bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP007: Epicardial Fat Thickness: Distribution of and Associations With Cardiovascular Risk Factors in the Framingham Heart Study
Authors: Chuang Michael L , Gona Philimon , Oyama-Manabe Noriko , Salton Carol J , Hoffmann Udo , Manning Warren J , O'Donnell Christopher J , Fox Caroline S
Published: July 2021

Introduction:
High pericardial fat volume (fatVOL) is associated with excess cardiovascular disease (CVD), but analyses for true fat volume can be time-consuming and require specialized software. Linear epicardial fat thickness (fatTHK) can be measured quickly from cardiac magnetic resonance (MRI) images and may serve as a surrogate for fatVOL. We sought to determine the distribution and CVD risk factor correlates of high fatTHK and to compare fatTHK with fatVOL in a community-dwelling adult cohort.

Methods:
Participants were drawn from the Framingham Heart Study Offspring cohort (N=995, aged 65±9 years, 54% women) and underwent cardiac MRI (SSFP sequence) and multidetector CT during 2002-2005. Clinical and risk factor covariates were obtained at the preceding cycle 7 examination (1998-2001). FatVOL was determined from volumetric MDCT data. FatTHK was measured from the MRI 4-chamber view over the midlevel right ventricular free wall at end-diastole. A healthy referent subsample (N=328), free of major CVD risk factors, was used to determine sex-specific cut points for high fatTHK. Odds ratios for high (>90th percentile) fatVOL and fatTHK versus common CVD risk factors were determined.

Results:
FatTHK was greater in men than women and increased with age in both sexes. FatTHK correlated with fatVOL at r=0.45 (p less than 0.001) High fatTHK was >=16.0 mm in men and >=13.3 mm in women, with 20.1% prevalence in men and 18.1 % in women. In both sexes, high fatVOL was associated (
Table
) with obesity, metabolic syndrome, dysglycemia, hypertension, prevalent CVD and hypertriglyceridemia. Similar associations, with slightly lower odds ratios, were seen for fatTHK.

Conclusions:
Greater fatTHK is associated with an excess burden of multiple CVD risk factors. Although correlation between linear fatTHK and true fatVOL was relatively modest, both measures appear to have similar associations with common CVD risk factors. FatTHK may be advantageous in that it can be determined quickly using standard MRI sequences for ventricular function.

Table.

Odds Ratios for High Pericardial Fat vs. Common CVD Risk Factors

fatVOL: Men
fatVOL: Women
fatTHK: Men
fatTHK: Women

Obesity, BMI >=30 kg/m2
4.34 (2.78–6.78)
3.13 (2.03–4.82)
2.52 (1.77–3.60)
2.62 (1.84–3.74)

Metabolic Syndrome
3.72 (2.38–5.83)
2.60 (1.65–4.08)
2.59 (1.75–3.84)
2.21 (1.53–3.17)

Dysglycemia, FPG >=100 mg/dL
2.64 (1.72–4.06)
3.05 (1.98–4.68)
1.75 (1.22–2.50)
1.56 (1.10–2.23)

Hypertension, S>=140 or D>=90 mmHg
2.51 (1.66–3.78)
1.96 (1.30–2.97)
2.10 (1.48–2.98)
1.58 (1.13–2.22)

Prevalent CVD
1.94 (1.17–3.21)
2.48 (1.41–4.38)
1.73 (1.17–2.55)
1.83 (1.19–2.81)

Triglycerides >=150 mg/dL
1.89 (1.25–2.86)
2.21 (1.43–3.42)
1.64 (1.15–2.34)
1.98 (1.38–2.82)

Low HDL: M<40, W<50 mg/dL
1.57 (1.03–2.38)
1.44 (0.91–2.28)
1.40 (0.98–1.99)
2.57 (1.80–3.67)
Abstract MP008: Fatty Liver, Visceral Adipose Tissue and Atherosclerotic Calcification: The Jackson Heart Study
Authors: Liu Jiankang , Bidulescu Aurelian , Musani Solomon K , Carr John J , Wilson James G , Taylor Herman A , Fox Caroline S
Published: July 2021

Background:
Both fatty liver and abdominal visceral fat (VAT) are independently associated with cardiometabolic risk factors. We investigated whether fatty liver and VAT are jointly associated with coronary artery (CAC) or abdominal aortoiliac (AAC) calcification.

Methods:
Jackson Heart Study (JHS) participants (n=2884, mean age 60 years, 65% women) underwent CT assessment for assessment of fatty liver, VAT, and CAC and AAC. Fatty liver was measured by liver attenuation (LA; low LA=high fatty liver). Cross-sectional associations between LA, VAT, CAC and AAC were examined in logistic regression models.

Results:
LA (per 1-standard deviation [SD] decrement) was associated with CAC in the age-, sex-adjusted (OR 0.84, 95%CI 0.7–0.9,
p=0.0001
) and multivariable adjusted model including age, sex, smoking and alcohol, systolic blood pressure, treatments for hypertension, dyslipidemia and diabetes, total cholesterol and HDLC (OR 0.89, 95%CI 0.8–0.9,
p=0.02
). The association persisted for LA with CAC when additionally adjusted for VAT (OR 0.89, 95%CI 0.8–0.9,
p=0.04
) or body mass index (BMI) (OR 0.89, 95%CI 0.8–0.9,
p=0.04
). Abdominal VAT (per 1-SD increment) was associated with CAC in age-, sex-adjusted models (OR 1.27, 95%CI 1.2–1.4,
p=0.0001
), but the association was attenuated in the multivariable adjusted model (OR 1.10, 95%CI 0.9–1.2,
p=0.09
) or with additional adjustment for LA (
p = 0.24
) or BMI (
p = 0.36
). For AAC, the associations with LA and VAT were only present in the age-, sex-adjusted model. In addition, we did not observe interactions between LA and VAT for CAC (
p=0.18
) or AAC (
p=0.24
).

Conclusion:
Fatty liver, but not VAT, is independently associated with atherosclerotic calcification in African American men and women and these observations persist after accounting for VAT or BMI.
Abstract MP018: Moderate-to-Vigorous Physical Activity: Evidence for a Displacement Effect on Sedentary Behaviour
Authors: Herman Katya M , Paradis Gilles , Mathieu Marie-Eve , O'Loughlin Jennifer , Tremblay Angelo , Lambert Marie
Published: July 2021

Background:
Sedentary behaviour has detrimental health consequences, distinct from those of physical inactivity. An individual can be both highly active and highly sedentary: While the displacement hypothesis proposes that time spent active displaces time that would otherwise be spent sedentary, the compensation hypothesis suggests that increased physical activity (PA) may be associated with increased sedentary behaviour (SED) in non-active time.

Objectives:
The aim was to assess whether higher levels of childhood participation in moderate to vigorous PA (MVPA) are associated with higher levels of SED, or whether time spent in SED is displaced by higher levels of MVPA.

Methods:
Participants were 290 boys and 245 girls aged 8–10 years in the QUebec Adipose and Lifestyle InvesTigation in Youth (QUALITY) study. PA and SED were assessed by accelerometer over a 1-week period (SED ≤ 100 cpm, MVPA ≥ 2296 cpm), and quantified as mean time spent per day. Total PA was the sum of light PA + MVPA. Self-reported data included sports participation (number of teams), television viewing and computer/video game use (hours/day). Spearman correlations and multiple linear regression (adjusting for age, sex, body mass index, Tanner stage, parental education, accelerometer wear-time) were used to assess associations between PA and SED variables.

Results:
Higher MVPA and VPA were negatively correlated with SED (r=−0.44 and −0.35; p<0.001), and positively correlated with total PA (r=0.58 and 0.45; p<0.001). SED was negatively correlated with TPA (r=−0.65, p<0.001). Only weak correlations were found between MVPA and sports participation, the latter not associated with SED. MVPA and VPA were not significantly correlated with TV, computer/video or total screen time; objectively measured SED was only weakly associated with specific sedentary behaviours. On average, for each additional 10 minutes of MVPA, children spent 14 minutes less in SED, or for each additional 5 minutes of VPA, 10 minutes less in SED. Associations were stronger in overweight/obese children compared to healthy weight children.

Conclusions:
Higher levels of MVPA in children displace SED, and are also associated with higher total PA over and above the additional amount of MVPA. The SED displacement benefits of higher MVPA may be greatest in overweight/obese children. Public health strategies should focus on both increasing PA and decreasing SED as essential targets to improve overall PA in children.
Abstract MP019: Should Global Cardiovascular Risk Guide Treatment of Stage One Hypertension? A Cost-effectiveness Analysis
Authors: Moran Andrew , Rasmussen Petra , Zhao Rachel , Coxson Pamela G , Guzman David , Pletcher Mark , Bibbins-Domingo Kirsten , Goldman Lee
Published: July 2021

Introduction:
Current U.S. hypertension guidelines base treatment on clinic blood pressure (BP) alone. International guidelines recommend adding global cardiovascular disease (CVD) risk to guide treatment. We projected incremental effectiveness and costs of treating stage 1 hypertension based on CVD risk assessment.

Methods:
We used the Coronary Heart Disease (CHD) Policy Model, a validated state-transition simulation of the CVD epidemic in the US, to model CHD and stroke events, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness (ICE) of increasingly aggressive treatment of hypertensive patients. Census and national survey data were used to estimate joint distributions of risk factors by age and sex; the CVD risk function was based on Framingham. We modeled treatment of BP to an approximate target <140/90 mmHg using standard dose medications, including averaged annual drug costs (e.g., $253 for a systolic BP reduction of 11.5 mmHg; $1,036 for reduction of 36.7 mmHg) and monitoring costs (2 or 4 visits/year for stage 1 or 2 plus 1 lab test/year for all). We compared a strategy in which only stage 2 hypertensives (≥160/≥100 mmHg) were treated to increasingly aggressive strategies in which stage 1 hypertensives (140-159/90-99 mmHg) with successively lower global CVD risk (15%, 10%, 5% risk, then all of stage 1) were also treated.

Results:
Reaching hypertension treatment targets with any policy simulated would prevent between 389,000 and 478,000 CVD events annually (
Table
). Treating all stage 2 and ≥15% CVD risk stage 1 hypertensives would be cost-saving and treating stage 1 with ≥10% or ≥5% CVD risk would incur modest costs. Treating all stage 1 would cost $161,000/QALY more than treating only ≥5% CVD risk.

Conclusions:
Treatment of low risk stage 1 hypertensives appears to come at high cost and limited added benefit unless treatment costs can be minimized. Using global CVD risk assessment might allow re-allocation of resources toward controlling hypertension in the highest risk patients.

Table

Simulated CVD outcomes, costs, and cost-effectiveness, 2010-2011, the CHD Policy Model

Scenario
Annual number hypertensives treated
Annual CVD events
Annual QALYs (millions)
Annual costs (millions, $US)

ICER
*

Base case, no intervention
-
2,387,000
127.67
$827,313
reference

Treat only stage 2
23,364,180
1,997,000
128.78
$825,264
cost saving

Treat stage 2 + stage 1 >=15% CVD risk
30,654,361
1,943,000
128.93
$824,541
cost saving

Treat stage 2 + stage 1 >=10% CVD risk
34,947,200
1,928,000
128.97
$824,898
$9,381

Treat stage 2 + stage 1 >= 5% CVD risk
44,321,985
1,913,000
129.02
$826,433
$28,931

Treat stage 2 + all stage 1
50,863,390
1,909,000
129.04
$828,290
$160,630

*ICER = difference in cost/difference in QALY in comparison with the next less effective strategy
Abstract MP021: Glycated Hemoglobin and Risk of Incident Hypertension in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Bower Julie K , Appel Lawrence J , Matsushita Kunihiro , Young J. H , Alonso Alvaro , Brancati Frederick L , Selvin Elizabeth
Published: July 2021

Introduction:
Diabetes and hypertension often co-occur and have shared risk factors. While hypertension is known to predict diabetes, hyperglycemia may also be independently associated with incident hypertension. We investigated glycated hemoglobin (HbA1c) as a predictor of incident hypertension in individuals in the Atherosclerosis Risk in Communities (ARIC) cohort.

Methods:
We conducted a prospective analysis of 9,603 middle-aged participants in the ARIC Study without hypertension at baseline. Using Cox proportional hazards models, we estimated the association between HbA1c at baseline and incident hypertension by two definitions: (1) self-reported hypertension during a maximum of 18 years of follow-up; and (2) measured blood pressure or hypertension medication use recorded at clinic visits for a maximum of 9 years of follow-up.

Results:
We observed 4,800 self-reported hypertension cases and 1,670 visit-based cases. Higher baseline HbA1c was associated with increased risk of hypertension and was robust to adjustment for a comprehensive list of confounders that included two measures of adiposity (body mass index and waist-hip ratio). Compared to nondiabetic adults with HbA1c <5.7%, HbA1c in the pre-diabetic range (5.7–6.4%) was independently associated with incident self-reported hypertension (HR 1.25, 95% CI: 1.16–1.34) and visit-detected hypertension (HR 1.18, 95% CI: 1.04–1.34). The HR per 1-% point higher HbA1c was 1.11 (1.06–1.16) among those with no history of diabetes and 1.06 (1.01–1.11) among those with diagnosed diabetes; the continuous associations between HbA1c and incidence of self-reported hypertension for individuals without diabetes are illustrated in the Figure.

Conclusions:
The association of HbA1c with incident hypertension suggests that elevated levels of circulating glucose may independently contribute to cardiovascular risk through higher blood pressure. Persons with elevated HbA1c, even without a prior diabetes diagnosis, are at increased risk of developing hypertension.
Abstract MP037: Plasma Organochlorine Concentration and Risk of Diabetes: the Nurses' Health Study
Authors: Wu Hongyu , Bertrand Kimberly A , Choi Anna L , Hu Frank B , Laden Francine , Grandjean Philippe , Sun Qi
Published: July 2021

Background:
Animal experiments have suggested that exposure to persistent organic pollutants (POPs) may lead to increased risk of type 2 diabetes. Although recent human studies supported this hypothesis, evidence from prospective investigations is sparse.

Objective:
To examine the associations of plasma POP concentrations with risk of incident type 2 diabetes in a prospective setting among US women.

Methods:
Study population was comprised of participants from two independent nested case-control studies in the Nurses’ Health Study, in which major polychlorinated biphenyl (PCB 118, 138, 153, and 180), p-p'- dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyltrichloroethane (DDT), and hexachlorobenzene (HCB) were measured. A non-parametric approach was used to derive standardized scores for plasma concentrations of lipid-adjusted POPs within each study to minimize between-study variation of the POP measurements. Risk of incident type 2 diabetes during the follow-up period (1990-2008) across the tertiles of the scores was examined.

Results:
Of 1,120 participants, we identified 48 incident type 2 diabetes cases. After adjusting for covariates assessed at blood draw in 1990, including smoking status, body mass index, and total fish intake, plasma HCB concentration was positively associated with type 2 diabetes risk: odds ratio (OR) (95% confidence interval [CI]) was 2.77 (1.17, 6.55,
P
for trend =0.022) comparing the highest vs. lowest tertile. Other POPs were not significantly associated with diabetes: the ORs (95% CI) were 1.10 (0.51, 2.34,
P
for trend =0.81) for p-p'-DDE, 0.93 (0.44, 1.95,
P
for trend =0.86) for DDT, and 0.88 (0.39, 1.97,
P
for trend =0.76) for sum of the 4 major PCBs, comparing the extreme tertiles.

Conclusion:
The significant association of plasma HCB concentration with diabetes risk supports a role of POP exposure in the etiology of type 2 diabetes. More prospective data are warranted to confirm these findings.
Abstract MP064: Dietary Contributors to Glycemic load in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Shikany James M , Letter Abraham J , Newby P. K , Ard Jamy D , Judd Suzanne E
Published: July 2021

Glycemic load (GL) is a measure that incorporates both the quality (i.e., glycemic index) and quantity of dietary carbohydrate and is a measure of the overall glycemic impact of the diet. In observational studies, high-GL diets have been associated with a greater prevalence of multiple coronary heart disease risk factors, including type 2 diabetes, overweight/obesity, dyslipidemia, inflammation, and abnormal blood clotting. To begin to develop interventions to reduce dietary GL, it is necessary to identify the major contributors to GL at the population level. We studied contributors to GL in 21,636 participants in the
REasons for Geographic And Racial Differences in Stroke
(REGARDS) study (7074 white men, 2472 black men, 7287 white women, and 4803 black women) whose mean (SD) age was 64.9 (9.3) years at baseline (2003-2007). Mean daily GL, as well as individual carbohydrate food and food group contributors to GL, were determined for each participant using intake data from the Block 1998 semi-quantitative food frequency questionnaire administered at baseline. Mean (SD) daily GL was 107.1 (44.1), 115.0 (53.8), 89.9 (40.6), and 100.0 (49.6) g/d in white men, black men, white women, and black women, respectively. Sugar-sweetened beverages was the main carbohydrate food group contributing to GL in both black men and women and were important contributors to GL in white men and women (Figure). Regular soft drinks in particular were the leading individual carbohydrate contributor to GL in black men (4.0 median % of daily GL). The main carbohydrate food group contributing to GL in both white men and women was breads. Dark breads were the leading individual carbohydrate contributors to GL in white men, white women, and black women (2.7, 3.2, and 2.4 median % of daily GL, respectively). Sugar-sweetened beverages were a major contributor to dietary GL in this sample of US adults, especially in blacks. Decreasing the consumption of these beverages should be considered in future interventions to reduce dietary GL.
Abstract MP066: The Role of Environmental Factors in Modifying Heritability of Coronary Heart Disease
Authors: SONG Ci , Chang Zheng , Magnusson Patrik , Ingelsson Erik , Pedersen Nancy L
Published: July 2021

Introduction
Coronary heart disease (CHD) is affected by both genetic and environmental factors. These classes of factors may act independently or interactively (gene-environment interactions). Recent large genome-wide association (GWA) studies have identified several genetic loci associated with CHD. However, few studies have considered the modifying effects of specific environmental factors on these associations, and the full extent of how those environmental factors affect the additive genetic component of CHD is not known.

Hypothesis
Our hypothesis was that modifiable environmental factors including smoking, alcohol intake, physical activity and body mass index (BMI) would affect CHD risk via interactions with genetic factors.

Methods
The environmental factors studied were smoking (ever regular smoker, never regular smoker); alcohol intake (never-drinking, drinking); physical activity (sedentary vs. non-sedentary); and highest BMI during life time (normal [less than 25 kg/m
2
], overweight [25 to 30 kg/m
2
], and obesity [more than 30 kg/m
2
]). All same-sex twins born before 1958 in the Swedish Twin Registry were included in the current study. We identified 6,133 incident CHD events as the first CHD onset without any prior myocardial infarction, stroke or heart failure. We estimated heritability of CHD conditioned on the above-mentioned environmental factors in up to 26,901 twin pairs with environmental information available. Parameter estimation and model fitting was conducted with structural equation modeling as implemented in the software package Mx.

Preliminary results
The overall heritability of CHD in our sample was 36% (adjusted for age and sex). Smoking and overweight/obesity significantly modified the additive genetic component of CHD (P<0.001 and P=0.038, respectively). Thus, heritability of CHD differed between smokers (29.0%) and non-smokers (42.5%). Further, heritability of CHD also differed among different categories of BMI: 29.9% among normal-weight, 27.1% among overweight and 23.6% among obese individuals. Neither alcohol consumption nor physical activity had any significant modifying effect on heritability of CHD (P=0.33 and 0.16, respectively)

Conclusion
In our nation-wide twin study of 26,901 twin pairs, purported measures of the environment affected heritability of CHD incidence. We demonstrated that smoking, as well as overweight and obesity modify heritability estimates, potentially indicating that genetic factors play a more prominent role for disease development in the absence of important environmental factors. Our results suggest that increased understanding of gene-environment interactions will be important for full understanding of the etiology of CHD.
Abstract MP072: Association of Urinary Kidney Injury Biomarkers with Kidney Function Decline: A Case-Control Study from the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Peralta Carmen A , Katz Ronit , Bonventre Joseph V , Sabbisetti Venkata , Siscovick David , Sarnak Mark , Shlipak Michael G
Published: July 2021

Background:
The urinary biomarkers of tubular injury ((urine neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1)) can indicate acute kidney injury before reductions in estimated glomerular filtration rate (eGFR) are clinically detectable. Whether elevations of these markers are associated with future risk of kidney disease has not been investigated.

Methods:
We studied the association of urinary NGAL and KIM-1 with kidney function decline in a 1:1 ratio case-control study among 686 MESA participants. NGAL and KIM-1 were measured at baseline (standardized for urinary creatinine) and expressed both as continuous and in deciles. eGFR was estimated by cystatin C. Cases were defined as persons with eGFR>60 ml/min/1.73m
2
who subsequently developed
incident CKD
(defined as eGFR<60 plus eGFR decline > 1ml/min/year) and/or had
rapid kidney function decline
(RKFD, ≥3ml/min/1.73m
2
/year) by the MESA year 5 visit. Of the 343 cases, 145 had incident CKD, 141 had RKFD and 57 had both. Controls were matched for age, gender, race, diabetes, and baseline eGFR. We adjusted for age, hypertension and presence of albuminuria (ACR ≥30 mg/g).

Results:
Higher levels of KIM-1 were significantly associated with kidney function decline, and these associations were strongest for the top decile compared to lowest decile. Presence of albuminuria only minimally attenuated the findings. NGAL levels were not associated with kidney function decline. (Table)

Model
OR (95%CI) for Incident CKD and/or Rapid Kidney Function Decline

KIM-1 (pg/ml)
*

KIM-1-Cr Ratio
*
(pg/mg)

KIM-1 ≥ 927 pg/ml (Top Decile)

NGAL (ng/ml)
*

NGAL-Cr Ratio
*
(ng/mg)

NGAL ≥ 36 ng/ml (Top Decile)

Age Adjusted

1.15 (1.02, 1.29)
1.17 (1.02, 1.34)
2.09 (1.21, 3.62)
1.04 (0.99, 1.10)
1.03 (0.98, 1.09)
1.63 (0.96, 2.78)

Age + HTN Adjusted

1.15 (1.03, 1.29)
1.16 (1.01, 1.33)
2.13 (1.22, 3.70)
1.04 (0.99, 1.10)
1.03 (0.98, 1.09)
1.58 (0.93, 2.71)

+ ACR ≥ 30mg/g

1.15 (1.02, 1.29)
1.13 (0.98, 1.30)
2.02 (1.15, 3.56)
1.04 (0.99, 1.10)
1.03 (0.97, 1.08)
1.55 (0.89, 2.70)

*

Per doubling. Top decile is compared to lowest decile

Conclusions:
KIM-1, a marker of tubular injury, is associated with future risk of kidney disease independent of albuminuria. Our findings suggest that urinary biomarkers of tubular injury are a promising tool for identifying persons at risk for CKD.
Abstract MP087: Relation of Risk Factor Profile at Baseline and 39-Year Follow-up to Peripheral Arterial Disease - - The Chicago Healthy Aging Study (CHAS)
Authors: Vu Thanh Huyen T , Liu Kiang , McDermott Mary M , Stamler Jeremiah , Lloyd-Jones Donald M , Garside Daniel B , Daviglus Martha L
Published: July 2021

Background:
Low burden of CVD risk factors (RF) at younger ages is associated with substantially reduced risk for future clinical CVD events. There is no information available regarding associations of long-term
patterns
in RF profile, from young adulthood to older age, with prevalence at older age of low ankle brachial index (ABI), a marker for peripheral arterial disease (PAD).

Methods:
Using data from the Chicago Healthy Aging Study (CHAS), we assessed associations of patterns in RF profile -- from baseline (1967-73) to follow-up (2007-10) -- with prevalence of PAD at follow-up (see Table for definitions of RFs and RF groups). ABI was calculated as the ratio of Doppler recorded systolic pressures in the lower and upper extremities, and categorized as follows: low ABI/PAD (ABI<1.00) vs. normal (1.00 ≤ABI ≤1.40). Participants with an ABI >1.40 (n=24) were excluded from the analysis.

Results:
The study sample consisted of 1,340 participants (27.8% women, 9.2% African Americans) ages 24-45 years, free of major ECG abnormalities and MI at baseline. After 39 years of follow-up, 15.5 percent of persons with no adverse baseline RF levels remained RF-free at follow-up (Group A). The prevalence of PAD was lowest in this Group A (3.7%) and highest (19.9% -- 5 times higher) in Group E, with ≥2 RFs at both baseline and follow-up (p-value < .001). Likewise, with adjustment for baseline age, sex, ethnicity, education, and minor ECG abnormalities, the odds for PAD in Group A was lowest compared with other groups. Further, decrease in number of RFs from baseline to follow-up (Group C) was associated with lower likelihood for PAD compared to increase in number of RFs over time (Groups B and D) and to presence of ≥2 RFs at both baseline and follow-up (Group E).

Conclusion:
Long-term absence of risk factors is associated with lowest prevalence of PAD at 39 year follow-up. Greater risk factor burden in young adulthood and development of risk factors over decades were both associated with greater likelihood of PAD later in life.
Abstract P009: The Association of Liver Enzymes with Subclinical Myocardial Damage
Authors: Lazo Mariana , Rubin Jonathan , Clark Jeanne M , Brancati Frederick L , Christman Andrea , Ndumele Chiadi , Hoogeveen Ron C , Ballantyne Christie M , Selvin Elizabeth
Published: July 2021

Background:
Nonalcoholic fatty liver disease (NAFLD) is present in up to 30% of the US population and is strongly associated with obesity and diabetes. While a number of studies support an association between NAFLD and cardiovascular disease, limited evidence exists for the association with subclinical myocardial injury.

Objective:
To test the hypothesis that elevated liver enzymes (Alanine aminotrasferase [ALT], Aspartate aminotranferase [AST] and Gamma-glutamyl transpeptidase [GGT]) in the absence of significant alcohol consumption are independently associated with subclinical myocardial injury, defined by elevated cardiac troponin-T measured using a highly-sensitive assay (hs-cTnT).

Methods:
We conducted a cross-sectional analysis of 9351 participants from the Atherosclerosis Risk in the Communities (ARIC) Study with information on ALT, AST and GGT , hs-cTnT, and no evidence of coronary heart disease or elevated alcohol consumption (>14 and >21 drinks/week for women and men, respectively). We used logistic regression models to examine the association between liver enzymes and elevated hs-TnT (hs-TnT >0.014 μ g/L ) defined in a healthy reference population. Our secondary outcome was detectable hs-TnT (>0.003 μ g/L ).

Results:
In this community-based population (mean age 63 years, 60% women, 78% white), 7.2% and 66.1% had elevated and detectable hs-TnT, respectively. Medians [range] of ALT, AST and GGT were 13 [1-381], 18 [5-358] and 21 [2-1277], respectively. Higher levels of ALT, AST and GGT, even within the normal range, were independently associated with elevated hs-TnT (Figure). ALT and AST were also independently associated with detectable hs-TnT. After excluding participants with heart failure, the results remained consistent.

Conclusions:
In this sample, elevated livers enzymes were independently associated with subclinical myocardial damage suggesting that NAFLD may contribute to myocardial injury beyond its effects on development of clinical atherosclerotic coronary disease.
Abstract P018: Circulating Levels of Endostatin are Related to Future Cardiovascular Mortality in Elderly subjects
Authors: Lind Lars , Rughe Toralph , Sundström Johan , Ingelsson Erik , Larsson Anders , Ärnlöv Johan
Published: July 2021

Background:
Endostatin, a biological active fragment of the extracellular matrix protein collagen XVIII, is known to be involved in angiogenesis. We evaluated if circulating lvels of this compound was related to future mortality in two different cohorts of elderly subjects.

Methods:
In the PIVUS cohort of 931 subjects all aged 70 years at baseline, 90 individuals died during a median follow-up of 7.9 years. In the ULSAM cohort of 748 men aged 77 years at baseline, 261 individuals died during a median follow-up of 8.1 years.

Results:
Circulating levels of endostatin were related to future all-cause mortality in both samples following adjustment for age, gender, education, exercise habits, smoking BMI, blood pressure, lipids, diabetes and prior cardiovascular disease (HR 1.54 for a 1 SD change, 95%CI 1.26-1.90, p<0.0001 in PIVUS and HR 1.35, 95%CI 1.18-1.54 in ULSAM, both p<0.0001). In ULSAM, in which the cause of death was known, the HR was higher for cardiovascular mortality (HR 1.47, 95%CI 1.22- 1.780, p<0.0001).

Conclusion:
Endostatin was related to future mortality in two elderly Swedish sohorts independently of life-style factors and cardiovascular risk factors. The fact that the HR for cardiovascular mortality was higher than for all-cause mortality indicates a role of endostatin in the pathogenesis of cardiovascular diseases.
Abstract P020:
1
H Nmr Metabonomic Profiling Identifies Novel Biomarkers for Cardiovascular Mortality
Authors: Al-Hussaini Abtehale , Tan Tsung , Sehmi Joban , Elliott Paul , Ala-Korpela Mika , Kooner Jaspal S , Chambers John C
Published: July 2021

Background
Cardiovascular disease (CVD) is the leading cause of death world-wide. Existing tools for identification of CVD risk have modest predictive power and discrimination. New biomarkers for CVD prediction are urgently needed.

Hypothesis
We have used
1
H NMR metabonomic profiling of serum to identify novel biomarkers for incident CVD.

Methods
We investigated 9,179 men and women participating in the London Life Sciences Population study. Participants were recruited between 2002-2008 from the lists of 58 GPs in London UK, and assessed for baseline CVD risk factors, including smoking, body mass index, waist circumference, blood pressure, fasting glucose and lipid profile. Participants were followed for CVD mortality to July 2011 (mean 5.5 years per person).
1
H NMR metabonomic profiling was done on baseline serum sample by 12T Bruker spectrometer, with quantification of 44 fatty acid and low molecular weight markers.

Results
There were 161 CVD deaths. Compared to survivors, people with CVD death were older, had higher prevalence of type-2 diabetes and cigarette smoking, higher blood pressure, body mass index, glucose, and lower total and HDL cholesterol (Table). Framingham risk scores were higher in cases with CVD death than survivors (18.7±0.9% vs. 11.4±0.7%, P=10
-31
). We found six NMR metabolites associated with incident CVD at P<0.05; odds ratios (95%CI) for CVD per 1SD increase in biomarker ranged from 1.19 (1.07-1.33, P=0.007) to 1.65 (1.44-1.89, P=3x10
-13
). The associations of NMR metabolites with CVD were not materially changed by adjustment for age, gender and Framingham risk score. The AUC for prediction of incident CVD was 0.74 using Framingham risk score alone, and 0.77 with incorporation of metabonomic measures.

Conclusions
We identified six novel biomarkers for incident CVD; these are independent of known CVD risk factors and may improve CVD risk prediction. Our findings demonstrate the potential utility of metabonomic profiling for biomarker discovery and risk stratification.

CVD deaths
Survivors
P

Total no of people
161
9018

Age (years)
61.6 (0.5)
53.4 (0.4)
0.001

Male gender (%)
98.2
85.8
<0.001

Smoking (%)
73
49
<0.001

Diabetes (%)
49
20
<0.001

Systolic blood Pressure (mmHg)
144.7 (22.7)
134.0 (19.2)
<0.001

Body mass index (kg/m
2
)

28.4 (5.6)
27.3 (4.3)
0.002

Total cholesterol (mmol/L)
4.8 (1.2)
5.2 (1.1)
<0.001

HDL cholesterol (mmol/L)
1.20
1.25
0.064

Glucose (mmol/L)
7.1
5.9
<0.001

Results provided as mean or %.
Abstract P045: Residential Traffic Exposure and Intima Media Thickness in Augsburg, Germany
Authors: Wolf Kathrin , Cyrys Josef , Birk Matthias , Meisinger Christa , Thorand Barbara , Wolfgang Rathmann , Thiery Joachim , Koenig Wolfgang , Seissler Joachim , Peters Annette
Published: July 2021

Background.
It has been suggested that long-term exposure to air pollution may lead to an increased risk of cardiovascular disease.

Hypotheses.
In this study, we hypothesized that long-term residential traffic exposure enlarges of intima-media thickness (IMT).

Methods.
We used data on 2712 individuals aged 31 to 82 years who participated in the cross-sectional KORA F4 (2006–2008) survey conducted in the region of Augsburg, Germany. The residential traffic exposure was assessed by specifying daily traffic intensity of and distance to nearest street, and of daily traffic load (sum of product of traffic intensity and length of all street segments) and total road length within a buffer of 50 and rings of 50 to 100 and 100 to 300 meters around the residences. IMT was measured as mean of first cm of left and right common carotid artery segments from all angles (mm). We used linear regression adjusting for sex, age, adipositas, education, occupation, smoking status, systolic and diastolic blood pressure, HDL- and LDL-cholesterol and statin intake.

Results.
Road length within a radius of 50 meters of a person’s residence was associated with an increased IMT 1.2% (95% CI, 0.2% to 2.3%) per increase in 140 road length (m). Other measures of traffic exposures showed no or weaker effects; for example the traffic load within a radius of 50 meters of a person’s residence was associated with an increased IMT 0.3% (95% CI, -0.4% to 1.0%) per increase in 600 vehicles per kilometer. No difference was observed between men and women.

Conclusions.
Long-term residential exposure by road traffic may contribute to the development of atherosclerosis. Additional estimates for traffic related pollution may help interpreting the results of the KORA study.
Abstract P046: Circulating Levels of Persistent Organic Pollutants are Related to the Change in Lipids During 5 Years Follow Up
Authors: Lind Monica , Salihovic Samira , Bavel Bert v , Lind Lars
Published: July 2021

Background:
When reporting circulating levels of persistent organic pollutants (POPs), usually lipid-normalized values are given. However, animal experiments and some human data support the view that exposure to POPs might change lipid values. The aim of the present study is to investigate if POP levels could predict future change in lipids levels.

Methods:
In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, lipids were measured at age 70 and at age 75 in 598 subjects without lipid-lowering medication. Twenty-one different POPs, including 16 PCBs, three pesticides (HCB, DDE and TNK), one dioxin (OCDD) and one brominated compound (BDE47) were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS) at age 70.

Results:
Strong relationships were seen between the baseline levels of PCBs 194, 206 and 209 and the degree of increase in total serum cholesterol and LDL-cholesterol during the 5 year follow-up. These relationships were generally stronger when lipid-normalized levels were used compared to wet-weight based levels. On the contrary, both HCB and TNK levels were inversely related to the change in LDL-cholesterol, with strongest associations found using wet-weight based levels. PCBs 194, 206 and 209 were inversely related to the change in HDL-cholesterol. None of the POPs were related to the change in serum triglycerides.

Conclusion:
POPs are related to the future change in lipids. This might explain why POP exposure previously has been linked to atherosclerosis and future cardiovascular disease. It might also question the use of lipid-normalization when studying relationships between POPs and metabolic diseases.
Abstract P048: Effect of Hurricane Katrina on Medication Adherence and Blood Pressure among Hypertensive Veterans
Authors: Thompson Angela M , Krousel-Wood M.A. , Mei Hao , Webber Larry , He Jiang , Bazzano Lydia
Published: July 2021

Background.
An increase in cardiovascular events and blood pressure (BP) has been reported in the aftermath of major natural disasters. This increase may be due to acute psychological stress, physiologic suffering, or lack of appropriate healthcare services in these situations.

Objectives.
Using retrospective cohort data from the Veterans Administration, we examined the impact of Hurricane Katrina on medication adherence and BP control among 1000 hypertensive patients from New Orleans, Louisiana compared to 1000 patients from an area not affected by the hurricane, Alexandria, Louisiana.

Methods.
Antihypertensive medication refills were identified from electronic pharmacy records, and blood pressure readings recorded during routine examinations were extracted from electronic patient data. Adherence to antihypertensive medications was assessed using the medication possession ratio (MPR), a standard method of quantifying refills. MPR was classified as low (<0.80) or high (≥0.80). Multivariable-adjusted regression methods were used to examine change in BP from the 6 months before the hurricane to 6 months after the hurricane.

Results.
In the year before Hurricane Katrina, the proportion of patients with low MPR was similar for patients in New Orleans (11.8% [106 of 902]) and Alexandria (11.3% [105 of 931], p-value=0.75 for group differences). In the year following the hurricane, there was a significant increase in the proportion of New Orleans patients with low MPR (24.1% [155 of 643]), compared to Alexandria (11.2% [94 of 838], p-value<0.001 for group differences). The unadjusted mean (95% Confidence Interval) increase in BP from the pre-Katrina to post-Katrina period was 6.6 (4.7, 8.3) mmHg systolic/5.7 (4.6, 6.8) mmHg diastolic and 2.1 (0.8, 3.5) mmHg systolic/1.2 (0.4, 2.0) mmHg diastolic among patients in New Orleans and Alexandria, respectively (p-value<0.001 for group differences). After adjustment for age, race, pre-Katrina BP, and post-Katrina MPR as a continuous variable, the mean increase in BP remained significantly higher among patients in New Orleans at 5.9 (4.3, 7.6) mmHg systolic/4.5 (3.5, 5.5) mmHg diastolic, compared to those in Alexandria where mean increase was 2.0 (0.8, 3.2) mmHg systolic /1.5 (0.7, 2.2) mmHg diastolic (p-value < 0.001 for group differences).

Conclusion.
BP significantly increased among hypertensive veterans in New Orleans as compared to Alexandria after Hurricane Katrina. This increase was only in part explained by changes in medication adherence. Future disaster planning should provide veterans with a rapid and easily-available method of accessing medications and health services and should anticipate increased BP and potential cardiovascular events among patients with hypertension.
Abstract P061: Effects of Black Tea With and Without a Fat Load on Vascular Function in Mildly Hypertensive Subjects
Authors: Grassi Davide , Draijer Richard , Desideri Giovambattista , Mulder Theo , Ferri Claudio
Published: July 2021

Introduction:
Endothelial dysfunction is an early biomarker for the development of cardiovascular disease and a predictor of future cardiovascular events. A number of intervention studies in healthy and diseased subjects have reported that endothelial function, as assessed by flow-mediated vasodilation (FMD), is positively affected by black tea consumption. On the other hand, high calorie fatty meals are detrimental to endothelial function.

Hypothesis:
To assess the effect of black tea with and without a fat load on FMD, digital volume pulse (DVP) and office blood pressure (BP) in never treated grade 1 hypertensive subjects without additional cardiovascular risk factors.

Methods:
According to a randomized, double-blind, controlled, cross-over design, 19 grade 1 hypertensives were assigned to consume black tea, containing 150 mg polyphenols or a placebo drink matched for caffeine, color and taste, twice a day for eight days, with a wash-out period in between of 13 days. On day 7 all measurements were performed in a fasted state, while on day 8 subjects consumed ultra-heat-treated whipping cream (1 gram fat per kg bodyweight) 30 minutes after consuming the test products. FMD, DVP and BP were measured at baseline and 1, 2, 3 and 4 hours after consumption of the test products.

Results:
Baseline FMD improved after 1-week tea consumption when compared to placebo (p<0.0001). An additional cup of tea further increased FMD at 1, 2, 3 and 4 hours after consumption when compared to baseline with maximal response 2 hours after intake (p<0.0001). Fat challenge significantly decreased FMD (p<0.0001), which was counteracted by tea consumption. Tea improved reflection index (small vessel tone; p<0.0001) and stiffness index (large arterial stiffness; p<0.0001) with additional effects after acute tea consumption with and without fat load. Further, tea decreased systolic and diastolic BP with and without a fat load (all p<0.0001).

Conclusions:
We demonstrate for the first time that moderate consumption of black tea protects against oral fat load-induced endothelial dysfunction in hypertensive but otherwise healthy subjects. The vascular benefits of tea are also reflected in improved endothelial function and peripheral arterial hemodynamics as well as blood pressure lowering under fasted and postprandial conditions. Our findings are of clinical relevance and interest, considering that the ingestion of the main daily meal has been suggested to be a trigger for acute myocardial infarction.
Abstract P064: Dietary Glycemic Index and Glycemic Load and Risk of Coronary Heart Disease in a Prospective Study Among US Male Health Professionals
Authors: Li Shanshan , Hu Frank B , Forman John P , Rimm Eric B
Published: July 2021

Introduction:
The associations between dietary glycemic index (GI) and glycemic load (GL) with subsequent risk of coronary heart disease (CHD) are inconclusive among men. The association is further complicated by the potential biological interactions between the carbohydrate quality of the diet and factors that may influence underlying insulin resistance.

Hypothesis:
We hypothesized that long-term exposure to a diet with high GI and GL would be associated with increased CHD risk in a cohort of US men, and the association would be further modified by fiber intake, alcohol consumption and BMI.

Methods:
We included 37,736 men aged 40–75 years from the Health Professional Follow-up Study, with no previous diagnosis of CHD, cancer, or type 2 diabetes. We confirmed 3,121 total incident CHD cases during 22 years of follow-up. Cox proportional hazard models were used to adjust for covariates.

Results:
After adjusting for lifestyle and dietary covariates, the hazard ratio (RR) and 95% confidence intervals comparing men in the highest vs. the lowest quintile was 1.16 (1.04, 1.31; p for trend=0.03) for dietary GI, and 1.09 (0.94, 1.27; p for trend =0.16) for GL. We found a significant effect modification by fiber intake (p=0.02); The associations between GL and CHD risk were strongest among participants in the lowest tertile of fiber intake (RR= 1.00, 1.00, 0.93, 1.11 and 1.16 with increasing quintiles of GL; RR=1.00, 0.68, 0.79, 0.73 and 0.76 for participants in the highest tertile of fiber intake). The association between GL and CHD was stronger among men with body mass index (BMI) greater than 25 kg/m2 than normal weight men, even though the test for interaction was only marginally significant (RR=1.00, 1.03, 1.05, 1.10, and 1.16 for increasing quintles of GL among men with BMI≥25 kg/m2 and RR= 1.00, 0.92, 0.96, 1.09 and 1.04 for men with BMI<25 kg/m2, p for interaction=0.09). Alcohol intake did not modify the association of GL with CHD (p for interaction=0.44).

Conclusion:
We observed a significantly increased risk of CHD with high GI diet and a modestly elevated association between GL and CHD among men with low fiber intakes or who were overweight or obese. No effect modification by alcohol was observed, but we did find that the association between GL and CHD was more pronounced among those with lower fiber intake or higher BMI.
Abstract P066: A Refined Carbohydrate Diet Attenuates Weight Loss in Insulin Resistant Individuals
Authors: Harris Kristina A , West Sheila G , Vanden Heuvel Jack P , Kris-Etherton Penny M
Published: July 2021

Introduction:
Weight loss is attenuated in individuals with insulin resistance (IR) who follow a traditional high-carbohydrate, calorie-restricted diet. However, the type of carbohydrate may modulate this response. We studied the effects of whole grains vs. refined grains on weight loss in individuals with increased waist circumference (M: >102 cm, F: >88 cm) and at least 1 other metabolic syndrome characteristic.

Hypothesis:
In a secondary analysis, we hypothesized that IR individuals (estimated by a triglyceride:high-density lipoprotein cholesterol ratio > 3.5) would lose more weight on a hypocaloric diet with whole grains vs. refined grains.

Methods:
Overweight or obese (BMI 25–42 kg/m2) men and women (n=50) 35–55 yrs were randomized to a controlled-feeding diet with whole vs. refined grains for 12 weeks [6 weeks isocaloric then 6 weeks hypocaloric (∼500 kcal/d)].

Results:
[All comparisons represented as IR mean±SEM vs. insulin sensitive (IS) mean±SEM, p-value)]. Compared to the IS group (n=29), the IR group (n=21) was predominately male (14 M/7 F vs. 11M/18F, p=0.04), weighed more (107.5±3.3 vs. 93.9±3.0 kg, p=0.005), and had increased waist circumference (113±2.2 vs. 106±1.5 cm, p=0.02). IR status did not affect overall percent body weight (%BW) lost over the course of the study (−4.0±0.4 vs. −4.5±0.3 %BW; p for interaction, time x IR status = 0.34). However, IR status did affect %BW lost when the type of carbohydrate was considered (p for interaction, time x IR status x diet = 0.04;
Figure
). Post-hoc analysis revealed that within the refined grain group, IR participants lost less %BW than the IS participants (−4.14±0.4 vs. −5.84±0.5 %BW, adjusted p=0.04). On the whole grains diet, %BW lost was similar in the IS and IR groups.

Conclusion:
In conclusion, IR individuals lost less %BW than IS individuals on the hypocaloric refined grain diet. Limiting refined grains may improve the efficacy of traditional weight loss diets in IR individuals.
Figure.
%BW lost in IR and IS groups on refined grain diet, *p=0.04.
Abstract P073: Increased Consumption of Wheat and Oat-based Wholegrain Foods does not Affect Serum Lipids and Lipoprotein Size and Distribution in Healthy Middle Aged People
Authors: Tighe Paula , Vaughan Nick , Duthie Garry , Brittenden Julie , Simpson William G , Duthie Susan , Horgan Graham , Thies Frank
Published: July 2021

Epidemiological studies suggest three daily servings of whole-grain foods (WGF) might lower cardiovascular disease (CVD) risk, at least partly by lowering serum lipid levels. Wheat and oats, the main WGF consumed in the UK, might induce different lipid responses. We aimed to assess the effects of three daily portions of WGF (provided as a mixture of wheat and oats or only wheat) on lipoprotein subclasses size and concentration. A dietary randomised controlled trial involving 233 middle aged healthy individuals was carried out. After a 4weeks run-in period on a refined diet, volunteers were randomly allocated to a control (refined diet), wheat or wheat + oats group for 12 weeks. Outcome measures were serum cholesterol as well as lipoprotein subclasses size and concentration, as measured by nuclear magnetic resonance. Blood lipid levels remained unchanged after 12 weeks intervention with WGF, whereas serum total- and LDL- cholesterol concentrations decreased slightly but significantly in the refined group compared with the wheat group. However, these changes were not associated with differences in lipoprotein subclasses’ size and concentration. Our results indicate that three portions of WGF, irrelevant of the type (wheat or oat-based) do not reduce cardiovascular risk by altering beneficially the size and distribution of lipoprotein subclasses.