bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P155: Low Socioeconomic Status Relates to Short-term Mortality Risk After Acute Myocardial Infarction, Especially in Men: Results From a Nationwide Study
Authors: van Oeffelen Louise , Agyemang Charles , Koopman Carla , Bots Michiel , Stronks Karien , Vaartjes Ilonca
Published: July 2021

Introduction
Previous studies show poorer short-term prognosis after an acute myocardial infarction (AMI) in subjects with a low socioeconomic status (SES). Yet, the magnitude of these relations may differ by age and sex. Data on these issues are however scarce.

Methods
A nationwide Dutch cohort of first AMI patients between January 1
st
1998 and December 31
st
2007 was identified through linkage of national registers. SES was defined as the standardized disposable income on household level in 1997. For every SES quintile, age- and sex- specific short-term mortality rates were quantified. Logistic regression models were used to estimate differences between SES quintiles in out-of-hospital mortality and 28-day case-fatality.

Results
We identified 70.368 first AMI patients with income data available, of which 55.860 were men and 14.508 were women. There were strong inverse associations between SES and both short-term mortality outcomes when comparing the lowest with the highest income quintile (out-of-hospital mortality: Odds Ratio (OR) 1.26; 95% Confidence Interval (95% CI) 1.18–1.34), 28-day case-fatality: OR 1.26; 95% CI 1.15–1.37). For men graded relations were found across quintiles of SES, whereas for women only differences between the lowest and the highest quintile were seen. These relations remained consistent across all age categories, except for women below 55 years of age.

Conclusion
The results from our nationwide study show an increased risk of short-term mortality after a first AMI in subjects with a low SES of all ages, which is most pronounced in men.
Abstract P161: Improved Gender and Racial-Ethnic Disparities in the Management of Acute Myocardial Infarction. Experience from a Community Hospital Serving a Large Hispanic Population in USA
Authors: Romero Tomas E , Velez Pablo , Wikoff Karen , Romero Camila X
Published: July 2021

Introduction:
Disparities in medical therapies and revascularization procedures have been reported for women and Hispanics in the management of Acute Myocardial Infarction (AMI) in USA.

Objectives:
A paucity of recent data on this subject from facilities with a large Hispanic patient (pts) base motivated this study.

Methods:
Records of consecutive 525 pts (55% women, 289 of 525) admitted between 2005-2007 with a suspected AMI to a Southern California non-profit Community Hospital.

Results:
Race/ethnicity was unknown in 40 pts; 48%, 252 of 525, were Hispanic; 30 %, 155 of 525, Non Hispanic Whites and 14%, 78 of 525, African-Americans and Asians. No gender differences in age (66.9±14.8), diabetes, hypertension, dyslipidemia, medical insurance were found. Men had more AMI (93%, 219 of 236 v/s 51%, 147 of 289, p<0.001), death (7.6%, 18 of 238 v/s 3.8%, 11 of 289, p<0.05), smoking, CATH, PTCA and CABG than women. However, there were no gender or Hispanic ethnicity differences in the proportion of procedures performed when an AMI was confirmed (Fig1). Hispanic women (HW) showed no differences in death, AMI, CATH, CABG and Stress Test as compared to Non Hispanic White Women (NHWW) with the exception of PTCA (31%, 22 of 71, vs. 50%, 21 of 42, p <0.03). A trend (NS) for more AMI in NHWW and CABG in HW was noted. Non Hispanic Whites had more private/commercial insurance than Hispanics (61%, 95 of 155 vs. 32.1%, 81 of 252, p<0.01), regardless of gender. No differences were found in the composite (admission, discharge) use of ASA/Antiplatelets, B-blockers, ACEI /ARB and lipid lowering treatment.

Conclusions:
No Gender and Hispanic race/ethnicity disparities in the management of AMI were found for most services. HW received less PTCA than NHWW, difference that may be multifactorial. Medical insurance inequalities between Non Hispanic Whites and Hispanics persist but apparently did not affect the AMI care. It is uncertain if these results are applicable to facilities in USA with different socioeconomic, racial/ethnic mix or resources.
Abstract P165: Geographic Co-morbidity of Cardiovascular Diseases in South Africa
Authors: Kandala Ngianga-Bakwin , Stranges Saverio , Manda Samuel O , Tigbe William
Published: July 2021

Background:
The growing burden of non-communicable diseases in Africa is well recognized. However, the interplay between chronic conditions and environmental and lifestyle factors is not well documented in this setting. We used statistical co-morbidity models to jointly estimate risks of four cardiovascular conditions: hypertension, coronary heart disease (CHD), stroke and hypercholesterolaemia that are known to share unhealthy diet and lifestyle as common risk factors.

Methods:
Data are from 13,827 adults (mean ±SD age 39 ±18, 58.4% women) interviewed in the 1998 South African Health and Demographic Survey aggregated to 52 health districts. We estimated shared-component spatial prevalence models to known individual risk factors, in addition to allowing for disease-specific spatially structured district random effects.

Results:
There appeared to be an associations between the district prevalence of hypertension and CHD (ρ =0.33), and stroke and hypercholesterolaemia (ρ =0.31). However, on the unadjusted disease-specific prevalence maps, it was not possible to prove geographical trends in prevalence. On covariate-adjusted smoothed maps, the disease-specific log-odds showed clearer spatial patterns. Hypertension and stroke were concentrated highly in south-western parts of the country; whereas CHD and hypercholesterolaemia were highly concentration in central north-eastern and the top north-eastern corridors, respectively. The shared component, which we took to represent nutrition and other lifestyle factors not accounted for in the model, had a larger effect on vascular disease prevalence in south-western areas of the country. The shared component appeared to have greater effect on hypertension and CHD, though the relative weights were not statistically significant.

Conclusion:
This study provides novel evidence on disease-specific risk and geographic distribution of cardiovascular risk in South Africa. Understanding the underlying risk interactions between diseases might be useful for public health resource allocation in this setting.
Abstract P169: Exposure to Prenatal Maternal Cortisol During the Third Trimester and Calculated Coronary Heart Disease Risk in Middle-Aged Offspring
Authors: Stinson Lynda J , Stroud Laura R , Buka Stephen L , Eaton Charles B , Lu Bing , Agha Golareh , Loucks Eric B
Published: July 2021

Prenatal exposure to maternal stress may be associated with coronary heart disease (CHD) risk, however few studies have direct measures of
in utero
stress (e.g. maternal cortisol levels) and offspring adulthood CHD risk factors. Increased prenatal stress during the third trimester was hypothesized to be associated with an increase in 10-year CHD risk in middle-aged offspring. Participants were 282 offspring from the New England Family Study. Third trimester maternal serum samples, collected between 1959 and 1966, were analyzed for maternal free cortisol. The validated Framingham Risk Algorithm calculated the 10-year risk score in offspring using the CHD risk factors: blood pressure, total cholesterol, HDL cholesterol, diabetes, smoking, age, and sex. Multiple linear regression, stratified by sex, assessed associations between ordinal tertiles of maternal cortisol and the natural log of the 10-year CHD risk score, adjusting for offspring’s age, race, body mass index (BMI), and
in utero
socioeconomic index (SEI). In females, maternal cortisol was positively associated with log 10-year CHD risk score (β=0.34, 95% CI: 0.12, 0.56, comparing highest to lowest maternal cortisol tertile), adjusting for age and race. Adjustment for SEI slightly attenuated effect size (β=0.26, 95% CI: 0.02, 0.50). Further adjustment for BMI attenuated effect size (β=0.14, 95% CI: -0.06, 0.35). Maternal cortisol was not significantly associated with CHD risk score among males. In conclusion, higher prenatal levels of maternal cortisol were positively associated with calculated 10-year CHD risk among middle-aged female offspring. Adjusting for offspring adulthood BMI substantially reduced effect size, suggesting in may be a mediating mechanism. Associations were not observed in males. Additional research is needed to these replicate results and to better understand mechanisms involved, including gender differences.
Abstract P176: Associations of Cardiovascular Disease Risk Factors with Aorto-Iliac Bifurcation Location
Authors: Forbang Nketi I , Ix Joachim , Allison Matthew , Wassel Christina , Criqui Michael
Published: July 2021

Objectives:
We investigated associations of cardiovascular disease (CVD) risk factors and calcified atherosclerosis with the aortic bifurcation location.

Background:
In older persons, the aorto-iliac bifurcation is found in a more caudal position along the lumbar spine. Little is known about what other factors may play a role in the location of the bifurcation.

Methods and Results:
We evaluated community living individuals, free of clinical CVD, who had completed abdominal, computed tomography (CT) scans. The aorto-iliac bifurcation distance (AIBD), bifurcation to L5-S1 disc space, was determined from CT scans. The 1,711 participants (51% male) in this study had a mean age of 62 ± 10 years, and a mean AIBD of 26 ± 15mm. Age was a strong correlate of AIBD, such that on average, individuals > 80 years had bifurcations positioned 16mm lower than individuals < 50 years. In multivariable linear regression, standardized for lumbar spine height, older age, smoking, hypertension, and larger aortic diameter (ADD) were each independently associated with a smaller AIBD (more caudal location of the bifurcation). In contrast, diabetes and elevated triglycerides were independently associated with a larger AIBD (more cephalad location).

Conclusions:
A more caudal position of the aorto-iliac bifurcation is associated with some, but not all, CVD risk factors. Future studies should access the position of the bifurcation as a useful surrogate for vascular aging, or a prognosticator for CVD.
Abstract P185: Investigation of Community and Home Factors in Child Physical Activity Levels
Authors: Graham MIchael , Shannon Vanessa , Ice Christa , Cottrell Lesley
Published: July 2021

It is known that physical activity (PA) behavior is influenced by many factors within the social ecological model. Using results from parent surveys distributed after their children’s completion of a cardiovascular risk screening program, we explored the relationship between home and community environments on the amount of PA in which children engaged. Our hypothesis was that more immediate factors such as parent activity would have a greater impact on child activity than factors in their community environments. A large sample (n=450) of children (ages 5-10 years) were examined. Children’s physical activity was assessed by adding the total minutes of active time weekly. Parent physical activity was measured with two self report items regarding the number of days per week they were active
.
Two scales were constructed to evaluate to effects of the home (9 items;
α
= .829) and community (16 items;
α
= .868). The home environment scale measured elements related to activity opportunities and home schedules; the community scale assessed presence of playgrounds, or safe sidewalks, for example. To assess associations between factors and children’s PA, we conducted a linear stepwise regression with child age, parent PA, Home scale, and Community scale as predictors and the log transformed total weekly activity time as the dependent variable. Sixteen percent of children’s PA was explained by the tested model. Figure 1 provides specific information about each variable. The home scale had the greatest weight (β=0.360, p<.001), and proved to have a larger predictive effect than parent PA. These findings are significant for identifying which aspects of a child’s surrounding to intervene for maximum impact on physical activity. Figure 1. R² Change between model levels
Abstract P186: A Randomized Preschool Trial To Promote Cardiovascular Health In Colombia: 18 Month Follow Up.
Authors: Céspedes Jaime , Briceño German , Farkouh Michael , Vedanthan Rajesh , Leal Martha , Dennis Rodolfo , Hunn Marilyn , Fuster Valentin
Published: July 2021

Introduction:
Educational programs for children can increase uptake of healthy lifestyle behaviors. However, the impact of educational programs in preschool-aged children in low- and middle-income countries is not known. We conducted a five month educational intervention in preschool facilities (PF) in Bogota, Colombia, to assess changes in preschooler’s knowledge, attitudes and habits (KAH) towards healthy eating and living an active lifestyle.

Methods:
We conducted a cluster, randomized, controlled trial, and randomly assigned 14 PF in Bogota to a five-month educational intervention (7 PF) or to usual curriculum (7 PF). The intervention included classroom activities and use of printed material and videos. A total of 1216 pre-school children, 928 parents, and 120 teachers participated. A structured survey was used to evaluate changes in KAH with a weighted total score (WTS). The primary outcome was change in children's WTS, and the secondary outcomes were change in parents’ and teachers' WTS. The control PF were provided the intervention after the initial evaluation. To assess sustainability, we evaluated both intervention and control groups at 18 months.

Results:
At 6 months, children in the intervention group showed 10.9% increase in WTS vs. 5.3% in controls, p<0.001, after adjustment for cluster, sex, age and teachers' educational level. Among parents, the equivalent results were 8.9% and 3.1%, respectively, p< 0.001, and among teachers 9.4% and 2.5%, p=0.06. At the 18-month extended follow-up, both the intervention and control children showed a significant further increase in WTS, p<0.001 (Figure 1). In parents and teachers in the intervened group, there was no significant increase in WTS, p=0.7417, and p=0.1197. In the control group, there was an increase in WTS in teachers but not in parents, p=0.001, and p=0.4239.

Conclusion:
A preschool based intervention, aimed at changing KAH related to healthy diet and active lifestyle, is feasible, efficacious and sustainable up to 18 months in very young children in Colombia.
Abstract P188: Preterm Birth is a Predictor of Future Maternal Intima Medial Thickness: The CARDIA Study
Authors: Catov Janet M , Lewis Cora E , Lee Minjae , Ramsey Patrick R , Wellons Melissa F , Gunderson Erica P
Published: July 2021

Introduction:
Preterm birth (PTB, delivery <37 weeks) may be a marker of a chronic pro- inflammatory response associated with excess risk of coronary artery disease.

Hypothesis:
We hypothesized that women with PTB would have elevated blood pressure, markers of inflammation (C-reactive protein [CRP], Interleukin-6 [IL-6]) as well as higher intima medial thickness (IMT) in the years following pregnancy. Further, we considered that these differences would persist after removing PTB cases due to self-reported hypertensive disorders of pregnancy (primary reason for indicated PTB).

Methods:
We studied 916 women (46% Black) who delivered 1,181 live births between enrollment in the Coronary Artery Risk Development in Young Adults (CARDIA) study (age 18-30 years) and 20 years later (age 38-50 years). CRP was measured at years 7, 15 and 20; IL-6 and common carotid IMT (average of the maximum wall thickness of the respective carotid artery segment based on 4 ultrasonic measurements for the common carotid arteries) were measured at year 20. Blood pressure, lipids, and anthropometrics were measured at baseline and 6 follow-up visits. Median concentrations of inflammatory markers and mean IMT were compared in women with and without a history of PTB. Change in blood pressure, lipids, body size and CRP concentrations according to PTB status was also evaluated using generalized estimating equations (GEE).

Results:
A total of 226 women (24.7%) reported at least one PTB. Women with PTBs had modestly higher pre-pregnancy systolic blood pressure (SBP) compared to women who delivered term births (106.3 vs. 104.9 mmHg, p=0.02); SBP was higher across follow-up (p=0.03 for group differences) and increased more rapidly over 20 years compared to women with term births (p<0.01 for group*time interaction). These differences remained significant after removal of women with hypertension in pregnancy. Women with PTB had modestly higher mean body mass index (BMI) at baseline, and differences were more robust beginning in year 7 of follow up. Compared to women with term births, women with PTB had borderline higher mean IMT at year 20, adjusted for age and BMI (difference=0.016 mm, p=0.06). Adjustment for blood pressure change from baseline to year 20 did not affect the estimate. Adjustment for race attenuated this difference (p=0.33), and after excluding women with self-reported hypertension in pregnancy IMT no longer differed by PTB status. CRP, IL-6 and lipids did not differ according to PTB status.

Conclusion:
Women with PTBs, regardless of hypertension during pregnancy, had higher blood pressure before pregnancy and in the two decades after pregnancy compared to women with term births. They also higher mean IMTs, explained in part by race. Differences in IMT may be limited to women who reported hypertension in pregnancy, and were not related to inflammatory markers. PTB may mark women at excess risk of atherosclerosis.
Abstract P194: Gene-Environment Interactions and Blood Lipid levels: a Twin Study
Authors: Masson Lindsey F , Cumming Alistair M , Tuya Chuluuntulga , Rance Kellie A , Wood Sharon , McNeill Geraldine
Published: July 2021

Genetic variation may affect blood lipid levels by directly determining levels (‘level genes’) and/or by influencing the response to environmental factors (‘variability genes’), i.e. gene-environment interaction. Previous dietary studies assessing variability gene effects have produced inconsistent results, perhaps due to a lack of statistical power, different dietary protocols, and/or differences in the age, sex, habitual diet, baseline lipid values and other genes of the participants. Monozygotic (MZ) twins can enhance our ability to identify variability genes because they are genetically identical and also share the same age, sex and aspects of their early environment. Therefore, all intrapair differences in blood lipid levels are due to environmental factors such as diet and lifestyle, and variation between genotypes in intrapair differences will indicate the existence of variability genes. We investigated the hypothesis that polymorphisms within the genes for apoB, apoE and lipoprotein lipase influence the blood lipid response to environmental factors. The subjects studied were 64 MZ male and female twin pairs aged 18-75 years who had been recruited for a study of coronary heart disease risk factors in twins. Blood samples already taken for analysis of fasting lipid levels were used for DNA extraction. Genotypes were determined for the polymorphisms apoB signal peptide insertion/deletion (I/D), apoB
Xba
I, apoE, and lipoprotein lipase
Pvu
II,
Hind
III and S447X. Mean intrapair differences in lipid levels adjusted for mean twin pair lipid level were calculated for each genotype group. In MZ twins, carriers of the apoB signal peptide D allele had smaller intrapair differences in total cholesterol (p=0.044) but larger intrapair differences in apoAI (p=0.035) than I/I twins, and apoE ε4 carriers had smaller intrapair differences in HDL-cholesterol than E3/3 and E3/2 twins (p=0.024). MZ twins with the
Pvu
II P-P- genotype had significantly greater intrapair differences in apoB than P-P+ or P+P+ twins. The
Xba
I,
Hind
III and S447X polymorphisms did not influence intrapair differences in lipid levels. In conclusion, the apoB signal peptide I/D, apoE and lipoprotein lipase
Pvu
II polymorphisms may act as variability genes and influence the susceptibility of blood lipid levels to dietary and pharmacological interventions for dyslipidaemia. The approach of using MZ twins to identify variability genes can be applied to other phenotypes, prior to determining the environmental factors that interact with the genes to influence the phenotype.
Abstract P195: Combination Therapy not the Intensity of Statin Therapy Improves LDL Goal Attainment in Clinical Practice
Authors: Victor Brett , Ahedor Lilian , Liu Longjian , Karalis Dean G
Published: July 2021

Background:
In clinical practice most coronary heart disease (CHD) patients (pts) are not achieving their recommend LDL goal of < 70 mg/dL. We assessed the impact of statin dose and combination therapy in achieving optimal LDL levels in CHD pts.

Methods:
We conducted a retrospective analysis of outpatient electronic health records (EHR) from a large cardiology practice from September 2008 to September 2009. The most recent lipid profile, lipid-lowering medications and doses were extracted from the EHR. Statin potency was assessed based on the brand and dose of statin.

Results:
We identified 9,950 CHD pts; 59% were on a statin alone (SA), 27% on a statin + another lipid-lowering drug, 4% on no statin but on another lipid-lowering drug and 10% were on no lipid-lowering drugs. Only 37% of SA pts achieved an LDL < 70 mg/dL, but did so more often than pts on no statin but on another lipid-lowering drug (37 vs. 18%; p < 0.0001). Among SA pts, 70% were on moderate to high potency statins. The intensity of statin therapy did not improve LDL goal attainment. Among pts on combination therapy, 41% on statin + ezetimibe (S+E) and 46% on statin + niacin (S+N) achieved an LDL < 70 mg/dL (p = 0.01 and < 0.0001 vs. SA). Only 14% of pts were on S+E and 9% on S+N. Statin plus fibrate did not improve LDL goal attainment compared to SA (35 vs. 37%; p = 0.23). Few pts were taking bile acid sequestrants (< 0.5%). If pts were switched to a high potency statin LDL goal attainment of < 70 mg/dL would increase to 46% and would increase further to 65% with combination therapy.

Conclusions:
Most CHD pts in clinical practice do not attain an LDL < 70 mg/dL, even among pts on high potency statins. The number of CHD pts on no statin is high. The combination of statin plus either ezetimibe or niacin is the most effective regimen to achieve an LDL < 70 mg/dL; however these drug combinations are used infrequently in clinical practice. Combination lipid-lowering therapy is needed to improve LDL goal attainment in CHD pts.
Abstract P198: Does Cetp Mass Contribute to the Response of LDL Particle Size to a 1-yr Lifestyle Modification Program in Viscerally Obese Dyslipidemic Men?
Authors: Pelletier Beaumont Emilie , Bergeron Jean , Alméras Natalie , Tremblay Angelo , Porier Paul , Després Jean-Pierre
Published: July 2021

Numerous studies have demonstrated improvements in lipid and lipoprotein levels with endurance exercise training and weight loss. However, less is known about the contribution of the enzyme cholesteryl ester transfer protein (CETP) to the response of lipoprotein levels to a physical activity/healthy eating lifestyle modification program.

Objective:
To examine the effect of a 1-year lifestyle modification program inducing loss of visceral adipose tissue on plasma CETP mass in abdominally obese dyslipidemic men.

Methods:
Plasma CETP mass concentration was measured by ELISA at baseline and after a 1-year lifestyle modification program in 116 abdominally obese men aged 30 to 65 years without diabetes. Visceral adiposity was assessed by computed tomography and a complete fasting plasma lipoprotein-lipid profile was also obtained at baseline and after the intervention.

Results:
After 1 year, no significant changes were observed in CETP mass (1.91±0.45 vs.1.93±0.49 mg/l, ns). However, both HDL (81.7±2.1 vs. 83.8±3.1 Å, p<0.0001) and LDL (252.1±3.9 vs. 253.6±3.7 Å, p<0.0001) particle sizes assessed by gradient gel electrophoresis were increased. Whereas no significant correlation between change in HDL size and CETP mass was observed, change in LDL size was significantly correlated with change in CETP mass (r=−0.30, p=0.001). We also divided men into two groups: men who showed no change or an increase in their CETP mass (ΔCETP≥0) and men who decreased their CETP mass (ΔCETP<0). Men who reduced their CETP mass after one year showed a greater increase in LDL size (Δ 2.37±3.18 vs.0.32±3.04 Å, p=0.0006) and a greater decrease in triglyceride levels (Δ-0.70±0.86 vs. −0.34±0.80 mmol/l, p=0.03) than men who showed no change or an increase in CETP mass. A Multivariate analysis revealed that 19% of the variance in the response of LDL size could be attributed to changes in triglyceride levels (15%) and in CETP mass (4%) (p=0.02).

Conclusion:
Whereas no significant change in CETP mass was observed, our results showed that individual variation in the response of CETP mass contributed to the response of LDL particle size to a 1-yr lifestyle modification program in viscerally obese dyslipidemic men.
Abstract P202: The Impact of Snoring with and without Overweight on the Incidence of Hypertension among Japanese General Population
Authors: Nagayoshi Mako , Tanigawa Takeshi , Yamagishi Kazumasa , Sakurai Susumu , Kitamura Akihiko , Kiyama Masahiko , Okada Takeo , Maeda Kenji , Ohira Tetsuya , Imano Hironori , Sato Shinichi , Iso Hiroyasu
Published: July 2021

Introduction:
Evidence for the longitudinal impact of snoring on incident hypertension in Asians is still limited. The objective of this study was to examine whether the impact of snoring with and without overweight (body mass index ≥25.0 kg/m
2
) on the incidence of hypertension among Japanese general population.

Hypothesis:
We assessed the hypothesis that the impact of snoring on incident hypertension among Japanese general population was more evident for non-overweight (body mass index <25.0 kg/m
2
) subjects probably because overweight is a primary determinant of both snoring and hypertension.

Method:
A total of 7,482 non-hypertensive persons (2,891 men and 4,591 women) aged 35-79 years from three communities in Japan who participated in the Circulatory Risk in Communities Study (CIRCS) were followed up for 7.9 years. Hazard ratios for the incidence of hypertension were calculated according to snoring (self-administered questionnaire) stratified by body mass index.

Results:
At baseline, 74 % of men and 59 % of women had sometimes or everyday snoring and 31 % of men and 28 % of women had being overweight. During the 7.9-year follow-up period, 1087 individuals (451 men and 636 women) developed hypertension. The multivariable-adjusted odds ratio (95%confidence interval) of incident hypertension for snoring compared with non-snoring was 1.37 (1.06 to 1.76) for men and 1.32 (1.10 to 1.58) for women. When stratified by body mass index at baseline, the significant association was observed only in non-overweight; the multivariable adjusted odds ratio of incident hypertension with non-overweight was 1.52 (1.12 to 2.04) for men and 1.39 (1.11 to 1.73) for women, and respective odds ratio for snoring with overweight was 1.11 (0.68 to 1.81) for men and 1.14 (0.83 to 1.53) for women compared with non-snoring categories although the interaction was not statistically significant. The population-attributable fraction (PAF) of snoring with non-overweight for incident hypertension was 26 % for men and 17% for women.

Conclusions:
Snoring may have larger impact on development hypertension among non-overweight Japanese men and women.
Abstract P209: Effects of Blood Pressure Lowering on Vascular Outcomes in Different Cardiovascular Risk Groups Among Patients With Type 2 Diabetes: New Results From Advance
Authors: van Dieren Susan , Kengne Andre Pascal , Chalmers John , Beulens Joline , van der Schouw Yvonne , Zoungas Sophia
Published: July 2021

Background/Aim:
Although patients with type 2 diabetes constitute a high risk group there is a gradation in cardiovascular risk which may lead to differences in outcomes and effects of treatment. The objective of this study was to assess for differences in treatment effects of the fixed combination of perindopril-indapamide across subgroups of cardiovascular risk.

Methods:
11,140 patients with type 2 diabetes, participating in the ADVANCE trial, were randomized to perindopril-indapamide or matching placebo. The UKPDS risk engine was used to calculate baseline 5-year coronary heart disease risk and to stratify patients into three risk groups (0-10%; 10–15%; >15%). Endpoints were composites of major macrovascular and microvascular events. Homogeneity of treatment effects across risk subgroups were tested by adding interaction terms to the Cox models.

Results:
The median estimated 5-year coronary heart disease risk at baseline was 10% (IQR 7%−16%). 1000 macrovascular and 916 microvascular events were recorded during a median follow-up of 4.3 years. The relative treatment effects were similar across all risk groups for all endpoints, with no heterogeneity (all
P
-values for heterogeneity ≥ 0.38). The hazard ratios for combined macro- and microvascular events were 0.89 (95% confidence interval: 0.77–1.03) for the moderate-high risk group and 0.92 (0.81–1.03) for the very high risk group. The absolute risk reductions were greater in the highest risk groups, with numbers needed to treat ranging from 38 to 244.

Conclusions:
Reductions in relative risk achieved with the fixed combination of perindopril-indapamide among patients with type 2 diabetes were consistent across subgroups defined by baseline cardiovascular risk, but reductions in absolute risk were greatest in those with the highest initial risk.

Acknowledgements:
This research was supported by a program grant from the National Health and Medical Research Council of Australia, the Center for Translational Molecular Medicine (CTMM) and the Netherlands Heart Foundation, Dutch Diabetes Research Foundation and Dutch Kidney Foundation (PREDICCt).
Abstract P212: Circulating Homocysteine, Aldosterone and Brain Natriuretic Peptide Levels Predict the Development of Metabolic Syndrome and Longitudinal Changes in Metabolic Syndrome Components: Findings from fhe Jackson Heart Study
Authors: Musani Solomon K , Vasan Ramachandran S , Bidulescu Aurelian , Liu Jiankang , Taylor Herman A , Fox Ervin R
Published: July 2021

Background:
The relative contribution of selected circulatory biomarkers that represent distinct biological pathways to the incidence of metabolic syndrome (MetS) in African Americans is not well elucidated despite the greater prevalence of cardiovascular diseases in this ethnic group. Thus, we aimed to assess the relative contribution of a panel of representative cardiometabolic biomarkers with the hypothesis that they are predictors of incident MetS and longitudinal changes in MetS components.

Materials and Methods:
At the end of the second JHS examination cycle (average 4.7 years from baseline), 178 participants of the total 1055 without prevalent MetS at baseline had developed MetS. We selected informative markers from a panel of 7 representing inflammation (C - reactive protein and leptin), neurohormonal activity (aldosterone, BNP, cortisol), and endothelial function (endothelin and homocysteine) that were significantly associated with incident metabolic syndrome (MetS). Biomarker selection was performed using stepwise selection in multivariable logistic regression models. We adjusted for baseline age, gender, systolic and diastolic BP, log triglycerides, fasting glucose and HDL cholesterol, and waist circumference measurements.

Results:
Serum homocysteine, aldosterone and B-natriuretic peptide (BNP) concentration were retained as significantly associated with incident MetS, with p-values 0.037, 0.008 and 0.022, respectively. The multivariable adjusted OR (95%CI) were 1.28 (1.02 to 1.62) for homocysteine; 1.33 (1.08 to 1.65) for aldosterone, and 2.47 (1.31 to 4.66) for 2nd BNP quartile compared to the first quartile. In multivariable analyses evaluating longitudinal change in MetS components (analyzed as continuous variables); homocysteine was significantly and positively associated with diastolic BP. Serum aldosterone was associated with all MetS risk factors, while higher levels of plasma circulating BNP were associated with all risk factors except sex-standardized waist circumference. Discussion and

Conclusions:
Higher circulating homocysteine and aldosterone levels were directly associated with the development of MetS and with longitudinal change of its components except HDL cholesterol and sex standardized waist circumference, which were negatively associated with aldosterone. The second and fourth quartiles of circulating plasma BNP concentration were significantly associated with greater odds of developing MetS than the first quartile. Further, higher concentration of BNP was associated with positive changes in all risk components except for HDL cholesterol and waist circumference. These results suggest that the biomarkers and their related pathways are essential in mediating metabolic risk in African Americans.
Abstract P218: Identification of One Retinoic Acid Responsive Element in Glucokinase Gene Promoter
Authors: Chen Guoxun , Li Rui , Chen Wei , Li Yang , Zhang Yan
Published: July 2021

Introduction:
Studies have shown that vitamin A (VA) status affected hepatic glycogen content and body lipid levels in rats. The active metabolite of VA, retinoic acid (RA), regulates gene expression via activation of both retinoic acid receptor (RAR) and retinoid X receptor (RXR) bound to retinoic acid responsive element (RARE). We have reported that retinoids synergized with insulin to induce glucokinase gene (
Gck
) in primary rat hepatocyes.
Hypothesis:
We hypothesize that the rat promoter of
Gck
contains RARE(s).

Methods:
To identify the RARE(s) in the
Gck
promoter, we have made (1) a series of luciferase reporter gene constructs containing shortened DNA fragments of
Gck
promoter; (2) expression vectors containing cDNAs of rat RARα, RXRα and RXRγ; (3) linker-scan mutant reporter constructs covering 0.2 kb of the proximal
Gck
promoter region and a 20 bp region which disrupt the RA response. The responses of these reporter constructs to RA and the effects of the co-transfection of RAR and RXR on their activation were analyzed in primary hepatocytes and INS-1 insulinoma cells using dual luciferase assay.

Results:
(1) RA and RA + insulin, not insulin, activated the reporter gene constructs containing 1, 0.8, 0.6, 0.4, and 0.2 kb of
Gck
promoter in primary hepatocytes (from 1.7- to 2.6-fold). (2) RA alone did not activate
Gck
promoter constructs in INS-1 cells. However, co-transfection of RAR with reporter gene constructs restored and improved RA response of them in INS-1 cells and primary hepatocytes, respectively. (3) Two consecutive linker-scan mutant reporter constructs covering about 20 bp of the proximal region of
Gck
promoter, but not the adjacent ones, completely lost the response to RA. (4) One of the five linker-scan mutant reporter constructs covering this 20 bp region completed disrupted the RA response, demonstrating the identification of a RARE.

Conclusions:
RA induces the activation of
Gck
promoter constructs in primary hepatocytes. INS-1 cells are a useful tool for analyzing liver
Gck
promoter activation by RA with co-transfection of RAR/RXR. For the first time, one RARE is identified in the proximal region of rat
Gck
promoter. Further studies are needed to determine the roles of this identified RARE in mediating
Gck
expression in responses to hormonal and nutritional stimuli.

Funding(This research has received full or partial funding support from the American Heart Association, National Center)
Abstract P223: Larger Effect Sizes of Established BMI Genetic Variants During Adolescence, a Vulnerable Period of Weight Gain
Authors: Graff Mariaelisa , North Kari E , Mohlke Karen L , Lange Leslie A , Lange Ethan M , Fox Caroline S , Cupples L. A , Harris Kathleen M , Gordon-Larsen Penny
Published: July 2021

In the past five years genome-wide association studies (GWAS) have identified common genetic loci associated with body mass index (BMI) mainly in European middle-aged adult populations. The influence of these loci in adolescence, a period of risk for weight gain, and whether there are different associations across adolescent groups at highest risk (e.g., ethnic minority populations), remains largely unknown. We examined whether obesity susceptibility loci identified from previous GWAS in adults were associated with BMI in an ethnically diverse adolescent cohort. Using 8918 participants from the National Longitudinal Study of Adolescent Health, or Add Health (aged 12-21 years in 1996, 52.6 % female), we assessed the association of 43 SNPs, selected based on statistical significance in previous GWAS, with BMI across four ethnic US subpopulations (5,296 European Americans, EA, 1,815 African Americans, AfA, 1,356 Hispanic Americans, HA, and 451 Asian Americans, AsA). Buccal cells from participants were extracted and genotyped using TaqMan (sample call rate: 97.5%, SNP call rate: 100%). Inverse normal transformed BMI residuals, adjusted for gender and age, were used in ethnicity-stratified models with SNPs in PLINK, assuming an additive model. An inverse-variance-weighted meta-analysis was used to combine results across the 4 ethnic groups. Average BMI across all ethnic groups was 23.6±5.2 kg/m2, ranging from 22.6±5.2 kg/m2 in AsA to 24.3±5.8 kg/m2 in AfA. The effect estimates for all 43 SNPs were directionally consistent across ethnicity with previously published results. Of the 43 SNPs, 20 were associated with BMI at p<0.05 in the meta-analysis (17 in EA, 7 in AfA, 4 in HA, and 5 in AsA). Based on t-test comparisons, 16 of the 20 SNPs had larger and 2 loci had smaller effect sizes (p<0.05) in the Add Health adolescent sample than published effect sizes for BMI in adults. Only FTO (rs9939609) showed significant heterogeneity across ethnicity (p=0.01 for I2=73.5).
TMEM18
(rs6548238, meta-analysis p-value p=1.32E-10), had one of the largest differences in effect size compared to middle-aged European adults (Willer et al 2009) with a per allele increase of 0.70±0.11 kg/m2 in this sample versus 0.26±0.07 kg/m2 in adults (beta[SE] difference = 0.44[0.08]; p=1.4E-08). Variants associated with BMI in adults were also associated with BMI in adolescents, with some comparatively larger effects during this vulnerable period. R01HD057194
Abstract P230: Individual and Cumulative Effect of Type 2 Diabetes Associated Genetic Variants on the Risk Of Cardiovascular Disease
Authors: Borglykke Anders , Grarup Niels , Sparsø Thomas H , Linneberg Allan , Fenger Mogens , Jeppesen Jørgen , Hansen Torben , Pedersen Oluf , Jørgensen Torben
Published: July 2021

Hypothesis Since type 2 diabetes is a major risk factor for cardiovascular disease (CVD) we hypothesised that diabetes associated single nucleotide polymorphisms (SNP) might be associated with increased risk of CVD. Aim To asses the individual and combined effect of 46 type 2 diabetes associated SNPs on the risk of incident CVD independently of diabetic status. Methods Data from the first Danish MONICA study was used (N=3753) and results were reproduced using the Inter99 study (N=6169). Using Cox proportional hazard regression adjusted for sex and with age as the underlying time-scale the individual effect of each SNP on incident CVD was analyzed. Risk was presented as hazard ratios (HR) per risk allele. Furthermore, the cumulative effect of the 46 SNPs was assessed by adding the number of diabetes risk increasing alleles to a genetic sum score. Both the single and cumulative effect was adjusted for diabetic status in order to see if any possible association with CVD persisted or if the effect was mediated through diabetes. Results During 74,386 person years 1411 incident cases of CVD (fatal and non-fatal) was registered in the MONICA study. In Inter99 729 events was registered during 51,976 person years. In the Danish MONICA study seven genetic variants were significantly associated with incident CVD independently of known diabetic status; SLC2A2 (HR 1.12, 95% CI 1.001-1.26), DGKB (1.11, 1.02-1.2), C2CD4A (1.11, 1.02-1.20), GCKR (1.10, 1.01-1.20), KLF14 (1.12, 1.03-1.21), NOTCH2 (1.16, 1.02-1.32) and JAZF1 (1.10, 1.02-1.20). The genetic score was significantly associated with increased risk of CVD (1.03, 1.02-1.05) per risk increasing allele. In Inter99 three genetic variants were found to be associated with risk of CVD independently of diabetes; SLC2A2 (1.24, 1.07-1.43), CDC123 (0.84, 0.73-0.97) and HNF1B (1.16, 1.03-1.29). The genetic score was not significantly associated with CVD. The results persisted after further adjusting for possible mediating factors like BMI, total cholesterol, HDL cholesterol and blood pressure. Conclusions We found in both studies several diabetes associated genetic variants significantly associated with an increased risk of incident CVD. The SLC2A2 (rs11920090) genetic variant was the only variant that was found to be significantly associated in both studies. This association persisted after adjusting for diabetic status suggesting an effect on CVD beyond the increased risk of diabetes. This potential pathway needs further exploration.
Abstract P232: Common Variants of the Estrogen Receptor 1 Gene Predict Decreased Blood Pressure Salt-Sensitivity in Men: The GenSalt Study
Authors: Kelly Tanika N , Rebholz Casey M , Gu Dongfeng , Hixson James E , Rao Dabeeru C , Cao Jie , Chen Jichun , Li Jianxin , Lu Fanghong , Ma Jixiang , Mu Jianjun , Whelton Paul K , He Jiang
Published: July 2021

Previous reports have documented increased blood pressure (BP) salt-sensitivity in women compared to men, suggesting that genes encoding sex hormones could influence BP response to sodium. In the current study, we examined the association between 799 single nucleotide polymorphisms (SNPs) in 44 genes involved in sex hormone biosynthesis, bioavailability and metabolism for their association with BP responses to sodium intervention separately in men and women. A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium feeding-study (307.8 mmol sodium/day) was conducted among 1,906 participants from 633 Han Chinese families. Nine BP measurements were obtained at baseline and the end of each intervention period using a random-zero sphygmomanometer. Additive associations between each SNP and BP responses to low and high-sodium interventions were assessed using a mixed linear regression model to account for familial dependencies. Among men, absolute BP responses to sodium interventions decreased with the number of minor alleles of estrogen receptor 1 (ESR1) markers rs9340844, rs9397453 and rs9383951. For example, men with genotypes C/C, C/T, and T/T of rs9397453 had respective mean DBP responses [95% confidence intervals (CI)] of: -2.67 (-3.13, -2.22), -1.23 (-1.98, -0.48), and 0.08 (-2.31, 2.47) mmHg to low-sodium intervention [p=1×10
-4
; false discovery rate (FDR)-q=0.04]; and 1.46 (1.03, 1.89), 0.19 (-0.54, 0.91), and -1.10 (-2.82, 0.61) mmHg to high-sodium intervention (p=2×10
-4
; FDR-q=0.04). In addition, mean SBP responses (95% CI) were: -5.70 (-6.19, -5.20), -4.34 (-5.37, -3.31), and -2.65 (-5.15, -0.16) mmHg, respectively, for low-sodium intervention (p=2×10
-3
; FDR-q=0.17); and 4.56 (4.12, 4.99), 3.47 (2.63, 4.30), and 1.97 (-0.49, 4.43) mmHg, respectively, for high-sodium intervention (p=3×10
-3
; FDR-q=0.40). ESR1 variants were not associated with BP responses in women, with highly significant genotype-gender interactions noted.

In summary, we identified strong, consistent associations between genetic variants in the ESR1 gene and decreased salt-sensitivity in men. Although replication of these findings is needed, our results support a role for sex-hormones in the etiology of this complex trait.

Funding(This research has received full or partial funding support from the American Heart Association, National Center)
Abstract P234: Genetic Variants of the Kallikrein-kinin System Associated with the Salt Sensitivity of Blood Pressure: The GenSalt Study
Authors: Gu Dongfeng , Zhao Qi , Kelly Tanika N , Hixson James E , Rao Dabeeru C , Cao Jie , Chen Jing , Li Jianxin , Chen Jichun , Ji Xu , Hu Dongsheng , Wang Xushan , Liu De-Pei , He Jiang
Published: July 2021

The kallikrein-kinin system (KKS) has been implicated in the pathogenesis of salt-sensitive hypertension in animal models. We comprehensively examined the association between genetic variants of the KKS and blood pressure (BP) response to dietary sodium intervention among participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study. A 7-day low-sodium dietary intervention followed by a 7-day high-sodium dietary intervention was carried out among 1,906 GenSalt participants from rural areas of north China. Nine BP measurements were obtained at baseline and on the last three days of each intervention period using a random-zero sphygmomanometer. The percentage changes in mean BP from baseline to low-sodium intervention and from low-sodium to high-sodium intervention were used to assess individual salt-sensitivity. A total of 205 tagSNPs and functional SNPs of eleven genes of the KKS (
BDKRB1
,
BDKRB2
,
CPN1
,
CPN2
,
CPM
,
ECE1
,
KLK1
,
KLKB1
,
KNG1
,
MME
,
SERPINA4
) were selected and genotyped in this study. Single marker analyses were conducted using the Family Based Association Test program. Genetic variants in the bradykinin receptor B2 (
BDKRB2
) and endothelin converting enzyme 1 (
ECE1
) genes showed significant associations with salt sensitivity even after adjusting for multiple testing using the false discovery rate method. SNP rs11847625 of
BDKRB2
was significantly associated with systolic BP (SBP) response to low-sodium intervention (
P
= 0.0001). Compared to its major allele G, carriers of the minor allele C had greater SBP decrease during low-sodium intervention. Furthermore, a haplotype containing allele C was associated with greater SBP increase to high-sodium intervention (
P
= 0.0009). Seven SNPs of
ECE1
, one of the degrading enzymes of kinins, were significantly associated with diastolic BP (DBP) response to low-sodium intervention (
P
values ranged from 0.0003 to 0.002). Two haplotypes in the linkage disequilibrium block including these seven SNPs were significantly associated with DBP response to low-sodium intervention (P=0.0004 and 0.003, respectively). Our study found that the genetic variants of the KKS were associated with salt sensitivity of BP. Replication and functional studies of the identified variants are warranted in the future.