bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P140: Maternal Smoking During Pregnancy and Risk of Congenital Heart Defects: A Systematic Review and A Meta-Analysis
Authors: Lee Laura , Lupo Philip
Published: July 2021

Objective:
Congenital heart defects (CHDs) are the most common group of structural malformations occurring in approximately 1 out of every 100 births. In addition to being the most prevalent birth defect, CHDs are the leading cause of death due to congenital malformations. Despite their prevalence and clinical importance, little is known about the etiology of CHDs, and there are currently no strategies for reducing their prevalence. Maternal smoking during pregnancy has been suggested as a potential risk factor for congenital heart defects, but the evidence is inconclusive. We systematically reviewed epidemiological studies and conducted a meta-analysis of the association between maternal cigarette smoking during pregnancy and the risk of CHDs among the infants.

Methods:
From a search of published literature through July 2011, we extracted 35 original human epidemiological studies that examined the association between maternal smoking during pregnancy (including a month before conception) and the risk of CHDs in offspring. Odds ratios (ORs) and 95% confidence intervals (CIs) were extracted from each study or calculated from available data, comparing smoking to no smoking during pregnancy. Summary risk estimates were also calculated for a number of CHDs subtypes (e.g., conotruncal defects, ventricular septal defects) using both fixed- and random-effects models. Random effects estimates were reported if there was evidence of heterogeneity among the studies. Effects of paternal and environmental smoking were not considered in our analysis.

Results:
We observed statistically significant positive association between maternal smoking anytime during pregnancy and the risk of CHDs (OR = 1.10; 95% CI: 1.01–1.19; number of cases (n) = 19,552). Additionally, we found a positive and significant association between maternal smoking and the risk of conotruncal defects in offspring (OR = 1.14; 95% CI: 1.03–1.26; n = 1953). Although not statistically significant, stronger elevated risks were observed for ventricular septal defects (OR = 1.11; 95% CI: 0.87–1.41; n = 4605) and atrial septal defects (OR = 1.34; 95% CI: 0.97–1.86; n = 565).

Conclusion:
Our systematic review and meta-analysis suggest maternal smoking is modestly associated with an increased risk of CHDs and some CHDs subtypes. This work adds to the existing body of evidence that implicated maternal smoking during pregnancy as a possible risk factor for CHDs. Future studies should consider evaluating paternal and environmental smoking exposure to better understand the relationship between smoking and CHDs.
Abstract P142: Smokers Can Lose Weight When They Quit Smoking
Authors: Pisinger Charlotta H , Toft Ulla , Jørgensen Torben
Published: July 2021

Background:
Smoking is one of the major risk factors of CVD. It is well-known that smokers increase weight when they quit smoking, and concomitant weight increase after smoking cessation may blunt beneficial effects of smoking cessation on e.g. glucose metabolism. However, not all smokers gain weight. To our knowledge, predictors of weight-loss after smoking cessation have not previously been investigated.

Methods:
in a large population-based study, the Inter99 study, 2,408 daily smokers were included at baseline. Out of these, 262 attended the five year follow-up and reported that they had not smoked for at least 12 months. Participants completed self-report questionnaires at baseline and follow-up. In multivariable logistic regression analyses we investigated predictors of weight-loss.

Results:
A total of 17.6% of the quitters had lost weight from baseline to 5 years follow-up. Neither sex, age, number of daily meals, energy intake, dietary quality, physical activity, alcohol consumption, nor change in physical activity or alcohol consumption from baseline to five year follow-up was associated with weight-loss at five year follow-up. Quitters with high education had significantly higher probability of weight-loss compared to quitters with low education (OR=3.88(1.04–14.50), p=0.044). Increasing BMI at baseline increased (OR=1.20(1.06–1.36), p=0.004) and increasing tobacco consumption decreased (OR=0.93(0.87–0.99), p=0.038) the probability of weight-loss. Furthermore, quitters who reported a healthier diet at five-year follow-up than at baseline had increased probability of weight-loss (OR=3.23(1.07–9.82), p=0.038). The mean weight-gain in quitters with normal baseline BMI was 5.66kg (±4.8), quitters who were overweight at baseline gained 5.32kg (±7.0) and quitters who were obese gained 1.98kg (±8.3), p=0.038.

Conclusion:
Weight-loss after quitting smoking is feasible and was achieved by about two out of ten quitters. High BMI, high education and low tobacco consumption at baseline and change to a healthier diet predicted weight loss in daily smokers who had quit for at least 12 months.

Discussion:
Obese smokers who had quit had the lowest weight-gain. A reason could be that normal-weight smokers are used to eat whatever they want, whereas obese smokers are used to focus on what and how much they eat. Obese smokers should definitely not be advised against quitting smoking in fear of further weight-gain. The large positive cardiovascular health effects of quitting overshadow the negative health effects of a small weight gain, and this study shows that weight-loss after smoking cessation is feasible, especially in obese smokers.
Abstract P150: Aldosterone Dysregulation Increases Cardiovascular Risk in African-American Youth
Authors: Harshfield Gregory A , Mulloy Evan , Beavers Melinda
Published: July 2021

Background:
The prevalence of hypertension and blood pressure-related target organ damage in African-Americans is among the highest in the world. We hypothesize that this is in part due to aldosterone dysregulation among African-Americans beginning in youth and leading to the early development of cardiovascular disease in this population. To begin to test this hypothesis, we examined ethnic differences in aldosterone regulation in normal, healthy adolescents.

Methods:
The subjects in this study were 145 (60 Caucasian, 85 African-American) healthy, normotensive youth aged 15–19 years. Testing was performed following 72 hours on a controlled sodium diet. Testing consisted of the collection of aldosterone, systolic blood pressure (SBP), and urinary sodium excretion (U
Na
V) during continuous water intake (400 ml total) over a 2 hour period. An echocardiogram was also performed to measure target organ changes. Log transformations were performed on aldosterone levels prior to analyses.

Results:
African-American compared to Caucasian subjects had higher casual SBP (109±10 v 104±10; p=.006) and relative wall thickness (0.32±.03 v 0.34±.04; p=.003). During the testing procedure African-Americans also had lower levels of aldosterone (4.78±.6 v 4.35±.6 pg/ml; p =.001). In the Caucasian subjects only, aldosterone was inversely correlated with U
Na
V (r=−0.427; p=.001) and U
Na
V was positively correlated with SBP (r=0.356; p=.001). The subjects were divided into those in the upper and lower quartiles of salt intake for further analysis. The interaction between race and salt intake was significant for aldosterone (F=7.173; p=.008). Caucasian subjects with high salt intake had lower aldosterone (4.56±.59 v 5.02±0.59 pg/ml). However, aldosterone levels did not differ by salt intake in African-Americans.

Summary and Conclusion:
African-American subjects did not show the expected associations between aldosterone and the pressure natriuresis relation. Furthermore, African-Americans on the high salt intake failed to suppress aldosterone. These findings are consistent with our hypothesis that aldosterone dysregulation in youth may lead to the early development of cardiovascular disease in Africans-Americans.
Abstract P171: Vitamin D and Cardiometabolic Risk Factors: The Jerusalem Perinatal Study
Authors: Moore Amy , Hochner Hagit , Sitlani Colleen , Williams Michelle A , Siscovick David S , Friedlander Yechiel , Enquobahrie Daniel A
Published: July 2021

Background:
Vitamin D, a pleotropic hormone, influences cellular and tissue functions that are potentially related to cardiometabolic risk. Vitamin D deficiency and insufficiency have also been related to cardiovascular diseases. However, relationships between vitamin D and cardiometabolic risk factors in young adults are not well-characterized.

Methods:
We examined associations of vitamin D with cardiometabolic risk factors among a subset of the Jerusalem Perinatal Study (JPS) population, a birth cohort of Jerusalem residents born between 1974 and 1976. Offsprings aged 30-35 years, sampled based on maternal pre-pregnancy body mass index (BMI) and offspring birth weight, and their mothers were recruited as part of the JPS-1 study. Data were collected using interviews and field physical examinations. Fasting blood specimens were obtained for vitamin D and biomarker (glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides) measurements. We used liquid chromatography-tandem mass spectroscopy to measure total vitamin D (25-[OH] D). Sample-weighted multiple regression models, adjusted for potential confounders, were used to examine associations, and determine coefficients and 95% confidence intervals.

Results:
Mean total vitamin D levels were 22.27ng/ml, 23.48ng/ml and 21.03ng/ml among all study participants, males (N=617) and females (N=588), respectively. Vitamin D levels were statistically different between males and females (p-value <0.001). Current smokers had higher vitamin D levels compared with non-smokers, even after adjustment for current BMI, ethnicity, occupation and other potential confounders (β=1.41, p-value= 0.039). Overall, higher vitamin D levels were associated with lower BMI (p-values 0.002) and lower diastolic blood pressure (p-values 0.011).

Conclusion:
Vitamin D is associated with cardiometabolic risk factors in young adults. The unexpected association between current smoking and higher vitamin D in our study needs replication and further investigation.
Abstract P172: Birth Weight, Maternal Pre-pregnancy Body Mass Index and Adulthood Vitamin D Levels: The Jerusalem Perinatal Study
Authors: Moore Amy , Hochner Hagit , Sitlani Colleen , Williams Michelle A , Siscovick David S , Friedlander Yechiel , Enquobahrie Daniel A
Published: July 2021

Background:
The intrauterine experience and pre-pregnancy maternal characteristics have demonstrated importance in the development of life course risk for chronic diseases. Vitamin D has been associated with several chronic diseases including cardiometabolic diseases. Whether offspring birth weight and maternal pre-pregnancy body mass index (BMI) are associated with adulthood vitamin D levels is unknown. Further, the role of adulthood BMI in these relationships is not clear.

Methods:
We examined associations of offspring birth weight and maternal pre-pregnancy BMI with offspring adulthood vitamin D levels among a subset of the Jerusalem Perinatal Study (JPS) population, a birth cohort of Jerusalem residents born between 1974 and 1976. Offspring aged 30-35 years, sampled based on maternal pre-pregnancy body mass index (BMI) and offspring birth weight, and their mothers were recruited as part of the JPS-1 study. Data were collected using interviews and field physical examinations. Fasting blood specimens were obtained for vitamin D measurements. We used liquid chromatography-tandem mass spectroscopy to measure total vitamin D (25-[OH] D). Sample-weighted multiple regression models, adjusted for potential confounders, were used to examine associations, and determine coefficients and 95% confidence intervals.

Results:
Mean total vitamin D levels was 23.48ng/ml among study participants. Birth weight was not related to vitamin D levels in adulthood. Pre-pregnancy BMI was inversely associated with offspring adulthood vitamin D levels, both before (β=-0.24, p-value=0.005) and after adjustment for birth weight (β=-0.24, p-value=0.015). However, the association was attenuated by including current offspring BMI in the models (β=-0.17, p-value=0.061) or both current BMI and birth weight (β=-0.16, p-value=0.120). In addition, the association between maternal pre-pregnancy BMI with current offspring BMI was not altered by adulthood vitamin D level.

Conclusion:
Maternal pre-pregnancy is potentially associated with adulthood vitamin D levels. This association may be mediated at least in part by offspring current BMI. Future studies are warranted to investigate whether the observed associations are due to genetic factors or other characteristics of the intrauterine environment.
Abstract P181: Cardiac Structure is Associated with Obesity and Blood Pressure But Not Inflammation
Authors: Palermo Robert A , Gidding Samuel S , DeLoach Stehpanie S , Keith Scott W , Falkner Bonita
Published: July 2021

Purpose:
The aim of this study was to identify risk factors associated with cardiac structure in a cohort of African American adolescents oversampled for obesity and high blood pressure (BP). Additional associations of cardiac structure with a pro-inflammatory adipokine profile (low adiponectin, elevated IL6, PAI-1 and CRP) were sought.

Methods:
A cross-sectional study was conducted using a two-by-two factorial design with four groups of African American adolescents based on BP (prehypertension or stage 1 hypertension=high BP) and body mass index (BMI > 95% =obese) designation. Measurements included: echocardiogram, anthropomorphics, BP (on 3 separate occasions), high sensitivity CRP and plasma adipokines (adiponectin, IL6, PAI-1). Standardized echocardiogram measurements were used to obtain left ventricular mass index (LVMI, g/m
2.7
) and left atrial diameter index (LADI, mm/m
2
). Ordinary least-squares regression with model selection by Mallow's Cp was used to determine if pro-inflammatory adipokine profile predicted LV mass and LA diameter in models including age, gender, BMI z-score, and systolic BP.

Results:
Data on 251 African American adolescents, ages 13-19, were analyzed. BMI-z score was strongly associated with a pro-inflammatory adipokine profile whereas high BP was not. Variation in LADI was significantly associated with BMI (β=0.12, p<0.01) and female gender (β=0.08, p=0.04). LVMI variation was significantly associated with BMI (β=3.53, p<0.01), age (β=0.71, p<0.01), female gender (β=-4.32, p<0.01), and systolic BP (β=0.10, p=0.03). Though significant in univariate models, inflammatory markers were not significantly associated with LADI or LVMI after BMI adjustment.

Conclusions:
In African American adolescents, BMI is an important determinant of LADI and LVMI. Obesity is associated with a pro-inflammatory adipokine profile but LADI and LVMI are not.

Table.

Regression modeling results after variable selection by Mallow C
p
: Left Atrium Diameter Index and Left Ventricular Mass Index (N = 251)

LADI
LVMI

Estimate (95% CL)
p-value
Estimate (95% CL)
p-value

Age (yr)

0.00063 (-0.021, 0.023)
0.955
0.71 ( 0.18, 1.24)
0.009

Gender (F)

0.08 ( 0.01, 0.16)
0.036
−4.32 (-6.13,-2.51)
<.001

BMI z-score

0.12 ( 0.08, 0.16)
<.001
3.53 ( 2.66, 4.40)
<.001

Systolic BP

0.0019 (-0.0017, 0.0055)
0.306
0.0952 ( 0.0085, 0.1819)
0.032
Abstract P182: Gender Difference in Response to Lifestyle Therapy in Obese Children with Combined Dyslipidemia
Authors: Pratt Rebecca , Quinzi Donna , Kavey Rae-Ellen W
Published: July 2021

Combined dyslipidemia(CDL) [moderate to severe elevation in triglyceride (TG), decreased HDL-cholesterol (HDL), mild elevation in total (TC) and LDL-cholesterol (LDL)] is common in obese children. Primary treatment is lifestyle change. We reviewed the response to a standard staged approach in consecutive children with CDL referred to a pediatric cardiology prevention clinic who returned for follow-up(F/U). The clinical protocol uses the same physician/ registered dietitian team to prescribe a change in diet composition (fat free milk; no sugar-sweetened beverages; simple carbohydrates replaced with complex carbohydrates) and daily exercise (1/2 hr/d of moderate exercise beyond current activity). Patients return at 3 m intervals and are discharged when TG and LDL have normalized; calorie control and/or medication are not introduced until the primary approach has been unsuccessful at second F/U. Over the last 21 mos, 53 pts(52 % male) have been managed with this approach. At baseline (B/L), mean age was 12.9+3y with no significant difference between males(Ms) and females(Fs). In 94%, B/L BMI was > 95
th
%ile. RESULTS (mean + SD):

ALL
F/U 1
F/U 2
MALE
F/U 1
F/U 2
FEMALE
F/U 1
F/U 2

B/L
B/L
B/L

TC

213+38
194+42
190+41
208+33
187+39
186+40
220+42
202+44
195+42

TG

282+136
205+110
193+98
283+131
182+78
173+89
279+141
230+133
215+105

HDL

40+12
39+10
40+10
39+8
38+7
39+7
41+15
41+13
41+12

LDL

127+41
118+39
114+41
123+40
115+40
110+43
132+44
121+39
119+38

For all pts, there was a significant mean decrease in TC (p=.007) and TG (p=.001) at the first F/U visit, sustained at second F/U with no significant change in LDL or HDL. The mean decrease in TC was similar in Ms(p=.028) and Fs(p=.022) but decrease in TG was greater in Ms(39%)(p=.0003) than in Fs (23%)(p=.036) (p=.059 between Ms and Fs). At F/U 2, 50% of Ms vs 20% of Fs had normalized TC and TG levels (p=.043). Although there was no specific approach to weight loss, mean BMI decreased by 0.4 kg/m
2
, with no difference between Ms and Fs. CONCLUSIONS: (1) A simple lifestyle change focused on change in diet composition and daily exercise can significantly improve CDL in obese children on short term F/U, without weight loss; (2) Normalization of the lipid profile is significantly more common in Ms than Fs. If confirmed in a prospective trial, these are potentially important findings for this large and growing patient group.
Abstract P183: Parents Play Significant Role in the Gender Differences Associated with Physical Activity in Elementary Students
Authors: Blankenship Chelsea R , Ice Christa , Shannon Vanessa , Cottrell Lesley
Published: July 2021

BACKGROUND
It has been proven that males engage in physical activity more than females starting at a young age. The goal of this study was to investigate gender differences based on parenting behaviors such as the frequency with which parents send their children out to play.

METHODS
Parents of children participating in a free cardiovascular risk-screening program (CARDIAC Project) completed a behavioral survey. Children (n =472; 43.3% female) who were enrolled in elementary school participated in the study. Parents provided information about children’s physical activity and their own ways in which they provided support of activity at home.
Children’s participation
in 12 activities was captured by total number of minutes per week. A combined mean activity score was calculated by summing the children’s total time across all of the activities.
Parent behavior
, specifically the frequency at which parents send their children outside to play was captured using a Likert scale where “1” represented never and “5” represented daily. Child gender and the amount of time allowed outside for play were then entered into a linear regression model to examine their role as potential predictors of child activity.

RESULTS
A significant gender difference (p<.001) was noted in children’s total activity time with boys (n = 237; 751 minutes/week) exhibiting higher mean activity each week than girls (n = 229; 521 minutes/week). Child gender and the amount of time allowed outside to play significantly predicted children’s activity levels overall. This model explained 28.9% of the variance in children’s activity levels (F = 20.25 (2); p<.001). Specifically, girls had less opportunity (3.75) than boys (4.05) to play outside.

CONCLUSION
A factor behind the lesser physical activity in female adolescents is significantly related to the decreased opportunity to play outside. Additional parenting practices will be shared if presented. In conclusion, parent behavior plays a significant role in the proven gender differences with childhood physical activity.
Abstract P200: Validity of self-reported hypothyroidism: Associations with cardiovascular risk factors in the CARDIA Study
Authors: Schreiner Pamela J , Golden Sherita , Zhu Na , Daviglus Martha
Published: July 2021

BACKGROUND:
Hypothyroidism (HYPOT), defined as having low levels of free thyroxine and elevated levels of thyroid-stimulating hormone (TSH), is a common condition linked to many adverse cardiovascular risk factors. Observational studies often rely on self-reported medical history that may or may not accurately reflect the presence of a condition or its adequate control.

METHODS:
We examined the association between self-reported HYPOT and levels of risk factors commonly altered by HYPOT using the Year 25 (2010-2011) CARDIA Study data. Systolic blood pressure, total, LDL- and HDL-cholesterol, triglycerides, body mass index (BMI), and Center for Epidemiologic Studies Depression (CES-D) score were measured using standardized methods. Crude means or geometric means were compared by HYPOT status with t-tests. Least-squared means adjusted for age, race, sex, center, smoking status, education, and BMI were estimated by HYPOT status using linear regression, and repeated with additional adjustment for levothyroxine or synthyroid use.

RESULTS:
After excluding 48 cases of hyperthyroidism, 4.6% (131/2851) of participants self-reported having HYPOT; mean age was 50.1 years, 55.3% were women, and 52.4% were white. Compared to those without HYPOT, those with HYPOT were more likely to be white (75.6% vs. 51.3%) and women (85.5% vs. 53.9%); crude mean systolic blood pressure was lower (114.9 vs. 120.3 mmHg, p=0.0002) and HDL-c was higher (61.7 vs. 57.9 mg/dL, p=0.03). After multivariable adjustment (
Table
), only BMI and triglycerides differed by HYPOT status. Adjustment for thyroid medication use did not materially alter mean differences.

CONCLUSION:
Self-reported hypothyroidism was inconsistently associated with risk factors commonly altered by thyroid abnormalities, regardless of medication status. These data suggest that TSH measurement is necessary to accurately identify individuals with low thyroid function leading to risk factor disturbances.

Multivariable-adjusted mean risk factor levels by self-reported HYPOT status

YES (n=131)
NO (n=2720)
p-difference

SBP (mmHg)
118.6
120.9
0.17

Total cholesterol (mg/dL)
194.1
191.0
0.39

HDL-c (mg/dL)
57.4
57.4
0.97

LDL-c (mg/dL)
109.4
110.6
0.74

Triglycerides (mg/dL)
*

114.5
100.5
0.021

BMI (kg/m
2
)

31.5
30.0
0.05

CES-D score
10.8
9.6
0.12

*

geometric mean
Abstract P205: Fair Agreement Between Stroke Patients and Family Members for Ascertaining Pre-Stroke Risk of Sleep Apnea
Authors: Reeves Sarah , Brown Devin , Chervin Ronald , Morgenstern Lewis , Smith Melinda , Lisabeth Lynda
Published: July 2021

Background
Obstructive sleep apnea is a risk factor for ischemic stroke and may play a role in post-stroke outcomes. Ascertaining self-reported information about pre-stroke sleep apnea risk in the acute stroke period is challenging as many stroke patients have deficits that hinder communication. We examined agreement between stroke patients and family members (proxy) with respect to pre-stroke risk of sleep apnea and hypothesized that agreement would be good.

Methods
Patient-proxy pairs (n=38) were interviewed as part of the Brain Attack Surveillance in Corpus Christi Project from May 2010 - April 2011. The Berlin Questionnaire was used to measure high risk of sleep apnea defined as at least two of the following: 1) snoring behaviors and witnessed apneas 2) daytime sleepiness and 3) hypertension or obesity. Patient-proxy agreement was assessed using a kappa coefficient.

Results
Average patient age was 70 (SD=12 years), 68% (n=26) were Mexican American and 32% (n=12) non-Hispanic white. An equal number of male and female patients participated (n=19), and average NIH Stroke Scale value at admission was 5.5 (SD = 6.4). Proxies were spouses (n=24) or children (n=14). Proxies had known patients for an average of 40 years (SD=15) and spoke with the patient daily (n=37) or weekly (n=1). Forty percent of patients (n=15) self-identified as high risk for sleep apnea and 52% of proxies (n=20) identified patients as high risk. Patient-proxy agreement for high risk of sleep apnea was fair (kappa=0.43;
table 1
) and was the same for both spouses and children.

Conclusions
Proxies can be used to assess pre-stroke risk of sleep apnea when a stroke patient is unable to participate as agreement for high risk of sleep apnea was fair. Proxies reported a high risk for sleep apnea with greater frequency than patients, suggesting there may be differences in observation of specific high-risk characteristics between proxies and patients.

Table 1.

Patient-Proxy Agreement for Risk of Sleep Apnea (n=38)

Patient Risk Assessment
Proxy Risk Assessment

Total

Low

High

Low

15
8
23

High

3
12
15

Total

18
20
38
Abstract P207: Nonalcoholic Fatty Liver Disease Interacts With Diabetes Increasing The Risk Of Atherosclerosis In The Family Heart Study
Authors: Feitosa Mary F , Reiner Alexander P , Wojczynski Mary K , North Kari E , Province Michael A , Carr Jeff J , Borecki Ingrid B
Published: July 2021

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes (T2D), which are risk factors for atherosclerosis. However, it is not clear whether NAFLD has an independent contribution to atherosclerosis. The burden of calcification in the coronary artery (CAC) can be measured by computed tomography (CT) and is a measure of atherosclerosis. CT measured liver attenuation (in Hounsfield Units) is inversely related to the amount of fat in the liver (FL), while elevated alanine aminotransferse (ALT, in U/L) levels indicate hepatic damage and is often used as a marker of NAFLD. We investigated whether NAFLD, defined by FL and ALT levels, is a significant predictor of the presence of CAC independent of insulin resistance (HOMA-IR: fasting glucose* fasting insulin/22.5) and overall obesity (BMI, kg/m
2
) in 2,550 European-American individuals. We employed a linear mixed model to account for the non-independence of family members, and included age, age
2
, sex, current cigarette smoking (yes/no), alcohol intake (yes/no) and clinical center in each model. Heavy drinkers (men: ≥ 21 drinks/week, women: ≥ 14 drinks/week) and subjects who tested positive for hepatitis-C antibodies were excluded from the analyses. In the multivariate model including FL, ALT, BMI, HOMA-IR, and T2D, neither FL nor ALT was associated with CAC; while BMI (p< 0.0001), HOMA-IR (p= 0.0150) and T2D (p= 0.0008) were significant. Also, we employed a similar multivariate regression model separately in subjects without T2D (not taking hypoglycemic medications and/or fasting glucose <126 ml/dL) and with T2D (but excluding subject taking insulin medication). In subjects without T2D, we found that ALT (p=0.0385, OR=1.126, 95% CI:1.006–1.260) was a significant predictor of CAC together with BMI (p< 0.0001) and HOMA-IR (p= 0.0082). In subjects with T2D, ALT (p=0.0376, OR= 0.590, 95% CI:0.361–0.964) was a significant predictor of CAC but not FL, BMI or HOMA-IR which may reflect the effect of other T2D medication. Further, we investigated whether T2D interacts with ALT modifying the risk of CAC independent of BMI and HOMA-IR. In the combined T2D and non-T2D subsets, we included the interaction term (T2D*ALT) in the multivariate model and found significant association of CAC with T2D*ALT (p= 0.0018, OR= 0.555, 95% CI: 0.0384–0.802), ALT (p= 0.0315, OR= 1.134, 95% CI: 1.011–1.271), and T2D (p=0.0001), together with BMI (p<0.0001) and HOMA-IR (p= 0.0156). In summary, we found that: (i) the association of NAFLD steatosis (FL) with CAC is mediated by overall obesity (BMI) and insulin resistance (HOMA-IR); (ii) ALT, indicating hepatic damage, is a significant predictor of atherosclerosis independent of BMI and HOMA-IR; and (iii) having hepatic damage along with T2D augments the risk of atherosclerosis.
Abstract P210: Calcified Atherosclerotic Plaque and All Cause Mortality in Diabetes: Diabetes Heart Study
Authors: Agarwal Subhashish , Herrington David M , Cox Amanda J , Jorgensen Neal , Xu Jianzhao , Carr John J , Freedman Barry I , Bowden Donald W
Published: July 2021

Introduction
Coronary artery calcium (CAC), a measure of atherosclerosis predicts mortality in both diabetes and the general population. The incremental utility of measuring atherosclerosis across multiple vascular beds beyond CAC for the prediction of mortality has not been reported. In this study we derived a composite atherosclerosis score (CAS) from multiple vascular beds and compared it with CAC in predicting all-cause mortality. We hypothesized that this composite score will be significantly better than CAC in predicting mortality.

Methods
A total of 803 participants, ages 39–86, with complete data on diabetes and vascular imaging in the Diabetes Heart Study (DHS) were followed for an average of 7.4 years. Computed tomography (CT) scans were performed at baseline to obtain measures of carotid (CAAC), coronary (CAC) and abdominal aorta (AAC) Agatston scores. A principal component analysis using studentized residuals of log transformed (CAAC+1), (CAC+1), and (AAC+1) adjusting for age, race, and gender was performed. We selected the first principal component as the CAS. Seven-year risk estimates for mortality were obtained using logistic regression models. Model 1 included age, gender, smoking, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and ethnicity and CAS. Model 2 included these risk factors plus CAC. We compared the estimation of mortality in Model 1 with CAS vs. Model 2 with CAC using chi-square values.

Results
Overall, 14% (116/803) of participants died during follow-up. CAS explained 70% of the variance, (eigenvalue of 2.1 with loading, CAAC, 0.57; CAC, 0.57; and AAC, 0.59). After adjusting for potential confounders, the odds ratio (95% CI) of all-cause mortality for 1-standard deviation (SD) increment was 2.12 (1.64–2.78) for CAS and 2.38 (1.77–3.35) for CAC. The area under the curve (chi-square value) with CAS or CAC to predict mortality was 0.76 (36) vs 0.76 (37) respectively.

Conclusion
Subclinical atherosclerosis, as measured by CT determined calcified plaque burden has increasing evidence supporting its role as a tool to stratify future risk for mortality. Here we demonstrated that the diagnostic accuracy between CAS and CAC are comparable and the predictive value of CAC alone for mortality is not further enhanced by inclusion of calcified plaque burden in carotid or abdominal aortic territories.
Abstract P215: Common Beta-cell-associated Genetic Variants and Hypertension or Anti-hypertensive Drugs do not Interact in Their Positive Associations With Risk for Rising Fasting Glucose or Incident Type 2 Diabetes in Framingham
Authors: de Miguel-Yanes Jose M , Porneala Bianca , Pencina Michael J , Fox Caroline S , Florez Jose C , Siscovick David S , Dupuis Josèe , Meigs James B
Published: July 2021

Background:
Hypertension (HTN) and some anti-HTN drugs raise fasting glucose (FG) levels and type 2 diabetes (T2D) risk. We hypothesized that common single nucleotide polymorphisms (SNPs) associated with FG or T2D that influence beta-cell function will interact with hypertension (HTN) or anti-HTN drugs in their positive associations with change over time in FG (ΔFG) or incident T2D.

Methods:
We studied 3,471 Framingham Offspring Study participants comprising 18,786 person-exams (mean age 49 yr; 54% women), in pooled (7 ∼4-yr periods) age-, sex-adjusted logistic regression models predicting T2D incidence, or age-, sex-, baseline FG-adjusted mixed linear models testing ΔFG (FG end minus beginning of period). T2D cases were excluded at baseline of each period, and people who started T2D treatment within a given period were removed for ΔFG analyses. We defined three HTN exposures: 1) HTN (SBP≥140/DBP≥90 mmHg) vs. no-HTN; 2) treated vs. untreated HTN; 3) five mutually-exclusive anti-HTN drug categories (beta-blockers, thiazides, renin-angiotensin system agents, combination, other) vs. untreated HTN, and two genetic exposures reflecting total beta-cell genetic risk burden: 16 FG-SNP and 33 T2D-SNP (only 8 overlap) additive genetic risk scores. We tested ∼4-year mean ΔFG and odds of T2D by HTN category and per-risk allele change in SNP scores, seeking first-order HTNxSNP significant interaction (P<0.05).

Results:
Versus no HTN, HTN (n=5,372 p-e) was associated with higher ∼4-year ΔFG (0.14 vs. 0.03 mmol/l; P<0.0001) and ∼3-fold increased odds of T2D (OR 3.3; P<0.0001). Versus untreated HTN, treated HTN (n=2,832 p-e) conferred higher ΔFG (0.18 vs. 0.12 mmol/l; P<0.0001) and 1.5-fold increased odds of T2D (P=0.0006). Versus untreated HTN, beta-blockers (n=676 p-e; OR=1.58), combined (n=499 p-e; OR=1.57) and other (n=569 p-e; OR=1.94) were associated with increased odds of T2D (all P<0.03). Per-SNP score risk allele, ΔFG increased by 0.03 mmol/l (P=2.2x10
−16
) and odds of T2D increased 17% (P=3.1x10
−08
). In joint models with interaction terms, all HTN-treatment category-by-SNP score interaction terms were non-significant. In joint models without interaction, HTN (P<0.0001) and HTN treatment (P<0.02), but no specific drugs (all but one P>0.02), and per FG-SNP or T2D-SNP risk allele (highest P value=0.0005), all independently predicted ΔFG or incident T2D.

Conclusion:
HTN, HTN treatment and common FG- and T2D-SNP genetic scores were independently associated with ΔFG and T2D incidence, but did not modify each other's association with ΔFG or T2D risk. Next, larger samples and individual SNP-by-specific drug category interaction tests might disclose some biological basis for T2D risk associated with anti-HTN therapy.
Abstract P221: Genome-wide Association Study Evaluating Genetic Determinants of Rosuvastatin Effects on Lp-PLA
2
Mass and Activity
Authors: Chu Audrey Y , Guilianini Franco , Barratt Bryan J , Nyberg Fredrik , Chasman Daniel I , Ridker Paul M
Published: July 2021

Aims:
Lipoprotein-associated phospholipase A2 (Lp-PLA
2
) is a pro-inflammatory enzyme bound to LDL-C and other lipoproteins in circulation that is associated with increased cardiovascular risk. There is little data regarding genetic determinants of Lp-PLA
2
mass and activity, and no prior data are available addressing genetic determinants of statin-induced changes for this inflammatory biomarker.
Methods and Results:
We performed a genome-wide association study of Lp-PLA
2
mass and activity at baseline and after 12 months of rosuvastatin therapy (20 mg/day) among 6,851 participants of European ancestry from the JUPITER trial. Genome-wide associations (p<5x10
-8
) were identified in
GCKR
and
CETP
for baseline Lp-PLA
2
mass, and at
MS4A4E
and the
APOC1
-
APOE
locus for baseline Lp-PLA
2
activity. A variant in
PLA2G7
, the gene encoding the Lp-PLA
2
enzyme was associated with Lp-PLA2 activity (p=3.1x10
-7
) at a sub-genome-wide significance (p<5x10
-6
); this association attained genome-wide significance after adjusting for either baseline apoB (p=2.9x10
-8
) or HDL-C levels (p=2.5x10
-9
). Two other sub-genome-wide associations with Lp-PLA
2
activity attained genome-wide significance after adjusting for baseline lipoproteins: at the
PSRC1
-
SORT1
locus (before adjustment, p=8.3x10
-7
; adjusting for triglycerides, p=3.4x10
-8
) and the
TMEM49
locus (before adjustment p=3.8x10
-6
, adjusting for HDL-C p=1.4x10
-8
). Among 2,673 statin-allocated participants, median reductions were approximately 30% for Lp-PLA
2
mass and activity (versus ~50% for LDL-C) after 12 months of statin therapy (all p-values <0.001). Variants in
ABCG2
and
LPA
were associated with statin-induced change in Lp-PLA
2
activity at genome-wide significance, and associations at sub-genome-wide significance (p<5x10
-6
) were observed for
EDG7
,
C14orf177
,
NOX5
,
AP3B2
and
RNF213
. All associations, with the exception of
AP3B2
, were substantially attenuated after adjustment for statin induced changes in LDL-C or apoB.

Conclusion:
Genome-wide associations at the
MS4A4E
and
TMEM49
loci may reflect novel influences on circulating levels of Lp-PLA
2
activity. In addition, genome-wide determinants of rosuvastatin-induced change in Lp-PLA
2
activity were observed in
ABCG2
and
LPA
, likely due to their impact on statin-induced LDL-C reduction.
Abstract P226: Exploring the Impact of Genetics for a General Cardiovascular Health Phenotype
Authors: Kumar Jitender , Hamsten Anders , Magnusson Patrik K , Pedersen Nancy L , Ingelsson Erik
Published: July 2021

A large number of genetic factors have recently been robustly associated with various individual cardiovascular traits, but less is known about genetic determinants of overall cardiovascular health; a trait that may reflect pleiotropic effects, as well as pathways involved in longevity. In order to find genetic factors responsible for maintaining general cardiovascular health, we performed meta-analyses of genome-wide association (GWA) data from two population-based cohorts. The TWINGENE cohort includes twins from Sweden born before 1958 (mean age, 64.9 years; 55% women), and the ULSAM cohort includes men born between 1920 and 1924 in Uppsala County, Sweden (mean age at DNA draw, 71.0 years). The present study was performed in 10,844 participants (9,740 and 1,104 from TWINGENE and ULSAM, respectively) with complete data on genotypes (Illumina OmniExpress in TWINGENE and Illumina CardioMetabochip in ULSAM) and phenotypes. Individuals without previously known coronary heart disease (CHD), heart failure, stroke, diabetes and hypertension, who had normal BMI (18.5-24.9 kg/m2), were normotensive (systolic blood pressure ≤140 mmHg), and had a preferable lipid profile (ratio of total cholesterol/high density lipoprotein ≤4.0) and HbA1c levels <6.5% were defined as cardiohealthy. We performed single marker association analyses with the cardiohealth phenotype as outcome using an additive genetic model adjusting for age, sex and smoking in PLINK (taking twinness into account for TWINGENE cohort). Summary statistics were subsequently meta-analyzed using inverse variance method in METAL. A total of 1,075 individuals (mean age, 61.5 years; 73% women) in TWINGENE and 54 individuals (mean age, 71.0 years) in the ULSAM cohort were identified as cardiohealthy. A non-synonymous variant (rs5880; Ala390Pro) in the CETP gene showed the strongest evidence for association (1.8*10-7). CETP encodes cholesteryl ester transfer protein, a key regulator of reverse cholesterol transport, and variants in this gene have been associated with several cardiovascular traits in recent GWA studies, such as CHD, metabolic syndrome and lipid fractions. Other genetic variants showing borderline significant association with the cardiohealthy phenotype included variants in or near ACCN1 that has been associated with factor VIII and von Willebrand factor, ATP6V04A that has been associated with F-cell level and SNX10 with smoking behavior. In the present meta-analysis comprising 10,844 individuals from the general population, we identified several genetic variants exhibiting suggestive association with cardiohealthy status. A few of these variants may exhibit pleiotropic effect modulating various risk factors involved simultaneously, thereby contributing towards cardiohealthy outcome. We are currently pursuing further replication and biological follow-up studies of these potential associations.
Abstract P231: Gene-by-smoking Interaction Analyses of Kidney Traits in the NHLBI Candidate-gene Association Resources Care Cohorts
Authors: Franceschini Nora , Liu Ching-Ti , Kao W Linda , Lange Leslie , North Kari E , Young Taylor , Nalls Michael , Cupples L Adrienne , Dreisbach Albert , Fox Caroline
Published: July 2021

Smoking is a known risk factor for progression of chronic kidney disease (CKD) but little is known of the role of smoking exposure on genetic effects of variants influencing kidney traits in the general population. We examined the evidence for effect modification of current smoking on the association of single nucleotide polymorphisms (SNP) with estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR), two well established markers of kidney disease, in 23,767 white and 8,110 African American individuals from five studies genotyped using the custom SNP array ITMAT-Broad-CARe (IBC array) in the CARe consortium. We obtained study- and race-specific residuals from linear regression models of natural log-transformed eGFR or UACR regressed on age, sex and study site. We then stratified residuals by current smoking exposure and performed genome wide association analyses using additive genetic models adjusted for 10 principal components, and accounting for family structure using mixed models, if needed. Meta-analyses across smoking-specific strata within each self-reported race were performed using the inverse variance weighted fixed effect models. We assessed smoking interaction using a heterogeneity test (P<0.10) and I
2
metric. Among SNPs reaching the array wide specific significance threshold (2.0x10
-6
) for association with eGFR or UACR, there was significant between smoking-strata heterogeneity for rs7422339 (
CPS1
, P=0.03, I
2
=77.7%) and rs13333226 (
UMOD
, P=0.06, I
2
=71.1%) for eGFR in whites, with larger decreases in eGFR among current smokers compared to past/never smokers. For UACR, rs1801239 (missense variant of
CUBN
, between smoking-strata heterogeneity P=0.09, I
2
=64.8%) T allele showed less protective effect among current smokers than non-smokers in whites only. These loci have been previously identified in genome wide association studies. Our findings, if replicated, suggest possible important interactions of smoking exposure on the genetic effects of known loci associated with kidney traits.

Funding(This research has received full or partial funding support from the American Heart Association, National Center)
Abstract P243: Myocardial Contraction Fraction, Diabetes, and Heart Failure: The Multi-Ethnic Study of Atherosclerosis
Authors: Bertoni Alain G , Akwo Elvis A , Bleumke David A , Lima Joao A , Hundley W G , Chen Haiying , Liu Songtao , Burke Gregory L
Published: July 2021

Background:
Persons with diabetes mellitus (DM) have altered cardiac structure and function, which increases heart failure (HF) risk. Myocardial contraction fraction (MCF) is an echocardiographic global measure of fractional shortening recently applied to cardiac MRI. We sought to determine if MCF differed by DM status and if MCF predicts HF in the Multi-Ethnic Study of Atherosclerosis, a cohort which enrolled ethnically diverse adults aged 45-84 who were free of clinical CVD.

Methods:
Analyses included 4991 with MRI data for whom DM status could be ascertained. Left ventricle (LV) volumes and mass (LVM) were calculated by the summation of disks method from cine short axis images. Ejection fraction (EF) is defined as LV stroke volume (SV) / end diastolic luminal volume. MCF is defined as LV SV/ end diastolic myocardial volume. DM was defined as using hypoglycemic drugs or a fasting glucose>125mg/dl. Linear regression was utilized for cross sectional analyses of the association between MCF and DM status, adjusting for age, gender, race/ethnicity, BMI, systolic BP, BP drugs, and smoking. Cox proportional hazards modeling was used to compare MCF, EF and LV mass quartiles as predictors of HF, adjusting for the above variables and DM.

Results:
At baseline the mean age was 61.5 (SD 10), 52% were female, 39% white, and 61% minorities; 13% had impaired fasting glucose (IFG) and 12% DM. The
table
indicates LV measurements. After adjustment, DM status remained associated with a lower MCF (IFG -0.02, 95% CI -0.03,-0.01; DM -0.032, 95%CI -0.04, -0.02). There were 96 incident HF events. Compared to the 4
th
quartile, the 1
st
MCF quartile was associated with HF (adjusted HR 2.2; 95%CI 1.13, 4.43) as was 1
st
EF quartile (adjusted HR 2.9; 95%CI 1.6, 5.2) and 4
th
quartile LVM (adjusted HR 5.4; 95%CI 2.2, 13.2). Among those with DM, 39% were in the 1
st
MCF quartile, compared to 27% in the 1
st
EF and 33% in the 4
th
LVM quartile.

Conclusions:
Incident HF is predicted by MCF. MCF may be a more sensitive marker for diabetic cardiomyopathy than EF or LVM.

Ventricular Measures by Diabetes Status

Glucose
Category

Parameter
Normal
100-125 mg/dl
Diabetes
p-value

MCF
0.66 (0.14)
0.61 (0.14)
0.59 (0.14)
<0.001

EF, %
69 (7)
69 (8)
68 (9)
0.11

SV (ml)
87 (20)
86 (19)
86 (19)
0.05

LMV (g)
142 (38)
153 (41)
157 (43)
<0.001

Mean (Std Dev)
Abstract P263: Racial Differences in the Association Between Physical Activity Levels During Early Adulthood and Visceral Adiposity at Middle Age: The CARDIA Study
Authors: Shay Christina M , Colangelo Laura A , Carnethon Mercedes R , Kershaw Kiarri N , Lewis Cora E , Reis Jared P , Sands Megan R , Shikany James M , Siscovick David S , Terry J Greg , Carr J Jeffrey , Jacobs David R
Published: July 2021

Background:
Excess visceral adiposity tissue (VAT) is associated with elevated free fatty acids that contribute to dyslipidemia, beta cell dysfunction, and insulin resistance. Greater physical activity (PA) is associated with lower VAT cross-sectionally, but whether PA during young adulthood is associated with VAT at middle age independent of general obesity is unclear.

Objective:
To quantify by sex and race the associations between PA levels in young adulthood with visceral adiposity measured 25 years later.

Methods:
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a population-based, prospective, observational study of black and white men and women. Habitual PA was determined as the average of baseline and year 7 levels (18–37 yrs) of the CARDIA Physical Activity Score. VAT (cm3) was assessed by computed tomography at the year 25 exam (43–55 yrs, n=1822).

Results:
Early adulthood PA levels were 15.2% lower in blacks compared to whites (p<0.001) and 30.0% lower in women compared to men (p<0.001); the lowest PA levels were observed in black women. Compared with the highest levels of PA, participants with moderate or lower PA during young adulthood exhibited higher VAT at middle age in linear regression models adjusted for covariates including year 25 BMI (Table 1). When stratified by race and sex, white men and women with higher PA levels exhibited lower VAT at middle age compared to white adults with moderate or lower PA; an association not observed in black men or women.

Conclusions:
White men and women engaging in higher PA levels at earlier ages may demonstrate lower visceral adiposity later in life, yet these findings suggest that PA may not be a solely effective approach at reducing/preventing cardiometabolic risk from excess visceral adiposity in black adults. Racial variations in the influence of young adulthood PA on visceral adiposity at middle age may reflect differential influences of PA, PA intensity, or other unmeasured risk factors (e.g., psychosocial stress) on adiposity distribution.