bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P179: Relation of Diet-Induced Metabolic Acidosis to Blood Pressure
Authors: Campanella Gianluca , Chan Queenie , Daviglus Martha L , Van Horn Linda , Miura Katsuyuki , Ueshima Hirotsugu , Zhao Liancheng , Stamler Jeremiah , Nicholson Jeremy K , Elliott Paul , Chadeau-Hyam Marc
Published: July 2021

Background:
Influences of nutrition on acid-base balance have long been recognized, and significant pathophysiological effects of diet-induced metabolic acidosis (DIMA) are now acknowledged, making it a potential target for preventive dietary interventions. Despite biological plausibility, recent cross-sectional and prospective studies have failed to provide consistent evidence supporting an association between DIMA and blood pressure (BP), systemic hypertension, or cardiovascular risk.

Objective:
To assess associations of validated DIMA indices computed from dietary information with BP, using data from the International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP).

Methods:
The INTERMAP Study is a cross-sectional epidemiological investigation with standardized quality-controlled methods. It includes 4,680 participants from four countries (China, Japan, UK, and USA) with detailed lifestyle, anthropometric, and dietary information, as well as two 24-hour urine samples. Participants reporting use of BP-lowering medications were excluded. Two indices were investigated: energy-adjusted Potential Renal Acid Load (PRAL, mEq/MJ/day), which quantifies the dietary acid-forming potential only, and Net Endogenous Acid Production (NEAP, mEq/1.73m
2
/day), which assesses the balance between endogenous acid production and PRAL, and thus provides a more accurate measure of DIMA. Analyses were stratified by ethnic group: non-Hispanic Whites (NHWs, N=1,397), Japanese (N=1,273), Chinese (N=804), and African-Americans (N=253). All models were adjusted for known hypertension risk factors. Additional analyses were conducted to investigate associations of DIMA indices with BMI.

Results:
NEAP was positively associated with BP in NHWs and Japanese. In NHWs, systolic BP: 0.08 (95% confidence interval: 0.03 to 0.13) mmHg higher per mEq/1.73m
2
/day in men, 0.19 (0.12 to 0.26) mmHg higher in women; diastolic BP: 0.06 (0.03 to 0.1) mmHg higher in men, 0.11 (0.06 to 0.16) mmHg higher in women. In Japanese, systolic BP: 0.11 (0.03 to 0.18) mmHg higher in men, 0.15 (0.07 to 0.25) mmHg higher in women; diastolic BP: 0.08 (0.02 to 0.13) mmHg higher in men, 0.11 (0.05 to 0.18) mmHg higher in women. These associations were not significant after controlling for BMI. PRAL was not significantly associated with BP in any model. NEAP was also significantly associated with BMI across ethnic groups, which is consistent with a possible mediating role of BMI in the association between NEAP and BP.

Conclusions:
Our data indicate ethnicity-specific positive associations of DIMA (as measured by NEAP) with BP, possibly mediated by obesity.
Abstract P183: FTO Genotype, Dietary Protein, and Change in Appetite: the Pounds Lost trial
Authors: Huang Tao , Qi Qibin , Li Yanping , Hu Frank , Bray George A , Sacks Frank M , Qi Lu
Published: July 2021

Objective:
A common "obesity-risk" variant rs9939609 in the FTO gene was recently found to affect appetite, and the gene is sensitive to regulation of amino acids. We examined the interaction between FTO genotype and protein intake on the long-term changes in appetite in a randomized controlled trial.

Research Design and Methods:
We genotyped FTO rs9939609 in 737 overweight adults in the 2-year Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) trial and assessed four appetite related traits including cravings, fullness, hunger, and prospective consumption.

Results:
We found that dietary protein significantly modified genetic effects on changes in food cravings at 6 months, after adjustment for age, sex, ethnicity, baseline body mass index, weight change, baseline value for food cravings (P for interaction=0.027). The A allele was associated with a greater decrease in food cravings among the participants with high protein diet intake (P=0.027), but not in those low protein diet group (P= 0.384). Weight regain from 6 months to 24 months attenuated the gene-protein interactions. Protein intakes did not modify the FTO genotype effects on other appetite measures.

Conclusions:
Our data suggest that individuals with the FTO rs9939609 A allele might obtain more benefits in reduction of food cravings by choosing a hypocaloric and higher protein weight-loss diet.

Keywords:
diet, genetic variation, food cravings, gene-diet interaction, weight-loss trial
Abstract P184: Effects of Sodium and Potassium Supplementation on Blood Pressure and Arterial Stiffness in Untreated (Pre)Hypertensives on a Low-Sodium, Low-Potassium Diet
Authors: Gijsbers Lieke , Dower James , Mensink Marco , Geleijnse Johanna M
Published: July 2021

Introduction:
We performed a 12-week randomized placebo-controlled crossover study to examine the effects of sodium and potassium supplementation on blood pressure (BP) and arterial stiffness in untreated (pre)hypertensive individuals on a low-sodium, low-potassium diet.

Methods:
During the study, subjects were on a fully controlled diet that provided on average 2.4 g/d of sodium (equals 6 g/d of salt) and 2.2 g/d of potassium. After a 1-week run-in period, 37 subjects received capsules with supplemental sodium (3 g/d, equals 7.5 g/d of salt), supplemental potassium (3 g/d), or placebo, for four weeks each (not separated by wash-out), in random order. Fasting office BP, 24-h ambulatory BP, and measures of arterial stiffness (SphygmoCor®) were assessed at baseline and after each treatment.

Results:
Subjects had a mean pre-treatment BP of 145/81 mmHg and 68% (25 of 37) had systolic BP (SBP) ≥140 mmHg. In 36 subjects who completed the study, sodium supplementation increased urinary sodium by 97.6 mmol/24h (2.2 g/d) and potassium supplementation increased urinary potassium by 62.9 mmol/24h (2.5 g/d), compared to placebo (Table). Sodium supplementation significantly increased office BP by 7.5/3.3 mmHg, 24-h BP by 7.0/2.1 mmHg and central BP by 8.5/3.6 mmHg. Potassium supplementation significantly reduced 24-h BP by 4.0/1.7 mmHg. Measures of arterial stiffness did not change.

Conclusion:
Increasing the intake of sodium has a strong adverse effect on BP in untreated (pre)hypertensive individuals. Increased potassium intake, however, lowers BP even when people are on a reduced sodium diet. Short-term changes in sodium and potassium intake have little effect on arterial stiffness.

Trial registration:
ClinicalTrials.gov Identifier: NCT01575041
Abstract P188: Urinary Sodium and Potassium Excretion and Cardiovascular Diseases in Patients with Chronic Kidney Disease: the Chronic Renal Insufficiency Cohort study
Authors: Mills Katherine T , Chen Jing , Yang Wei , Appel Lawrence , Kusek John , Alper Arnold B , Delafontaine Patrice , Keane Martin G , Mohler Emile R , Ojo Akinlolu O , Rahman Mahboob , Ricardo Ana C , Soliman Elsayed Z , Steigerwalt Susan , Townsend Raymond R , He Jiang
Published: July 2021

Introduction:
Chronic kidney disease (CKD) patients are at an increased risk of cardiovascular disease (CVD) compared to the general population. Prior studies have produced contradictory results for the associations of sodium and potassium intake with the risk of CVD. In addition, these associations have not been investigated in patients with CKD.

Hypothesis:
We assessed the prospective associations between urinary sodium and potassium excretion and CVD event rates among patients with CKD.

Methods:
The Chronic Renal Insufficiency Cohort Study (CRIC) is a prospective cohort study of 3,939 participants with CKD from seven locations in the United States. Dietary sodium and potassium intake are assessed by averaging three 24-hour urinary measures and calibrating to sex-specific mean 24-hour urinary creatinine excretion. Composite CVD event is defined as myocardial infarction (MI), stroke, or congestive heart failure (CHF). CVD events are reported every six months and confirmed by medical record adjudication.

Results:
Over an average 6.5 years of follow-up, 660 CVD events were observed. The highest quartile (>197.7 mmol/24 hours) of adjusted sodium excretion had a hazard ratio (HR) of 1.52 (95% confidence interval 1.23, 1.88; p for trend across quartiles 70.5 mmol/24 hours) of adjusted potassium excretion had a HR of 1.46 (1.14, 1.87; p for trend across quartiles 0.0009) for composite CVD events compared to the lowest quartile (≤41.2 mmol/24 hours). When modeled continuously, every 100-mmol/24 hours higher adjusted sodium excretion was associated with an increased HR of 1.25 (1.14, 1.36) for composite CVD events, 1.25 (1.13, 1.39) for CHF, 1.32 (1.08, 1.61) for stroke, and 1.09 (0.93, 1.27) for MI. In addition, every 50-mmol/24 hour higher adjusted potassium intake was associated with an increased HR of 1.25 (1.10, 1.41) for composite CVD events, 1.32 (1.15, 1.52) for CHF, 1.11 (0.81, 1.54) for stroke, and 1.00 (0.79, 1.27) for MI.

Conclusions:
Our study found that high dietary sodium and potassium are both associated with an increased risk of CVD among patients with CKD. These findings suggest that reductions in high dietary sodium and potassium intake might reduce the risk of CVD among patients with CKD.
Abstract P191: Erythrocyte Polyunsaturated Fatty Acid, Weight Gain, and Risk of Becoming Overweight in Middle-aged and Older Women
Authors: Wang Lu , Manson JoAnn E , Rautiainen Susanne , Gaziano J. Michael , Buring Julie E , Tsai Michael Y , Sesso Howard D
Published: July 2021

Background:
Laboratory studies suggest that ω3 and ω6 polyunsaturated fatty acids (PUFA) may have divergent effects on the development of obesity. Epidemiologic studies comparing the associations for ω3 and ω6 PUFA are limited.

Objective:
We prospectively examined whether the baseline proportions of ω3 and ω6 PUFAs on erythrocyte membranes were associated with the risk of becoming overweight and changes in body weight in the Women’s Health Study (WHS).

Methods:
We identified WHS participants in a previous nested case-control study of hypertension who reported a body mass index (BMI) <25 kg/m
2
at baseline. Baseline fatty acid (FA) composition of erythrocyte membranes was measured as biomarkers of dietary FA intake using gas chromatography. Women who subsequently reported a BMI ≥25 kg/m
2
during follow-up were defined as becoming overweight. Body weight change was calculated as the difference in reported body weight from baseline to annual follow-up questionnaires.

Results:
Among 534 women with baseline BMI <25 kg/m
2
, 186 became overweight during an average of 10 years of follow-up. After initial adjustment for age, race, randomized treatment, the hazard ratios (HR) and 95% confidence interval (95% CI) for becoming overweight across increasing quartiles of erythrocyte PUFA were 1.00, 0.77 (0.49-1.21), 1.12 (0.75-1.67), and 1.19 (0.79-1.77) for
cis
ω6 PUFA (p, trend: 0.31), 1.00, 0.90 (0.61-1.31), 0.76 (0.51-1.13), 0.71 (0.45-1.10) for
cis
ω3 PUFA (p, trend: 0.09), and 1.00, 1.37 (0.84-2.22), 1.57 (1.01-2.43), and 1.58 (1.01-2.46) for ω6 to ω3 PUFA ratio (p, trend: 0.046). Additional adjustment for lifestyle and dietary factors did not substantially attenuate these associations, with HR (95% CI) of 1.00, 1.26 (0.76-2.08), 1.44 (0.91-2.28), and 1.56 (0.97-2.51) across increasing quartiles of ω6 to ω3 PUFA ratio (p, trend: 0.064). Analysis of longitudinal change in body weight showed similar associations. After multivariable adjustment, the mean±standard error of weight gain over an average of 10 years of follow-up across increasing quartiles of erythrocyte PUFA were 2.34±0.49, 1.92±0.53, 2.86±0.54, and 3.10±0.53 kg for
cis
ω6 PUFA (p, trend: 0.04), 2.97±0.52, 2.60±0.53, 2.74±0.53, 2.16±0.51 kg for
cis
ω3 PUFA (p, trend: 0.095), and 2.13±0.51, 2.65±0.54, 2.77±0.53, 2.98±0.52 kg for ω6 to ω3 PUFA ratio (p, trend: 0.05).
trans
PUFA 18:2 was not associated with the risk of becoming overweight or longitudinal weight gain. Analyses of joint categories of ω3 and ω6 PUFA did not show significant interaction
.

Conclusion:
In this prospective study, we found suggestive evidence that the proportion of
cis
ω6 PUFA on erythrocyte membrane was positively associated, and
cis
ω3 PUFA inversely associated, with the risk of becoming overweight and weight gain in initially normal-weight women.
Abstract P192: Healthy Eating Index and Metabolically Healthy Obesity in U.S. Adolescents and Adults
Authors: Camhi Sarah M , Evans E. W , Hayman Laura L , Lichtenstein Alice H , Must Aviva
Published: July 2021

Purpose:
Studies of dietary intake between metabolically healthy obese (MHO) and metabolically abnormal obese (MAO) cardiometabolic profiles have been limited to macronutrient and micronutrient composition in postmenopausal women. Thus, the purpose of this study is to determine whether diet quality, measured by total and component Healthy Eating Index 2005 (HEI-2005), is different between MHO and MAO in a nationally representative sample.

Methods:
Data from two National Health and Nutrition Examination Surveys (2007-2008; 2010-2011) were used to identify 133 obese (≥85th BMI %tile) adolescents 12-18 years, and 1164 obese (≥30kg/m2) adults 19-85 years. Adolescents and adults were classified as MAO if they had ≥2 cardiometabolic risk factors (adults: blood pressure ≥130/85 mmHg; triglycerides ≥150 mg/dL, HDL-C men <40, women <50 mg/dL; glucose ≥100 mg/dL; or on relevant medications; adolescents: triglycerides ≥150 mg/dL; HDL-C <40/50 mg/dL for boys/girls; blood pressure ≥90th %tile for age, gender, and height; glucose ≥100 mg/dL or on relevant medications), or MHO if they had <2 cardiometabolic risk factors. HEI-2005 scores were calculated from in-person 24-hour recall. Age group (12-18 years n=133, 19-44 years n=491; 45-85 years n=673) general linear regression models were used to determine whether total and component HEI-2005 scores differed between MHO and MAO after controlling for age, race, gender, NHANES wave, BMI and moderate to vigorous physical activity.

Results:
MHO adolescents (n=45; 72%) had better quality diets as indicated by a higher total HEI-2005 score compared with MAO (MHO vs. MAO, mean ± SE; p-value for difference: 55.2 ± 1.2 vs. 47.8 ± 2.6; p=0.005), higher milk scores (5.2 ± 0.4 vs. 3.5 ± 0.7; p=0.03), and higher scores from calories from solid fats, alcohol beverages, and added sugars (SoFAAS) (15.5 ± 0.7 vs. 11.6 ± 1.0, p=0.007). The SoFAAS component score is reverse coded where a higher score indicates better adherence to diet recommendations (<20%). Adults 19-44 years with MHO profiles (n=229, 46%) had higher HEI-2005 scores compared with MAO (54.0 ± 1.0 vs. 51.3 ± 0.8; p=0.008) and higher whole grain scores (0.9 ± 0.1 vs. 0.4 ± 0.07, p=0.003). No significant differences between MHO (n=127; 23%) vs. MAO in HEI-2005 scores or its component scores were observed in adults 45-85 years of age.

Conclusion:
MAO and MHO cardiometabolic profiles are characterized by differences in HEI-2005 total and component scores, though these differ by age group. Results suggest potential intervention targets which may improve cardiometabolic risk within obesity.
Abstract P199: Keep Moving, Your Health Depends On It: Impact Of Improved Physical Activity And Weight Loss In A Wellness Program
Authors: Oni Ebenezer T , Aneni Ehimen , Rouseff Maribeth , Tran Thinh , Guzman Henry , Das Sankalp , Brown Doris , Santiago-Charles Joann , Ochoa Teresa , Mora Joseph , Gilliam Cynthia , Lehn Virginia , Castillo Beatriz , Roberson Lara , Veledar Emir , Feldman Theodore , Agatston Arthur S , Post Janisse , Nasir Khurram
Published: July 2021

Negative impact of CVD as the leading cause of death in the US is worsened by the significant burden of obesity and associated morbidity and concerns about the growing population inactivity. The American Heart Association has emphasized worksite-based interventions to improve CV health. We evaluated the benefits of improved physical activity(PA) and weight loss(WL) among employees of the Baptist Health South Florida enrolled in a wellness intervention program.

Methods:
Employees with two or more Cardio-metabolic risk factors , such as total cholesterol ≥ 200 mg/dl, systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, hemoglobin A1C ≥ 6.5%, and body mass index (BMI) ≥ 30 were enrolled in an intervention program themed “My unlimited potential”. Interventions were focused on diet and PA modifications. We defined improved physical activity as the difference in the metabolic equivalents (METs) at 12 weeks follow-up and at baseline. WL (lbs) was the difference in weight at follow-up. The relationship between WL and changes in METs was explored in an ordered logistic regression.

Results:
Overall 203 (48±10 years, 78% females) employees were enrolled with a retention rate of 89% (n=181) at 12 weeks follow-up. At baseline the median weights was 211 lbs., and mean METs- 8.6, while at follow-up the median weight was 200 lbs, and the mean METs 11. At 12 weeks follow up 38% had significant WL (lost >5% of baseline weight). The median WL was 8.4 (IQR 4.8-13.0) lbs and the mean change in METs was 2.4±1.8. Median WL increased with increasing tertiles of METs change; tertile1- 6.5(4-11) lbs., tertile2- 9(6-13)lbs. tertile3- 11(7-15)lbs. Increased PA was related to increased WL across BMI categories adjusting for age, gender and baseline weight.

Conclusion:
This study points strongly toward the benefit of increasing PA among other lifestyle modification interventions in controlling weight. Although further follow-up of this population to evaluate sustainability of change is needed, our results clearly relate improved PA and health.
Abstract P215: Sleep Medication and Incident Stroke: The REGARDS Study
Authors: Petrov Megan E , Howard Virginia J , Kleindorfer Dawn O , Grandner Michael , Molano Jennifer R , Howard George
Published: July 2021

Introduction:
Preliminary evidence suggests sleep medications are associated with risk of vascular events; however, the long-term association with stroke risk is understudied. The aim of this study was to investigate the relation between sleep medication use and incident stroke.

Methods:
Within the REasons for Geographic And Racial Differences in Stroke study, 21,678 black and white participants (≥45 years) with no history of stroke were studied. Participants were recruited from 2003–2007. From 2008–2010, participants self-reported their prescription and over-the-counter sleep medication use over the past month. Suspected stroke events were identified on 6-month telephone contact, and associated medical records retrieved and physician adjudicated. Proportional hazards analysis was used to the estimate hazard ratios for incident stroke associated with sleeping medication use (0, 1–14, and 15+ days per month) controlling for sociodemographics, stroke risk factors, mental health symptoms, and sleep apnea risk.

Results:
At baseline, 9.6% of the sample used prescription sleep medication and 11.1% used over-the-counter sleep aids. Over an average follow-up of 3.3±1.0 years, 297 stroke events occurred. Over-the-counter sleeping medication use was associated (p = 0.014) with increased risk for incident stroke, with a 46% increased risk for use between 1 and 14 days a month (HR = 1.46; 95% CI: 0.99 - 2.15) and a 65% increased risk for use on 15 or more days (HR = 1.65; 95% CI: 0.96 - 2.85). There was no significant association with prescription sleep medications (p = 0.80).

Discussion:
Over-the-counter sleep medication use may independently increase the risk of stroke beyond other risk factors in middle-aged to older individuals with no history of stroke.
Abstract P219: Constant Numbers but Change in Stroke Subtype of Patients with First-Ever Minor Stroke/TIA from 2002 to 2012 in London, Canada
Authors: Bogiatzi Chrysi , Hackam Daniel G , McLeod Ian A , Spence David J
Published: July 2021

Introduction:
In Canada, major stroke hospital admission decreased by 27.6% and stroke mortality decreased by 28.2% between 1994 and 2004. However, there are no regional data on rates of incident minor stroke/TIA. We hypothesized that there has been a decrease in minor stroke/TIA over time due to better management of cerebrovascular risk factors.

Methods:
We included patients who diagnosed with a minor stroke/TIA in the regional Urgent TIA Clinic in London, Ontario, Canada from 2002 to 2012. We used a valid and reliable classification system for subtypes of ischemic stroke (SPARKLE) to categorize patients into five etiological stroke subtypes. Secular trends of minor stroke/TIA and the five ischemic stroke subtypes, represented with Lattice Plots, were analyzed using Poisson regression analysis with spline trend function.

Results:
Between 2002 and 2012, we identified 3,445 eligible patients. There was no decrease in minor stroke/TIA during the study period (348 patients in 2002 versus 261 patients in 2012, p=0.65 for trend). However, there was a significant increase in cardioembolic stroke/TIA, with a corresponding decrease in all other ischemic stroke subtypes. Patients in 2012 were one year younger compared to patients in 2002 (p=0.04).

Discussion:
Stroke mortality and major stroke incidence have decreased over time, but numbers of patients who experience a first-ever minor stroke/TIA have remained constant. With more intensive medical therapy there may have been a shift from major to minor stroke occurrence, given that more recent patients are younger than patients presenting in previous years. Further investigation is required to identify prevailing stroke risk factors in this population to decrease the burden and incidence of stroke/TIA.
Abstract P220: Exposure to Secondhand Smoke and the Risk of Stroke
Authors: Malek Angela M , McClure Leslie A , Cushman Mary , Lackland Daniel T
Published: July 2021

Background:
Stroke is a leading cause of death worldwide, and is a major public health concern in terms of morbidity, mortality, economic costs, and loss of productivity. While exposure to secondhand smoke (SHS) is a risk factor for cardiovascular disease, associations of SHS with risk of stroke have been inconsistent.

Hypothesis:
We investigated the hypotheses that SHS exposure is associated with increased incidence of stroke and stroke subtypes (ischemic stroke and hemorrhagic stroke) among non-smokers, including never and former smokers.

Methods:
The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled a U.S. population sample of 30,239 Caucasian and African-American men and women aged >=45 years in 2003-7 and is following them for stroke outcomes. We calculated the hazard ratio (HR) of stroke among non-smokers with SHS exposure using Cox proportional hazard models.

Results:
The cohort, without prevalent smoking, stroke and TIA (n=21,743), included 62% Caucasians and 38% African-Americans, with 55% females. Twenty-three percent reported SHS exposure the year prior to enrollment, and these individuals were more likely to be younger, African-American, male (all p<0.001), and have higher C-reactive protein (CRP) and white blood count (WBC) (p<0.05) compared to those not exposed. SHS exposure was associated with a 31% increased risk of any stroke event after adjustment for demographic, socioeconomic, and behavioral factors (Table 1). The association was seen only in ischemic, but not hemorrhagic stroke. Associations were slightly diminished after adjusting for traditional stroke risk factors, and markedly attenuated to the null after further addition of inflammation markers.

Conclusions:
SHS exposure was not related to stroke after accounting for inflammation markers. Further research is needed to confirm these findings.
Abstract P221: Effects of Immediate Antihypertensive Treatment in Men and Women with Acute Ischemic Stroke: The CATIS Study
Authors: Zhao Qi , Zhang Yonghong , Chen Jing , Xu Tan , Chen Chung-Shiuan , Tong Weijun , Bazzano Lydia A , He Jiang
Published: July 2021

Gender difference in the risk and prognosis of ischemic stroke has been reported. We examined the effects of immediate antihypertensive treatment on clinical outcomes among acute ischemic stroke by gender in the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). CATIS was a randomized, single-blind, and blinded end-point trial conducted in 4,071 acute ischemic stroke patients (2,604 men and 1,467 women). Eligible stroke patients with elevated systolic blood pressure (SBP) were randomly assigned to receive antihypertensive treatment (lowering SBP by 10-25% within the first 24 hours after randomization and BP < 140/90 mm Hg within 7 days) or control (discontinuing all antihypertensive medications). The primary outcome was a combination of death and major disability (defined by a modified Rankin score ≥ 3) at day 14 (or at discharge if earlier than 14 days) and 3-month post-treatment follow-up. The primary outcome was not significantly different between the treatment and control groups in either men or women. The primary outcome event rates for the two comparison groups were 31.6% and 32.1% in men (
P
= 0.79) and 37.3% and 36.1% in women (
P
= 0.65) at day 14; and were 23.6% and 24.5% in men (
P
= 0.60) and 28.0% and 26.6% in women (
P
= 0.56) at 3-month follow-up. The secondary outcomes were not different between treatment and control groups among men and women at 14 days or hospital discharge and at 3 months. The median modified Rankin scores (interquartile range) for the comparison groups were 2.0 (1.0-3.0) and 2.0 (1.0-3.0) in both men and women at day 14 or hospital discharge. The modified Rankin score, recurrent stroke, vascular event, and all-cause mortality at 3-month follow-up were similar between the treatment and control groups for both men and women. For example, the vascular event rates for the comparison groups were 2.4% and 3.0% in men (
P
= 0.34) and 2.4% and 2.9% in women (
P
= 0.58). There were no significant treatment and sex interactions for any of the primary and secondary outcomes. In conclusion, these data suggest that immediate antihypertensive treatment within the first 48 hours after stroke onset has no gender-specific effect on short-term outcomes of patients with acute ischemic stroke.
Abstract P231: Uric Acid Is Associated with Metabolic Syndrome in Children and Adults: The Bogalusa Heart Study
Authors: Sun Dianjianyi , Zhang Xiaotao , Li Shengxu , Fernandez Camilo , Chen Wei , Srinivasan Sathanur R , Berenson Gerald S
Published: July 2021

Background:
Elevated serum uric acid (UA) is commonly found in subjects with metabolic syndrome (MetS). This study assessed the hypothesis that UA is associated with levels of individual MetS components and the degree of their clustering patterns in different age periods.

Methods:
The study sample consisted of 2614 children (1577 whites, 1037 blacks; 1333 males; aged 4-18 years) and 2447 adults (1682 whites, 1765 blacks; 1072 males; aged 19-54 years) examined during 1987-2010. The adverse levels of MetS components, including body mass index (BMI), mean arterial pressure (MAP), triglycerides to HDL cholesterol ratio (TG/HDLC), and homeostasis model assessment of insulin resistance (HOMA), were defined as >75th percentile specific for age, race and sex. Observed/expected (O/E) ratio and intra-class correlation (ICC) were used as a measure of the degree of clustering of categorical and continuous variables, respectively.

Results:
UA was significantly positively associated with only BMI in children, and with all four components in adults. Odds ratios of UA associated with MetS were 1.74 in children and 1.92 in adults (p<0.001 for both), adjusted for race, sex and age. Trends in O/E ratios with UA quartiles are shown in the figure below. ICCs of 3- and 4-component clusters increased with increasing UA quartiles in children; however, only BMI-MAP-HOMA cluster showed an increasing trend of ICC in adults.

Conclusions:
The results suggest an important role of UA in the development of MetS in pediatric and adult populations. The findings provide further insights into the potential pathophysiological mechanisms of MetS and have implications for identification and treatment of high risk individuals for MetS in early life.
Abstract P233: Plasma essential fatty acids and type 2 diabetes risk: the Hoorn Study
Authors: Alssema Marjan , Cabout Mieke , Nijpels Giel , Stehouwer Coen D , Zock Peter L , Brouwer Ingeborg A , Elshorbagy Amany K , Refsum Helga , Dekker Jacqueline M
Published: July 2021

Background:
A high consumption of the polyunsaturated fatty acids linoleic acid (LA) and alpha-linolenic acid (ALA) instead of saturated fatty acids is known to reduce CHD risk, but data on the relation between LA and ALA intake and Type 2 Diabetes Mellitus (T2DM) risk are limited and inconsistent. Plasma levels of LA and ALA provide a relatively accurate reflection of the intake over several weeks or months, because of the essential nature of these fatty acids.

Objective:
To investigate the association of the percentage of LA and ALA in plasma lipids with fasting plasma glucose (FPG), post-load glucose (PLG) and glycated hemoglobin (HbA1c) as markers of T2DM risk.

Methods:
The study population included 667 Dutch men and women, aged 50-75 years from the population-based Hoorn Study. Baseline data for the current study were collected between 2000 and 2001, with follow-up in 2008. Linear regression models were used in cross-sectional and prospective analyses.

Results:
In cross-sectional analyses, plasma LA (per %) was significantly and inversely associated with FPG (
B
= -0.022 [-0.044, 0.000]) and PLG (
B
= -0.096 [-0.155, -0.036]), but not with HbA1c (
B
= 0.000 [-0.014, 0.014]), after adjustment for age, gender, total energy intake, BMI, waist-to-hip ratio, physical activity, fiber, dietary saturated fat intake, alcohol intake and education level. In prospective analyses, plasma LA was not significantly associated with FPG, PLG or HbA1c after adjustments for baseline glucose. In addition, no significant associations were found between plasma ALA and markers of T2DM risk in cross-sectional or prospective analyses.

Conclusion:
Plasma LA, but not ALA, was inversely associated with fasting and post-load glucose levels in cross-sectional, but not in prospective analyses. Further studies are needed to elucidate the exact role of plasma LA and ALA levels and dietary polyunsaturated fatty acids in glucose metabolism.
Abstract P236: Association of Obesity-related Genomic Loci and Type 2 Diabetes among Chinese Population
Authors: Kong Xiaomu , Zhang Xuelian , Zhao Qi , He Jiang , Chen Li , Zhao Zhigang , Li Qiang , Ge Jiapu , Chen Gang , Guo Xiaohui , Lu Juming , Weng Jianping , Jia Weiping , Ji Linong , Xiao Jianzhong , Shan Zhongyan , Liu Jie , Tian Haoming , Ji Qiuhe , Zhu Dalong , Zhou Zhiguang , Shan Guangliang , Yang Wenying
Published: July 2021

Obesity is one of the most important risk factors for type 2 diabetes (T2D). The aim of this study is to examine the associations between established obesity-related genomic loci and T2D as well as multiple quantitative glycemic traits among Chinese population. Single nucleotide polymorphisms (SNPs) near or within genes
NEGR1
,
SEC16B
,
TMEM18
,
ETV5/DGKG
,
BAT2
,
BDNFOS
,
BDNF
,
FAIM2
,
MC4R
,
KCTD15
,
MTCH2
,
GNPDA2
,
NPC1
,
MAF
,
PTER
,
PRL
,
PCSK1
,
PFKP
,
CTNNBL1
,
NRXN3
,
MSRA
,
SLC30A10
and
TFAP2B
from 23 independent genomic loci were genotyped among 5,338 T2D patients and 4,663 controls. An additive genetic model was assumed. Logistic and linear regression models were used to examine the associations of these genomic loci with T2D and glycemic traits, respectively. Two SNPs near
MC4R
(rs12970134) and
GNPDA2
(rs10938397) genes were significantly associated with T2D after adjusting for age and gender (OR [95% CI] = 1.14 [1.06, 1.22] for per A allele of rs12970134,
P
= 4.75х10
-4
; OR [95% CI] = 1.10 [1.03, 1.17] for per G allele of rs10938397,
P
= 4.54х10
-3
). When body mass index (BMI) and waist circumference was further adjusted for in logistic regression models, the association of
MC4R
with T2D maintained significant (OR [95% CI] = 1.10 [1.02, 1.20],
P
= 1.81х10
-2
) and that of
GNPDA2
attenuated to non-significance (OR [95% CI] = 1.06 [0.98, 1.14],
P
= 1.26х10
-1
). In addition, eight loci (near or within
SEC16B
,
BDNF
,
KCTD15
,
MAF
,
PRL
,
PCSK1
,
CTNNBL1
and
NRXN3
genes) showed significant associations with quantitative glycemic traits in the controls even after adjusting for BMI and waist circumference (
P
< 0.05). For example, the G allele of SNP rs10146997 in the
NRXN3
gene was associated with higher fasting insulin level (β [SE] = 0.064 [0.026],
P
= 1.31х10
-2
), HOMA-IR (β [SE] = 0.064 [0.027],
P
= 1.71х10
-2
) and lower insulin sensitivity (assessed by Matsuda index, β [SE] = -0.051 [0.026],
P
= 4.67х10
-2
) compared to the A allele. The T allele of SNP rs6013029 in the
CTNNBL1
was associated with greater fasting insulin(β [SE] = 0.098 [0.038],
P
= 1.02х10
-2
), HOMA-IR (β [SE] = 0.100 [0.039],
P
= 1.13х10
-2
) and HOMA-B (β [SE] = 0.104 [0.053],
P
= 4.73х10
-2
), as well as lower insulin sensitivity (β [SE] = -0.096 [0.039],
P
= 1.47х10
-2
) compared to G allele, suggesting its potential role in insulin resistance. In conclusion, these data suggest that these obesity-related genomic loci may be associated with T2D and glycemic traits after accounting for BMI and waist circumference among Chinese population.
Abstract P239: The Effect of BMI on Cardiovascular and Metabolic Syndrome Risk Factors in an Appalachian Pediatric Population
Authors: Weber Katelynn , Fischl Andrea F , Murray Pamela J , Conway Baqiyyah
Published: July 2021

Background:
Few studies have determined the effect of BMI on cardiovascular and metabolic syndrome risk factors in a primarily White, rural pediatric population. This study characterized a rural pediatric population by BMI category.

Methods:
Data on 11,084 individuals <20 years of age (mean 12.3, SD 5.0) were obtained from the C8 Health Project, a project that collected blood samples and self- or parent/guardian-reported demographics, medical diagnoses, height, and weight in 2005-2006 following a perfluorooctanoic acid (C8) contamination of drinking water in West Virginia and Ohio. Metabolic syndrome was defined as the presence of at least 3 standard criteria for diagnosis in a pediatric population (BMI >97
th
percentile, triglycerides >110 mg/dL, HDLc <40mg/dL, and fasting blood glucose >110mg/dL). Results were stratified by BMI category (<85% as normal, 85%-95% as overweight, and >95% as obese). Tests for linear trends across BMI categories and correlations with C8 were conducted.

Results:
The population was 51% male, 96% White, and 20% reported an average household income <$10,000. Forty percent (n=4406) were overweight or obese. Table 1 presents characteristics by BMI category. Total cholesterol, LDLc, and VLDLc, triglycerides, non-fasting glucose, fasting insulin, white blood cell count, and C-reactive protein increased with BMI percentiles, while HDLc and serum albumin decreased. No association was seen with fasting glucose. Serum creatinine also increased with BMI category. The point prevalence of metabolic syndrome was 4% (n=473). Serum C8 was not correlated with any variables.

Conclusions:
An alarming 40% prevalence of overweight and obesity was observed in this rural pediatric population. Because of the increase seen with cardiovascular and metabolic syndrome risk factors as BMI increased, this rural pediatric population may experience earlier onset of associated disease and complications. This warrants further public health involvement to decrease this Appalachian population’s risk.
Abstract P247: Multi-pollutant Mixtures and Digital Vascular Function in the Framingham Heart Study
Authors: Ljungman Petter L , Wilker Elissa H , Rice Mary B , Austin Elena , Schwartz Joel , Gold Diane R , Koutrakis Petros , Vita Joseph A , Mitchell Gary F , Vasan Ramachandran S , Benjamin Emelia J , Mittleman Murray A , Hamburg Naomi M
Published: July 2021

Background:
Studies of ambient air pollution and microvascular function have shown conflicting results.

Aim:
We investigated whether the association between fine particle mass with diameter ≤2.5μm (PM
2.5
) and microvascular function varies according to air pollution characteristics.

Methods:
We assessed baseline pulse amplitude and the ratio of fingertip pulse wave amplitude pre- and post- brachial artery occlusion (PAT ratio) in 1,365 participants of the Framingham Offspring and Third Generation Cohorts. We used K-means clustering to categorize mixtures of air pollutants into 5 distinct clusters of days with similar multi-pollutant profiles using elemental data and gases. We assessed the interaction between preceding day PM
2.5
and cluster adjusting for season, meteorology and covariates.

Results:
We observed differences in associations between PM
2.5
and baseline pulse amplitude by cluster (P=0.02 for interaction). On days with either low overall PM
2.5
levels but dominated by road and traffic dust and a high proportion of ultrafine particles (cluster 1) or high contributions of oil and wood combustion (cluster 5), higher PM
2.5
was associated with higher baseline pulse amplitude (see Figure). In contrast, on days with either a strong contribution of crustal materials, a mixture of fine and ultrafine particles, or agglomerated particles from regional sources (cluster 2, 3, and 4 respectively), PM
2.5
was not significantly associated with baseline pulse amplitude. We observed similar, non-significant associations between PM
2.5
and PAT ratio across the air pollution mixture clusters (P=0.14 for interaction).

Conclusions:
Air pollution mixtures with contributions from heating oil and wood combustion or traffic and road dust, both having high proportions of ultra-fine particles, were associated with altered microvascular tone. Our findings suggest that specific mixtures of particulate pollution may have distinct vascular consequences and support further studies of air pollution clusters to inform public policy. .
Abstract P248: Green Space and Mortality Following Ischemic Stroke
Authors: Wilker Elissa , Wu Chih-Da , McNeely Eileen , Mostofsky Elizabeth , Spengler John , Wellenius Gregory , Mittleman Murray
Published: July 2021

Background:
Residential proximity to green space has been associated with physical and mental health benefits, but whether green space is associated with post-stroke survival is not well understood.

Methods:
We identified patients ≥21 years of age admitted to the Beth Israel Deaconess Medical Center (BIDMC) between April 1, 1999 and October 31, 2008 with neurologist-confirmed acute ischemic stroke. Demographics, presenting symptoms, medical history and imaging results were abstracted from medical records at the time of hospitalization for stroke onset. The time of stroke symptom onset or time last seen normal was documented by the attending stroke neurologist at the time of hospital presentation. Participant addresses were geocoded and linked to average Normalized Difference Vegetation Index (NDVI) derived from satellite-based estimates within a 250x250m grid (July 2000-2012), distance to roadways with more than 10,000 cars/day, and 2000 US census block group. We identified deaths through June 2012 using the Social Security Death Index (SSDI).

Results:
We observed 929 deaths among 1,645 patients with complete data (median follow up: 5 years). In multivariable Cox models adjusted for indicators of medical history and demographic and socioeconomic factors, patients living in locations in the lowest quartile of green space had 28% higher rate of post-stroke mortality (95% Confidence Interval (CI): 4% to 59%) than those living in the highest quartile of green space (p-trend=0.009). This association remained significant after adjustment for residential proximity to a high traffic road.

Conclusions:
Residential proximity to green space is associated with higher rates of survival after ischemic stroke in multivariable adjusted models. Further work is necessary to elucidate the underlying mechanisms for this association and to better understand susceptibility factors that may contribute to greater mortality in low green space areas.
Abstract P249: Urinary Cadmium and Cardiovascular Health: Findings from the Survey of the Health of Wisconsin
Authors: Malecki Kristen M , Nieto F. Javier
Published: July 2021

Mounting evidence in both human and animal studies suggest cadmium exposure increases the risk for cardiovascular disease morbidity and mortality. Recent evidence have found associations between cadmium exposures and mortality in the general US population, however, studies of incident CVD events have been mixed. Consequently, there is a need to better understand determinants of variations in cadmium exposure and the association of current population exposure levels with cardiovascular risk factors in diverse population-based studies.

Data from a sub-sample of 300 participants from the 2008-11 waves of the Survey of the Health of Wisconsin (SHOW) were used to study the association between urinary cadmium levels and cardiovascular health. SHOW is based on a probabilistic statewide sample of adult (21-74 years old) residents of the state of Wisconsin. Good cardiovascular health (CVH) was defined as recommended by the American Heart Association, using a combination of “ideal or intermediate” levels of seven factors and health behaviors (body mass index, cholesterol, glucose, diet, physical activity, blood pressure and smoking). Associations of log-linear estimates of creatinine-adjusted cadmium levels (ug/g creatinine) and CVH were examined using logistic and linear regression models. Covariates included individual-level demographics (race/ethnicity and gender), SES (median family income and education), smoking status (current or former vs. non), and diet (fruits and vegetable consumption).

Urinary cadmium levels (ug/g creatine) were statistically higher than comparable national estimates among women (geometric mean = .36;95% CI =.30-.44) and populations living 200% above federal poverty estimates (geometric mean =.32; 95% CI .28-.38). Higher cadmium levels were associated with good CVH (OR 1.4; 1.06-1.90). Using linear regression log-cadmium levels were inversely associated with BMI (ß=-1.04; p-value=.002) after adjustment for sociodemographic, smoking and dietary factors. Stratified analyses found associations held among non-smokers but not current or former. Cadmium was not associated with any other individual CVH factors.

Paradoxically, findings suggest that urinary cadmium levels, a marker of chronic cadmium exposure, are associated with high SES, lower levels of BMI and good cardiovascular health in this population based sample, further exploration and long-term follow-up are warranted.
Abstract P253: Genome-Wide Association Study of Electrocardiographic Left Ventricular Hypertrophy among Persons of European Ancestry: the Kaiser Permanente/UCSF GERA Cohort
Authors: Iribarren Carlos , Shen Ling , Round Alfred D , McNulty Edward , Okin Peter M , Risch Neil , Schaefer Catherine , Jorgenson Eric
Published: July 2021

Electrocardiographic (ECG)-derived left ventricular hypertrophy (LVH) is a recognized phenotype of hypertensive target organ damage and an independent risk factor for cardiovascular disease morbidity and mortality, and has been shown to be 20 to 40% heritable. A major prior collaborative study (EchoGen) relied on echocardiography measurement of LVH. We report here the results of the first genome-wide association study of an ECG index of LVH, the Cornell voltage, in a large US, population-based cohort. The Kaiser Permanente/UCSF Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort enrolled 110,266 persons, of whom 84,760 (77%) were of European ancestry (EA). Twelve-lead ECGs (obtained as part of routine medical care) were available in 59% (n=52,423; 62% female, mean age ± SD, 62 ± 13 years) of EA members of the GERA cohort. For those with more than 1 ECG (75%), one was selected at random. We programmatically derived from the digital tracings the Cornell voltage as R in aVL plus S in V3 (in mV). Mean ± SD Cornell voltages were 1.39 ± 0.58 mV in men and 1.16 ± 0.55 mV in women. Genotypes were generated on 674,518 SNPs using a custom designed Affymetrix Axiom array, and imputation was conducted using the 1000 Genomes data as a reference set. We identified 10 genetic loci (nearest genes: NFIA, CRIM1, CCDC141, HAND1, VGLL2, CTNNA, TBX3, SIPA1L1, ZNF595, and PROCR) with genome-wide significant associations (p<5*10
-8
) with Cornell voltage as a continuous variable. Five of the loci (NFIA, CRIM1, HAND1, TBX3, and SIPA1L1) have previously been reported to influence QRS and PR intervals, while the other loci are novel. Interestingly, none of these loci were associated with left ventricular mass in the EchoGen consortium. Sex-specific analyses supported the association of these loci in both men and women; six loci were associated at a genome-wide significant level in these stratified analyses, including TBX3 and ZNF595 in both men and women, CCDC141, SIPA1L1, and PROCR in men, and VGLL2 in women, despite reduced sample sizes. These results may help elucidate both the biological and genetic basis of this clinically relevant phenotype.
Abstract P254: Genome-wide Association and Admixture Study of Iron-related Phenotypes in African Americans
Authors: Li Jin , Lange Leslie A , Duan Qing , Willis Monte S , Li Yun , Taylor Herman A , Wilson James G , Lange Ethan M
Published: July 2021

Introduction:
Iron deficiency is a heritable risk factor for various serious diseases, including cardiovascular disease (CVD). Genome-wide association studies (GWAS) have identified several variants associated with iron-related phenotypes in individuals of primarily European descent. African Americans (AA) have, on average, greater levels of iron deficiency compared to European Americans, but no large-scale genetic studies for iron-related phenotypes have been performed in individuals of African ancestry to date.

Methods:
We conducted genome-wide admixture mapping studies and GWASs for serum iron, serum ferritin, transferrin saturation (SAT), and total binding iron capacity (TIBC) in 2347 AA participating in the Jackson Heart Study (JHS).

Results:
Higher proportions of estimated global African ancestry were significantly associated with lower levels of iron (p=2.4x10
-5
), SAT (p=0.0019) and TIBC (p=0.042) and a number of chromosomal regions were observed to have local ancestry estimates nominally associated with these measures. We observed significant associations (P < 5x10
-8
) between serum TIBC levels and multiple independent single nucleotide polymorphisms (SNPs) around
TF,
a well-established region for iron and transferrin levels in Caucasians, and SNPs near two novel genes:
HDGFL1
and
MAF.
In addition, we replicated four other established loci in our AA samples including
SLC17A1
,
HFE
,
HIST1H2BJ
and
TMPRSS6
.

Conclusions:
1) We observed SNPs in or near three genes,
TF
,
HDGFL1
and
MAF
that were significantly associated with TIBC in AA. 2) We observed that both global and local genetic admixture are important predictors of iron measures in AA, further implicating the importance of certain genetic risk factors in the AA population. 3) We have also replicated four other established loci in our AA samples demonstrating the importance of some genetic risk factors for iron related measure across multiple populations. Future fine-mapping studies, incorporating less common variants, and functional studies should be undertaken to better characterize these loci and to ultimately identify the functional variants directly influencing TIBC levels in AA.