bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP012: Sexual Maturation Independently Contributes to Adiposity Differences between African American and Caucasian Girls
Authors: Staiano Amanda E , Broyles Stephanie T , Gupta Alok K , Katzmarzyk Peter T
Published: July 2021

Introduction:
The prevalence of obesity is higher among African American girls compared to Caucasian girls. However, on average, African American girls also reach puberty earlier.

Hypothesis:
Sexual maturation affects adiposity differences between African American and Caucasian girls.

Methods:
The sample included 117 African American and 82 Caucasian girls aged 5–18 years. Waist circumference (cm) was measured in our outpatient clinic. Total body fat (grams) was measured by dual-energy x-ray absorptiometry. Abdominal subcutaneous and visceral adipose tissue mass (SAT and VAT in grams) were measured by magnetic resonance imaging. Abdominal images were obtained between the highest point of the liver and the lower pole of the right kidney. Analyzed slices centered on the lumbar inter-vertebral space (L4-L5), were 4.76 cm apart, and depending on the participant’s stature included 2 slices below and 2–5 slices above the L4-L5 interspace. Sexual maturity (breast development on a scale of 1–5 according to the criteria by Tanner) was determined, either by self-report (ages >9 years) or physician assessment (ages 5–9 years).

Results:
In linear regression models adjusted for age and race, sexual maturation significantly predicted waist circumference (beta=8.1, 95% CI=5.9 to 10.2), total body fat (beta=6767.2, 95% CI=4935.7 to 8598.8), SAT (beta=1988.4, 95% CI=1383.9 to 2592.9) and VAT (beta=56.6, 95% CI=36.8 to 76.4). African American girls had significantly higher waist circumference (p=0.0089), body fat (p=0.0171), and SAT (p=0.0184) compared to Caucasian girls when controlling for age only, but these ethnic differences attenuated to non-significance when sexual maturation was controlled. In linear regression models adjusted for age, sexual maturation, and body fat, although the race differences (African American compared to Caucasian girls) in SAT and waist circumference were attenuated, VAT was significantly lower (p<.0001).

Conclusion:
Sexual maturity was a significant independent predictor of adiposity in African American and Caucasian girls. Controlling for sexual maturation attenuated the race difference in waist circumference, body fat, and SAT, whereas the race difference remained in VAT. In conclusion, these results indicate that it is important to consider differences in sexual maturation when evaluating differences in adiposity between African American and Caucasian girls.
Abstract MP015: Resistance Exercise and Incident Metabolic Syndrome in Men
Authors: Lee Duck-chul , Sui Xuemei , Artero Enrique G. , Blair Steven N.
Published: July 2021

Introduction:
There is little evidence on the association between resistance exercise and incident metabolic syndrome.

Hypothesis:
We examined the hypothesis that resistance exercise reduces the risk of developing metabolic syndrome in men.

Methods:
Participants were 6,098 men aged 18 to 83 years (mean age, 46) who received an extensive preventive medical examination during 1987–2006, and were free of cardiovascular disease, cancer, and metabolic syndrome at baseline. Resistance exercise was assessed by self-reported muscle strengthening activities using either free weights or weight training machines. We used the frequency of resistance exercise (0, 1, 2, 3, 4, and ≥5 days/week) as our main exposure categories. Metabolic syndrome was defined as the presence of ≥3 of the following criteria: waist circumference >102 cm, triglycerides ≥150 mg/dL, high-density lipoprotein cholesterol <40 mg/dL, systolic/diastolic blood pressure ≥130/85 mm Hg or physician-diagnosed hypertension, and fasting glucose ≥100 mg/dL or physician-diagnosed diabetes according to the National Cholesterol Education Program Adult Treatment Panel III. Follow-up was calculated from the baseline examination to the first event of metabolic syndrome or the last examination through 2006. Cox regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of incident metabolic syndrome across resistance exercise. Age, examination year, body mass index, current smoking, heavy alcohol drinking (>14 drinks/week), abnormal electrocardiography, and aerobic exercise (inactive, low, medium, and high) were included in the multivariate regression model.

Results:
During the 5-year mean follow-up, 1,088 men developed metabolic syndrome. About 62% of men did not participate in resistance exercise, 3% of men participated in 1 day/week of resistance exercise, and 35% of men met the Physical Activity Guidelines for resistance exercise (≥2 days/week). Resistance exercise was inversely associated with incident metabolic syndrome after adjusting for possible confounders including aerobic exercise (trend
P
<0.01). Compared with no resistance exercise, the HRs (95% CIs) of developing metabolic syndrome were 0.83 (0.55–1.26), 0.88 (0.70–1.11), 0.85 (0.72–1.02), 0.62 (0.43–0.88), and 0.74 (0.51–1.07) for 1, 2, 3, 4, and ≥5 days/week of resistance exercise, respectively. Men meeting the recommended resistance exercise (≥2 days/week) had 18% lower risk of developing metabolic syndrome (HR=0.82, 95% CI=0.71–0.94) compared with men not meeting the recommendation (0 or 1 day/week of resistance exercise).

Conclusions:
Participating in resistance exercise may reduce the risk of developing metabolic syndrome in adult men.
Abstract MP024: Low Serum Vitamin D is Associated with Musculoskeletal Pain in Statin Users
Authors: Buettner Catherine , Morioka Travis Y
Published: July 2021

Introduction:
Statin use is associated with higher prevalence of self-reported musculoskeletal pain in the general population. Non-blinded studies have shown improvement in myalgia symptoms and increased tolerance to statin use after treatment of vitamin D deficiency. In this study, we hypothesized that lower serum vitamin D concentration would be associated with a higher odds of self-reported musculoskeletal pain among statin users.

Methods:
Using the National Health and Nutrition Examination Survey (NHANES) 2001–2004, we performed logistic regression to examine the association between vitamin D concentration and self-reported musculoskeletal pain and to evaluate if statin use modified the association. We evaluated vitamin D deficiency using a serum vitamin D concentration considered in the deficient range in clinical practice and representing the lowest quintile of vitamin D concentrations in the population studied (less than15 ng/mL). We adjusted for the effects of age, sex, race, smoking, BMI, physical activity, health status, peripheral vascular disease, coronary heart disease, diabetes, osteoporosis, arthritis, statin use and use of pain medications in logistic regression models. We also explored concentration-related trends of the effect of vitamin D on musculoskeletal pain.

Results:
Among 6217 participants age 40 years and older, the mean vitamin D concentration was 23.5 ng/mL (95%CI 22.4 ng/mL, 24.2 ng/mL). Statin medications were used by 17% of the participants in the last 30 days. Statin users had higher odds (aOR 1.6, 95%CI 1.2, 2.1) of self-reported musculoskeletal pain in any area (specifically including the lower extremities, lower back, upper extremities, and upper back) compared with non-users. Vitamin D deficiency was not a predictor of musculoskeletal pain (aOR 1.0, 95%CI 0.8, 1.3) in the overall sample. Among 1145 statin users, we found statin use modifies the effect of vitamin D deficiency on musculoskeletal pain (p for interaction = 0.02). Compared to statin users with a vitamin D concentration 15 ng/mL or higher, those with vitamin D concentration less than 15 ng/mL had higher odds of musculoskeletal pain (aOR 1.8, 95% CI 1.1, 3.1). We did not observe a concentration-related trend between increasing vitamin D concentrations and musculoskeletal pain (p for trend=0.7).

Conclusion:
In conclusion, after controlling for multiple confounders, a vitamin D concentration less than 15 ng/mL was not found to be associated with musculoskeletal pain in the overall sample in this population-based study. However, statin use modifies the relationship between vitamin D deficiency and musculoskeletal pain, such that a vitamin D concentration less than 15 ng/mL is associated with higher odds of self-reported musculoskeletal pain among statin users.
Abstract MP030: Insufficient Sleep Increases Caloric Intake but not Energy Expenditure
Authors: Calvin Andrew D , Carter Rickey E , Levine James A , Somers Virend K
Published: July 2021

Introduction:
Identifying and mitigating factors that promote obesity will have a large public health impact. Sleep may be an important regulator of metabolism and energy expenditure. Voluntary sleep restriction is common, with 27% of US adults regularly getting ≤6 h of sleep per day. Epidemiologic evidence suggests a link between short sleep duration and obesity. Human experiments suggest that acute sleep deprivation reduces the anorexigenic hormone leptin, increases the orexigenic factor ghrelin, and promotes caloric intake. Meanwhile, increased energy expenditure during prolonged wakefulness may counterbalance any increased caloric intake associated with a lack of sleep.

Hypothesis:
We hypothesized that 8 days of modest sleep restriction would reduce leptin, increase ghrelin, promote caloric intake, and increase activity energy expenditure.

Methods:
We studied 17 healthy individuals age 18–40 y. Subjects completed a protocol consisting of one week of home actigraphy, a 3 night acclimation phase, followed by an 8 night experimental phase in which they were randomized to sleep
ad lib
or two-thirds of their normal sleep time. Blood was collected at the end of the two periods, food was freely available and caloric intake was calculated daily, and activity energy expenditure was assessed by a comprehensively validated system comprised of inclinometers and accelerometers. Sleep was confirmed using continuous electroencephalography. Mean change from the acclimation period ± standard deviation are presented, with statistical testing by two sample t tests on the changes between acclimation and experimental periods.

Results:
Subjects included 11 men and 6 women, of whom 8 were randomized to sleep deprivation and 9 served as controls. Sleep duration during the acclimation period averaged 6.5±0.9 h/day but fell to 5.2±0.1 h/d among those randomized to sleep deprivation. The sleep deprivation group consumed +549±583 kcal/d, whereas those randomized to
ad lib
sleep consumed −143±420 kcal/d (P<0.01). Activity energy expenditure by did not change in either group (+1.2±33.0% vs +8.4±34.0%, P=0.68). Sleep deprivation was associated with a trend towards increased leptin (+8.4±4.7% versus −9.8±13.5%, P=0.12) and decreased ghrelin (−4.9±5.3% vs +4.6±7.0%, P=0.38).

Conclusions:
Eight days of modest sleep restriction, similar to that encountered in everyday life, was associated with a striking increase in caloric intake with no change in activity energy expenditure. Contrary to expectations, we observed a trend towards increased circulating concentrations of leptin and reduced concentrations of ghrelin, more consistent with a consequence of a positive energy balance than a cause. Our data suggest that chronic sleep restriction may be an important and modifiable behavior promoting obesity.
Abstract MP048: Partner Violence is Associated with Higher Blood Pressure in Men and Women
Authors: Clark Cari J , Everson-Rose Susan A , Michael Resnick , Borowsky Iris , Brady Sonya S , Krueger Robert , Connett John C , Alonso Alvaro , Franco Suglia Shakira
Published: July 2021

Introduction:
Women are more likely to experience distress and injury from intimate partner violence (IPV), and may also be at greater risk of higher blood pressure than male victims. However, most prior epidemiologic research has not included men and has not examined perpetation, despite the predominance of mutually violent relationships. Therefore, this study investigates sex differences in the relationship between exposure to IPV victimization and perpetration and systolic blood pressure (SB).

Methods:
The study included 3447 (52% female; mean(sd) age=22(3)) participants of Waves 3 (2001–2002) and 4 (2007) of the publically-available subset of the National Longitudinal Study of Adolescent Health. Frequency of psychological, physical, sexual IPV and IPV-related injury were ascertained with the Revised Conflict Tactics Scales at Wave 3. Exposure to IPV was categorized as no IPV victimization or perpetration (ref), only low victimization and / or perpetration, high victimization and low/no perpetration, high perpetration and low/no victimization, and both high victimization and perpetration. SBP was measured at Wave 4 using standard procedures. Potential confounders (age, educational attainment, race, history of child abuse) and mediators (depressive symptoms, breakfast consumption, moderate physical exercise, BMI, smoking, alcohol consumption) were recorded at Wave 3. Multivariable weighted linear regression was used to test the relationship between SBP and IPV by adjusting for confounders then by adjusting for the proposed mediators. Analyses were stratified by sex and a multiplicative term was tested.

Results:
Approximately 30% of the sample reported IPV exposure (n=2050), of which 23% (n=831) experienced low victimization and or perpetration, 5% (n=157) high victimization, 6% (N=203) high perpetration, 6% (n=206) both high victimization and perpetration. Women were slightly more likely to report high perpetration and both high victimization and high perpetration (p<0.01). In separate models controlling for confounders, experiencing both high victimization and perpetration was associated with 4.02 mmHg SBP higher in men (95% CI: 0.32, 7.72) and 2.51 mmHg SBP higher in women (95% CI: 0.18, 4.84) compared to those with no IPV. In addition, reporting high perpetration was associated with 3.83 mmHg higher SBP in men (95% CI: –0.72, 8.38), while high victimization was associated with 2.94 mmHg higher SBP for women (95% CI: –0.61, 6.49). Further adjustment for the hypothesized mediators slightly attenuated the findings. The multiplicative term (IPV X sex) was marginally significant (p=0.09).

Conclusions:
Exposure to high levels of victimization and perpetration is associated with higher levels of SBP for men and women. High victimization alone is related to higher SBP for women while high perpetration is related to higher SBP for men.
Abstract MP050: Race and Gender Group Specific Trends in Length of Stay for Acute Myocardial Infarction: The Atherosclerosis Risk in Communities (ARIC) study, 1987–2008
Authors: Loehr Laura R , Liu Xiaoxi , Baggett C. , Guild Cameron , Michos Erin D , Couper David , Rosamond Wayne D
Published: July 2021

Introduction:
Since the 1980’s, length of stay (LOS) for acute MI (AMI) has declined in the US. However, little is known about trends in LOS for non-white racial groups and whether change in LOS is related to insurance type or hospital complications.

Methods:
We determined 22 year trends in LOS for nonfatal (definite or probable) AMI among black and white residents age 35–74 in 4 US communities (N=396,514 in 2008 population) under surveillance in the ARIC Study. Events were randomly sampled and independently validated using a standardized algorithm. All analyses accounted for sampling scheme. We excluded MI events which started after admission (n=1,677), events within 28 days for the same person (n=3,817), hospital transfers (n=571), and those with LOS=0 or LOS >66 (top 0.5% of distribution, N= 144) leaving 22,258 weighted events for analysis. The average annual change in log LOS was modeled using weighted linear regression with year as a quadratic term. All models adjusted for age and secondary models adjusted for insurance type (Medicare, Medicaid, private, or other), and complications during admission (cardiac arrest, cardiogenic shock, or heart failure).

Results:
The average age-adjusted LOS from 1987 to 2008 was reduced by 5 days in black men (9.5 to 4.5 days); 4.6 days in white women (9.4 to 4.8 days); 4 days in white men (8.3 to 4.3 days) and 3.6 days in black women (9.0 to 5.4 days). Between 1987 and 2008, the age-adjusted average annual percent change (with 95% CI) in LOS was largest for white men at −4.40 percent per year (−4.91, −3.89) followed by −3.89 percent (−4.52, −3.26) for white women, −3.72 percent (−4.46, −2.89) for black men, and −2.94 percent (−3.92, −1.96) for black women (see Figure). Adjustment for insurance type, and complications did not change the pattern by race and gender.

Conclusions:
Between 1987 and 2008, LOS for AMI declined significantly and similarly in men and women, blacks and whites. These changes appear independent of differences in insurance type and hospital complications among race-gender groups.
Abstract MP056: Subclinical Coronary Artery Disease is Present in 28% of Adults 43-55 Years of Age: Recent Findings of the CARDIA Study
Authors: Carr J J , Shay Christina M , Jacobs David R , Saldana Santiago , Terry J G , Sidney Stephen , Lui Kiang , Schreiner Pamela J , Lewis Cora E , Shikany James M , Reis Jared P , Goff David C
Published: July 2021

Background:
Coronary artery disease (CAD) starts in childhood and progresses to advanced lesions in adult life. The coronary artery calcium (CAC) score is a measure of subclinical CAD that indicates advanced coronary atheroma and independently predicts future clinical events. Our objective was to document the prevalence and amount of subclinical CAD among black and white adults in early adult life.

Methods:
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a U.S. population-based, prospective, observational study of black and white men and women. Initially 5,115 participants age of 18-30 yrs were recruited in 1985-6. CAC was measured using non-contrast cardiac CT and reported as the Agatston score at three exams 15, 20 & 25 years after the baseline visit.

Results:
CAC prevalence was 10.1%(309/3046), 18.6%(583/3140) and 28.1%(890/3160) when the returning cohort was between 33-45 yrs, 38-50 yrs, and 43-55 yrs, respectively (see figure). Prevalence of CAC at all time points was greater in men than women and highest in white men. In the most recent exam, black men had a lower prevalence of CAC (34.3% vs 47.7%) compared to white men but similar distribution of CAC amount. Quartiles of CAC among men with any CAC were: black men 10, 48, 183 and white men 14, 42, 173 (Q1, Q2(median) and Q3 respectively). Change in CAC score among participants in the two most recent CT exams was observed in 29.8% (774/2600). Of those participants, 89.3%(691/774) had any increase in CAC score and 66.7%(516/774) an increase of 10 units or greater. Prevalence of CAC was highly correlated with age and no period effect was observed.

Conclusions:
28% of adults less than 55 years of age have advanced plaque in their coronary arteries indicating significant subclinical disease burden. Prevalence is highest in white men, followed by black men and then women in these age ranges. Black men, given CAC, have a comparable amount of CAC to white men. Subclinical CAD is prevalent in early adulthood and once initiated appears to progress in the vast majority of adults.
Abstract MP065: Genetic Loci Associated With Plasma Phospholipid Fatty Acids in the De Novo Lipogenesis Pathway: A Meta-analysis of Genome-wide Association Studies From the Charge Consortium
Authors: Wu Jason H , Lemaitre Rozenn N , Tanaka Toshiko , Guan Weihua , Manichaikul Ani , Foy Millennia , Kabagambe Edmond K , Jacobs David R , Rich Stephen S , Siscovick David S , Nettleton Jennifer A , Bandinelli Stefania , Ferrucci Luigi , Fornage Myriam , Tsai Michael Y , Steffen Lyn M , Mozaffarian Dariush ,   On Behalf of the CHARGE Fatty Acid Working Group
Published: July 2021

Background
Palmitic acid (16:0), stearic acid (18:0), palmitoleic acid (16:1n-7), and oleic acid (18:1n-9) are major saturated and mono-unsaturated fatty acids that are synthesized via de novo lipogenesis (DNL) or obtained from the diet. Circulating levels of these fatty acids are linked to several diseases including diabetes and heart disease. Prior family and twin studies suggest high heritability of circulating levels, but potential genes involved are unknown.

Objective
To carry out a Genome-Wide Association Study (GWAS) to investigate genetic determinants of circulating levels of these fatty acids.

Methods
GWAS in 5 population-based cohorts (n=8,961) of European ancestry. Each study conducted linear regression analysis using an additive genetic model. All analyses were adjusted for age, sex, site of recruitment, and principal components to account for possible population genetic substructure where appropriate. Study-specific results were combined using inverse-variance weighted meta-analysis.

Results
We found SNPs at 7 novel loci linked at GWA significance to levels of one or more of these fatty acids (
Figure
). Directionality is reported for minor alleles. SNPs in
ALG14
were associated with higher levels of 16:0 (
P
=2.7x10
-11
) and lower levels of 18:0 (
P
=2.7x10
-11
). SNPs in
FADS1
/2 were associated with higher 18:1n-9 (
P
=2.2x10
-32
) and 16:1n-7 (
P
=6.6x10
-13
), and lower 18:0 (
P
=1.3x10
-20
). SNPs in
LPGAT1
were associated with lower 18:0 (
P
=2.8x10
-9
). SNPs in
GCKR
(
P
=9.8x10
-10
) and
HIF1AN
(
P
=5.7x10
-9
) were associated with higher 16:1n-7, whereas those in
PKD2L1
(
P
=5.7x10
-15
) and another locus on chromosome 2 (not near known genes) were associated with lower 16:1n-7.

Conclusion
Our findings provide novel evidence that common variations in genes with diverse functions, including protein glycosylation, polyunsaturated fatty acid metabolism, phospholipid modeling, and glucose- and oxygen-sensing pathways, are associated with circulating levels of fatty acids in the DNL pathway.
Abstract MP069: A Genetic Association Study of D-dimer Levels with 50K SNPs from a Candidate Gene Chip in Four Ethnic Groups: the Candidate Gene Association Resource (CARe) consortium
Authors: Weng Lu-Chen , Tang Weihong , Rich Stephen S , Smith Nicholas L , Redline Susan , O’Donnell Christopher J , Basu Saonli , Reiner Alexander P , Delaney Joseph A , Tracy Russell P , Palmer Cameron , Young Taylor , Yang Qiong , Folsom Aaron R , Cushman Mary
Published: July 2021

Introduction:
D-dimer, a marker of blood coagulation and fibrinolysis, is a widely-used biomarker of venous thromboembolism. While the coagulation factors V, III, II and fibrinogen alpha chain genes contain known genetic determinants of D-dimer, other determinants are not well characterized, especially in populations other than European Americans (EAs); no data have been reported for Asian American populations.

Hypothesis:
Large-scale candidate gene association analysis will identify D-dimer related gene variants in EA, African-American (AA), Chinese, and Hispanic populations.

Methods:
Four cohorts, comprised of 6,848 EA, 2,192 AAs, 670 Chinese, and 1,286 Hispanics from Cleveland Family Study, Cardiovascular Health Study, Framingham Heart Study, and Multi-Ethnic Study of Atherosclerosis in the Candidate Gene Association Resource (CARe) consortium, were included. The inverse normal transformed residual of D-dimer was used in genetic analysis. About 50,000 SNPs located in 2,100 inflammation and atherosclerosis-related genes were genotyped using the custom ITMAT-Broad-CARe (IBC) chip and analyzed by linear regression adjusted for age, sex, study site, and principal components to account for potential population stratification in each cohort and race group. Significance was set at p<2x10-6 after accounting for multiple testing.

Results:
Twelve SNPs in the coagulation factor V gene and 3 SNPs in the fibrinogen alpha chain genes exceeded the significant p-value threshold in EA. The top SNPs in these two regions were rs6025 (p-value=7.41x10-16) and rs13109457 (p-value=7.52x10-7), respectively. The signals for the remaining significant SNPs in these two regions were no longer statistically significant after adjusting for the known functional SNPs in each region (rs6025 and rs6050, respectively). The top signal at the coagulation factor V gene was replicated in Hispanics but not other race groups. Neither AA nor the other race groups replicated the signals for fibrinogen alpha chain gene. No additional variants in AA, Chinese, or Hispanics showed significant associations with D-dimer, but several SNPs in neuregulin 1 and Bruton agammaglobulinemia tyrosine kinase for AA and vanin 1 for Chinese were suggestively associated with D-dimer levels (p-value<5x10-5).

Conclusion:
Our study replicated previously reported associations of D-dimer with coagulation factor V and fibrinogen alpha chain variants in EAs and identified coagulation factor V variation in Hispanics. Additional studies are required to confirm the suggestive findings in AAs, Chinese, and Hispanic populations.
Abstract MP075: Fetuin-A and Risk of Ischemic Stroke Among Women
Authors: Jimenez Monik C , Sun Qi , Hu Frank B , Manson JoAnn E , Rexrode Kathryn M
Published: July 2021

Introduction:
Fetuin-A, a protein secreted primarily by the liver, has been associated with non-alcoholic fatty liver disease and insulin resistance. A recent study found that high fetuin-A levels were associated with increased cardiovascular risk, particularly for ischemic stroke; however, the data have not been replicated.

Methods:
A nested case-control design was utilized to examine the relationship between fetuin-A and ischemic stroke among female participants of the Nurses’ Health Study who provided blood samples. A total of 462 incident cases of ischemic stroke were identified and confirmed by medical records according to the National Survey of Stroke criteria between 1990-2006 and were matched to 462 controls by age, menopausal status, hormone therapy use, and smoking status. Fetuin-A was measured on blood samples collected and stored between 1989-1990. Conditional logistic regression was used to evaluate the multivariable adjusted association between fetuin-A and ischemic stroke.

Results:
Fetuin-A levels were higher in those with elevated cholesterol (p=0.02), current hormone use (p=0.002) and hypertension (p=0.05) in univariate analyses. Significant partial spearman correlations, adjusted for matching factors, were found between fetuin-A and triglycerides (r=0.18; p<0.001), C-reactive protein (r=0.12; p=0.002), and BMI (r=0.13; p<0.001). Fetuin-A quartiles were not significantly associated with increased risk of incident ischemic stroke when adjusted for matching factors, or when additionally adjusted for other CVD risk factors (see Table 1). Further adjustment for other biomarkers, modestly strengthened the association, but p for trend remained nonsignificant (p=0.37).

Conclusions:
In this population of women, fetuin-A was not significantly associated with a greater risk of ischemic stroke. Further research is needed to explore this association.

Table 1

Multivariable adjusted relative risk (95% CI) of ischemic stroke by Fetuin-A quartiles

Quartiles of Fetuin-A
p-value for trend

Q1
Q2
Q3
Q4

Range (μ g/mL)

<377
377-<449
449-<526
526-1538

Cases/Controls

108/116
136/115
102/113
112/116

Model 1
*

1.00
1.22 (0.86-1.75)
0.92 (0.62-1.35)
1.05 (0.71-1.55)
0.79

Model 2

†

1.00
1.32 (0.88-1.99)
1.00 (0.64-1.56)
1.28 (0.81-2.01)
0.52

Model 3

‡

1.00
1.34 (0.88-2.03)
1.06 (0.67-1.69)
1.24 (0.78-1.98)
0.59

Model 4

§

1.00
1.41 (0.82-2.42)
1.00 (0.55-1.84)
1.33 (0.73-2.42)
0.37

*

Model 1: Conditional on matching factors (age, menopausal status, hormone use, smoking)

†

Model 2: Model 1 + aspirin use, alcohol intake, physical activity, healthy diet score, current post-menopausal hormone use

‡

Model 3: Model 2 + aspirin use, alcohol intake, physical activity, healthy diet score, current post-menopausal hormone use, history of diabetes, elevated cholesterol, high blood pressure, and CHD or revascularization.

§

Model 4: Model 3+ HbA1c, ln(CRP), ln(triglycerides), ln(cholesterol/HDL)
Abstract MP089: Cardiovascular Protection Profile and All-cause and CVD Mortality among U.S. Adults
Authors: Yang Quanhe , Cogswell Mary , Flanders W. Dana , Hong Yuling , Zhang Zefeng , Loustalot Fleetwood , Gillespie Cathleen , Merritt Robert , Hu Frank
Published: July 2021

Introduction:
Epidemiologic studies suggest that multiple cardiovascular (CVD) protection-factors (i.e., non-smoking, physically active, normal blood pressure, normal blood glucose, normal total cholesterol, non-obese, and healthy diet) are associated with significantly reduced risk of cardiovascular disease incidence and mortality.

Hypothesis:
We assessed the hypothesis that the increased number of CVD protection-factors is associated with reduced risk for all-cause and CVD mortality and adherence to low CVD risk profile could result in significant lower rates of all-cause and CVD mortality.

Methods:
We used the Third National Health and Nutrition Examination Survey (NHANES III 1988-1994) Linked Mortality File (through 2006), a prospective cohort study of a nationally representative sample of 12,861 U.S. adults to examine the prevalence, associations, and population attributable fraction (PAF) of seven CVD protection-factors in relation to risk of all-cause and CVD mortality.

Results:
Only 3.1% of U.S. adults had all seven CVD protection-factors. The average follow-up was 14.5 years. After multivariable adjustment for potential confounders, hazard ratios (HR) were: 0.30 (95% CI 0.22-0.40), 0.21 (0.12-0.34), and 0.17 (0.09-0.32), comparing individuals with ≥six protection-factors to those with ≤one protection-factors for all-cause, CVD, and IHD mortality respectively. Elevated blood pressure was responsible for the largest number of all-cause and CVD death followed by smoking and poor diet. Overall, 59% (95% CI 27-78) of total deaths and 66% (95% CI 22-88) CVD death would have been avoided during the average of 14.5 years follow-up if the population were changed to the high CVD protection-factors status (with ≥six protection-factors).

Conclusions:
Few adults in this U.S.-based study population had all seven desirable CVD protection-factors. The presence of an increasing number of CVD protection-factors was associated with a progressively lower risk of total and CVD mortality. Comprehensive population-based initiatives are needed to improve modifiable CVD risk factors, resulting in substantial reductions of all-cause and CVD mortality in the U.S. population.
Abstract MP093: Clinical Features, Treatment Practices, and Short-term Outcomes of Patients < 55 Years of Age Hospitalized with an Acute Coronary Syndrome: The Global Registry of Acute Coronary Events
Authors: Awad Hamza , Anderson Frederick A , FitzGerald Gordon , Gore Joel , Goldberg Robert
Published: July 2021

Limited data are available describing the magnitude, clinical features, treatment practices, and short-term outcomes of comparatively young adults hospitalized with acute coronary syndromes (ACS). The objectives of this large multinational observational study, using data from the GRACE Registry, were to describe nearly decade long trends in these endpoints among adults < 55 years old who were hospitalized with an ACS between 1999 and 2007. The overall proportion of young adult patients in our study population was 23% (n=15,052 of 65,119) and this proportion remained relatively constant over the study years. Baseline demographic and clinical characteristics of our study sample did not change significantly, whereas, the length of hospital stay declined by more than 1 day, on average, during the years under study. The overall in-hospital and 30-day multivariable adjusted case-fatality rates (CFRs) declined by approximately one-third (table) between 1999 and 2007 (crude 30-day CFR= 2.4% in 1999 and 1.7% in 2007). The use of evidence-based cardiac therapies demonstrated to improve outcomes of patients with an ACS increased significantly over time. In conclusion, improving trends in short-term outcomes of comparatively young patients hospitalized with an ACS during the nearly decade long period under study likely reflect enhanced primary and secondary prevention and treatment efforts. Odds of Dying in Younger Patients Hospitalized with an Acute Coronary Syndrome

Study Period
Crude Odds Ratios of In-Hospital Death

Multivariable Adjusted Odds Ratios of In-Hospital Death
*

Crude Odds Ratios of 30-day Death

Multivariable Adjusted Odds Ratios of 30-day Death
*

1999-2001º
1.0
1.0
1.0
1.0

2002-2004
0.89 (0.82-0.97)
0.83 (0.76-0.91)
0.93 (0.86-1.0)
0.83 (0.76-0.90)

2005-2007
0.74 (0.67-0.81)
0.66 (0.60-0.74)
0.74 (0.68-0.81)
0.62 (0.57-0.69)

*

Adjusted for age, sex, length of hospital stay, and medical history ºreferent period
Abstract P001: Dietary and Plasma Magnesium and Risk of Coronary Heart Disease among Women
Authors: Chiuve Stephanie E , Rexrode Kathryn M , Sun Qi , Taylor Eric N , Curhan Gary C , Manson JoAnn E , Albert Christine M
Published: July 2021

Background:
Plasma magnesium (Mg) has been strongly associated with lower risk of fatal coronary heart disease (CHD) and sudden cardiac death, which may be due to its anti-arrhythmic properties. Mg also affects endothelial function, inflammation, blood pressure and diabetes and thus may impact atherosclerosis in general. We examined the association between magnesium, measured in diet and plasma, and risk of fatal, nonfatal and total CHD among women in the Nurses’ Health Study.

Design:
The association for Mg intake was examined prospectively among 86,361 women free of disease in 1980. Mg intake and other covariates were ascertained updated every 2-4 years through questionnaires and 3661 cases of CHD (1214 fatal/2447 nonfatal) were documented through 2008. For plasma Mg, we conducted a nested case-control analysis with 405 CHD (63 fatal/342 nonfatal) cases, matched to controls (1:1) on age, smoking, fasting status, and date of blood sampling.

Results:
Dietary magnesium was inversely associated with risk of CHD, even after controlling for diet and CHD risk factors (RR comparing extreme quintiles: 0.75; 95%CI: 0.64, 0.89;
P
trend=0.002) (Table 1). The relationship with plasma Mg was less linear (
P
trend=0.09) with a potential threshold effect at the 2
nd
quintile. The RR of CHD comparing plasma Mg >2.0 v. ≤2.0 mg/dl was 0.49 (95%CI: 0.32, 0.74). The associations for dietary and plasma Mg appeared stronger for fatal versus nonfatal CHD. The RR (95%CI;
P
trend) comparing the highest to lowest quintile of dietary Mg was 0.60 (0.45, 0.79;
p
<0.001) for fatal and 0.85 (0.70, 1.04;
p
= 0.14) for nonfatal CHD. The RR (95%CI) comparing plasma Mg >2.0 v. ≤2.0 mg/dl was 0.23 (0.07, 0.81) for fatal and 0.55 (0.35, 0.86) for nonfatal CHD.

Conclusions:
Higher levels of Mg, in diet and plasma, were associated with lower risk of total CHD among women. The consistent inverse association found between two measures of Mg and CHD risk supports the hypothesis that Mg might lower CHD risk through multiple mechanisms, and may be most strongly protective for fatal events.
Abstract P006: Flow-Mediated Dilation is Inversely Associated with Cardiovascular Disease Risk: a Meta-Analysis of Prospective Studies
Authors: Ras Rouyanne T , Streppel Martinette T , Zock Peter L , Draijer Richard
Published: July 2021

Background -
Flow-mediated dilation (FMD) is an accepted technique to quantify endothelial (dys)function. The predictive value of FMD for future cardiovascular disease (CVD) risk has been investigated in several prospective studies. The purpose of the present study was to systematically review these studies and to quantify the relationship between FMD and CVD risk. It was hypothesized that the risk of experiencing a cardiovascular event later in life would be smaller when having a higher FMD value at baseline.

Methods -
Potentially relevant prospective studies were searched in several databases and by hand searching, through March 2011. Studies were selected based on predefined selection criteria. The statistical analysis was performed separately for continuous (per 1% increase in FMD) and categorical (when having a high vs. low FMD) risk estimates for CVD. The pooled overall risk estimate was calculated based on a random-effects model while weighting each study by the inverse of its variance. Potential sources of heterogeneity were investigated as well as presence of publication bias.

Results -
In total, 23 studies including 14,753 subjects were eligible for inclusion in the present meta-analysis. Subjects were followed for an average duration of 42.9 months (range: 12.1-94.6 months). The average age was 60.1 years (range: 46.0-78.6 years). In 8 out of 23 studies, asymptomatic subjects were included whereas in 15 studies, subjects were diagnosed as having various forms of diseases. In studies reporting continuous risk estimates, the pooled overall risk estimate for CVD expressed per 1 % increase in FMD was 0.90 (95%CI: 0.86, 0.94). One study, that was the only study including exclusively renal patients, reported results that significantly differed from this estimate. Excluding this study from the analysis did not materially affect the pooled overall risk estimate (RR = 0.92 (95%CI: 0.88; 0.95). Based on studies with categorical risk estimates, the pooled overall risk estimate for CVD when having a high FMD vs. a low FMD was 0.49 (95%CI: 0.38, 0.63). Covariate analysis revealed that health status significantly affected the association between FMD and CVD risk with a stronger association in diseased populations. Presence of publication bias could not be excluded.

Conclusions -
Our findings show that baseline FMD is inversely associated with CVD risk, particularly in diseased populations. Further studies should address the impact of underlying health status on the relationship between FMD and CVD.
Abstract P012: Cardiac Biomarkers of Newborn Myocardial Injury, Cardiomyopathy and Inflammation are Associated with Indicators of Premature Cardiovascular Disease in Childhood: The National Institutes of Health Project VIVA Study
Authors: Lipshultz Steven E , Miller Tracie L , Wilkinson James D , Gold Diane R , Oken Emily , Baccarelli Andrea , Mantzoros Christos S , Litonjua Augusto A , Rifai Nader , Rifas-Shiman Sheryl L , Colan Steven D , Gillman Mathew W
Published: July 2021

Objective:
To examine associations of cord blood cardiac biomarker levels in normal newborns with cardiovascular outcomes and adiposity in childhood.

Methods:
Among a sample (N=49) from 1120 Project Viva pediatric participants, selected to be ∼1/3 white, 1/3 black, 1/3 Hispanic, and whose gestational age at birth was ≥34 wks, we examined relations of cord blood levels of cardiac troponin T (cTnT, a biomarker for myocyte injury), high sensitivity C-reactive protein (hsCRP, a generalized marker of systemic inflammation) & N-terminal pro-brain natriuretic peptide (NT-proBNP, a biomarker of LV pressure or volume overload, cardiomyopathy, cardiac neurohormonal activation) with child outcomes at ages 3 & 7 years.

Results:
Forty six percent (22 of 49) were female. Mean cTnT was 47.0 pg/mL (range=15.1-87.3 pg/mL; detection limit=10 pg/ml). Mean NT-proBNP was 663 pg/mL (range=166-2042 pg/mL; normal <150 pg/ml) and mean hsCRP was 0.07 mg/L (range=0.03-0.18 mg/L; normal <1mg/L). For each 100 pg/mL increase in NT-pro-BNP, the ratio of subscapular: triceps skinfolds (central fat distribution) at 3 yrs was slightly higher (0.98 [95% CI -0.20, 2.16], P=0.10) and fat mass/m2 (DXA) at 7 yrs was higher (0.18 [95% CI 0.03, 0.33], P=0.02). For each 0.1 mg/L increase in hsCRP, the heart rate was 8.7 beats per minute lower (95% CI -15.8, -1.6, P=0.02) at age 7 years.

Conclusions:
Biomarkers of cardiomyopathy, inflammation, and cardiac injury are commonly elevated at birth. In this pilot study, cardiomyopathy and inflammation biomarkers were associated with higher central fat distribution and fat mass and lower resting pulse rate up to 7 years later. Larger cohort studies are needed to further examine cardio-metabolic outcomes related to these cord blood cardiac biomarkers.
Abstract P014: Cardiovascular Risk Factors Associated with Low Dehydroepiandrosterone Sulfate
Authors: Jimenez Monik C , Manson JoAnn E , Rexrode Kathryn M
Published: July 2021

Introduction:
Low dehydroepiandrosterone sulfate

(DHEAS) levels recently have been related to elevated risk of ischemic stroke. However, the association between DHEAS and traditional cardiovascular risk factors remains unclear.

Methods:
Blood samples were collected in 1989-1990 among 32,826 participants of the Nurses’ Health Study. Samples were assayed for DHEAS, lipids, and other biomarkers as part of a nested case control study evaluating risk of ischemic stroke and 340 stroke-free controls with complete data were available. Lifestyle covariates were ascertained in 1988. Stepwise logistic regression models were used to evaluate the association of between CVD risk factors and low DHEAS (<42 μ g/dL), while stepwise linear regression was used to evaluate the association with continuous DHEAS. Stepwise models utilized an entry threshold of α=0.20 and exit criterion of α=0.10.

Results:
The mean level of DHEAS was 78.38 μ g/dL (s.d. 50.02; median=67.03) in this population of women aged 43-69 years (median=62). Age was strongly associated with lower DHEAS. Women with history of heart disease and higher total/HDL cholesterol were more likely to have low DHEAS. In stepwise logistic regression analyses, age (OR=2.94; 95%CI: 1.73-5.00 for 10 yrs) and history of heart disease (OR=1.84; 95% CI: 0.91-3.70) were identified as risk factors for low DHEAS. In stepwise linear regression modeling, age, postmenopausal hormone use, history of heart disease and C-reactive protein (CRP) were associated with lower DHEAS levels while alcohol use was associated with higher DHEAS levels (Table 1). Body mass index, smoking, diabetes, glycosylated hemoglobin and lipids were not associated with low DHEAS.

Conclusions:
In this population of healthy women, lower levels of DHEAS were associated with older age, history of heart disease, postmenopausal hormone use, higher CRP and lower levels of alcohol consumption. Further research is needed to explore these associations.

Table 1

Multivariable
*
adjusted estimates for DHEAS by cardiovascular disease risk factors

DHEAS (continuous μ g/dL)

β

†

95%CI

Age

‡

−28.40
−36.75, -20.05

History of Heart disease
−18.76
−39.23, 1.71

Postmenopausal Hormone Therapy Use
&

−12.01
−21.99, -2.04

CRP

£

(mg/L)

−0.66
−1.37, 0.04

Alcohol

#

(g/day)

2.95
0.46, 5.45

*

All variables mutually adjusted for one another

†

Estimated from stepwise logistic regression model

‡

per 10 year increase in age
&
Ref = No use of postmenopausal hormone therapy

£

per 1 unit increase in C-reactive protein (CRP- mg/L)

#

per 5 unit increase in alcohol consumption (g/day)
Abstract P023: Relationship Between Vitamin D Status and Incidence of Macro-vascular Events in the Veterans Affairs Diabetes Trial (VADT)
Authors: Alele Jimmy D , Hunt Kelly J , Hollis Bruce W , Luttrell Deirdre K , Luttrell Louis M ,   VADT Study Group
Published: July 2021

BACKGROUND:
Few studies have examined the relationship between vitamin D levels and incident cardiovascular events in large well-characterized type 2 diabetes cohorts.

METHODS:
We performed prospective analyses to determine associations between vitamin D status and vascular endpoints among 936 Veterans Affairs Diabetes Trial (VADT) participants (mean age 59.7 years; 96.7% male; 40.4% minority). 25 (OH)-vitamin D was measured a median of two years after entry into the VADT study and participants were subsequently followed an average of 3.7 years for outcomes. Cox proportional hazard models were used to calculate hazard ratios (HRs) for macrovascular endpoints in relation to vitamin D quartile. The primary composite endpoint included documented myocardial infarction; stroke; death from cardiovascular causes; new or worsening congestive heart failure; surgical intervention for cardiac, cerebrovascular, or peripheral vascular disease; inoperable coronary artery disease; and amputation for ischemic gangrene.

RESULTS:
On average VADT participants had high cardiovascular risk at entry into the study: 65.3% of the patients recruited were obese, 38.5% had previously had a vascular event, 78.7% had hypertension and 59.5% were using statins. During follow-up, 17.2%, 5.0%, 5.9%, 2.4% and 6.6% of participants had a primary composite endpoint, myocardial infarction, chronic heart failure, cardiovascular death or all-cause death, respectively. After adjusting for age, minority status, treatment arm and history of prior event, individuals in the lowest quartile of vitamin D (i.e., 1 to 15.9 ng/ml) were at similar risk of the primary composite endpoint [HR=1.26 (95% CI: 0.81, 1.96)], myocardial infarction [HR=1.13 (95% CI: 0.53, 2.42)], congestive heart failure [HR=1.44 (95% CI: 0.67, 3.06)], cardiovascular death [HR=0.86 (95% CI: 0.28, 2.63)], and death from any cause [HR=1.04 (95% CI: 0.53, 2.04)] as individuals in the highest quartile of vitamin D (i.e., 29.9 to 77.2 ng/ml).

CONCLUSIONS:
These data indicate that vitamin D status had no significant impact on the incidence of macrovascular events in a cohort of high-risk veterans with type 2 diabetes mellitus in which traditional risk factors were managed according to current treatment guidelines.

SUPPORT:
This work was supported by American Heart Association Grant-in-Aid AHA0755466U and the Research Service of the Charleston SC VA Medical Center.
Abstract P025: Perceived Stress and Incidence of Type 2 Diabetes: a 35-Year Follow-up Study of Middle Aged Swedish Men
Authors: Novak Masuma
Published: July 2021

OBJECTIVE_
To explore the incidence cases of diabetes over 35 years of follow-up in middle-aged Swedish men in relation to their severity of stress at baseline.

RESEARCH DESIGHN AND METHODS_
This was a population-based random sample of 7 495 men derived from the Primary Prevention cohort study (Gothenburg) aged 47-55 years and without prior history of diabetes at baseline (1970-1973). Self-perceived psychological stress during the previous years was assessed with a single-item in the questionnaire. Incident diabetes from hospital discharge and death registries was collected during the 35 years follow-up. Cox proportional hazards regression was used to evaluate association of stress with incidence of diabetes.

RESULTS_
During the follow up of 35 years, 884 men developed diabetes. The crude incidence rate was 46.32 per 1000 persons-years. At baseline, 15.5% men reported to experience permanent stress. The age-adjusted cumulative incidence of type diabetes in men who had permanent stress was 16%, compared with 12% for those with no or periodic stress. In age-adjusted Cox regression analysis, men with permanent stress had a higher risk of diabetes incident (hazard ratio 1.52 [95% CI 1.26-1.82]) compared with men with periodic or no stress (referent). The excess risk of diabetes incident associated with permanent stress remained significant after adjusting for age, socioeconomic status (SES), smoking, physical inactivity, alcohol abuse, height, BMI, serum-cholesterol, hypertension, systolic and diastolic blood pressure.

CONCLUSIONS_
Perceived permanent stress in middle aged Swedish men was an important long-term predictor of diabetes incidence. The association of stress was independent of SES, lifestyle and other conventional type 2 diabetes risk factors. The significant impact of stress on diabetes, as demonstrated in this study, emphasizes need for prevention strategies including intervention programmes for people with permanent stress.