Socioeconomic Status is Associated with Higher BNP and Prolonged QTc Intervals among Heart Failure Patients with Preserved Ejection Fraction
Authors: Allen Norrina B , Badon Sylvia , Shah Sanjiv J
Published: July 2021

Background:
Prior studies have shown that high B-type natriuretic peptide (BNP) levels and prolonged QTc intervals are associated with increased mortality, particularly sudden cardiac death, among heart failure (HF) patients. Whether neighborhood socioeconomic status (nSES) impacts BNP or QTc remains unknown.

Methods:
This study included consecutive patients enrolled from the outpatient clinic of the Northwestern Heart Failure with Preserved Ejection Fraction (HFpEF) Program from June 2007 to November 2010 after hospitalization for HF and followed through May 2011. Patients’ residential addresses were geocoded to identify their census tract of residence. Census 2000 data were used to create a single, summary score of nSES based on residential income, education and employment for each census tract and was divided into tertiles. Outcomes included post-discharge BNP and QTc, obtained within 1 month after HF hospitalization during the outpatient HFpEF clinic visit GEE models were used to examine the association between nSES and BNP and QTc adjusting for age, race, gender, NYHA class, blood pressure, obesity, smoking, glucose, eGFR, and comorbidities.

Results:
Among the 368 HFpEF patients, 37.0% were female, 50.5% White, avg. age was 64.8 yrs and 45.9% had NYHA class 3+. Higher nSES was significantly associated with lower BNP levels and shorter QTc intervals (Table). The adjusted BNP levels per nSES tertile were 718 pg/mL (±101.4) for the lowest nSES tertile, 508 pg/mL (± 75.3) for the intermediate nSES tertile and 454.2 pg/mL for the highest nSES tertile. Simlarly, QTc interval decreased with increasing tertile of nSES from 464.1 ms (± 5.7) in the lowest nSES tertile to 457.2 ms (± 5.8) and 448.9 ms (± 5.4) for the intermediate and highest tertiles, respectively.

Conclusion:
Low nSES is associated with increased BNP levels and a longer QTc interval in HFpEF patients. These findings may explain the association of nSES with higher rates of sudden cardiac death and worse outcomes among HF patients in disadvantaged neighborhoods.
Abstract P309: Foreclosure Rates During Economic Recession and Cardiovascular Health: Paradoxical Results from the Survey of the Health of Wisconsin
Authors: Nieto F. Javier , Malecki Kristen M , Tapia Granados José Antonio
Published: July 2021

Contrary to conventional wisdom, research has shown that economic recessions are associated with decreases in mortality and, conversely, mortality increases during times of economic expansion. Most of these studies are based on unemployment data and few have examined morbidity data as outcomes.

The present analyses used data from the 2008-11 waves of the Survey of the Health of Wisconsin (SHOW) to study the association between county rates of foreclosures during the 2009-10 economic recession and cardiovascular health. SHOW is based on a probabilistic statewide sample of adult (21-74 years old, n = 1,643) residents in Wisconsin. The cardiovascular health (CVH) index was defined using a combination of “ideal or intermediate” levels of seven risk factors and health behaviors (body mass index, cholesterol, glucose, diet, physical activity, blood pressure and smoking). Foreclosure rates for the 72 counties of Wisconsin were obtained from commercially available data for the period 2000-2012. Other covariates included Census-based neighborhood socioeconomic status (SES), individual-level SES, and measures of mental wellbeing (using the Depression, Anxiety and Stress Scale, DASS).

Of the 1,643 participants, 1.0% had ideal CVH (“ideal” in all 7 metrics) and 25.6% had overall “good” (ideal or intermediate) CVH (at least one “intermediate,” but no “poor” in any of the 7 components). The prevalence of good CVH was higher in younger, white, higher education and income participants, and those living in suburban areas. Participants recruited from counties in the top quartile of foreclosure rates in 2009 (at the peak of the economic recession) had higher prevalence of good CVH. Compared to the lowest quartile, the demographics-adjusted odds ratio of good CVH were 2.0 (95% CL 1.4-2.9), 2.1 (1.4-3.1) and 2.7 (2.8-3.9) for the 2nd, 3rd, and 4th quartile of foreclosure rates, respectively (p-trend=0.003). Additional adjustment of individual/county SES and measures of individuals’ mental health did not materially change these results. These paradoxical associations were not present when using foreclosure data from years preceding the recession as primary exposures (2000-07).

In conclusion, county foreclosure rates, a marker of the severity of the 2009 economic recession in local communities, appears to be associated with better cardiovascular health. These results are consistent with previous research linking recessions with better health outcomes. However, interpreting these results as meaning that foreclosures improve health at the individual level might be subject to ecological fallacy. Additional analyses controlling for unmeasured confounders and possible selection biases are needed to further understand the significance of these findings.
Abstract P318: Risk factors for 10-year coronary artery calcium progression in the Multi-Ethnic Study of Atherosclerosis
Authors: Gassett Amanda J , Sheppard Lianne , McClelland Robyn L , Kronmal Richard A , Budoff Matthew J , Blaha Michael J , Kaufman Joel D
Published: July 2021

Coronary artery calcium (CAC) progression has previously been observed to predict coronary events above and beyond its association with baseline CAC. Prior studies show associations between CAC progression and risk factors, but were limited by short follow-up or restriction to individuals with advanced disease. We examined the relationship between risk factors for clinical events and the progression of CAC in MESA, a prospective cohort study.

Participants were 6810 adults without CVD at recruitment in 2000-2002. Agatston scores for extent of calcification were assessed 1-4 times (mean 2.5) over a 10-year period with interim exams spaced at approximately 2-4 years. Mean follow-up time for those with at least 2 scans was 5.0 years. An innovative approach to mixed effects models jointly modeled the associations between risk factors and CAC both at baseline and with CAC progression rate. This method is less biased than controlling for baseline CAC, since the same risk factors are associated with both baseline and progression. Hence, time-varying factors can adjust progression rate, and data from participants with varying follow-up time and number of measurements_even those measured only at baseline_are incorporated.

Mean CAC progression rate was 25 CAC units/year. All models were adjusted for age, sex, site, and race/ethnicity. Strong effects were observed for age, male sex, hypertension, and diabetes. Effects for statins likely reflect poor health status, rather than a causal effect of medication. Simultaneous adjustment for all risk factors produced similar results except the effect of statin use was not observed. See table for estimates and confidence intervals.

In conclusion, CAC progression is associated with risk factors for clinical coronary events, confirming that processes involved in CAC progression mirror development of clinical atherosclerosis. The methods applied for the analysis of repeated continuous noninvasive measures of atherosclerosis extent can also be applied to evaluating novel risk factors.
Abstract P321: Coronary Artery Remodeling and Subclinical Atherosclerosis: the CARDIA study
Authors: Carr John J , Terry James G , Yeboah Joseph , Ge Yaorong , Lovato James F , Polonsky Tamar S , Reis Jared , Goff David , Liu Kiang , Jacobs David
Published: July 2021

Atherosclerosis related inflammation and plaque result in expansive remodeling of the coronary artery, a finding associated with plaque rupture and clinical events. The extent of expansive coronary remodeling in adults prior to the development of clinical disease is largely unknown. We tested the hypothesis that middle-aged adults who have subclinical coronary artery disease also have larger coronary artery diameters.

Methods:
Submillimeter thin slice, non-contrast cardiac CT images were obtained in 1197 black and white men and women in the Coronary Artery Risk Development in Young Adults (CARDIA) Study during the year 25 examination (2010-2011, mean age 50 years). Average coronary artery diameter(mm) and cross sectional area (mm2) were measured sequentially along the length of each vessel and averaged for the left main (LM) and proximal circumflex (LCX), left anterior descending (LAD), and right coronary (RCA) arteries. Presence/absence of coronary artery calcifications [CAC (0 versus >0 AU)] was measured independently. Multivariable linear regression models were used to examine the association of CAC with artery size.

Results:
Coronary diameter was larger in blacks compared to whites (p<0.05) and in men compared to women (p<.0001) following adjustment for age and study center. Presence of CAC was associated with larger diameter coronary arteries after adjustment for age, race, sex, education, height, and study center (Table, model 1). These associations remained following additional adjustment for established cardiovascular risk factors, with the exception of the left main segment (Table, model 2), and were similar for vessel area as for vessel diameter (not shown).

Conclusion:
Coronary arteries are larger in middle-age individuals with vs without CAC, supporting the hypothesis that atherosclerosis leads to expansive coronary remodeling. Coronary remodeling by non-contrast CT is a measure that may provide new information on cardiovascular risk and prediction of clinical cardiovascular events.
Abstract P325: Association of Risk Factors and Extra-coronary Atherosclerosis with Progression of Coronary Artery Calcification in the Framingham Heart Study
Authors: Onuma Oyere K , Pencina Karol M , Massaro Joseph M , Hoffman Udo , O'Donnell Christopher J
Published: July 2021

Background:
Progression of coronary artery calcification (CAC) is associated with future incidence of adverse cardiovascular disease. However, the interplay of CAC progression and atherosclerosis in different vascular beds has been less studied. We tested for the association of risk factors and baseline abdominal aortic calcification (AAC) with CAC progression in a large community cohort.

Methods:
We determined risk factors, baseline AAC/CAC, and CAC progression in a sample of 1994 asymptomatic white participants from the Framingham Heart Study (FHS) who had undergone serial CT scanning within an average of 6.1 years. The primary outcomes were: (a) incident calcification (CAC > 0) in participants free of CAC at baseline; and (b) absolute progression of CAC (CAC follow-up > CAC baseline) in participants with detectable baseline CAC. To test the effect of risk factors and baseline AAC/CAC on CAC progression, we employed multivariable stepwise logistic and linear regression models of CAC progression with/without AAC, adjusted for traditional CVD risk factors.

Results:
There were 1118 participants free of CAC at the baseline scan, of which 18.8% developed CAC in the follow-up scan. Of the 776 participants with detectable CAC at baseline, 84.9% developed progression of baseline CAC. In both subsets, AAC was a highly significant predictor of CAC incidence or progression, independent of other risk factors. Of note, the stepwise model including baseline AAC as a candidate for entry resulted in the same set of non-AAC predictors of CAC incidence or progression as the model without AAC. Table 1 displays the final logistic regression results for the cohort free of CAC. The AUC improved to 0.738 compared to an AUC of 0.722 for the model without AAC (p=0.002).

Conclusion:
AAC is a strong independent predictor of CAC progression determined by incident CAC and CAC progression. Addition of AAC to the model that predicts incident CAC improves discrimination in a cohort free of baseline CAC.
Abstract P326: Progression of ECG Abnormalities through Young Adulthood and Early Cardiovascular Events: Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Lloyd-Jones Donald M , Ning Hongyan , Liu Kiang , Lewis Cora E , Schreiner Pamela J , Sidney Stephen X , Huffman Mark D , Soliman Elsayed Z
Published: July 2021

Background:
In older adults, ECG abnormalities are associated with significant independent risk for cardiovascular disease (CVD). However, the progression of ECG abnormalities from young adulthood to middle age and the implications of ECG progression as a risk marker for premature CVD events are poorly described.

Methods:
CARDIA is a NHLBI-funded longitudinal cohort study of black and white men and women aged 18-30 years at baseline (Year 0) in 1985. We included all CARDIA participants (ppts) who had resting 12-lead ECGs performed at the Year 0, 7 and 20 examinations. We classified ppts into one of 3 strata based on ECG findings (Minnesota code normal, minor, major) across time: 1) Always Normal at all 3 exams; 2) baseline minor or major abnormalities with Regression/No Progression over time; or 3) Progression of ECG from normal to minor or major, or minor to major, over time. We used Cox proportional hazards models to assess risk for adjudicated incident CVD events (MI, stroke, CHF) by ECG stratum during 25 years’ follow up.

Results:
There were 2193 ppts: 63.0% were Always Normal, 14.2% had Regression/No Progression, and 22.8% showed Progression. Those with Progression were more likely to be black and to smoke and had a slightly higher BMI. Baseline ECG abnormalities (major or minor) were not associated with increased risk for CVD. Among the Always Normal, Regression/No Progression and Progression groups, CVD incidence rates (per 1000 p-y) were 0.73, 0.13 and 1.85, respectively. In unadjusted models, those with Progression were 2.5 times more likely than those with Always Normal ECGs to develop incident CVD; these findings were attenuated by adjustment for demographics and clinical risk factors (Table). Those with Regression/No Progression were at lower risk.

Conclusions:
Progression of ECG findings from normal to abnormal or from minor to major abnormalities during young adulthood may be a useful marker of risk, identifying those destined to develop premature CVD events.
Abstract P332: Framingham Risk Score to Predict Subsequent Coronary Artery Calcification in a Young Adult Population
Authors: Pu Jia , Vanness Dave , Johnson Heather , Kreling David , Young Henry , Chewning Betty
Published: July 2021

Introduction:
Coronary artery calcification (CAC) has been identified as an independent predictor of coronary events, suggesting the potential use of CAC for risk assessment in asymptomatic individuals. However, ionizing radiation exposure associated with CAC CT scans remains a concern. If elevated risk for developing subclinical cardiovascular disease (CVD) could be identified based on less invasive risk assessment, such as the Framingham risk score, intensified prevention and screening services could be provided to this targeted population.

Hypothesis:
This study aims to assess the association between the Framingham risk score in early adulthood and subsequent subclinical CVD measured by CAC. Additional risk factors including demographics, socioeconomic status and health behaviors were tested in terms of their capabilities to enhance prediction of subclinical CVD beyond the Framingham risk score.

Methods:
This study used the Coronary Artery Risk Development in Young Adults (CARDIA) data, with a total of 5,115 Caucasian and African American males and females. Information collected at examination year 10 was used to calculate the Framingham risk score. CAC was measured ten years later (examination year 20). Participants’ demographics, health behaviors (alcohol consumption, BMI, and exercise), socioeconomic status and medical needs at year 10 were identified as potential risk factors associated with the subsequent presence of CAC beyond the Framingham risk score. Multiple logistic regression was used to examine the adjusted association between CAC, Framingham risk score and proposed risk factors. Model comparison was estimated using the area under the receiver operating characteristic curve (AUC) and Akaike information criterion (AIC).

Results:
By year 20, CAC was present in 19% of the CARDIA population. The Framingham risk score in young adulthood was strongly associated with the subsequent presence of CAC ten years later, regardless of race and gender. Overall, 42% of the CARDIA participants with elevated Framingham risk scores at year 10 had CAC at year 20, compared to 16% of participants with normal scores. The Framingham risk score may underestimate the risk of CAC for males compared to females (Negative Predictive Value: 75% vs. 91%). Beyond the Framingham risk score, the subsequent presence of CAC was associated with being overweight or obese in all populations, at-risk alcohol consumption in African American males, and having high school level or lower education and financial hardship in African American females.

Conclusions:
Our findings support the potential use of the Framingham risk score as a screening tool for subsequent subclinical atherosclerosis in a young adult population. However, other gender-specific risk factors beyond the Framingham risk score such as obesity also may be important to better predict subclinical CVD risk, especially in male populations.
Abstract P335: The Number of Coronary Arteries with Calcified Plaque is Increased in Type 1 Diabetes
Authors: Duca Lindsey M , Kinney Gregory L , Alman Amy C , Snell-Bergeon Janet K
Published: July 2021

Adults with type 1 diabetes (T1D) have a higher risk for cardiovascular disease than non-diabetic (non-DM) adults. Coronary artery calcification (CAC) is a marker for subclinical atherosclerosis and the Agatston CAC score is the standard used today. The aim of our study was to look at the number of coronary arteries with calcified plaques to determine if more diffuse disease is present in adults with T1D for a given level of CAC. In addition, we examined risk factors associated with the number of coronary arteries with CAC, as this could be a novel way to risk-stratify individuals.

This study consisted of 1169 participants (T1D n=535 and non-DM n =634) with a mean ± SD age of 39±9 years. CAC was measured by electron beam CT (EBCT) using two scans performed five minutes apart and the maximum number of coronary arteries with CAC was used in the analysis. CAC lesions were determined in the left main, left anterior descending, circumflex, and right coronary arteries, with a maximum number of arteries with CAC ranging from zero to four. Chi square analysis was used to compare the number of coronary arteries with CAC by diabetes group. Subjects were then divided into categories based on their CAC score (>0-10, 10-100, >100-300, >300) and poisson regression was used in multivariable analysis to examine associated risk factors.

Adults with T1D had a significantly higher number of coronary arteries with CAC lesions than the non-DM adults (p > 0.0001). Among subjects with CAC>300 (n=58), adults with T1D had more coronary arteries with CAC than the controls (p = 0.03), but there were no differences in number of arteries with CAC among the other Agatston score categories. In multivariable analysis, HDL and LDL cholesterol, BMI, and hypertension were all independently associated with the number of coronary arteries with CAC lesions when adjusting for age, diabetes and CAC score (p<0.0001). There were no significant associations of number of arteries with CAC with smoking status or hemoglobin A1c. People with T1D were still significantly more likely to have more coronary arteries with CAC lesions than non-DM individuals after adjusting for the above factors.

In conclusion, T1D patients have more diffuse subclinical atherosclerosis, as indicated by a greater number of coronary arteries with CAC compared with non-DM adults. The number of coronary arteries with calcified plaque was independently associated with traditional CVD risk factors, even when accounting for CAC score. These findings are important because traditionally just the Agatston CAC score is used to determine CVD risk, but the number of coronary arteries affected could indicate how diffuse the subclinical artherosclerosis is prompt for aggressive treatment of traditional risk factors.
Abstract P336: Diabetes and Impaired Fasting Glucose are Associated with Pulse Wave Velocity in Older Adults: the ARIC Study
Authors: Loehr Laura R , Snyder Michelle , Selvin Elizabeth , Palta Priya , Pankow James , Griswold Michael , Heiss Gerardo , Wagenknecht Lynne
Published: July 2021

Introduction:
Arterial stiffness measured by pulse wave velocity (PWV) predicts cardiovascular disease and mortality. Diabetes and impaired fasting glucose (IFG) have been related to arterial stiffness in smaller studies. We assessed whether diabetes and impaired fasting glucose are associated with greater arterial stiffness measured by PWV in older adults, and to evaluate gender as a modifier.

Methods:
PWV data on 5,147 men and women with mean age of 75.5 years (range 66-90) examined in 2011-2013 by the Atherosclerosis Risk in Communities (ARIC) study were analyzed. Diabetes was defined as fasting glucose >126 mg/dl or on hypoglycemic agents and IFG as non-diabetics with fasting glucose 100-125 mg/dl. Technicians measured carotid-femoral (cfPWV) and brachial-ankle (baPWV) velocities at least twice using the Omron VP-1000 plus system (Colin Co., Ltd., Komaki, Japan). The mean of the last two available measurements was used. The path length for cfPWV was calculated by: path length (cm) = carotid to femoral distance (cm) - (suprasternal notch - carotid distance (cm)). Path length for baPWV was automatically calculated using height-based formulas. Multivariable linear regression was used to model the cross-sectional association between diabetes status and PWV. The multivariable association of age categories with PWV was evaluated for comparison to the effect size of diabetes.

Results:
Participants were 57% female, 20% African-American, and 73% hypertensive. Among them 1,354 had diabetes (26%) and 2,295 (45%) had impaired fasting glucose. After adjustment for age, race-center, gender, heart rate, hypertension, BMI, and smoking status (current, former and never), cfPWV was 87 cm/s higher on average for those with diabetes, and 21 cm/s higher for those with IFG, as compared to those free of diabetes or IFG. In comparison, a 4 year increase in age (after multivariable adjustment) was associated with 64 cm/s higher cfPWV among non-smokers without diabetes. Estimates for baPWV were smaller than those for cfPWV but showed a similar pattern. There was no significant interaction by gender (P >0.1).

Conclusion:
Diabetes and impaired fasting glucose are both associated with arterial stiffness in older adults. We estimate that the magnitude of the cross-sectional effect of diabetes on arterial stiffness is equivalent to 4 years of arterial aging.
Abstract P348: A Novel Antioxidant Score Independently Predicts CVD Mortality Better than Any Single Antioxidant: Longitudinal Data from the Third National Health and Nutrition Examination Survey (1988-94)
Authors: McCrea Cindy E , Vernarelli Jacqueline A , Kris-Etherton Penny M , Sauder Katherine A , West Sheila G
Published: July 2021

Despite the implication of oxidative stress in CVD development, neither blood levels of nor supplementation with any one individual antioxidant is consistently related to CVD incidence and death. Thus, the relationship between diet-derived antioxidants and CVD remains unclear. However, many analyses consider the predictive value of only a few antioxidant markers in isolation, which may not reflect overall antioxidant status. We developed an antioxidant score and tested the hypothesis that it would be a more robust predictor of CVD death than concentrations of single antioxidants in aging adults. Quintiles of 10 serum antioxidant concentrations (α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene, vitamins A, C, E, retinyl esters and selenium), collected at baseline from 7094 (weighted N = 58,875,272) adults aged 50+ years enrolled in the Third National Health and Nutrition Examination Survey (1988-1994) were used as predictors in a time-to-death analysis using Cox regression modeling. Forty-two percent (N=3695, weighted to 26189208) of the sample was deceased at 12-18 year follow-up, with 1362 deceased due to CVD. In models adjusted for known demographic, behavioral and biological risk factors, concentration quintiles of the individual antioxidants α-carotene, lycopene, selenium and retinyl ester were significantly associated with CVD death (ps for trend ranged from 0.015 to 0.042, HRs of quintile 1 vs 5 ranged from 1.34 to 1.52). A stepwise regression method was used to identify the best combination of candidate markers, and an antioxidant score was computed using only those 6 markers (vitamins C and E, lycopene, selenium, α and β-carotene). Quintiles of the antioxidant score were also significantly associated with risk of death (p for trend = 0.004, HR for Q1 vs. Q5 = 1.88) and in a more predictive manner than a score using all 10 antioxidants (p for trend = 0.016, HR for Q1 vs. Q5 = 1.69). After controlling for traditional risk factors, an antioxidant score including vitamins C and E, lycopene, selenium, α and β-carotene was more strongly associated with rates of CVD death than individual antioxidants in a large nationally representative sample of aging adults. An antioxidant score may more closely reflect oxidative status than measures of single dietary antioxidants, and therefore be more useful when assessing risk of CVD death.