bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P235: Genetic Variants in
TCF7L2
Modulate Dietary Fat Intake on Changes in Body Composition During a Weight-Loss Intervention
Authors: Mattei Josiemer , Qi Qibin , Hu Frank B , Sacks Frank M , Qi Lu
Published: July 2021

Introduction:
Polymorphisms mapping to
TCF7L2
have been associated with increased risk of type 2 diabetes, impaired glucose and insulin metabolism, and adiposity. Recent observational studies and short-term randomized trials suggest dietary factors, especially fat, may modify
TCF7L2
genotype in relation to weight loss. The effect has yet to be verified in long-term intervention settings.

Hypothesis:
We assessed the hypothesis that two well-recognized
TCF7L2
single nucleotide polymorphisms (SNPs) modulate the response to diets of different fat content, in relation to long-term changes in anthropometry and body composition in a 2 year weight-loss intervention trial.

Methods:
The effect of
TCF7L2
SNPs rs7903146 and rs12255372 on changes at 6 months and 2 years in body mass and body composition measures obtained from DEXA scans was evaluated in 590 overweight/obese Caucasian participants of Pounds Lost, a 2-year weight-loss randomized clinical trial of diets differing in macronutrient proportions. Adjusted means were obtained for variant main effect and for interaction with assigned diet group as low-fat (20% from calories) vs. high-fat diet (40%).

Results:
After adjusting for age, sex, center, and baseline measure, rs12255372 TT (risk allele) carriers had significantly greater decrease at 6 months in BMI, total body fat and trunk fat mass, and marginal decrease in weight (
P
for interaction= 0.042, 0.029, 0.033 and 0.056, respectively), than those without this genotype, when following a low-fat diet. A significant interaction (
P
=0.035) with the randomized diet was observed for rs7903146 and change in lean mass at 6 months. No significant associations were observed at 2 years.

Conclusion:
In conclusion, overweight/obese individuals with the risk genotype of
TCF7L2
rs12255372 may reduce their body mass and adiposity by following a diet lower in total fat.
Abstract P236: The Heritability of Submaximal Exercise Heart Rate Response to Regular Exercise is Accounted for by Nine SNPs
Authors: Rankinen Tuomo , Sung Yun Ju , Sarzynski Mark , Rice Treva K , Rao DC , Bouchard Claude
Published: July 2021

Regular physical activity is the most effective non-pharmacological strategy to lower heart rate both at rest and during submaximal physical work. We have previously shown that endurance training-induced changes in heart rate are heritable (h
2
=0.34). However, few genes associated with heart rate training responses have been identified. The purpose of this study was to perform a genome-wide association study (GWAS) to uncover DNA sequence variants associated with submaximal exercise heart rate training responses in the HERITAGE Family Study. Heart rate was measured during steady-state exercise at 50 Watts (HR50) on two separate days both before and after a 20-week endurance training program in 473 white subjects from 99 families. Illumina HumanCNV370-Quad v3.0 BeadChips were genotyped using Illumina BeadStation 500GX platform. After quality control procedures, 320,000 single-nucleotide polymorphisms (SNPs) were available for the GWAS analyses. Associations between HR50 training response (ΔHR50) and the SNPs were tested using the MERLIN software package (single-SNP analyses) and standard regression models (multivariate analyses). Furthermore, conditional heritability analysis (MERLIN) was used to test the contribution of the most significant SNPs to the heritability of ΔHR50. Exercise training induced an average reduction of 11 bpm in HR50 (SD = 9.9 bpm, p<0.0001), while individual training responses ranged from a 12 bpm increase to a 42 bpm decrease. The strongest associations for ΔHR50 (adjusted for age, sex, BMI and baseline HR50) were detected with SNPs at the
YWHAQ
locus on chromosome 2p25 (p=8.1x10
-7
),
RBPMS
locus on 8p12 (p=3.8x10
-6
) and
CREB1
locus on 2q34 (p=1.6x10
-5
). In addition, 37 other SNPs showed p-values < 9.9x10
-5
. After removing redundant SNPs, the ten most significant SNPs explained 35.9% of the ΔHR50 variance in a multivariate regression model. Conditional heritability test showed that nine of these SNPs (all intragenic) accounted for 100% of the ΔHR50 heritability. Our results indicate that SNPs in nine genes related to cardiomyocyte and neuronal functions as well as cardiac memory formation fully account for the heritability of submaximal exercise heart rate response to regular physical activity in the HERITAGE Family Study.
Abstract P244: Comorbidities and Physical and Cognitive Impairments in Elderly Heart Failure Patients: Impact on Total Mortality: The Cardiovascular Health Study (CHS)
Authors: Murad Khalil , Goff David C , Morgan Timothy M , Burke Gregory L , Kitzman Dalane W
Published: July 2021

Background:
Comorbidities and physical and cognitive impairments are common in patients with heart failure (HF) and often associated with greater mortality. However, the prevalence of these conditions and their associated mortality risk in elderly patients with incident HF is unknown.

Method:
We examined the prevalence of 9 comorbidities and 4 measures of physical and cognitive impairments in 558 participants from CHS (age 79.2 ± 6.3, 52% men) with incident HF diagnosed between 1990 and 2002. Participants were followed prospectively until mid 2008 (an average follow up time of 4.7 years) to determine the associated mortality risk.

Results:
The burden of comorbidities was high; 60% of participants had ≥ 3 comorbidities, and only 2.5% had none. Impairment in ≥ 1 activity of daily living (ADL) and ≥ 1 instrumental activity of daily living (IADL) was present in 22.5% and 43.7% of participants, respectively. Significant cognitive impairment (modified mini-mental state exam (3MSE) score < 80) was present in 17% of participants. During follow up, 504 participants died, with 1-year and 5-year survival rates of 0.81 and 0.44 respectively. In a multivariable-adjusted model, the following were significantly associated with greater total mortality (hazard ratio: 95% confidence interval): comorbidities including diabetes mellitus (1.64: 1.33–2.03), chronic kidney disease (moderate (1.32: 1.07–1.62); severe (3.00: 1.82–4.95)), cerebrovascular disease (1.53: 1.22–1.92), and depression (1.44: 1.09–1.90); Physical impairment (1 ADL impaired (1.30: 1.04–1.63); ≥ 2 IADL impaired (1.49: 1.07–2.04)); and cognitive impairment (3MSE score < 80 (1.33: 1.02–1.73)).

Conclusion:
Elderly patients with incident HF have high burdens of comorbidities and physical and cognitive impairments that significantly contribute to their high mortality rates.
Abstract P246: Heart Failure Performance Measures: Eligibility and Implementation In the Community
Authors: Berardi Cecilia , Chamberlain Alanna M , Bursi Francesca , Redfield Margaret M , McNallan Sheila M , Weston Susan A , Jiang Ruoxiang , Roger Veronique L
Published: July 2021

Background:
The goal of heart failure (HF) performance measures is to improve the quality of care by enabling the practice implementation of guidelines. The guidelines define the population eligible for each measure. Little is known about the proportion of eligible patients to which these measures are applicable in the community.

Methods:
We determined the eligibility for and the adherence to performance measures and beta-blocker therapy in a community-based cohort of hospitalized patients diagnosed with incident HF from January 2005 to April 2011.

Results:
Of 294 inpatients with first ever HF (mean age 72 ± 15 years, 48% men), ejection fraction was measured in 292 (99%) patients during hospitalization. Of these, 97 (33%) had an ejection fraction <40% and were thus candidates for beta-blocker and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB) therapy. After excluding individuals with absolute contraindications, 71 patients were eligible to receive ACE inhibitors or ARB, and 86 were eligible to receive beta-blockers (figure). Among those eligible, 83% received ACEI/ARB and 91% received beta-blockers. Excluding those with relative contraindications, 70 patients were eligible for beta-blockers and 90% of them received it. Among the 139 (47%) individuals with HF and atrial fibrillation, 35 were eligible for warfarin and 49% received it. Of the 36 current smokers, 22 (61%) received cessation counseling during hospitalization.

Conclusions:
In the community, among patients hospitalized with HF eligible for performance measures, the implementation of performance measures varies by measure and can be improved for some. However, most community HF patients are not eligible for performance measures and other approaches should be identified to improve their care and outcomes.
Abstract P252: A Gene-centric Association Study of Venous Thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology Study
Authors: Tang Weihong , Cushman Mary , Pankow James S , Heckbert Susan , Basu Saonli , Weng Lu-Chen , Folsom Aaron R
Published: July 2021

Objective:
Venous thromboembolism (VTE) is a common disease associated with a high mortality rate. A few variants in genes for factor V (FV Leiden), prothrombin, antithrombin, proteins C and S, and blood groups have been documented to confer VTE risk, but other genetic determinants for VTE likely exist.

Methods:
We performed an association study for VTE using a gene-centric approach in the Longitudinal Investigation of Thromboembolism Etiology (LITE) Study, which comprises the Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts. A total of 280 VTE cases were ascertained in 9,827 participants of European ancestry in ARIC and 136 cases in 3,952 participants in CHS. The average follow-up time was 16 and 10 years in ARIC and CHS, respectively. Nearly 50,000 single nucleotide polymorphisms (SNPs) located in 2,100 candidate genes were genotyped by the Candidate gene Association Resource (CARe) gene chip. In each study, the association between each SNP and VTE was assessed with an additive genetic model using Cox proportional-hazards regression adjusted for age, sex, and field center. Data from ARIC and CHS were meta-analyzed using inverse-variance, fixed-effects models. SNPs with minor allele frequency < 1% or extreme p-values from Hardy-Weinberg disequilibrium test were excluded.

Results:
After adjusting for multiple testing, the thresholds for statistical significance and suggestive associations were set at 2.0x10−6 and 2.0x10−4, respectively. Four SNPs at the factor V gene locus exceeded the statistical significance threshold, with the top SNP being FV Leiden (rs6025, hazard ratio=3.01, p=9.7x10−17). Five SNPs showed suggestive associations with VTE (hazard ratios =1.29∼1.66), including those from the cholesteryl ester transfer protein (1 SNP), carboxypeptidase E (1 SNP), ABO (2 SNPs), and estrogen receptor 2 (1 SNP) genes.

Conclusions:
Among these genes, the FV Leiden variant and ABO are involved in coagulation and their associations with VTE have been previously confirmed. The other three genes have no known involvement in coagulation or hemostasis and thus, if replicated in future studies, may represent novel pathways.
Abstract P256: Myocardial Infarction is not a Risk Factor for Hospital-Acquired Venous Thrombosis: The Medical Inpatients Thrombosis (MITH) Study
Authors: Zakai Neil A , Callas Peter W , Repp Allen B , Cushman Mary
Published: July 2021

Introduction:
Venous thrombosis (VT) complicating medical admission is common and the risk factors are poorly understood. Myocardial infarction (MI) is often considered a risk factor for hospital-acquired VT with very little data other than expert opinion to support this assertion. We hypothesized that due to use of antithrombotic medications and early mobilization that MI may not be a hospital-acquired VT risk factor.

Methods:
All cases of VT complicating medical admission were found between 01-2002 and 06-2009 at a 500 bed teaching hospital using ICD-9 discharge codes and confirmed by medical record review. Controls were frequency matched 2:1 to cases by admission year and medical service and weighted by the inverse sampling probability. Acute MI was defined as acute MI on the discharge summary, and prior MI as mention of prior MI on the admission note. We used multivariable weighted logistic regression and the Taylor series to calculate odds ratios and 95% confidence intervals (CI) for VT for acute MI and prior MI. Models included age and sex, and a VT risk score previously developed.

Results:
Two-hundred ninety-nine cases of VT complicated 64,334 admissions (4.6 per 1000 admissions), 16 VT occurred in the 7,240 patients admitted with acute MI (2.2 per 1000 admissions). The table presents the percent of cases and hospital admissions with prior MI and acute MI, and the age- and sex-adjusted OR and multivariable-adjusted OR for VT. Prior MI was associated with a reduced odds of VT in both models (
Table
) while acute MI was not associated with VT accounting for VT risk factors (OR 0.83 95% CI 0.34, 2.01).

Discussion:
In contrast to ‘conventional wisdom’, prior MI and acute MI were not risk factors for hospital-acquired VT. For acute MI, short hospital stays, use of antithrombotic medications, and early mobilization after the MI may affect hospital-acquired VT risk. For prior MI, statin use and lifestyle changes may reduce hospital-acquired VT risk, however further work is needed to confirm this finding.

Table

Association of Acute MI and History of MI with Hospital-Acquired VT

Cases (%) (n = 299)
Hospital Admissions (%) (n = 64,334)
Odds Ratio for VT

Age-,Sex- Adjusted

Multivariable Adjusted
*

Past History of MI
5.8%
25.9%
0.44 (0.27, 0.73)
0.35 (0.18, 0.67)

MI on Admission
5.3%
11.3%
0.49 (0.23, 1.02)
0.83 (0.34, 2.01)

*

Adjusted for VTE prophylaxis use (mechanical and pharmacologic), full anticoagulation use, heart rate >100 on admission, hypoxic or ventilated on admission, history of VT, fracture in past 3 months, cancer in past 12 months, past history of congestive heart failure, and past history of a rheumatologic or inflammatory disease.
Abstract P279: Trends in Treatment and Control of Vascular Risk Factors in U.S. Stroke Survivors: Results from the National Health and Nutrition Examination Surveys (NHANES), 1999-2008
Authors: Shah Nilay S , Huffman Mark D , Ning Hongyan , Lloyd-Jones Donald M
Published: July 2021

Introduction:
Treatment and control of vascular risk factors reduce the likelihood of recurrent stroke in stroke survivors. Current nationally-representative data are sparse regarding prevention treatment and control rates.

Methods:
We evaluated rates of blood pressure, cholesterol, and dysglycemia treatment and control (to goal levels) in a weighted sample of 936 adult stroke survivors using data from five consecutive two-year NHANES cycles, 1999 to 2008. We used weighted linear regression to estimate time trends.

Results:
The Figure shows sex-specific trends in mean systolic and diastolic blood pressure, total and HDL cholesterol, glucose, and hemoglobin A1c from 1999 to 2008. All measures remained unchanged over the study period, except for a decrease in mean (SE) systolic blood pressure in women from 142 (3.4) to 131 (1.9) mmHg, and total cholesterol in men from 5.4 (0.2) to 4.6 (0.2) mmol/L (p < 0.05 for both). Blood pressure treatment rates did not change in either sex, but control rates increased in women from 23% (11 of 38) in 1999–2000 to 59% (50 of 93) in 2007–2008 (p = 0.03). Cholesterol treatment rates increased in women from 28% (19 of 73) to 34% (51 of 127) (p = 0.01) without increases in control to goal levels. In contrast, cholesterol control rates increased in men from 62% (17 of 23) to 78% (40 of 50) (p = 0.01). Dysglycemia treatment rates decreased in women from 20% (18 of 73) to 10% (15 of 127) (p = 0.02) but not in men, and control rates did not significantly change in either sex. Anti-platelet medication use also increased from 24% (36 of 157) to 34% (84 of 241) (p = 0.05).

Conclusions:
Despite improvements in blood pressure and cholesterol control rates in women and men, respectively, stroke secondary prevention through treatment and control of vascular risk factors remains substantially sub-optimal. Urgent action is needed to identify and close these gaps to reduce stroke morbidity and mortality in this high-risk group.
Abstract P280: The Association between Perceived Mental Stress and Mortality from Cardiovascular Disease is Modified by Education Level: The JACC Study
Authors: Zhang Wen
Published: July 2021

Background and Objective:
Perceived mental stress has been associated with increased mortality from cardiovascular disease for Japanese men and women (Iso H et al. Circulation 2002), but it is uncertain which subgroup is vulnerable for an adverse effect of mental stress because of the limited number of deaths in 8-year follow-up. We extended the follow-up to 15 years which enable us to conduct the stratified analysis by educational level in order to test our hypothesis that high education individuals are vulnerable for an adverse effect of mental stress.

Design:
We examined the above hypothesis in a cohort of 99,449 Japanese (41,656 men and 57,793 women) aged 40 to 79 years, who had no history of stroke, coronary heart disease or cancer at baseline. Perceived mental stress was assessed at baseline by a lifestyle questionnaire administered between 1988 and 1990 under the Japan Collaborative Cohort (JACC) Study, followed up to the end of 2006.

Results:
We documented a total of 3,801 (1,963 men and 1,838 women) deaths from total cardiovascular disease (ICD 10th revision, codes 101–199). The multivariable hazard ratio (95%, CI) of mortality from total cardiovascular disease for high versus low perceived mental stress was 1.22 (1.09 to 1.39, P for trend=0.01) in total subjects, 1.15 (0.99–1.34, P for trend=0.05) in men and 1.29 (1.09 to 1.52, P for trend=0.02) in women after adjusting for age, sex, body mass index, smoking status, alcohol intake, sports time, walking time, hours of sleep, and psychological variables, including anger, hurry, self estimation of quick response, hopelessness, sense of joyfulness, being trusted and fulfillment. That association was stronger for persons with higher education (>=12 years) than those with lower education (<12 years). The respective multivariable hazard ratio were 1.69 (1.20–2.38, P for trend<0.01) and 1.18 (1.05–1.34, P for trend=0.02) in total subjects, 1.69 (1.14–2.51, P for trend<0.01) and 1.10 (0.93–1.30, P for trend=0.20) in men, 1.76 (0.84–3.61, P for trend=0.08) and 1.27 (1.07–1.50, P for trend=0.06) in women, although the interaction for mental stress and education did not reached statistical significance.

Conclusion:
An adverse effect of perceived mental stress on cardiovascular health was confirmed in the longer-term follow-up and it may be pronounced for higher education group than for lower educational group.
Abstract P290: Stroke and Coronary Heart Disease - Predictive Power of Standard Risk Factors Until Old Age
Authors: Giang Kok Wai , Bjorck Lena M , Novak Masuma , Lappas George , Rosengren Annika
Published: July 2021

Introduction and Aim:
The SCORE model, based on age, sex, current smoking and systolic blood pressure, and serum cholesterol, was created to identify persons at increased risk for fatal cardiovascular disease (CVD) defined as death from coronary heart disease (CHD) or stroke within 10 years. We aimed to examine the short-term and long-term risk for CHD and stroke separately.

Methods and Results:
The Primary Prevention cohort study comprising 7174 men free from previous history of CHD, stroke and diabetes and aged 45 to 55 at baseline examination (1970–73) were followed up for 35 years. To estimate the cumulative effect of CHD and stroke, all participants were stratified into one of four risk groups defined by their burden of risk according to the SCORE factors. The 35 year relative risk (RR) for the men with the highest risk compared to those with the lowest was 3.38 (95 % CI 2.84–4.02) for CHD and 1.60 (95% CI 1.28–2.00) for stroke. When adjusted for competing risk the estimated 10 year cumulative risk for high risk individuals was 19.4% for CHD and 3.6% for stroke which increased substantially to 87% and 70% respectively after 35 years.

Conclusions:
The 10 year risk for CHD and stroke as calculated by the SCORE factors differs which indicates that the cumulative risk in middle age men based on the SCORE model can effectively be used to predict CHD but not stroke to the same extent. However, over an extended follow-up period until old age, the cumulative risk for stroke increased markedly such that high risk individuals developed a high cumulative risk for both CHD and stroke after 35 years.
Abstract P293: Perivascular Adipose Tissue of the Descending Aorta is Associated with SLE and Vascular Calcification
Authors: Shields Kelly J , Barinas-Mitchell Emma , Tepper Ping , Gingo Matthew R , Kao Amy H , Manzi Susan , Sutton-Tyrrell Kim
Published: July 2021

Introduction:
Women with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD). Traditional CVD and SLE related risk factors have been implicated, but do not fully account for this increased risk. Adipose produces pro-atherogenic components and visceral adipose is most strongly associated with vascular dysfunction and metabolic disorder. The proximity of perivascular adipose tissue (PVAT) to blood vessels may exacerbate vascular dysfunction and progression of CVD.

Hypothesis:
We hypothesized that SLE participants have increased PVAT surrounding the descending thoracic aorta with increased coronary artery calcification (CAC) and aortic calcification (AC) compared to healthy controls. PVAT is hypothesized to be positively associated with increased CAC and AC.

Methods:
Women participating in the: “Heart Effects on Atherosclerosis and Risk of Thrombosis in SLE” (HEARTS) study were clinically CVD-free, diagnosed with SLE for 2 years and age and race matched to healthy women, excluding those with diabetes (SLE, n=153; Control, n=158). The EBT scans were performed using an Imatron C-150 scanner. CAC/AC were quantified using Agatston scores and the PVAT was quantified using standard attenuations values for adipose tissue (−190 to −30 HU) on commercially available software. The total PVAT volume (tPVAT) was calculated by summing the areas and multiplying by the length of the participant’s aorta.

Results and Conclusions:
The SLE group had a greater tPVAT than the control group (p=0.0071) despite no differences in age, BMI, metabolic syndrome (MS), or waist or hip circumference. The SLE group was more likely to be hypertensive (p<0.0001) and had a larger waist to hip ratio (p=0.001 ) reflecting vascular dysfunction and a different adipose distribution. Total PVAT was associated with SLE (OR: 1.02, p=0.020) and the association remained significant after adjusting for CVD risk factors including BMI and MS (OR: 1.03, p=0.028). Based on linear regression analysis, the tPVAT in both SLE and controls was influenced by postmenopausal status, CRP, BMI, and MS, while history of smoking also influenced the control tPVAT. Unadjusted AC was associated with SLE by a factor of 2.3 (p=0.01), while there was no statistical difference between SLE and control for CAC. In logistic regression analysis, tPVAT was associated with AC (1.07,p<0.0001), which remained significant after adjusting for CVD and inflammatory factors including BMI and MS. The CAC (1.05,p<0.0001) association was attenuated with BMI and MS. In conclusion, tPVAT is greater in clinically CVD-free SLE versus control participants and is associated with AC independent of overall adiposity.
Abstract P307: Chitin-Glucan Fiber Effects on Oxidized Low-Density Lipoprotein: A Randomized Controlled Trial
Authors: Evans Joseph L , Bays Harold , Maki Kevin C , Evans Mal , Maquet Veronique , Cooper Raymond , Anderson James W
Published: July 2021

Oxidized low-density lipoprotein (OxLDL) is believed to play a role in the progression of atherosclerotic coronary heart disease (CHD) and the development of diabetes complications. This randomized, double-blind, placebo-controlled study of a novel insoluble fiber derived from the mycelium
Aspergillus niger
, chitin-glucan (CG) (ARTINIA™), evaluated 135 patients with fasting LDL-cholesterol 130-189.9 mg/dl and fasting glucose <=125 mg/dl. Participants were randomly assigned to receive CG (4.5 g/day; n=34), CG (1.5 g/day; n=33), CG (1.5 g/day) plus olive extract (n=33), or matching placebo (n=35) for 6 weeks. The primary outcome measure was the between-group difference in OxLDL. Secondary outcome measurements included effects upon lipid, glucose, insulin, and F2-isoprostane levels. After 6 weeks, CG 4.5 g/day (CG-4.5) significantly reduced mean OxLDL 3.8 U/L compared to baseline (58.0 U/L vs 61.8 U/L, respectively;
P
=0.006), and reduced OxLDL 4.97 U/L compared to placebo (P=<0.05). Other treatment groups generally had no significant effect upon OxLDL. CG treatment groups reduced LDL-cholesterol levels 3.2–;6.5% compared to placebo (P<0.05). In this study population without diabetes mellitus or elevated glucose levels, CG did not significantly affect high density lipoprotein cholesterol, triglycerides, glucose, insulin, F2-isoprostanes, or the homeostasis model assessment of insulin resistance. Treatments were well tolerated and with adverse experiences comparable to placebo. These results suggest that chitin-glucan, a novel insoluble fiber, may significantly reduce OxLDL and LDL-cholesterol levels, which may have therapeutic implications for patients at risk for CHD or other diabetes complications.
Abstract P308: γ-Glutamyltransferase and Mortality from Cardiovascular Disease: EPOCH-JAPAN
Authors: Li Yuanying , Iso Hiroyasu , Cui Renze , Nagasawa Shinya , Murakami Yoshitaka , Miura Katsuyuki , Ueshima Hirotsugu , Okamura Tomonori
Published: July 2021

Background:
Recently, γ-Glutamyltransferase (γ-GTP) has been positively associated with risk of cardiovascular disease (CVD), especially among non-drinkers. But the evidence is limited in Asian populations. The present study investigated the association between γ-GTP with mortality from ischemic stroke, hemorrhagic stroke and coronary heart disease in Japanese men and women, and further in non-drinkers.

Methods:
A total of 41,040 Japanese (men/women: 15,987/25,053) aged 40-79 years with no self-reported history of CVD at baseline from the Evidence for Cardiovascular Prevention from Observational Cohorts in Japan (EPOCH-JAPAN) which is a pooled analysis comprising 13 well-qualified Japanese cohorts for examining the relationship between health examination measures and CVD mortality. Sex-specific hazard ratios(HRs) and their 95% confident intervals(CIs) of CVD mortality for one-standardized deviation increment of log-transformed γ-GTP were calculated by Cox hazard models, adjusting for age (continuous), smoking status (never, past, 1–20/day and ≥21/day), drinking status (never, past and current), and sex-specific quintiles of body mass index, triglycerides, total cholesterol, systolic blood pressure, aspartate transaminase and alanine transaminase in multivariable model.

Results:
During an average 8.7-year follow-up, there were 314 (146 men and 168 women) deaths from stroke, 154 (101men and 53 women) deaths from coronary heart disease, and 701 (361 men and 340 women) deaths from total CVD. A significant association was found in the multivariable model between γ-GTP and mortality form stroke and total CVD in men, and mortality from coronary heart disease and total CVD in women. The respective multivariable HRs (95% CI) were 1.36 (1.13–1.65) and 1.17 (1.03–1.33) in men, and 1.76 (1.36–2.28) and 1.33 (1.19–1.49) in women. Because the proportion of current drinkers was 73% in men and 29% in women, we further examined the associations in non-drinkers. The respective multivariable HRs (95% CI) were 1.58 (1.08–2.31) and 1.42 (1.13–1.80) in male non-drinkers and 1.72 (1.28–2.33) and 1.32 (1.16–1.51) in female non-drinkers.

Conclusions:
γ-GTP was positively associated with CVD mortality in both Japanese men and women, specifically in non-drinkers.
Abstract P314: Response of the Cardiometabolic Risk Profile to Coronary Artery Bypass Surgery Followed by a 1-year Lifestyle Modification Program: A Pilot Study
Authors: Lévesque Valérie , Poirier Paul , Marette André , Mathieu Patrick , Després Jean-Pierre , Larose Éric
Published: July 2021

Introduction:
A coronary artery bypass graft (CABG) surgery induces an important physiological stress which could impact on cardiometabolic risk (CMR) variables. Furthermore, lifestyle modification programs are effective in secondary prevention.

Objective:
The present pilot study explored the response of CMR variables to a CABG surgery followed by a 1-year intervention targeting the improvement of lifestyle habits (nutrition/physical activity) in patients with established coronary artery disease (CAD).

Methods:
Anthropometric measurements, assessment of lipid profile and magnetic resonance imaging were performed before and after CABG surgery (n=32) and 1 year after the lifestyle modification program (n=26). An oral glucose tolerance test (OGTT) and a maximal treadmill test (modified Bruce) were also performed after surgery and at the end of the intervention program.

Results:
Six weeks after surgery, but before initiation of the lifestyle modification program, patients significantly reduced their body mass index (BMI) (Δ=−1.0 kg/m
2
, p<0.0001), waist circumference (Δ=−3.4 cm, p<0.0001), fat mass (Δ=−2.7 kg, p<0.0001), visceral (Δ=−25.5 cm
3
, p=0.007) and total abdominal adipose tissue volumes (Δ=−27.4 cm
3
, p=0.008). They also significantly decreased their LDL-C (Δ=−0.7 mmol/L, p=0.0003) and total cholesterol (Δ=−0.7 mmol/L, p<0.0001), as well as their total cholesterol/HDL-C ratio (Δ=−0.8, p=0.009). In response to the lifestyle modification program, subjects further improved their CMR profile with additional decreases in their BMI (Δ=−0.9 kg/m
2
, p=0.02) and waist circumference (Δ=−4.3 cm, p=0.002) as well as visceral (Δ=−36.2 cm
3
, p=0.03), subcutaneous (Δ=−29.1 cm
3
, p=0.005) and total abdominal adipose tissue volumes (Δ=−61.1 cm
3
, p=0.01). They also significantly reduced glucose area under the curve (Δ=−128.6 ρmol/L, p=0.0005) measured during the OGTT, TG/HDL-C ratio (Δ=−0.47, p=0.0006), triglycerides (Δ=−0.12 mmol/L, p=0.03), total cholesterol/HDL-C ratio (Δ=−0.34, p=0.003) and increased HDL-C levels (Δ=+0.2 mmol/L, p=0.0002). Cardiorespiratory fitness (CRF) was also improved significantly as reflected by an increase in VO
2
max (Δ=+4.0 mlO
2
/kg/min, p<0.0001) and by a reduced heart rate assessed at a standardized workload (3.5 mph, 2% slope) (Δ=−9 bpm, p<0.0001). All changes in cardiometabolic risk variables were observed despite a reduction in the use of cardiometabolic drugs in some patients. A multiple regression analysis showed that improvement in CRF largely explained (r
2
=0.61, p=0.0003) the improvement in 2-hours plasma glucose (OGTT) in response to the lifestyle modification program.

Conclusion:
Results of this pilot study suggest that the CMR profile of high risk patients with CAD is improved by the CABG surgery itself. In addition, a 1-year lifestyle modification program generates further cardiometabolic benefits.
Abstract P315: Increase in Stress May Contribute to Lower Heart Rate Variability in Healthy Young Subjects
Authors: Costa Amanda C , Silva Ana Gabriela C , Ribeiro Cibele T , Fregonezi Guilherme A , Dias Fernando A
Published: July 2021

Background:
Stress is one of the risk factors for cardiovascular disease and decreased heart rate variability is associated to increased mortality in some cardiac diseases. The aim of the study was to assess the impact of perceived stress on cardiac autonomic regulation in young healthy volunteers.

Methods:
35 young healthy volunteers (19 to 29 years old, 6 men) from a Brazilian population were assessed for perceived stress by the translated and validated Perceived Stress Scale (PSS, 14 questions) and had the R-R intervals recorded at rest on supine position (POLAR RS800CX) and analyzed (5 minutes, Kubius HRV software) by Fast-Fourier Transform for quantification of Heart Rate Variability (HRV).

Results:
Average data (±SD) for age, heart rate, BMI, waist circumference and percentage of body fat (%BF) were: 21.3±2.7 years; 65.5±7.9 bpm; 22.3±1.9 Kg/m
2
; 76.0±6.1 cm and 32.1±6.6%; respectively. The mean score for the PSS-14 was 23.5±7.2 and for the HRV parameter as follow: SSDN=54.8±21.2ms; rMSSD=55.9±32.2ms; low-frequency (LF)= 794.8±579.7ms
2
; High-frequency (HF)= 1508.0±1783.0 ms
2
; LF(n.u.)= 41.1±16.2; HF(n.u.)= 58.9±16.2; LF/HF=0.89±0.80 and Total power (TP)= 3151±2570ms
2
. Spearman nonparametric correlation was calculated and there was a significant correlation of PSS-14 scores and LF (ms
2
) (r=−0.343; p= 0.044). Other HRV variables did not shown significant correlation but also had negative values for Spearman r (TP r=−0.265, p=0.124; HF r=−0.158; SSDN r=−0.207; rMSSD r=−0.243, p=0.160). LF/HF and LF(n.u.) did not correlate to PSS-14 having Spearman r very close to zero (LF/HF r=−0.007, p=0.969; LF(n.u.) r=−0.005, p=0.976). No correlation was found for HRV parameters and BMI and there was a trend for statistical correlation of %BF and LF (ms
2
) (r=−0.309, p=0.071).

Conclusions:
These data demonstrate a possible association of perceived stress level and HRV at rest. Changes in LF can be a consequence of both sympathetic and parasympathetic activity, however, analyzing the other variables HF, TP, SSDN and rMSSD (all negative Spearman r) and due to the lack of changes in LF/HF ratio and LF(n.u.) we interpret that increased stress may be associated to decrease in overall heart rate variability. These changes were seen in healthy individuals and may point out an important mechanism in cardiovascular disease development.
Abstract P323: The Effect of Smoking Cessation on Weight at 12 Months in Patients Post-Myocardial Infarction
Authors: Grandi Sonia M , Filion Kristian B , Gervais Andre , Joseph Lawrence , O'Loughlin Jennifer , Paradis Gilles , Pilote Louise , Rinfret Stephane , Eisenberg Mark J
Published: July 2021

Background:
Current guidelines recommend smoking cessation and weight management for secondary prevention in post-myocardial infarction (MI) patients. However, little is known about the effects of smoking cessation on weight change post-MI.

Methods:
We examined this question using data from a randomized, double-blind, placebo-controlled trial investigating the effect of bupropion on smoking cessation in patients immediately following a MI. Weight change was compared between 3 groups: patients who reported complete abstinence, those who reported intermittent smoking, and those who reported persistent smoking during the 12-month follow-up. Analyses were restricted to patients who attended all follow-up visits (N=179). Weight was collected by research nurses at follow-up. Abstinence was defined by self-report in the previous 7 days and a carbon monoxide level ≤10 ppm.

Results:
During follow-up, 92 patients were abstinent, 49 were intermittently smoking, and 38 were consistently smoking. At baseline, 68.7% of patients were male, and the mean age was 53.9 years (SD 10.0). The mean weight and BMI at baseline were 78.4 kg (SD 17.7) and 27.3 kg/m
2
(SD 5.0), respectively. Mean body weight increased in all 3 groups during follow-up (
Figure
). However, patients who remained abstinent were more likely to gain weight than those who smoked persistently (difference 3.3 kg, 95% CI 0.9, 5.6). No difference in weight change was present between persistent and intermittent smokers. Both intermittent and persistent smokers reduced their daily cigarette consumption between baseline and 12-month follow-up (mean difference −15.5, 95% CI −19.1, −11.9 and −15.8, 95% CI, −19.9, −11.7, respectively).

Conclusions:
Patients who remain abstinent are more likely to gain weight 12 months post-MI. Given the importance of weight management in this population, strategies to ensure long-term weight control among patients who quit smoking are needed.
Abstract P325: The Prognostic Utility of Vitamin D and Its Seasonal Variation in Chest Pain Patients with Suspected Acute Coronary Syndrome Recruited from a Coastal Population in Western-Norway
Authors: Naesgaard Patrycja A , Pönitz Volker , Brúgger-Andersen Trygve , Aarsetoey Hildegunn , Grundt Heidi , Brede Cato , Staines Harry , Nilsen Dennis W
Published: July 2021

Background:
Several studies have shown a correlation between low vitamin D levels and cardiovascular risk. Serum concentration of 25-hydroxy-vitamin D (25(OH)D) is an established marker of vitamin D status. The purpose of this study was to assess the prognostic utility of 25(OH)D status in 871 chest-pain patients with suspected acute coronary syndrome (ACS) from Western-Norway.

Methods:
Serum samples for determination of 25(OH)D were obtained at admission. Baseline data consisted of serum levels of Troponin T (TnT), high sensitive C-reactive protein, creatinine, glucose, lipids and B-type natriuretic peptide measured in EDTA plasma, as well as clinical parameters, including age, gender, previous MI, angina pectoris, previous revascularizations (percutaneous coronary intervention or coronary artery bypass graft), congestive heart failure, diabetes mellitus, smoking status, hypercholesterolemia (total cholesterol > 250 mg/dl or statin treated hypercholesterolemia), beta-blocker prior to enrolment, hypertension, body mass index and seasons (defined as November through April and May through October). The main endpoint was total mortality in the total population and in the TnT positive group (TnT > 0.01 ng/mL). Multivariate analysis was performed in 794 patients with a complete set of baseline variables.

Results:
The mean age was 69.6 and 39% were females. After 24 months follow-up, 136 patients had died. The mean vitamin D value was 53.8 nM (95% CI, 52.2 nM - 55.4 nM) between November 2002 and April 2003, and 50.2 nM (95%CI, 48.1 nM - 52.3 nM) between May 2003 and October 2003; p = 0.008. In the univariate analysis of all cause mortality in the total population, the hazard ratio (HR) for 25(OH)D in the highest quartile as compared to the lowest quartile was 0.63 (95% confidence interval (CI), 0.38 - 1.03), p = 0.065, and in the TnT positive patients the HR was 0.58 (95% CI, 0.33 - 1.03), p = 0.062. No difference in mortality was found between the vitamin D quartiles in the TnT negative population. The results remained statistically non-significant in the multivariate analysis.

Conclusion:
In an univariate analysis there was a trend towards higher mortality in the lowest quartile of vitamin D as compared to the highest quartile in our chest pain population with suspected ACS. Furthermore, there was a statistically significant seasonal difference in vitamin D levels.
Abstract P333: Post-Stroke Outcomes Vary by Etiologic Stroke Subtype in the Atherosclerosis Risk in Communities Study
Authors: Jones Sara B , Sen Souvik , Offenbacher Steven , Lakshminarayan Kamakshi , Rosamond Wayne D
Published: July 2021

Background:
Early risk of recurrent stroke and mortality after stroke differ by subtype, but less is known about long-term outcomes and all-cause hospital readmission. Understanding these differences may have implications for secondary prevention and treatment of stroke. We examined rates of recurrent stroke, all-cause hospital readmission, and mortality by index stroke etiologic subtype.

Methods:
Atherosclerosis Risk in Communities Study cohort participants with a definite/probable first-ever stroke were identified and followed until death or 12/31/2008. The association between index and recurrent stroke subtype and median times to first recurrent stroke and first hospital admission were assessed according to index stroke subtype (infarction: thrombotic, cardioembolic [CE], and lacunar; hemorrhagic: subarachnoid [SAH] and intraparenchymal [IPH]). Incidence rates of recurrent stroke, all-cause hospitalization, and death were calculated by index subtype. Reasons for hospitalization were identified using primary ICD-9 codes. Recurrent stroke outcomes for hemorrhagic subtypes are not reported here due to small numbers of events.

Results:
A total of 987 persons with first-ever stroke were identified and followed for an average 5.3±5.0 years post-stroke (48.7% thrombotic, 20.0% CE, 18.5% lacunar, 8.6% IPH, and 4.2% SAH). During follow-up, there were 183 recurrent strokes among 147 participants, 3234 hospitalizations among 746 participants, and 529 deaths. Only 139 (14.1%) participants had none of these events during follow up. Roughly 70% of recurrent strokes were of the same subtype as the index stroke; however, only a third were the same when the index stroke was lacunar. Time to first recurrent stroke varied by subtype (median days [range]; thrombotic, 930.5[2-4692]; CE, 271[2-5566]; lacunar, 789[5-4361]) while time to first hospitalization was more similar, ranging from 102.5[4-3634] among CE to 370[6-6506] among IPH. Incidence rates of recurrent stroke (per 100 person-years) were highest after lacunar stroke (4.4) followed by thrombotic (3.7), and CE (2.7). All-cause hospital readmission rates were: thrombotic (58.8), CE (88.9), lacunar (60.1), IPH (59.4), and SAH (35.3); and mortality rates were: thrombotic (9.0), CE (15.1), lacunar (7.4), IPH (22.3), and SAH (7.3). Non-stroke related hospitalizations, including heart failure, ischemic heart disease, and diabetes were not uncommon after stroke, particularly after thrombotic and CE strokes.

Conclusion:
While the highest mortality was observed for IPH, there was significant burden of recurrent stroke and all-cause hospitalization for other stroke subtypes, especially lacunar and CE. Hospital readmission rates were high for all subtypes, suggesting there may be opportunities to reduce post-stroke readmissions. Prevention efforts tailored according to etiologic stroke subtype may be warranted.
Abstract P341: An Approach for Defining Cognitive Decline in Epidemiologic Studies
Authors: Gillett Sarah R , Letter Abraham J , McClure Leslie A , Wadley Virginia G , Unverzagt Frederick W , Kissela Brett M , Kennedy Richard E , Glasser Stephen P , Levine Deborah A , Cushman Mary
Published: July 2021

Introduction:
Prospective studies of cognitive decline are vital for the identification of risk factors and preventative strategies, but there is no established definition of cognitive decline in epidemiologic studies. To plan a case-cohort biomarker study, a panel of experts sought to identify 500 participants with significant cognitive decline in the REasons for Geographical and Racial Differences in Stroke (REGARDS) cohort.

Methods:
REGARDS is a population-based cohort of 30,239 black and white Americans enrolled from 2003-7 in their homes and followed by telephone. Global cognitive function was measured serially using the Six Item Screener (SIS), and learning, memory, and executive function using Word List Learning (WLL), Word List Recall (WLR), and Animal Fluency (AF) tests. In an initially cognitively intact cohort (SIS > 4 at baseline), cognitive decline was defined as performance 1.5 SD below the age-, race-, sex-, and education-based norms on 2 of 3 cognitive domain scores (AF, WLL, WLR).

Results:
Median follow up time was 3.6 years for the WLL/WLR and 3.0 years for AF. A score of >1.5 SD from predicted on at least 2 of the 3 cognitive domains at the most recently administered test identified 543 cases. Further restriction to >1.6 SD identified 497 cases. Most (85.5%) cases were impaired on WLL and WLR only; 14.5% of cases had impairment on AF (
Figure 1
). By design, age, sex, race, and education did not differ between cases and non-cases. Residence in the stroke belt region, lower income, diabetes, heart disease, current smoking, alcohol abstinence, lack of weekly exercise, higher body mass index, and higher C-reactive protein were associated with case status.

Conclusion:
Defining cognitive decline based on deviation from age-, race-, sex-, and education- predicted scores on at least 2 cognitive domains identified a case phenotype that was associated with other demographic and adverse vascular risk factors.
Abstract P343: Comparison of Two-stage and One-stage Meta-analyses: An Example of eGFR-Cardiovascular Mortality Association (for CKD-PC collaborators)
Authors: Sang Yingying , Matsushita Kunihiro , Mahmoodi Bakhtawar K , Astor Brad C , Coresh Josef , Woodward Mark
Published: July 2021

Purpose:
Individual participant data (IPD) meta-analysis provides precise statistical estimates. Two approaches to meta-analyze IPD are currently used. The 1-stage approach fits a regression model to a pooled dataset including all studies. The 2-stage approach fits models in individual studies and meta-analyzes the estimates. However, their comparability has not been well described. We compare these methods for eGFR-cardiovascular mortality association in the CKD Prognosis Consortium (CKD-PC).

Methods:
For the 1-stage method, we fitted a Cox stratified model, allowing each study to have a unique baseline hazard but assuming a common hazard ratio (HR) for eGFR across studies. For the 2-stage method, we first fitted a Cox model in each study, and then meta-analyzed HRs using a fixed-effect (assuming one true HR for eGFR across studies) and a random-effects (allowing some variance of true HR) model. eGFR was fitted as linear splines in all models.

Results:
In a sample of 18 of 46 cohorts joining CKD-PC (191,276 participants and 8,732 cardiovascular deaths [CHD, stroke, or heart failure]), these methods gave nearly identical estimates except for the width of the confidence intervals (
Figure
). The 95% CIs were wider as methods made fewer assumptions - narrowest for 1-stage method, slightly wider for the fixed-effect 2-stage and wider for the random-effects 2-stage method.

Conclusion:
The two-stage and one-stage meta-analyses provided nearly identical estimates for the eGFR-cardiovascular mortality relationship. The random-effects 2-stage method will provide conservative estimates with wider 95% CIs but this is necessary in the presence of heterogeneity.