bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10: Increased Consumption of Fruits and Vegetables and Weight Change Over Time
Authors: Bertoia Monica L , Mukamal Kenneth J , Cahill Leah E , Hou Tao , Ludwig David S , Mozaffarian Dariush , Willett Walter C , Hu Frank B , Rimm Eric B
Published: July 2021

Introduction:
Current dietary guidelines recommend eating a variety of fruits and vegetables. However, based on nutrient composition, specific fruits and vegetables may be more or less beneficial for weight maintenance.

Hypothesis:
Fruits and vegetables with a higher fiber content or lower glycemic load are more strongly associated with weight maintenance and even weight loss, in part through mechanisms related to increased satiety.

Methods:
We examined the association between increased consumption of fruits and vegetables and change in body weight among participants <65 years of age from three large prospective cohort studies: 41,608 women in the Nurses’ Health Study (NHS) I, 20,143 men in the Health Professionals Follow-up Study, and 67,533 women in the NHS II. Beginning in 1986, these associations were examined during 24 years of follow-up within 4-year time intervals, adjusting for simultaneous changes in other lifestyle factors such as diet, smoking, and physical activity.

Results:
Increased consumption of one serving per day of several types of fruits was inversely associated with weight gain over 4 years, for example -1.11 lbs (95% CI, -1.43 to -0.80 lbs) for berries and -0.96 lbs (95% CI, -1.20 to -0.72 lbs) for apples/pears. Increased consumption of several vegetables was also inversely associated with weight gain, for example -2.15 lbs (95% CI, -2.58 to -1.73 lbs) for tofu/soy and -1.18 lbs (95% CI, -1.73 to -0.64 lbs) for cauliflower. On the other hand, increased consumption of some vegetables was positively associated with weight change, for example corn (1.69 lbs; 95% CI, 0.90 to 2.48 lbs) and peas (0.81 lbs; 95% CI 0.16 to 1.46 lbs).

The magnitude of weight change associated with increased consumption of high fiber vegetables (-0.37 lbs; 95% CI -0.48 to -0.27 lbs) was larger than that for low fiber vegetables (-0.13 lbs; 95% CI -0.23 to -0.02 lbs). Increased consumption of low glycemic load vegetables was associated with a greater magnitude of weight change, -0.37 lbs (95% CI, -0.63 to -0.11 lbs), compared to high glycemic load vegetables, -0.01 lbs (95% CI, -0.14 to 0.11 lbs). In contrast, weight change associated with fruit consumption did not vary by fiber content or glycemic load.

Conclusions:
Increased consumption of total fruits and vegetables was inversely associated with weight change over 4 years, however we found wide-ranging associations for specific foods, partly due to the fiber content and glycemic load of vegetables but not fruits.
Abstract 13: Detection of Abnormal Glucose Tolerance Status in Africans is improved by combining A1C with Fasting Glucose
Authors: Sumner Anne E , Thoreson Caroline K , O'Connor Michelle Y , Ricks Madia , Chung Stephanie T , Lozier Jay , Sacks David B
Published: July 2021

Diabetes is reaching epidemic proportions in Africa. Therefore it is critical to invest scarce resources in effective tests. Both the World Health Organization and the American Diabetes Association have approved A1C and fasting plasma glucose (FPG) as diagnostic alternatives to the OGTT for the detection of pre-diabetes and diabetes. However, A1C thresholds for the diagnosis of abnormal glucose tolerance are dependent on >90% of hemoglobin (Hb) being HbA. This could be problematic for Africans, as the prevalence of variant Hb including both sickle (S) and HbC are high. When either HbS or HbC is present as a trait, the concentration of HbA is usually<60%. Our goal was to test in African immigrants whether A1C or A1C combined with FPG have sufficient sensitivity to be an effective diagnostic alternative to the OGTT. Two hundred and six self-identified healthy Africans living in the Washington DC area (140 men, 66 women, age 36±10y (mean±SD, range 20-64y) were enrolled. The African region of origin for the participants was West 57% (112 of 206), Central 27% (56 of 206) and East 19% (38 of 206). Every participant had an OGTT. HPLC was performed to determine the presence of variant Hb and A1C levels. Variant Hb occurred in 21% (44 of 206) of Africans. FPG, 2h glucose and A1C were: 90±13 mg/dL, 131±40 mg/dL and 5.5±0.7% respectively. On the basis of the OGTT, 30% (61 of 206) had newly identified pre-diabetes and 6% (12 of 206) had diabetes. For the detection of abnormal glucose tolerance, the pre-diabetic and diabetic participants were combined into a single group. For comparison to the OGTT, diagnostic thresholds were FPG≥100 mg/dL and A1C≥5.7%. In Africans without variant Hb, the sensitivity for the diagnosis of abnormal glucose tolerance by A1C was 53%. In the presence of variant Hb, the sensitivity of A1C to detect abnormal glucose tolerance fell to 40%. When either A1C or FPG were positive, sensitivity for the diagnosis of abnormal glucose tolerance in Africans with and without variant Hb was 67% and 64%, respectively. In short, A1C alone is not a satisfactory diagnostic test in Africans and this was magnified in the presence of variant Hb. However, when A1C was combined with FPG the sensitivity rose to the mid-sixties and did not vary by variant Hb status. Thus, to detect abnormal glucose tolerance status in Africans combining A1C with FPG makes it unnecessary to know variant Hb status and improves diagnostic capability.
Abstract 20: Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality: the Cardiovascular Health Study
Authors: Wu Jason H , Lemaitre Rozenn , King Irena , Song Xiaoling , Siscovick David , Mozaffarian Dariush
Published: July 2021

Background:
While omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce CHD, controversy remains about benefits vs. harms, including depending on types of n-6 PUFA and diseases examined.

Aims:
To assess associations of circulating n-6 PUFA including linoleic acid (LA, the major dietary PUFA), Γ-linoleic acid (GLA), dihomo-Γ-linoleic acid (DGLA), and arachidonic acid (AA),with incident total and cause-specific mortality in the Cardiovascular Health Study (CHS), a community-based US cohort.

Methods:
Among 2,692 participants age≥65y and free of CVD at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total (fatal or nonfatal) incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA biomarkers with risk were assessed by multivariable Cox regression.

Results:
During 33,091 person-years of follow-up (1992-2010), 1920 deaths occurred (including 660 cardiovascular deaths), as well as 414 fatal and 410 nonfatal CHD events, and 150 fatal and 384 nonfatal strokes. In multivariable models, higher LA was associated with lower risk of total mortality, with extreme quintile HR 0.84 (95% CI 0.71-0.98,
P-
trend 0.002). Lower death was largely attributable to CVD rather than non-CVD causes, especially nonarhythmic CHD mortality (HR 0.50, 95% CI 0.31-0.80,
P-
trend 0.001). Phospholipid GLA, DGLA, and AA levels were not associated with total or cause-specific mortality; e.g., for AA and CHD death, the extreme quintile HR was 0.98 (95% CI 0.71-1.37,
P-
trend 0.72). Evaluated semi-parametrically, LA showed graded (monotonic) inverse associations with total mortality (
Figure 1A
). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA (Bonferroni corrected
P
=NS,
Figure 1B
).

Conclusion:
Higher circulating LA, but not other n-6 PUFA, is inversely associated with total and CHD mortality in older adults.
Abstract 21: Accounting For Smoking Behavior In Genome-wide Analysis Of Obesity Phenotypes: The Giant (genetic Investigation Of Anthropometric Traits) Consortium
Authors: Justice Anne , Winkler Thomas , Ngwa Julius , Czajkowski Jacek , Young Kristin , Hadley David , Graf Mariaelisa , Chasman Daniel , Qi Qibin , Zillikens M. Carola , Feitosa Mary F , Ahluwalia Tarunveer S , Franks Paul , Kilpeläinen Tuomas O , Haller Toomas , Monda Keri , Bouchard Claude , Heard-Costa Nancy L , Direk Nese , Tiemeier Henning , Borecki Ingrid , Loos Ruth , North Kari , Cupples L. Adrienne
Published: July 2021

Obesity, especially central obesity, and cigarette smoking (SMK) are both important risk factors for cardiovascular disease (CVD). Yet, smokers often exhibit lower body mass index (BMI) and higher waist circumference (WC) compared to non-smokers; also, smoking cessation leads to weight gain. Genome-wide association (GWA) studies have identified genetic loci that are associated with risk of overall and central obesity; yet little is known about whether and how SMK influences the genetic susceptibility to obesity. This study aims to discover genetic loci that are associated with obesity, measured as BMI and WC adjusted for BMI (WC
a
), and where the effects are hidden by SMK. We used results from 42 studies including up to 126,767 subjects with GWA data available through the GIANT Consortium. Each study employed three association models while considering smoking status (current vs. not current smokers): 1) SNP effects adjusted for SMK (SNPadjSmk), 2) SNP by SMK interaction effects (SNPxSMK), and 3) joint effect of SNP and the SNP x SMK interaction effect (SNPxSMK
J
). Study specific results were combined by inverse-variance weighted fixed-effects meta-analyses of the study specific results in men and women separately and then combined sexes. A total of 53 SNPs for WC
a
reached genome-wide significance (GWS) (p<1E-8) by adjusting for and allowing for interaction with SMK (SNPadjSMK and SNPxSMK
J
), 27 of these loci are novel for WC
a
. Additionally, SNPadjSMK and SNPxSMK
J
models identified a total of 49 SNPs associated with BMI that reached GWS, including 15 novel loci.

While no loci reached GWS for SNPxSMK on BMI, one novel SNPxSMK association with WC
a
near
PRNP
reached GWS in women.
PRNP
is highly expressed throughout the CNS and especially the hippocampus, as are many obesity-related genes.
PRNP
also plays a role in the body’s response to oxidative stress, making it a likely candidate gene for interaction with smoking as well. Of the GWS SNPs, 47 WC
a
and 41 BMI loci are nearby (<500 kb) previously established loci for traits of interest (e.g. SMK, obesity, CVD, VAT, lipids, T2D, T1D and other anthropometrics). We identify one locus with strong evidence of interaction with SMK on obesity, and notably, we find several new loci associated with obesity by accounting for the influence of SMK. Our results highlight the importance of appropriately modeling genetic associations by considering known biological relationships between phenotypes and the environment.
Abstract 26: Long-term Blood Pressure Variability though Young Adulthood and Cognitive Function in Midlife; The Coronary Artery Risk Development in Young Adults (CARDIA)Study
Authors: Yano Yuichiro , Ning Hongyan , Allen Norrina , Reis Jared P. , Liu Kiang , Greenland Philip , Lloyd-Jones Donald
Published: July 2021

Background:
Blood pressure variability (BPV) consists of short-term BPV (e.g., diurnal BPV) and long-term BPV (e.g., visit-to-visit BPV). The prospective association of long-term BPV though young adulthood with cognition in midlife is unknown.

Methods:
CARDIA is a multicenter community-based study that included participants (ppts) aged 18 to 30 years at baseline (Year 0: Y
0
) in 1985-86 with follow-up examinations at Y
2
, Y
5
, Y
7
, Y
10
, Y
15
, Y
20
, and Y
25
. BP was measured at each exam, and visit-to-visit BPV was assessed by standard deviation (SD), coefficient of variation (CV), maximum minus minimum BP difference (MMD), and average real variability (ARV) across 7 visits (Y
0-20
). Cognitive function was assessed at Y
25
by the Digit Symbol Substitution Test (DSST, a measure of psychomotor speed; n=2,318), the Rey Auditory Verbal Learning Test (RAVLT, a measure of short-term verbal memory; n=2,321), and the modified Stroop test (executive function; n=2,307). We performed separate multivariable-adjusted linear regression models, and also adjusted for baseline BP (Y
0
), change of BP (Y
20
-Y
0
), or cumulative BP from Y
0
to Y
20
(mmHg х year) to determine whether BPV is associated with cognition independent of long-term BP level.

Results:
At the Y
25
examination, included ppts had a mean age of 50 years, 57% were women and 43% were black. BPV measured by higher SD and ARV in both systolic and diastolic BP was significantly associated with lower DSST and lower RAVLT. SD and ARV remained significant even after further adjustment for baseline BP, change of BP, or cumulative BP (Table). Measures of BPV were not associated with the Stroop test. Associations between the CV and MMD measures of BPV with cognitive function were similar to those of SD (not shown).

Conclusions:
Long-term BPV over 20-years through young adulthood is associated with worse psychomotor speed and verbal memory in midlife, independent of BP levels. These results may have implications for understanding the pathogenesis of cognitive dysfunction in older adults.
Abstract 32: Loss of Ideal Cardiovascular Health Factors from Early Young Adulthood to Middle Age
Authors: Gooding Holly C , Shay Christina M , Gillman Matthew W , Ning Hongyan , Chiuve Stephanie E , Allen Norrina B , Reis Jared , Labarthe Darwin R , Liu Kiang J , Lloyd-Jones Donald M
Published: July 2021

Introduction:
Adults who reach middle age with ideal blood pressure, cholesterol, and glucose levels have lower rates of CVD mortality compared to those with one or more adverse levels. AHA identified four healthy lifestyle factors (HLFs) - BMI, smoking, diet, and physical activity - important for preventing loss of this low CVD risk state. The purpose of this study was to quantify associations between combinations of HLFs measured in young adulthood and loss of ideal CVH factors into middle age.

Methods:
Analyses included 2,421 young adults (age 18-30 years at baseline in 1985-6) in the Coronary Artery Risk Development in Young Adults study who met criteria for ideal CVH factors at baseline: untreated blood pressure <120/80 mmHg, total cholesterol <200 mg/dL, fasting blood glucose <100 mg/dL and absence of CVD. Cox proportional hazards regression models were used to estimate hazard ratios for loss of all ideal CVH factors status over 25 years of follow-up according to 16 combinations of HLFs measured in young adulthood: BMI <25kg/m2, physical activity >300 exercise units, never smoking/quitting ≥ 12 months prior, and scoring in the top tertile of the AHEI diet score. Models were adjusted for age, sex, race, education, and study center.

Results:
Most (86%, 69 of 80) young adults with 0 HLFs lost the all ideal CVH factor status by middle age. Relative to young adults with no ideal HLFs, those with all 4 ideal HLFs were least likely to lose the low risk CVD state (HR 0.53, 95% CI 0.40-0.70). In the absence of ideal BMI, no combination of other HLFs was significantly protective (Figure 1). When analysis was restricted to the 1,708 young adults with ideal BMI, participants with ideal smoking, diet, and physical activity had a lower likelihood of losing the ideal CVH factor state compared to those with ideal BMI only (HR 0.79, 95% CI: 0.63-0.99).

Conclusions:
Ideal BMI in early young adulthood was protective against loss of ideal CVH factors over time. Among those with ideal BMI, ideal smoking status, diet, and physical activity conferred additional benefit.
Abstract 56: Prognosis of Patients with Acute Myocardial Infarction by Hospital Discharge Diagnosis
Authors: Levitan Emily B , Olubowale Olusola T , Gamboa Christopher , Brown Todd M , Muntner Paul , Rhodes J D , Safford Monika M
Published: July 2021

Background:
Research on acute myocardial infarction (AMI) in medical claims largely focuses on hospitalizations where AMI is the primary discharge diagnosis (dx). Limited data are available on AMIs occurring as a secondary dx during hospitalization.

Hypothesis:
We hypothesized that mortality following AMI is higher when the primary dx is not AMI.

Methods:
We examined REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants with definite or probable AMIs adjudicated using published guidelines. Participants were categorized by hospital discharge dx from the discharge summary: primary dx, secondary dx, or no dx of AMI. All-cause and cardiovascular mortality after AMI, detected though active follow-up and the National Death Index, were compared using Kaplan-Meier curves with log-rank tests and Cox proportional hazard models adjusted for sociodemographics, medical history, and characteristics of the AMI (clinical evidence of ischemia, peak troponin, and heart failure during hospitalization).

Results:
Of 877 participants with AMI, 37% had AMI as primary dx, 12% had AMI as a secondary dx, and 51% had no dx of AMI. All-cause mortality (n = 284) was higher among participants with AMI as a secondary dx or without a dx of AMI than among participants with AMI as primary dx, but cardiovascular mortality (n = 150) was similar across groups (
Figure
). Compared to participants with AMI as primary dx, adjusted hazard ratios for all-cause mortality were 1.03 (95% CI 0.68-1.57) and 1.17 (95% CI 0.84-1.62) and for cardiovascular mortality were 0.79 (95% CI 0.46-1.37) and 0.91 (95% CI 0.60-1.38) for participants with AMI as a secondary dx and without a dx of AMI, respectively.

Conclusions:
Studies of AMI based on primary discharge dx likely under count the number of AMIs and exclude a population with similar prognosis in terms of all-cause and CVD mortality, once clinical differences considered. Further study into the characteristics, in-hospital and post-discharge management of these patients may be warranted.
Abstract 61: Associations of Cardiorespiratory and Musculoskeletal Fitness with Body Mass Index and Waist Circumference: Fitness versus Fatness in a Population-based Sample of Chilean 8th Graders
Authors: Garber Michael D , Lobelo Felipe , Sajuria Marcelo
Published: July 2021

Background:
In addition to excess adiposity, low cardiorespiratory fitness (CRF) and low musculoskeletal fitness (MSF) are important, independent risk factors for future cardio-metabolic disease in adolescents. To the best of our knowledge the fitness versus fatness relationship has not been studied in a population-based sample in Latin America.

Hypothesis:
We hypothesized that the physical fitness variables of CRF and MSF will be negatively associated with BMI and WC in an adolescent population in Chile, independent of potential confounders, but that a significant proportion of adolescents with poor body composition will exhibit healthy fitness levels.

Methods:
This cross-sectional study was based on a representative, single-stage, stratified cluster sample of 19,929 8th graders (median age = 14 years) in the 2011 National Education Survey from all regions of Chile. CRF was assessed with the 20 m shuttle run test, MSF with standing broad jump, and body composition with BMI and WC. CRF, MSF, BMI, and WC were classified according to health-related standards, validated against cardio-metabolic risk factors. Gender-stratified logistic regression models for both CRF and MSF included socioeconomic status, age, region, the other fitness variable, BMI, and WC. Analyses were weighted and considered complex sample design.

Results:
In both genders, the adjusted prevalence of high-risk CRF was higher among students with high-risk BMI (boys: prevalence ratio (PR) = 1.88; girls: PR = 1.71; both p<0.05) and with high-risk WC (boys: PR = 1.77; girls: PR = 1.21; both p<0.05), compared with their healthy counterparts. BMI but not WC was an independent correlate of high-risk MSF in girls (PR = 1.32; p<0.05). Both BMI (PR=1.64; p<0.05) and WC (PR=1.11; p<0.05) were independent correlates of high-risk MSF in boys. A substantial proportion of students with poor body composition had healthy fitness, and vice versa: 46% of boys and 25% of girls with high-risk BMI had healthy CRF. Conversely, 35% of boys and 55% of girls with high-risk CRF had a healthy BMI. Similarly, 47% of boys and 51% of girls with high-risk BMI had healthy MSF whereas 43% of boys and girls with high-risk MSF had a healthy BMI.

Conclusions:
In this large representative sample of Chilean adolescents, BMI and WC were inversely correlated with CRF and MSF. Nonetheless, the sizeable proportion of adolescents with poor body composition but healthy fitness, and vice versa, underscores the importance of assessing both CRF and MSF for a more complete representation of adolescent cardio-metabolic risk.
Abstract 64: Echocardiographic Determinants of Change in Cardiorespiratory Fitness in Response to Exercise Training: The DREW Study
Authors: Pandey Ambarish , Ayers Colby , Blair Steven N , Church Timothy S , Swift Damon L , Earnest Conrad P , Berry Jarett D
Published: July 2021

Background:
Although exercise training is associated with an improvement in cardiorespiratory fitness (CRF), there is substantial individual heterogeneity in the response to exercise training. To our knowledge, the contribution of baseline left ventricular structure to the variability in exercise training response has not been studied.

Methods:
We included 147 subjects from the Dose Response to Exercise in Women (DREW) study cohort who were randomized to 4, 8, 12 kilocalories/kg/week of aerobic training for 6 months and had a baseline transthoracic echocardiogram. CRF was evaluated at baseline and 6 month follow up using a cycle ergometer and quantified as peak absolute oxygen consumption (VO2abs L O2/min) and peak relative oxygen consumption (mLO2/kg/min). Change in CRF was defined as the difference in VO2abs between the two examinations. Baseline demographic, clinical and echocardiographic characteristics were compared among subjects across tertiles of CRF change. Multivariable adjusted linear regression analysis was used to determine the association between echocardiographic measures at baseline and the change in CRF in response to exercise training.

Results:
Participants were middle age (mean age: 57), obese (mean BMI: 31), and with low baseline CRF (average METs: 4.3). As expected, lower baseline CRF and a higher exercise training dose were associated with a greater increase in CRF. In addition, posterior wall thickness (PWT), interventricular septal thickness (IVST), and indexed left ventricular mass (LVmi) were all found to be inversely associated with change in CRF in response to exercise training after adjustment for age, body mass index, baseline CRF, blood pressure and exercise training dose (see Table). Other echocardiographic measures (i.e. systolic and diastolic function) were not associated with change in CRF.

Conclusions:
Both left ventricular mass and wall thickness are independent predictors of CRF change in response to exercise training among obese, sedentary postmenopausal females.
Abstract MP01: Association of Objectively-measured Physical Activity with Cardiovascular Risk in Mobility-limited Older Adults
Authors: Buford Thomas W , Hire Don G , Ambrosius Walter T , Anton Stephen D , Church Timothy S , Dodson John A , Marsh Anthony P , McDermott Mary M , Nocera Joe R , White Daniel K , Yank Veronica , Pahor Marco , Manini Todd M
Published: July 2021

Introduction:
In middle-aged adults, time spent being sedentary is associated with cardiovascular (CV) health risks independent of structured physical activity (PA). However, data are sparse regarding the impact of sedentary behavior on CV risk in older adults. The extent to which the absolute duration or intensity of daily PA reduces CV risk in older adults is also unknown.

Objectives:
Our objective was to examine the cross-sectional association between objectively-measured sedentary behavior and predicted CV risk among older adults in the Lifestyle Interventions and Independence for Elders (LIFE) study. The secondary objective was to evaluate associations between the duration/intensity of daily PA and predicted CV risk.

Methods:
LIFE is a randomized clinical trial to determine if regular PA prevents mobility disability among mobility-limited older adults. Activity data were collected by hip-worn accelerometer at baseline prior to participation in study interventions. Only participants with at least three days of accelerometry data (≥ 10 hrs wear time) were included. Unadjusted and adjusted linear regression was used to model the relationship between accelerometry measures and predicted 10-year Framingham risk of Hard Coronary Heart Disease (HCHD; i.e. myocardial infarction or coronary death). Adjusted models included demographic confounders (e.g. education, race, income) and health parameters (e.g. depression, cognition, arthritis) not in the risk score. Accelerometry cut-points were (in counts/min): sedentary behavior: < 100; low-intensity activity: 100-499; higher intensity activity: > 500.

Results:
Participants (n = 1170; 78.7 ± [SD] 5.3 years; 66.1% female) had a median HCHD risk of 10.3% (25
th
-75
th
%: 5.7-18.6). Over a mean accelerometer wear time of 8.1 ± 3.2 days, participants spent 77.0 ± 8.2% of their time sedentary. They also spent 16.6 ± 5.0% of their time in low-intensity PA and 6.4 ± 4.4% in higher-intensity PA. For all PA performed (> 100 counts/min), participants achieved a median of 393.4 (337.8-473.5) counts/min. In the unadjusted model, time spent sedentary (β = 2.41; 95% CI : 1.94, 2.89), in low-intensity PA (-2.56; -3.03, -2.08), and in higher-intensity PA (-1.60; -2.09, -1.11) were all associated with HCHD risk (all p’s < 0.001). These associations remained significant after adjustment. The mean intensity of daily PA was not significantly associated with HCHD risk in any model (p > 0.05).

Conclusions:
Daily time spent being sedentary is positively associated with predicted 10-year HCHD risk among mobility-limited older adults. Duration, but not mean intensity, of daily PA is inversely associated with HCHD risk score in this population.
Abstract MP05: Mid-Life Vitamin D Levels are Not Associated with Cognition and Dementia Risk in Whites and Blacks: the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Schneider Andrea L , Lutsey Pamela L , Alonso Alvaro , Gottesman Rebecca F , Sharrett A R , Carson Kathryn A , Post Wendy S , Knopman David S , Mosley Thomas H , Michos Erin D
Published: July 2021

Introduction:
Recent studies, mainly performed in elderly whites, suggest that vitamin D, measured by 25-hydroxyvitamin D [25(OH)D], is important for cognition. Less is known about the association of 25(OH)D measured in mid-life with cognition and dementia risk in whites and blacks.

Hypothesis:
We hypothesized that lower concentrations of 25(OH)D would be associated cross-sectionally with lower cognitive test scores and prospectively with greater decline in cognitive test scores and with increased risk of dementia.

Methods:
We conducted cross-sectional (1993-1995), change (1993-1995 to 2004-2006), and prospective (follow-up through 2010) analyses of 1,652 participants in the ARIC Brain Ancillary Study with measured 25(OH)D (1993-1995). 25(OH)D was analyzed in race-specific tertiles and continuously. Cognition was measured by 3 tests: Delayed Word Recall (DWR), Digit Symbol Substitution (DSS), and Word Fluency (WF). Dementia was defined by hospitalization ICD-9 codes. Adjusted race-stratified linear regression and Cox proportional hazards models were used.

Results:
Mean age of participants was 62 years, 60% were female, and 48% were black. Mean 25(OH)D was higher in whites than blacks (25.5 versus 17.3 ng/ml, p<0.05). Over a median of 16.6 years, there were 145 incident hospitalized dementia cases. In prospective analyses, lower levels of 25(OH)D trended towards an association with increased dementia risk in whites and in blacks, but these results were not statistically significant (lowest versus highest tertile: whites, HR: 1.32 [95% CI: 0.69, 2.55]; blacks, HR: 1.53 [95% CI: 0.84, 2.79]) (Figure).

Conclusion:
In contrast to prior studies performed in elderly populations, our study did not find significant associations between lower levels of 25(OH)D in mid-life with lower cognitive test scores at baseline, change in score over time, or increased dementia risk.
Abstract MP06: Gait Speed is Associated with Subclinical and Clinical Atherosclerosis - Analysis from the AGES Reykjavik Study
Authors: Gudnason Vilmundur , Siggeirsdottir Kristin , Launer Lenore J , Harris Tamara B , Aspelund Thor
Published: July 2021

Background:
Coronary events are major causes of morbidity and mortality in the population and are consequences of atherosclerotic coronary artery disease. The development of atherosclerosis is a long standing process. Measuring subclinical atherosclerosis allows examination of the determinants of the disease without using hard end points. We studied the functional ability of individuals measured as gait speed and its relationship with prevalent subclinical atherosclerosis and incident coronary events.

Material and Methods:
Participants were from the AGES Reykjavik Study, a population study of 5174 men and women (57%), mean age 76.5 (SD 5.5) followed for coronary events (MI, PCI, CABG) for a median of 8.1 years. Subclinical atherosclerosis (IMT and plaque) was examined with ultrasound of the carotid arteries and Agatston score of coronary artery calcium (CAC) by CT at entry into the study. Gait speed was measured by time of 6 m walk. Cox proportional hazard was used to assess the effect of gate gait speed, on CHD events, verified from hospital records. Logistic regression was used to estimate the association of subclinical CHD to atherosclerosis, adjusted for baseline age, sex and CHD risk factors.

Results:
There was a gradual increase in risk of CHD by quintile of 6m walk speed with HR of 2.0 (95% CI 1.7 - 2.4) in the top compared to bottom quintile adjusted for age and sex. After further adjustment for conventional risk factors attenuation to a HR of 1.8 (95% CI 1.5 - 2.2) was seen. When the subclinical markers was examined, there was a gradual increase in CAC by slower gate speed (p< 0.0001), much more pronounced in men, who had higher CAC than women. Similar picture was seen for plaque (p <0.0001) in the carotid arteries, but a statistically significant association was not found for IMT (p=0.09).

Conclusion:
Gait speed is strongly associated with manifest CHD in this population of free living old people. When subclinical measurements of arterial disease are used, those clearly measuring atherosclerosis - CAC and plaque of the carotid - are associated with worse gait speed. On the other hand gait speed was not associated with IMT, which much less clearly reflects atherosclerosis. The simple physical performance test, of the time it takes to walk 6 m used in this study, captured clinical CHD and subclinical cardiovascular status measured by imaging. This simple performance measurement might therefore be of potential use for peripheral practitioner in selecting those individuals who might benefit from detailed cardiovascular assessment.
Abstract MP20: Vitamin D Supplementation Increases Global DNA Methylation in Overweight and Obese African Americans with Vitamin D Deficiency
Authors: Zhu Haidong , Huang Ying , Bhagatwala Jigar , Parikh Samip , Havens Robyn , Kotak Ishita , Dong Yanbin
Published: July 2021

Introduction:
Vitamin D deficiency is associated with cardiovascular disease, diabetes and cancer. Individuals with obesity or darker skin are at risk for vitamin D deficiency. Our genome-wide methylation study has shown that African Americans with vitamin D deficiency have reduced levels of methylation compared with controls. Global decrease in DNA methylation, a common feature of cancer, is associated with genomic and chromosomal instability. Therefore, we aimed to test our hypothesis that vitamin D supplementation will increase global DNA methylation level in overweight and obese African Americans with vitamin D deficiency.

Methods:
We recently conducted a 16 weeks randomized, placebo controlled clinical trial of vitamin D3 supplementation (NCT01583621). A total of 65 young overweight and obese African Americans (13-45 years, 83% females) with vitamin D deficiency (25-hydroxyvitamin D3 [25(OH)D] < 20 ng/ml) were randomly assigned to receive a supervised monthly oral vitamin D3 dose of placebo (n=16), 18,000 IU (~600 IU/day, the current RDA; n=15), 60,000 IU (~2,000 IU/day; n=17), or 120,000 IU (~4,000 IU/day, the deemed tolerable upper intake level; n=17). Global DNA methylation level (percentage of 5-methylcytosine, %5-mC) was quantified using leukocyte DNA with the MethylFlash Methylated DNA Quantification kit (Epigentek) in a total of 58 participants.

Results:
At baseline, serum 25(OH)D levels were positively correlated with %5-mC (r=0.26, p=0.04) in the entire cohort. A significant increase was observed in the changes of serum 25(OH)D from baseline to 16 weeks (0.9 ± 2.0, placebo; 8.6 ± 2.1, 600 IU/day; 20.1 ± 2.0, 2,000 IU/day; and 21.2 ± 2.0 ng/ml, 4,000 IU/day; p<0.01). In addition, a significant dose-responsive increase was observed in the changes of %5-mC from baseline to 16 weeks (0.00 ± 0.18, placebo; 0.02 ± 0.20, 600 IU/day; 0.29 ± 0.17, 2,000 IU/day; and 0.66 ± 0.18%, 4,000 IU/day group; p<0.01). This response remained significant even after adjusting for age, sex and BMI. Moreover, the changes in %5-mC were significantly correlated with the changes in serum 25(OH)D (r=0.60, p=0.02) in the 4,000 IU group.

Conclusions:
Vitamin D supplementation increases global DNA methylation level in a dose-responsive manner. Increased global DNA methylation, subsequently increased genomic and chromosomal stability may be one of the underlying mechanisms by which vitamin D exerts its beneficial effects on cardiovascular disease, diabetes and cancer. Large scale vitamin D supplementation clinical trial is warranted to verify our findings.
Abstract MP29: Patient Characteristics And Outcomes Associated With In-hospital Onset Of Acute Decompensated Heart Failure
Authors: Kalbaugh Corey A , Chang Patricia P , Matsushita Kunihiro , Agarwal Sunil K , Caughey Melissa , Ni Hanyu , Rosamond Wayne , Wruck Lisa , Loehr Laura
Published: July 2021

Introduction:
There has been little focus on hospitalized acute decompensated heart failure (ADHF) that develops after admission, which may occur because of comorbid conditions, over-administration of fluid or post-surgical complications.

Aims:
To compare patient characteristics, case fatality, and hospital length of stay (LOS) associated with ADHF that develops after hospital admission as compared to those with ADHF at admission.

Methods:
Hospitalizations with possible ADHF were sampled, based on HF ICD codes, among those aged > 55 years from the four communities of the Atherosclerosis Risk in Communities Study (2005-2010). Medical records were abstracted with events classified by physician panel or computer classified. Case fatality was obtained through the National Death Index. We identified 4,503 (unweighted) events with definite/probable ADHF, after excluding those with unknown time of decompensation (n=81), hospital transfers (n=102), and race other than black or white (n=118). Demographic and clinical characteristics were compared by ADHF onset (at/after admission). Logistic regression was used to evaluate the association of ADHF onset with in-hospital mortality, and 28-days and one-year mortality, adjusted for demographics and comorbidity. Linear regression was used to evaluate the association of ADHF onset with log-transformed hospital LOS, adjusted for demographics. All analyses were weighted to account for the stratified sampling design.

Results:
Of 21,052 (weighted) ADHF events, 7.4% (n=1561) developed ADHF after admission. Patients with ADHF occurring after admission were older (mean: 79 vs. 75 years), and more likely white and female. Those with ADHF at admission were more likely to have a positive smoking history, COPD, and to be on dialysis. Presence of diabetes, hypertension and coronary artery disease were not significantly different between groups. In hospital mortality (16.5% vs. 6.3%; OR= 2.7, 95% CI=1.9-3.8) and 28-day mortality (23.9% vs. 10.1%; OR= 2.4, 95% CI=1.7-3.4) was higher among those who developed ADHF after admission. One-year case fatality was similar (39.4% vs. 33.6%; OR= 1.2, 95% CI=0.9-1.6). Unadjusted mean LOS was longer for those with ADHF occurring after admission (12.8 days, 95% CI=11.8-13.8) than those with ADHF at admission (7.2 days, 95% CI=6.8-7.6). The adjusted and geometric mean LOS was 1.3 days (95% CI=1.2-1.4) longer for those who developed ADHF after admission.

Conclusion:
Although patients with ADHF onset after admission were slightly older, differences in comorbidity do not indicate an easily identifiable subgroup for closer in-hospital monitoring. Development of ADHF after admission was associated with an alarmingly high early case fatality and longer hospital LOS compared to those with ADHF at hospital admission.
Abstract MP40: Vital Exhaustion as a Predictor of Recurrent Cardiac Events in Patients with Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Williams Janice E , Kop Willem J , Kucharska-Newton Anna , Couper David J , Mosley Thomas
Published: July 2021

Several studies have demonstrated a positive relationship between vital exhaustion and incident coronary heart disease (CHD), but the association of exhaustion with recurrent cardiac events has not been established in large, epidemiologic studies. Vital exhaustion is considered the end-stage of prolonged psychological distress and is characterized by excessive fatigue, increased irritability, and a sense of demoralization. We assessed the hypothesis that vital exhaustion predicts recurrent cardiac events (myocardial infarction and CHD-related mortality) among middle-aged men and women with documented CHD. Participants were 589 black or white men and women (mean age = 59.8; range = 47 - 69 years) with a history of CHD at the 1990-1992 clinical examination of the ARIC Study. Vital exhaustion was measured at the same ARIC examination using the 21-item Maastricht Questionnaire, and scores were categorized into quartiles. Recurrent cardiac events were monitored in short term (0-5 years), mid- term (6-13 years), and long-term (14-19 years) follow-up. Cox proportional hazards regression models were adjusted for age, sex, race-center, educational level, body mass index, plasma LDL-and HDL-cholesterol levels, hypertension status, and pack-years of cigarette smoking. During short term follow-up, the risk for recurrent cardiac events among participants in the highest quartile of vital exhaustion was twice that of participants in the remainder of the sample (HR = 2.08; 95% C.I: 1.24 to 3.48). The risk was less strong but remained statistically significant in mid-term (HR = 1.77; 95% C.I: 1.26 to 2.48) and long-term (HR = 1.54; 95% C.I: 1.12 to 2.11) follow-up. In conclusion, vital exhaustion is positively associated with short-term and long-term risks for recurrent cardiac events among middle-aged men and women with established coronary heart disease, independent of the traditional biomedical risk factors.
Abstract MP52: Increased Intake of Non-Dairy Sugars in Foods and Beverages is Positively Associated with Annual Increases in Waist Circumference among Overweight and Obese Adolescent Females
Authors: Lee Alexandra , Chowdhury Ritam , Welsh Jean
Published: July 2021

Introduction:
Waist circumference (WC) is an important measure of adiposity that predicts cardiovascular disease risk in adolescents. Previous studies have shown a positive association between sugar-sweetened beverages and WC in adolescents but it is unknown if this effect differs when sugars are consumed in foods vs. beverages.

Hypothesis:
Increased sugar consumption from both foods and beverages is associated with increased WC.

Methods:
NHLBI’s Growth and Health Study was a 10-year cohort study of Caucasian (n=1,166) and African-American (n=1,213) girls aged 9 and 10 at baseline who were recruited from three sites in the US in 1987 and 1988. Minimum WC was measured annually except at baseline. Diet was assessed using a three-day food record in eight of ten years; nutrient content was determined using the Nutrient Data System for Research. Girls were grouped by weight status (normal vs. overweight or obese). One-year changes in WC and in consumption of liquid and solid non-dairy sugars were calculated by subtracting each year’s measure from its value for the subsequent year. A linear mixed model was used to accommodate multiple observations per individual. After modeling change in sugar consumption as quintiles, a linear trend was observed and further modeling was conducted using continuous change in sugars consumption. Model I adjusted for race, age, puberty stage, initial WC, initial BMI, change in height, dieting status, initial and change in physical activity, initial and change in % energy from fat and % energy from carbohydrates, and initial consumption of sugars. Model II additionally adjusted for initial and change in total energy.

Results:
Among normal weight girls using Model I, significant increases in WC were observed with each additional teaspoon of liquid, 0.19mm (0.05, 0.33) (p=0.006), but not solid sugars 0.11mm (-0.02, 0.24) (p=0.11). These increases were no longer significant after adjusting for total energy in Model II. Among overweight and obese girls in Model I, increases in WC were observed with each additional teaspoon of solid sugars, 0.42 mm (0.22, 0.62) (p<0.0001) and liquid sugars, 0.26 mm (0.09, 0.44) (p=0.004). This association was slightly attenuated but still significant after controlling for total energy with WC increases of 0.31 mm (0.10, 0.52) (p=0.005) with each teaspoon of solid sugars and 0.19 mm (0.005, 0.37) (p=0.049) with each teaspoon of liquid sugars.

Conclusions:
Increases in non-dairy sugars from both foods and beverage were associated with increased WC among overweight and obese adolescents, both before and after adjusting for total energy intake.
Abstract MP62: Beneficial Effects of Dietary Potassium on Adolescent Blood Pressure
Authors: Buendia Justin R , Bradlee M. L , Singer Martha R , Moore Lynn L
Published: July 2021

Childhood blood pressure (BP) is an important predictor of adult blood pressure. Identification of modifiable risk factors for elevated blood pressure levels during adolescence has the potential to reduce the risk of adult hypertension. Longitudinal data on the effects of dietary sodium and potassium on adolescent BP are lacking. The objective of the study was to examine the effects of dietary potassium, sodium, and the potassium:sodium ratio (K:Na) throughout adolescence on blood pressure at the end of that period and to determine whether these effects are modified by other dietary factors. Data from 2330 girls, initially ages 9-10, and followed for 10 years in the National Growth and Health Study, were used to address these questions. Mean potassium and sodium intakes were 3.1 and 2.0 g, respectively, from an average of 6.6 sets of 3-day diet records. Analysis of covariance (ANCOVA) models were used to estimate mean systolic (SBP) and diastolic (DBP) blood pressures at 18-20 yrs of age, controlling for height, race, TV/video viewing time, physical activity, total energy intake, and BMI. Girls in the highest tertile of potassium intake (vs. lowest) had the lowest adjusted mean SBP (108.46 vs. 109.43 mm Hg; p-trend=0.030) and DBP (65.18 vs. 65.94 mm Hg; p-trend=0.073) at the end of follow up. Similar results were observed for the K:Na ratio (SBP 108.07 vs. 109.50 mm Hg; p-trend=0.021; DBP 65.02 vs. 65.85; p-trend=0.151). Finally, mineral intake as a part of a healthy eating pattern was examined. In this analysis, girls with a higher K:Na ratio (≥0.7) combined with high intakes of total fruit and vegetable (FV), fiber, or dairy had SBP levels that were approximately 2 mm Hg lower at the end of follow up than those with lower intake (p<0.05 for all diet patterns). Adolescents with a higher K:Na ratio with higher total FV or fiber intakes also had the lowest DBP levels at the end of follow up. Dietary sodium intake was generally unrelated to BP levels regardless of other diet patterns. Adolescent girls who consumed a high potassium and K:Na alone and particularly in the context of healthy eating patterns throughout adolescence had lower SBP and DBP levels at the end of adolescence. This study suggests that dietary potassium may play a more important role than sodium in determining adolescent BP levels. Thus, increasing dietary potassium intakes during childhood may reduce the risk of hypertension later in life.
Abstract MP63: Randomized Trials of Low-Fat vs. Other Diet Interventions on Weight Loss: A Meta-Analysis
Authors: Tobias Deirdre K , Chen Mu , Willett Walter , Hu Frank B
Published: July 2021

Introduction:
The effectiveness of low-fat diets for weight loss has been debated for decades. Dozens of randomized control trials (RCTs) have assessed whether decreasing the intake of total fat leads to weight loss, giving mixed results.

Hypothesis:
We hypothesized that low-fat dietary interventions do not lead to greater weight loss when comparator diet intervention intensity is considered.

Methods:
We conducted a systematic review and meta-analysis. RCTs were included if they compared a low-fat dietary intervention to any control diet with at least 1 year of follow-up. We estimated the combined fixed effect inverse variance weighted mean difference of low-fat vs. comparison diets. Several a priori stratified analyses were considered to explore heterogeneity.

Results:
Fifty studies met inclusion criteria, reporting 1-10 years of follow-up on 70,054 participants. Overall, low-fat dietary interventions resulted in 0.51kg greater weight loss compared to other diets (95% CI = -0.62, -0.40, p<0.001; I2 = 83%). However, when trials where greater attention was given to the low-fat group were excluded, comparator diets led to greater weight loss than low-fat diets (n=30; WMD=0.87, 95% CI=0.56, 1.17, p<0.001). Similarly, when the type of comparator diet was considered, low-fat diets were only beneficial compared to control groups who were simply asked to maintain their usual diet (n=18; WMD = -1.03, 95% CI = -1.18, -0.88, p<0.001). When equal attention was given to intervention groups, low-carbohydrate diets (n=15; WMD = 1.13kg, 95% CI = 0.53, 1.73, p<0.001) and other “healthy” diets without a low-fat component (n=20; WMD = 0.77kg, 95% CI = 0.42, 1.13, p<0.001) led to greater weight loss than low-fat diets. Comparison diets, irrespective of type, were associated with 1.30kg greater weight loss than low-fat diets when the interventions were intended to be isocaloric (n=19; 95% CI = 0.92, 1.69, p<0.001).

Conclusions:
Low-fat dietary interventions are not more effective than other diets for weight loss when differences in intervention intensity between treatment groups are considered. Rather, evidence from long-term (>=1 year) randomized trials indicates low-carbohydrate or other healthful dietary pattern interventions without a low-fat focus may be more effective for weight loss than low-fat dietary interventions. Further evidence is needed to establish the role of these interventions in longer-term weight loss and weight maintenance.