bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP21: No Significant Association of n-3 polyunsaturated Fatty Acids (PUFAs) with T-helper Type 1 (Th1) Cells: Results From the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Sagawa Naoko , Olson Nels C , Vishnu Abhishek , Ahuja Vasudha , Doyle Margaret F , Psaty Bruce M , Jenny Nancy S , Siscovick David S , Lemaitre Rozenn N , Steffen Lyn M , Tsai Michael Y , Sekikawa Akira
Published: March 2022

Introduction:
T-helper type 1 (Th1) cells provide important stimulatory and regulatory signals to immune cells and are positively associated with subclinical atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Fish and fish oils are a major source of n-3 polyunsaturated fatty acids (PUFAs), and several studies in Japanese populations with high fish consumption reported inverse associations with subclinical atherosclerosis. Animal studies have suggested an inverse relationship of n-3 PUFAs with Th1 cells; however, this has not been investigated in humans. We hypothesized that n-3 PUFAs would have an inverse association with Th1 cells in MESA.

Methods:
We included 895 MESA participants with data on n-3 PUFAs at exam 1 (2000-02) and Th1 cells at exam 4 (2005-07) (age 61±10 years, 467 women, 396 Caucasians, 219 Hispanics, 185 African-Americans, 95 Chinese-Americans). Th1 cells were measured by flow cytometry as a percentage of CD4+ lymphocytes that were interferon-γ+ (%Th1). Phospholipid n-3 PUFAs (% of total fatty acids), defined as the sum of eicosapentaenoic and docosahexaenoic acids, were measured by gas chromatography. Dietary intake of n-3 PUFAs was evaluated by food frequency questionnaire (n=847). General linear models were used to analyze cross-sectional associations of n-3 PUFA quartiles with %Th1 adjusting for covariates.

Results:
Mean n-3 PUFA and %Th1 levels were 4.8±2.1% and 15.9±8.3%. n-3 PUFAs were not significantly associated with %Th1 (P for trend=.58). The association remained non-significant after adjusting for covariates. Dietary intake of n-3 PUFAs also showed no significant association with %Th1 (Table).

Conclusion:
Circulating levels and dietary intake of n-3 PUFAs were not significantly associated with %Th1 in this multi-ethnic U.S. population. n-3 PUFA levels in this cohort may be too low to have an effect on Th1 levels. Further research is needed to assess potential benefits of n-3 PUFA supplementation and dietary consumption of fish on T helper cell profiles and atherogenesis.
Abstract MP34: Association of Overweight and Obesity with an Incidence of Heart Failure: A Systematic Review and Meta-analysis
Authors: Krittanawong Chayakrit , Tunhasiriwet Anusith , Zhang HongJu , Prokop Larry J , Tweet Marysia S , Chirapongsathorn Sakkarin , Wang Zhen , Sun Tao , Hayes Sharonne N
Published: March 2022

Introduction:
Obesity is a growing global health problem associated with substantial morbidity and mortality. The risk of obesity on incident new-onset heart failure is controversial. The aim of this systematic review and meta-analysis was to explore the association between overweight, obesity and incident new-onset heart failure.

Methods:
We systematically searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from database inception through April 2015. Prospective cohort studies were included if the studies reported hazard ratios (HRs) of the association between overweight or obesity and new-onset heart failure (HF) relative to individuals with normal weight. Data were extracted by one reviewer followed by independent screening and extraction of study characteristics and outcome data by two other reviewers. Conflicts were resolved through consensus. Random-effects meta-analyses were used to pool the hazard ratio from the included studies. Subgroup analyses were performed to explore the potential sources of heterogeneity.

Results:
Out of 1,865 retrieved articles, we identified 10 relevant studies. Median follow-up was 12 years with a total of 82,167 individuals and 4,570 total HF events. Compared to normal body weight (body mass index (BMI) <25 kg/m2), overweight (BMI 25-29.9 kg/m2) was associated with 27% higher risk of new-onset heart failure events (pooled HR, 1.27; 95% confidence intervals (95% CI): 1.15-1.41; p<0.001; I
2
= 0%) and obesity (BMI ≥30 kg/m2) was associated with a two-fold increased risk for new-onset heart failure events (pooled HR, 2.09; 95% CI, 1.68-2.60; p<0.001; I
2
= 67.8%).

Conclusions:
Compared with normal-weight individuals, both overweight and obesity were independently associated with significantly higher incidence of heart failure. These results highlight the need for better understanding of mechanisms of obesity and heart failure.
Abstract MP46: Usual Walking Pace is More Strongly Associated with Lower Risk of Heart Failure Than Total Physical Activity in the Women’s Health Study
Authors: Djousse Luc , Chae Claudia , Buring Julie E , Lee I-Min
Published: March 2022

Background:
While previous studies have reported lower risk of coronary heart disease with physical activity, limited data exist on the relation of physical activity with heart failure risk in a community setting.

Objective:
To test the primary hypothesis that physical activity is inversely associated with HF risk in a cohort of apparently healthy women and a secondary hypothesis that walking time and usual walking pace are associated with lower risk of HF.

Methods:
Prospective cohort study of 39,635 participants from the Women’s Health Study. Information on leisure-time physical activity, including walking time and usual pace, was self-reported at baseline and HF was ascertained through annual follow-up questionnaires with validation through review of medical records. We used Cox regression to estimate multivariable adjusted hazard ratios of HF.

Results:
During a mean follow-up of 17.2 years, 635 cases of HF occurred. The mean age at baseline was 54.6 ± 7.0 years. Median physical activity was 8.4 MET-h/week (IQR: 2.7-20.2); about 18% of women did not walk regularly while 32% reported walking pace of 3+ miles per hour. In a multivariable adjusted model, hazard ratios (95% CI) for HF were 1.0 (ref), 0.73 (0.57-0.95), 0.86 (0.69-1.07), 0.70 (0.54-0.92), and 0.93 (0.66-1.05) for physical activity of <3.75, 3.75-7.4, 7.5-14.9, 15-22.4, and 22.5+ MET-h/week, respectively (p trend 0.043). However, the association was attenuated upon additional adjustment for usual walking pace (corresponding HR: 1.0 (ref), 0.77 (0.60-1.01), 0.93 (0.73-1.18), 0.77 (0.58-1.02), and 0.94 (0.73-1.22), p trend 0.47). Walking time showed a J-shaped relation with risk, that also was attenuated after adjustment for pace and MET-h/wk (HR: 1.0 (ref), 1.19 (0.94-1.50), 1.06 (0.80-1.39), 0.69 (0.50-0.97), 0.84 (0.63-1.12), and 0.87 (0.63-1.20) for walking time of 0-19 min/wk, 20-59 min/wk, 1h/wk, 1.5h/wk, 2-3h/wk, and 4+h/wk, respectively). In contrast, usual walking pace was inversely associated with HF risk even after adjustment for total physical activity and walking time with multivariable adjusted HR of 1.0 (ref), 0.97 (0.75-1.24), 0.88 (0.70-1.10), and 0.74 (0.55-0.98) for walking pace of 0, <2, 2-2.9, and 3+ miles per hour, respectively, p trend 0.038).

Conclusions:
Our data show inverse associations of total leisure-time physical activity with HF risk that was attenuated after adjustment for usual walking pace. In contrast, usual walking pace was inversely and robustly associated with HF risk while walking time showed a J-shaped relation.
Abstract MP59: Orthostatic Hypotension and Risk of Falls in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Juraschek Stephen P , Daya Natalie , Appel Lawrence J , Miller Edgar R , Windham B G , Pompeii Lisa , Griswold Michael , Heiss Gerardo , Kucharska-Newton Anna , Selvin Elizabeth
Published: March 2022

Background:
Orthostatic hypotension (OH) is considered an important risk factor for falls, but prospective studies have been small and inconsistent.

Methods:
We examined the association between OH assessed at baseline in 12,661 middle-aged participants of the ARIC Study (1987-1989). OH was considered present if there was a drop in blood pressure (systolic ≥20 mm Hg or diastolic blood pressure ≥10 mm Hg) when moving from the supine to standing position after three minutes. Changes in systolic or diastolic blood pressures were also examined as continuous variables. The outcome of interest was any fall identified from ICD9 discharge codes from hospitalization records or Centers for Medicare & Medicaid Services claims data. The association of OH and risk of fall was characterized using Cox proportional hazard models.

Results:
At baseline, the mean age was 54 years; participants were 55% women and 47% black; 5% (N = 651) had OH. During a median follow-up of 23 years, there were 2,274 new falls. The incidence rate, using age as the time axis, was 2.8 per 1,000 person-years among participants with OH versus 2.3 per 1,000 person-years among those without OH (P = 0.03). OH was significantly associated with long-term risk of fall even after adjustment for demographics and other risk factors (Figure legend) (HR 1.25, 95% CI 1.04-1.49). Furthermore, postural change in diastolic blood pressure was more strongly associated with risk of falls (HR 1.07 per -5 mm Hg in diastolic blood pressure; P < 0.001) than postural change in systolic blood pressure (HR 1.02 per -5 mm Hg in systolic blood pressure; P = 0.01). This association appeared linear without evidence of a threshold effect (Figure).

Conclusions:
In an ambulatory population, OH, and in particular, postural change in diastolic blood pressure, were significant, independent risk factors for falls over a long period of time. Future studies should determine whether targeted therapies can reduce falls in persons with OH.
Abstract MP63: Loss of Ideal Blood Pressure in Childhood: Age-specific Emergence of Gender and Race/ethnic Disparities
Authors: Hardy Shakia T , Holliday Katelyn M , Chakladar Sujatro , Engeda Joseph C , Heiss Gerardo , Lin Danyu , Shay Christina M , Zeng Donglin , Avery Christy L
Published: March 2022

Introduction:
Gender and race/ethnic disparities in the burden of adverse blood pressure (BP) levels in adulthood have origins in childhood. Proper timing of primordial prevention efforts could narrow inequalities in BP trajectories across the life course. Few studies have characterized the ages at which children transition from ideal BP by gender and race/ethnicity, using contemporary multiethnic populations.

Methods:
We utilized the prevalence of ideal (<90th percentile for SBP and/or DBP), intermediate (90th-95th percentile or SBP ≥120 or DBP ≥80 mm Hg) and poor (>95th percentile for SBP and/or DBP) BP levels among African American (AA), European American (EA), and Mexican American (MA) NHANES participants (2007-2012, n=4,566) to estimate race/ethnic, age (8-19 years), and sex-specific net probabilities of transitioning between levels of BP using novel Markov-type modeling.

Results:
At age 8, the prevalence of ideal BP differed more by gender than by race/ethnicity, with the prevalence of ideal BP among boys (AA: 87%; EA and MA: 89%) being lower than the prevalence of ideal BP in girls (AA: 92%, EA 94%, MA 96%). From age 8, the magnitude of net declines in ideal BP also varied by gender and race/ethnicity. For example, between ages 8-11, the population of AA boys with ideal BP declined a net 1.6% [95% confidence interval (CI): 1.3-1.8%] annually, net declines that were approximately 25% greater than net declines estimated in EA and MA boys. For all race/ethnic groups, annual net declines in ideal BP among girls were less than half the decline of their male counterparts. Between 12-15 years of age, the largest declines for both genders occurred in AAs (AA boys: 2.1%, 95% CI: 1.7-2.5%; AA girls: 0.9%, 95% CI: 0.7-1.1%). By age 19, the annual net declines in ideal BP increased to approximately 2.9% (95% CI: 2.3-3.5%) and 1.4% (95% CI: 1.1-1.7%) per year for AA boys and AA girls, respectively. These declines, together with earlier net transition patterns widened ideal BP disparities in both boys (AA 68%, EA 73%, MA 75%) and girls (AA 84%, EA 89% MA 93%) at age 19.

Conclusions:
Disparities in transitions from ideal BP emerge during childhood and early adolescence, with disparate, rapid declines in ideal BP observed in boys and AAs, thus introducing BP disparities. Research emphasizing safe and effective primordial prevention efforts in childhood is necessary to preempt disparities and their maintenance.
Abstract MP70: Impact of Cardiovascular Health Metrics on Life Expectancy and All-cause Mortality in Middle-aged and Elderly Men and Women
Authors: Lee Chong-Do , MA Tongyu
Published: March 2022

Purpose:
We investigated the combined impact of 7 ideal cardiovascular health metrics on life expectancy and lifetime risk of all-cause mortality in middle-aged and elderly US men and women.

Methods:
Cox proportional hazards regression was used to examine the associations of single and combined number of 7 health metrics and all-cause mortality after adjustment for multiple risk factors. Survival analysis (modified version) was used to compute lifetime risk of all-cause mortality at 40 years of age to 80, with death free of chronic diseases as a competing event. We followed 7,848 men and women, aged 40 to 80 years, who participated in the Third National Health and Nutrition Examination Survey. All participants completed baseline lifestyle factors and lifestyle behavior questionnaires. The 7 ideal cardiovascular health metrics were defined as physically active, never smoked, a healthy diet, waist girth (<102/88 cm), untreated blood pressure (<120/80 mmHg), untreated total cholesterol (<200 mg/dL), and untreated fasting glucose (<100 mg/dL) defined by the American Heart Association (AHA). We further categorized these variables as having 0, 1, 2, 3, 4, 5, 6 or 7 combined cardiovascular health metrics.

Results:
During an average of 13.2 years of follow-up (103,851 person-years), there were a total of 2,297 all-cause deaths (915 CVD, 546 cancer, 210 respiratory disease, 86 diabetes mellitus). After adjustment for multiple risk factors, men and women with all 6 or 7 combined ideal health metrics had a 68% (95% CI: 43% to 83%) lower risk of all-cause mortality compared with men and women with zero ideal health metrics. The lifetime risks of all-cause mortality (at 40 years of age) across 0, 1, 2, 3, 4, 5, and 6 or 7 ideal health metrics were (95% CI) 60.2% (55.6, 64.8), 51.9% (48.4, 55.4), 43.6% (40.3, 46.9), 37.1% (33.0, 41.3), 35.1% (29.6, 40.5), 33.8% (24.8, 42.8), and 19.4% (5.1, 33.7), respectively. Men and women with increasing number ideal health metrics had a substantially lower lifetime risk of all-cause mortality. Men and women with 6 or 7 compared with 0 combined ideal health metrics had a longer life expectancy by 13.5 years (95% CI: 6.8 to 19.5 years). Approximately 53% (95% CI: 15% to 74%) of all-cause deaths might have been avoided if men and women had adopted all 6 or 7 combined health factors and healthy lifestyle behaviors.

Conclusion:
Adopting the AHA’s 7 ideal cardiovascular health metrics is associated with lower lifetime risk of all-cause mortality and longer life expectancy in middle-aged and elderly US men and women.
Abstract MP83: Exomechip Meta-analysis of 526,508 Individuals From Five Ancestries Identifies Coding Variation in
MC4R
and
KSR2
Associated with Body Mass Index
Authors: Highland Heather M , Turcot Valérie , Lu Yingchang , Schurmann Claudia , Justice Anne E , Young Kristin L , Graff Mariaelisa , Locke Adam E , Wang Judy , Lenzini Petra , Cupples L A , Frayling Timothy , Hirschhorn Joel N , Lettre Guillaume , Lindgren Cecilia M , North Kari E , Borecki Ingrid B , Loos Ruth J ,   BBMRI,   GoT2D,   CHARGE,   GIANT Consortia
Published: March 2022

Increased body mass index (BMI) increases risk of chronic diseases including heart disease, stroke, and type 2 diabetes (T2D). Through genome-wide association studies (GWAS), 97 genetic variants, mostly common (MAF>5%) and non-coding, have been identified for BMI. To investigate the role of coding variants with putative functional effects (missense, nonsense, splicing, stop gain), we meta-analyzed ExomeChip data of 526,508 individuals from over 110 studies, predominantly of European ancestry. Individual studies performed association analyses using Rvtest or RareMetalWorker; results were subsequently combined in single variant meta-analyses and gene-based tests (SKAT, VT) stratified by ancestry using RareMETALS. Gene-based tests were grouped based on functional annotation and
in silico
predicted impact on proteins for variants with a MAF<5%. Among the 245,497 variants analyzed, of the 93 loci that reached array-wide significance (P<2E-07); 56 were novel or independent of previously identified BMI loci. This includes low frequency variants in
ACHE
(rs1799805, p.H353N, p=8.01E-10, EAF=4%, β(SE)=0.032(0.005) SD/allele),
HIP1R
(rs34149579, p.V67F, p=1.88E-08, EAF=4%, β(SE)=-0.027(0.005) SD/allele) and
MC4R
(rs13447324, p.Y35X, p=2.37e-11, EAF=0.01%, β(SE)=0.64(0.09) SD/allele). Eight gene-based associations were significant (p<2.5E-06), including
GIPR
(p=7.17E-09), whose effects were independent of the common GWAS proxy in the gene (rs1800437, p. E354Q, p=7.91E-30, MAF=20%, β(SE)=-0.029(0.003) SD/allele).
GIPR
is part of the
GLP1
pathway responsible for the secretion of postprandial insulin. Other gene-based associations were largely driven by a single variant, such as for
KSR2
(p=7.15E-09),
RAPGEF3
(p=8.91E-15) and
PRKAG1
(p=2.75E-12).
Ksr2
knockout mice are obese. Multiple variants in
KSR2
have been shown to associate with severe early onset obesity. Mutations in
KSR2
disrupt the Raf-MEK-ERK pathway, resulting in impaired fatty acid oxidation and glucose oxidation.
RAPGEF3
is involved in the
GLP1
pathway and regulates glucose sensitivity of the K
ATP
channel, which regulates insulin secretion.
PRKAG1
is involved in AMPK signaling and has previously been associated with T2D and weight gain on antipsychotic medication. Taken together, by interrogating coding variants in a large sample set, we have identified both additional genes and variants associated with BMI, some of which may be causal.
Abstract P006: A Population-based Approach to Sudden Unexpected Death Epidemiology
Authors: Hodonsky Chani J , Pursell Irion W , Chen Sarah , Devlin Carter , Mounsey J. P , Simpson Ross J
Published: March 2022

Introduction:
Sudden cardiac death accounts for 150,000 to 400,000 deaths in the United States annually. Published studies of sudden death use restrictive inclusion criteria such as timing of death, death-certificate disease attribution, hospital transport, attempted resuscitation, and victim survival status. These case definitions may undercount minority victims, victims who are socially isolated, or victims with limited healthcare access, leading to mischaracterization of sudden death in the general population. The SUDDEN study is a population-based epidemiologic analysis of out-of-hospital sudden unexpected death (OHSUD) in North Carolina that aims to characterize OHSUD incidence in the general population and identify associated risk factors.

Methods:
Wake County, North Carolina, is a predominantly urban county with approximately 4,700 adult deaths in a 2013 population of 974,289. All possible sudden unexpected deaths over one year in Wake County were collected via EMS. Death certificates, medical records, and post mortem examination data were used to determine demographic information and comorbidities. Of 1,138 18- to 64 year olds identified as possible OHSUD victims, 187 cases were adjudicated into the study population. Population-based estimates were age- and sex-standardized to 2013 North Carolina mortality tables to estimate a statewide OHSUD count.

Results:
Out-of-hospital sudden unexpected death accounted for approximately 14% of all deaths in adults under age 65. Up to 13.5% of all 2013 Wake County deaths outside of a healthcare institution were attributable to OHSUD. Approximately 2/3 of SUDDEN cases would have been excluded by timing criteria in commonly used sudden death case definitions. Hypertension, ischemic heart disease, hypercholesterolemia, COPD, and diabetes were all highly prevalent in Wake County OHSUD victims. OHSUD accounted for 48% of deaths in 18- to 64-year-olds with diseases of the heart, stroke/cerebrovascular disease, or chronic lower respiratory disease listed as the cause of death. 52% of all 2013 OHSUD in Wake County listed a cardiac primary cause on the death certificate; 37% were listed as having non-cardiac causes, with the remaining listing an unknown or a non-natural cause (e.g., trauma). Excluding non-cardiac causes of death would misclassify over 1,500 OHSUD victims per year in North Carolina alone.

Discussion:
Sudden death incidence estimates vary widely according to published exclusion criteria, leading to a mischaracterization of a disease that needs to be addressed on a national level. Restrictive exclusion criteria used in published studies of sudden death underestimate the incidence of OHSUD and divert resources from populations that would benefit the most from targeted interventions.
Abstract P008: Repeatability of Ectopic Beats From 48-hour Ambulatory Electrocardiography: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Meyer Michelle L , Soliman Elsayed Z , Wruck Lisa , Mosley Thomas H , Poon Anna , Whitsel Eric A , Alvaro Alonso , Heiss Gerardo , Loehr Laura R
Published: March 2022

Background:
Ectopic beats, defined by premature atrial contractions (PACs) and premature ventricular contractions (PVCs), are one of the most common findings on the electrocardiogram (ECG). Excess ectopic beats on ambulatory ECG monitoring are associated with atrial fibrillation (AF), stroke and death in symptomatic patients and in population-based studies. However, the repeatability of ECG-enumerated ectopic beats has not been sufficiently examined in a general population.

Objectives:
Characterize the repeatability of PACs and PVCs in a community-based population of older adults.

Methods:
Ambulatory, 48-hour ECG was measured in a subsample of the Atherosclerosis Risk in Communities Study (ARIC; 2011-2013) at two locales. Participants were randomly invited to participate in the repeatability study (n=92). Following an identical, standardized protocol, the participants wore a Holter monitor for two, 48-hour periods separated by a mean of 38 days (range: 11, 130 days) and completed a symptom questionnaire during each period. Each visit included new electrodes and Holter placement. All participants wore monitors for 48 hours and had recordings with <1% noise. Participants with AF (n=4) or paced rhythm (n=2) were excluded (total n=86; mean age 74.6 years; 56 females, 55 black). Visit-specific quartiles and 80th percentile cut-points for the total counts of PACs and PVCs over the 48 hour monitoring period were used. Between-visit agreement was quantified using the weighted kappa for quartiles and kappa for 80th percentile cut-points.

Results:
About 17% of the participants reported symptoms of dizziness, palpitations, or chest pain while wearing the monitor. During the 48-hour recordings, all participants had ≥1 PAC count and 2 participants had a 0 PVC count. The overall median (interquartile range (IQR)) was 266 counts (IQR: 80, 1,692.5) for PACs and 223 counts (IQR: 17.5, 1,085.5) for PVCs. The median between-visit difference (visit 2 - visit 1) was -12.5 counts for PACs (IQR: -154, 65) and 0 counts for PVCs (IQR: -78, 320). The between-visit, weighted kappa for count quartiles was 0.70 (95% confidence interval (CI): 0.61, 0.80) for PACs and 0.68 (95% CI: 0.58, 0.78) for PVCs. The kappa for counts >80th percentile was 0.56 (95% CI: 0.34, 0.78) for PACs and 0.71 (95% CI: 0.52, 0.90) for PVCs.

Conclusion:
Between-visit agreement is high to moderate for 48-hour, Holter-based PACs and PVCs quantiles, according to common interpretations for kappa coefficients. When paired with pending examination of how agreement varies over shorter duration recordings within the 48-hour monitoring period, the present results can facilitate epidemiologic and clinical applications in which knowledge of measurement error, variability and misclassification are needed to inform risk assessment.
Abstract P017: Serum Vitamin D, Sex Hormones, and Erectile Dysfunction in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Zhao Di , Ouyang Pamela , De Boer Ian H , Lutsey Pamela L , Farag Youssef M , Guallar Eliseo , Siscovick David , Post Wendy S , Blaha Michael J , Kalyani Rita R , Billups Kevin L , Michos Erin D
Published: March 2022

Background:
Activated Vitamin D regulates testosterone (T) and estradiol (E2) synthesis. 25-hydroxyvitamin D [25(OH)D] deficiency has been associated with low T levels in men with conflicting associations described in women. Low 25(OH)D is associated with increased cardiovascular (CVD) risk and possibly with erectile dysfunction (ED) in men. We examined the association of 25(OH)D with sex hormones (SH) in men and women and with ED in men in a multi-ethnic cohort (mean age 63 yrs).

Methods:
25(OH)D,T, E2, dehydroepiandrosterone (DHEA), and SH binding globulin (SHBG) levels were measured at MESA exam 1 (2000-2002), and bioavailable T calculated. Self-reported ED was recorded at exam 5 (2010-2012). Using linear regression, we evaluated the multivariable adjusted cross-sectional associations of 25(OH)D and SH separately by sex. Among men, we used logistic regression to assess the association of 25(OH)D with odds of low T<10.41 nmoI/L (300 ng/dl) [9.4%] at exam 1 and with ED at exam 5.

Results:
After adjusting for demographic and lifestyle variables, higher 25(OH)D levels were associated with greater total T and SHBG in men and with greater E2, SHBG, and lower bioavailable T and DHEA in women [
Table
]. Compared to ≥30 ng/ml, 25(OH)D deficiency (<20 ng/ml, 31% men and 32% women) was associated with increased odds of low T in men in age/race model [1.37 (1.05, 1.77)] but was attenuated after adjusting for lifestyle variables [1.19 (0.91, 1.55)]. Among 1796 men with 25(OH)D and T at exam 1, 45% were found to have ED at exam 5. Neither 25(OH)D deficiency nor low T was associated with ED. In all analyses, results were similar after further adjusting for CVD risk factors.

Conclusion:
Higher 25(OH)D levels were associated with higher SHBG in both men and women, greater T in men, and greater E2 and lower DHEA in women independent of adiposity and lifestyle. 25(OH)D deficiency and low T were not associated with prevalent self-reported ED assessed 10 years later. Future studies are needed to determine if treating low vitamin D can influence sex hormone levels.
Abstract P023: Subclinical Inflammation and Weight Change in Middle-aged and Older Adults
Authors: Quaye Emmanuel M , Selvin Elizabeth , Ndumele Chiadi , Matsushita Kunihiro , Bandeen-Roche Karen , Stevens June , Palta Priya , Wagenknecht Lynne , Coresh Josef
Published: March 2022

Introduction:
C-reactive protein (CRP) is a marker of inflammation that is associated with obesity; inflammation also plays a role in the onset of cachexia. CRP and its relationship with weight change (gain and loss) is less well understood, particularly in studies including both middle-aged and older adults.

Hypothesis:
Elevated CRP is associated with both subsequent body mass index (BMI) gain and even more strongly associated with subsequent BMI loss in middle-aged and older adults.

Methods:
We analyzed BMI (kg/m2) changes in 11,136 ARIC participants followed since Visit 2 (1990 - 92) when CRP was measured (Table 1). BMI change between study visits was categorized as stable (<+/-2 kg/m2, average of <+/-13 lbs.), gain or loss (>+/-2 kg/m2). High sensitivity CRP (hs-CRP) was classified according to AHA/CDC guidelines for CVD risk. Multinomial logistic regression was used to characterize the association of BMI change with categories of hs-CRP.

Results:
Table 1 shows BMI change and its associations with categories of hs-CRP. Multinomial logistic regression demonstrated that individuals who had high CRP in midlife at visit 2 had increased odds of both subsequent BMI gain and loss both in the next 6 years (visit 2 to visit 4) and in the following 15 years (visit 4 to visit 5). Inflammation in late midlife (visit 4, median age: 62) was also predictive of subsequent BMI gain and loss (to visit 5, median age: 75). Similar associations were seen after further adjustment for diabetes, hypertension, physical activity and smoking (p<0.05).

Conclusion:
Elevated CRP was associated with subsequent BMI gain, but was more strongly associated with subsequent BMI loss in both midlife and older age. These findings suggest that inflammation is a marker associated with weight change that may help distinguish between healthy and unhealthy weight loss in middle-aged and older adults.
Abstract P029: Relationships Among Indicators of Oxidative Stress and Antioxidants: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Gross Myron D , Sanchez Otto A , Jacobs David R
Published: March 2022

Introduction:
Oxidative stress associates with cardiovascular disease risk. Various biochemical measurements have been identified as indicators of oxidative stress. In CARDIA, multiple measures of oxidative stress were performed over 2 exams, allowing comparisons among indicators. We hypothesized that the indicators would be highly correlated with each other.

Methods:
Blood and urine samples were collected in the year 15 (2000-2001) and year 20 exams of CARDIA. CARDIA is a cohort study that began in 1985-1986 with black and white men and women at 4 sites in the US. The samples were processed under stable conditions and frozen at -70
o
C until analysis. Analysis was performed for F
2
-isoprostanes (GC-MS); the carotenoids α- and β-carotene, β-cryptoxanthin, and zeaxanthin/lutein which were summed to form (Sum4Carot, HPLC); urate (enzymatic); γ-tocopherol (HPLC); γ-glutamyl transferase (GGT, enzymatic); and oxidized LDL (ELISA).

Results:
Correlations between the various indictors of oxidative stress are tabulated. See Table 1. F
2
-isoprostanes, urate, and γ-tocopherol were in the range 0.21-0.29, and all three were also inverse with Sum4Carot (range -0.18 to -0.29). Oxidized LDL correlated with urate and γ-tocopherol, but not with F
2
-isoprostanes or GGT, and GGT had correlations<0.1 with all indicators.

Conclusion:
Several indicators (F
2
-isoprostanes, Sum4Carot, γ-tocopherol, and urate) correlated as predicted; e.g. an inverse relationship between F
2
-isoprostanes and Sum4Carot. Urate and γ-tocopherol have weak antioxidant properties, but are associated with oxidative stress in some situations and have a positive correlation with F
2
-isoprostanes herein. Nonetheless, the indicators cannot replace each other and each indicator provides a unique view of oxidative stress. Oxidized LDL and GGT appear to reflect alternative aspects of oxidative stress. Thus, the indicators cannot be interpreted in a universal manner. These observations reflect the complexity of oxidative stress. Further assessment is needed.
Abstract P032: Cardiovascular Risk Factors and Brachial Distensibility in Children
Authors: Edwards Nicholas M , Khoury Philip R , Urbina Elaine M
Published: March 2022

Introduction:
Our previous cross-sectional studies demonstrated a relationship between elevated cardiovascular risk factors and arterial stiffness in adolescents. Other investigators showed longitudinal associations between cardiovascular risk factors at age 9 and adult arterial stiffness. Therefore we sought to determine if risk factor-related increase in arterial stiffness could be demonstrated even earlier in childhood.

Hypothesis:
In 10-year-old children, elevated blood pressure and BMI will be associated with less brachial distensibility (greater arterial stiffness).

Methods:
A community sample of 232 children (age 9.6 ± 0.5 years, 52% male, 83% white) in follow up from a longitudinal study were enrolled and had the following measures collected: height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), brachial distensibility (BrachD, PulseMetric, San Diego, CA). Pearson correlation coefficients were calculated and general linear modeling was performed to evaluate the relationships between cardiovascular risk factors and arterial stiffness.

Results:
Participants had a mean BMI of 18.6 ± 3.4 kg/m^2, waist-to-hip ratio (WHR) of 0.9 ± 0.05, BMI z-score of 0.5 ± 1.1, SBP of 96 ± 9 mm Hg, DBP of 53 ± 11 mm Hg, SBP z-score of -0.5 ± 0.8, DBP z-score of -0.7 ± 1, and BrachD of 7.4 ± 2.2 percent change per mm Hg. The following cardiovascular risk factors were significantly associated with BrachD: WHR (r = -0.19, p = 0.005), BMI z-score (r = -0.16, p = 0.01), and SBP z-score (r = -0.14, p = 0.04). Modeling revealed both WHR and BMI z-score but not SBP z-score were associated with BrachD independent of age, sex, and race. After reducing a model simultaneously adjusting for all multiple risk factors and demographic variables, WHR, race, and age remained independently associated with BrachD.

Conclusions:
Associations between multiple cardiovascular risk factors (WHR, BMI, SBP) and arterial stiffness (brachial distensibility) are present in children as young as 10 years old, with WHR maintaining an independent association in a model adjusted for multiple covariates. These findings build on previous evidence that early exposure to cardiovascular risk factors can affect vascular health and support the contention that threats to cardiovascular health should be met aggressively in childhood.
Abstract P050: Perceived Discrimination and Incident Type 2 Diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Whitaker Kara M , Everson-Rose Susan A , Pankow James S , Rodriguez Carlos J , Lewis Tene T , Kershaw Kiarri N , Diez Roux Ana V , Lutsey Pamela L
Published: March 2022

Introduction:
Perceived discrimination is associated with risk factors for type 2 diabetes, including measures of adiposity. However, the relationship between perceived discrimination and incident diabetes is unknown.

Objectives:
To determine whether perceived discrimination is related to incident diabetes, and whether this association varies by race/ethnicity, age or sex.

Methods:
Included in this analysis were 5,310 MESA participants aged 45-84 years, without a history of diabetes at baseline. Perceived discrimination was measured using the Lifetime Discrimination scale, which assessed experiences of unfair treatment in 6 life domains (e.g. fired or denied a promotion, unfair treatment by police, not hired for a job, having life made difficult by neighbors). Participants were also asked to attribute their experiences of discrimination to various factors (e.g. race/ethnicity, age, sex, religion). Incident diabetes was identified at four follow-up examinations as fasting glucose ≥126 mg/dL or use of diabetes medications. Multivariable-adjusted Cox proportional hazard regression was used to model lifetime discrimination as a continuous and categorical variable (0, 1, ≥2 domains).

Results:
A total of 654 incident diabetes cases accrued over a median follow-up of 9.4 years (range 0.9-11.4). Lifetime discrimination reported in ≥ 2 domains (versus none) was associated with a 34% increased risk of incident diabetes, after adjustment for potential confounders or mediators (Table). Similar patterns were observed when we evaluated discrimination attributed to race/ethnicity only, or to a combination of other sources. There were no differences in the strength of association by race/ethnicity, age or sex.

Conclusions:
Lifetime discrimination was associated with increased risk of incident diabetes, regardless of attribution. These associations were independent of obesity, behavioral and psychosocial factors. Future research is needed to explore the mechanisms of the discrimination-diabetes relationship.
Abstract P058: Men with Impaired Glucose Tolerance Have Lower Self-rated Health Than Men with Impaired Fasting Glucose, an Association Mediated by Physical Activity
Authors: Diurlin Sven G , Eriksson Maria C , Daka Bledar , Lindblad Ulf , Larsson Charlotte A , Hellgren Margareta I
Published: March 2022

Aim:
Previous studies have shown that individuals with type 2 diabetes (T2D) and impaired glucose tolerance (IGT) have lower self-rated health than normoglycemic individuals. Less is known about individuals with impaired fasting glucose (IFG). The aim of this study was to examine differences in self-rated health between individuals with IGT and those with IFG, taking into account the mediating effect of lifestyle.

Methods:
In 2002-2005, a total of 2816 individuals 35-74 years were randomly selected for a population-based study in the southwest of Sweden (The Skaraborg Project). All participants performed an oral glucose tolerance test (OGTT) and had anthropometric measurements and blood pressure taken. Fasting venous blood samples were drawn and validated questionnaires on lifestyles were completed. Self-rated health (SRH) was ranked on a five-graded scale, and dichotomized into “good or very good” (1-2) or “fair, bad or very bad” (3-5). Leisure time physical activity (LTPA) was reported on a four-graded scale and dichotomized into sedentary/low LTPA or moderate/high LTPA. At baseline, 213 individuals with IGT and 129 with IFG were detected and used for further analyses in this cross-sectional study.

Results:
Individuals with IGT were found to have lower self-rated health than individuals with IFG (OR=1.62, CI: 1.01-2.60, p=0.047). There was a borderline interaction between sex and IGT/IFG considering self-rated health (p=0.055) and the difference in self-rated health was seen particularly in men when adjusted for age and BMI (OR=2.13, CI: 1.13-4.02, p=0.020). The results remained significant when also adjusting for smoking, history of CVD and lack of sleep, but became insignificant when including physical activity in the model (OR=1.8, CI: 0.91-3.58, p=0.094). Individuals with IGT reported a lower level of physical activity than those with IFG (OR=2.2, CI: 1.30-3.75, p=0.004) when adjusting for age, BMI and history of CVD. No significant differences were seen in alcohol consumption (P=0.209) or smoking (p=0.150).

Conclusion:
This study shows that individuals with IGT had significantly worse self-rated health than individuals with IFG and also a less physically active lifestyle. These results indicate that physical inactivity might be an important explanatory factor behind the observed association between low self-rated health and IGT. These findings are important to consider in care-taking and treatment of patients with IGT and IFG in primary care.
Abstract P065: Exposure to Traffic and Fine Particulate Matter and Aortic Calcium in the Framingham Offspring and Third Generation Cohorts
Authors: Dorans Kirsten S , Wilker Elissa H , Li Wenyuan , Rice Mary B , Ljungman Petter L , Schwartz Joel , Coull Brent A , Buring Julie E , Kloog Itai , Koutrakis Petros , D’Agostino Ralph B , Massaro Joseph M , Hoffmann Udo , O’Donnell Christopher J , Mittleman Murray A
Published: March 2022

Background:
Exposure to traffic and ambient air pollution is associated with an increased risk of cardiovascular disease, potentially through atherosclerosis promotion. Few studies have assessed associations of these exposures with thoracic aortic calcium (TAC) or abdominal aortic calcium (AAC), which are correlates of atherosclerosis.

Objective:
We assessed whether living close to a major road and residential exposure to fine particulate matter (PM
2.5
) were associated with TAC and AAC in a community-based Northeastern U.S. cohort.

Methods:
TAC was measured from 2002[[Unable to Display Character: –]]2005 and AAC up to two times (2002[[Unable to Display Character: –]]2005; 2008[[Unable to Display Character: –]]2011) among participants from the Framingham Offspring or Third Generation Cohorts. We first assessed associations of residential distance to a major road and PM
2.5
exposure (2003 annual average from a spatiotemporal model) with detectable aortic calcium. We used logistic regression for TAC and generalized estimating equations (logit link) for AAC. As aortic calcium scores were right-skewed, we next used linear regression models and mixed effects models to assess associations with log-transformed TAC and AAC, respectively, among participants with aortic calcium scores > 0 (95% CIs bootstrapped). We also assessed associations with AAC progression. Models were adjusted for demographic variables, individual and area-level markers of socioeconomic position and time.

Results:
Among 3518 participants with TAC or AAC measured, 52% had AAC measured twice. Mean age was 55.8 years; 50% female. There were no associations of distance to a major road or PM
2.5
with detectable TAC or AAC, though some estimates were in the opposite direction than expected (
Table
). There were no associations with extent of TAC or AAC (
Table
), or with AAC progression.

Conclusions:
Proximity to a major road and PM
2.5
were not associated with the presence or extent of aortic calcium, or with AAC progression in this cohort from a region with relatively low PM
2.5
levels. Future work should explore these associations in other populations.
Abstract P071: Creating Claims-based Risk Scores for Incident Coronary Heart Disease
Authors: Mefford Matt , Huang Lei , Safford Monika , Muntner Paul , Levitan Emily
Published: March 2022

Background:
A claims-based coronary heart disease (CHD) risk score may be useful to control for confounding and identify high risk groups in research using administrative data.

Objective:
To derive and validate a claims-based risk score for incident CHD in 2004-2011 Medicare 5% national samples and validate in the REasons for Geographic and Racial Differences in Stroke (REGARDS)-Medicare link population.

Methods:
We included Medicare beneficiaries with no evidence of CHD who had fee-for-service health insurance. When examining prescriptions, Medicare part D coverage was required. CHD was defined as the first inpatient claim for acute myocardial infarction (AMI). Three groups of predictors were included in the risk models (group 1: traditional CHD risk factors, group 2: other diagnoses and demographic characteristics, group 3: medications). Using Cox proportional hazards models, c-statistics and 95% CI were calculated for model discrimination and CHD rates were calculated across deciles of predicted risk testing calibration.

Results:
Of 990,836 individuals in the derivation cohort, 28,086 (2.8%) developed AMI over 5 years. The average age was 67.5 years, 57.6% (570,722/990836) were female, and 83.6% (828,338/990,836) were white, 10.7% (106,020/990,836) black, and 5.7% (56,477/990,836) other ethnicities. Models with group 1 variables had a moderate discrimination (
Table
). Adding group 2 variables improved model discrimination. Comparing the Framingham CHD risk score to our model with group 1 + 2 variables yielded similar discrimination. Group 3 variables (prescriptions) improved discrimination to 0.727 (0.714 - 0.741). Prediction models overestimated risk in the top decile in the Medicare 5% sample and the REGARDS-Medicare link population.

Conclusion:
In patients with no history of CHD, models including demographics and diagnoses from claims data exhibited discrimination and calibration similar to the Framingham Risk Score. The inclusion of prescription information further improved discrimination.
Abstract P074: Time to First Treatment Modification Among New Statin Users
Authors: Burke James P , Paoli Carly J , McPheeters Jeffrey , Gandra Shravanthi R , Simpson Ross J
Published: March 2022

The benefits of lipid lowering therapy (LLT) include reductions in all-cause mortality and fatal CV disease. Studies have shown high rates of LLT discontinuation and poor persistence.

This study examined time to treatment modification and types of treatment modifications among patients initiating statin and ezetimibe therapy.

This retrospective claims-based study used medical, pharmacy and enrollment data from a large US health plan. Patients had commercial or Medicare Advantage Part D (MAPD) coverage from 1/1/07 to 12/31/12 and were followed for the earlier of 3 years, disenrollment or 12/31/13 (index date= date of first statin and/or ezetimibe use). Treatment modifications included switching, subtraction, dose escalation or reduction, augmentation, reduction, and discontinuation. Patients were assigned to one of three mutually exclusive cohorts: secondary CVD prevention, high risk primary prevention, and primary prevention. Arteriosclerotic cardiovascular disease (ASCVD) was also identified. The first episode of care was defined as the time from the index date to the first treatment modification (episode 1) and subsequent therapy modifications (episodes 2-4) were also examined.

The sample included 662,540 patients (mean age 57.4 years, 52.5% male, 19.2% MAPD). Overall mean time to first modification was 341.9 days (SD=333.7; median=200.0). Mean and medians were similar across cohorts but decreased with each subsequent episode of care. Discontinuation at 42.0% (with 70.5% restarting) was the most common treatment modification in the ASCVD cohort followed by switching (10.4%) and statin dose increase (10.3%). The other cohorts followed a similar pattern.

Patients remained on their index therapy for a substantial period of time. Surprisingly, there was little difference across risk groups. Initial choice of statin therapy by physician and patient may represent an opportunity to limit unnecessary statin and/or ezetimibe therapy modifications and to improve adherence.
Abstract P079: Body Fat Changes Mediate the Effects of Antiretroviral Therapy on Blood Pressure and Blood Glucose Levels in People Living with HIV in a Sub-Saharan African Setting: A Mediation Analysis
Authors: Nduka Chidozie U , Uthman Olalekan A , Kimani Peter K , Malu Abraham O , Stranges Saverio
Published: March 2022

Background:
Previous studies of HIV-infected patients show significant associations of highly active antiretroviral therapy (HAART) with worsening blood pressure and blood glucose levels; however, the mechanisms involved are less clear. Therefore, we sought to investigate the potential mediating effects of body fat changes on HAART-associated increases in blood pressure and blood glucose levels among people living with HIV.

Methods:
Four Hundred and Six consenting patients (≥ 18 years) attending a tertiary HIV clinic in semi-urban Nigeria were recruited between August and November 2014 as part of a cross-sectional study. We performed bias-corrected bootstrap tests of mediation using 95% confidence intervals (CI) to determine the mediating effects of body mass index and waist circumference (mediators) on the total effects of HAART exposure (primary predictor) on blood pressure and blood glucose levels (outcomes), while adjusting for potential confounders including age, sex, smoking status, CD4 cell count and duration of HIV infection.

Results:
Waist circumference remained a significant partial mediator of the total effects of HAART exposure on increasing systolic blood pressure (coefficient: 1.01, 95% CI 0.33 to 2.52, 11% mediated), diastolic blood pressure (coefficient: 0.68, 95% CI 0.26 to 1.89, 9% mediated) and blood glucose levels (coefficient: 0.67, 95% CI 0.14 to 1.67, 25% mediated) after adjusting for all potential confounders; whereas, no significant mediating effect was observed with body mass index or combined body mass index/waist circumference.

Conclusion:
Our findings suggest that body fat, especially central fat accumulation, may mediate HAART-associated increases in blood pressure and blood glucose levels among HIV-infected patients, independent of the role of traditional risk factors. The use of waist circumference as a complementary measure of body fat to body mass index may improve the clinical prediction of hypertension and diabetes among HIV-infected patients on antiretroviral therapy.