bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP25: Adiposity-related DNA Methylation as a Predictor of Coronary Heart Disease in Adult African Americans: The Atherosclerosis Risk in Communities Study
Authors: Nguyen Steve , Guan Weihua , Grove Megan L , Bressler Jan , Li Yun , Fornage Myriam , Boerwinkle Eric , North Kari E , Pankow James S , Demerath Ellen W
Published: March 2022

Background:
Epigenetic modifications such DNA methylation variation comprise a potentially useful new class of biomarkers that may improve coronary heart disease (CHD) risk stratification, or better capture early pathophysiological processes. However, replicated associations of DNA methylation and CHD are few, and existing studies are primarily cross-sectional and restricted to European ancestry populations. Given the strong association of excess adiposity with CHD risk, we tested 41 DNA methylation variants (CpG sites) that were previously reported to be associated with BMI in African Americans (AA), and tested their association with incident CHD in AA adults.

Methods:
Genome-wide DNA methylation variation was assayed at a single time point in stored frozen leukocyte samples using the Illumina HM450K chip in a subset of 1,797 AA participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of cardiovascular disease risk conducted in four U.S. communities. Methylation beta values and other continuous covariates were winsorized prior to analysis to reduce outlier influence. Incident CHD cases were identified through annual telephone interviews and medical records review. Proportional hazards regression (frailty) models examined the relationship between DNA methylation beta values and incident CHD with separate models for each of the 41 CpGs, with a random effect specified for chip. Fully adjusted models included age, BMI, sex, center, education, household income, leisure time activity, alcohol and tobacco use, white blood cell count and imputed cell type differentials. To explore the relationship between DNA methylation and CHD risk accounting for major CHD risk factors, mediator models additionally contained prevalent hypertension status, blood glucose, and total and HDL cholesterol. A Bonferroni-corrected p value of 0.00122 was set as the threshold for statistical significance.

Results:
There were 224 cases of incident CHD out of 1,797 individuals at risk. One CpG, cg09664445 near CLUH was significantly associated with incident CHD in the full (HR=1.47, 95%CI=1.26, 1.72) and mediator model (HR=1.46, 95% CI=1.24, 1.71) while cg06500161 near ABCG1 was significant in the full model only (HR=1.34, 95% CI=1.15, 1.56).

Conclusion:
Two obesity-related DNA methylation variants were associated with incident CHD independent of known risk factors and potential confounders. In the literature, CLUH is involved in mitochondrial biogenesis while promoter hypermethylation of ABCG1 was previously found to increase CHD risk and atherosclerosis. Replication in additional cohorts is required to further investigate the predictive value of DNA methylation variants over established risk factors and biomarkers for CHD.
Abstract MP38: Plasma Lipophilic Index and Risk of Coronary Heart Disease in Postmenopausal Women
Authors: Liu Qing , Lichtenstein Alice H , Matthan Nirupa R , Liu Simin , Allison Matthew A , Howard Barbara V , Martin Lisa W , Valdiviezo Carolina , Manson JoAnn E , Eaton Charles B
Published: March 2022

Introduction:
Fatty acids (FAs) are essential components of cell membranes and play an integral role in membrane fluidity. The lipophilic index (LI, defined as the sum of the products between FA percentage and melting points (°C) of each FA, divided by the total percentage of FAs) is a novel index that captures the overall FA profile and reflects lipoprotein fluidity. Limited studies have evaluated the relationship between plasma LI and CHD risk, and none has assessed this association among postmenopausal women.

Hypothesis:
Higher plasma LI is associated with increased CHD risk among postmenopausal women.

Methods:
In a nested case-control study in Women’s Health Initiative Observational Study, we measured levels of plasma phospholipid FAs, expressed as molar percentage (mol%), in 1214 matched CHD cases (including myocardial infarction and coronary death) and controls. Multivariate conditional logistic regression was used to calculate ORs for CHD risk between each quartiles (based on controls) of LI after adjusting for confounders.

Results:
The mean age of the women was 67.8±6.8 years, average BMI was 27.6±6.0, 89.5% were White, 6.6% were current smokers, 41.2% were hypertensive, and 15.2% had dyslipidemia. The median plasma LI among cases and controls were 22.5 and 22.1, respectively. Palmitic acid (16:0) and stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2), and docosahexaenoic acid (22:6) were the most common saturated, monounsaturated, n-6 and n-3 polyunsaturated FAs, respectively. The association between quartiles of LI and CHD risk are shown in Table below. After multivariate adjustment in the parsimonious model, plasma LI was significantly associated with an increased risk of CHD: OR=1.61 (95% CI 1.25-2.07,
P
for trend<0.01) comparing extreme quartiles. This association was attenuated to 1.57 (1.22 - 2.03,
P
for trend<0.01) in the fully adjusted model.

Conclusion:
Our study indicated that higher plasma LI, which represents lower FA fluidity, was associated with higher risk of CHD among postmenopausal women.
Abstract MP40: Postprandial Lipemia and the Risk of Coronary Heart Disease and Stroke. The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Kats Dmitry , Sharrett A. R , Nambi Vijay , Heiss Gerardo
Published: March 2022

Introduction:
Delay in the clearance of circulating triglyceride (TG)-rich lipoproteins from circulation following the consumption of fatty foods is reportedly atherogenic. The literature on the risk of incident cardiovascular events attributed to postprandial lipemia (PPL) is inconclusive, however.

Objective:
To quantify the degree to which PPL is associated with incident coronary heart disease (CHD) and stroke in Caucasians and African Americans.

Methods:
Members of the community-based ARIC cohort (n=559) who were free of manifest cardiovascular disease in 1990-1993 (visit 2) participated in a substudy during visit 2 comparing PPL in cases of subclinical atherosclerosis versus controls free of carotid artery atherosclerosis. Postprandial TG, TG-rich lipoprotein triglycerides (TRL-TG), retinyl palmitate (RP), and apolipoprotein B48 to apolipoprotein B100 ratio (apoBR) concentrations were measured from blood samples collected at 0 (fasting), 3.5 and 8 hours after consumption of a fatty meal. The area under the curve (AUC) of the lipid value versus time was calculated for each PPL measure and transformed into weighted standard deviation units. Crude, age-sex adjusted, and fully adjusted associations of risk for validated incident CHD and stroke events (as individual and merged outcomes) by 2013 attributed to each AUC variable were estimated using Cox proportional hazard regression. For fully adjusted models, a stepwise method was applied to select from the following visit 2 covariates: race (Caucasian vs. African American), body mass index (BMI), carotid intima media (IMT), hypertension status, low and high density lipoprotein cholesterols, and cigarette smoking status. Additionally, individual associations of TG, TRL-TG, RP, and apoBR with incident events were evaluated by race and for categories of BMI and IMT.

Results:
Of 559 individuals without manifest cardiovascular disease in 1990-1993 (visit 2), 127 (23%) developed CHD and 27 (5%) experienced a stroke by 2013. None of the PPL parameters measured at visit 2 were associated (p>0.05) with incident CHD or stroke by 2013 in crude, age-sex adjusted, or fully adjusted models. Similarly, stratified analyses did not identify significant associations between any of the PPL measures and incident events across race, BMI, or IMT subgroups.

Conclusion:
Extended follow up of a well-characterized, population-based cohort indicates that the extent of postprandial lipemia is not associated with risk of coronary heart disease or stroke.
Abstract MP44: Lifetime Marijuana Use is Not Associated with Incident Cardiovascular Disease in Middle-Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Reis Jared P , Auer Reto , Goff David , Lewis Cora , Pletcher Mark , Rana Jamal , Sidney Steve
Published: March 2022

Background:
Marijuana is the most frequently used illicit drug in the US. Its use is expected to rise given recent state policies that relax criminalization and permit medicinal use. Although several mechanisms exist by which marijuana might contribute to chronic cardiovascular conditions, few data are available. We sought to determine the association of lifetime marijuana use with the development of incident CHD and CVD.

Methods:
Participants were 5,114 white and black adults aged 18-30 years in 1985-86 from the multicenter, community-based CARDIA Study who have been followed for over 25 years. We estimated cumulative years of exposure in “marijuana-years,” with one marijuana-year equal to 365 days of marijuana use using repeated assessments every 2-5 years. Incident CHD included fatal or nonfatal myocardial infarction, angina, or CHD death. Incident CVD included CHD, stroke, hospitalized heart failure, and intervention for peripheral arterial disease. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. Lifetime marijuana use and all time-varying covariates were entered as time-dependent variables.

Results:
Approximately 16% of the cohort were lifetime never users of marijuana, while 35%, 22%, 14%, and 13% reported lifetime use of <0.5, 0.5-<2, 2-<5, and ≥5 marijuana-years, respectively. During a median of 26.9 years of follow-up (132,120 person-years), there were 104 and 216 cases of CHD and CVD, respectively. Compared to never use, categories of lifetime marijuana use showed no evidence for a higher or lower risk for CHD or CVD, regardless of the level of multivariable adjustment (Table). Findings did not vary significantly by age, sex, race, family history, 10-year risk of CVD, or use of other illicit drugs (p-interaction >0.3, for all).

Conclusions:
In this long-term follow-up study of young adults at baseline, lifetime use of marijuana at these levels was not associated with incident CHD or CVD in middle-age.
Abstract MP45: Effects of an mHealth Adaptive Intervention on Vascular Health and Cardiorespiratory Fitness
Authors: Jarrett Catherine L , Tucker Wesley J , Hurley Jane C , Todd Michael , Bhuiyan Nishat , Fernandez Jacqueline A , Adams Marc A , Angadi Siddhartha S
Published: March 2022

Introduction:
Behavioral economics-based interventions for increasing steps/day may improve cardiorespiratory fitness (CRF; Peak O2 uptake - VO2peak), central/aortic blood pressure, and vascular stiffness. The purpose of this study was to examine the effects of adaptive (Ad) physical activity (PA) goals (daily step goals based on prior 10-day window and a percentile algorithm) vs. static (St) PA goals (10,000 steps/day) combined with either immediate (Im) financial micro-incentives or delayed (De) incentives (Groups: Ad+Im; Ad+De; St+Im; St+De) on VO2peak, blood pressure and vascular stiffness. We hypothesized that participants randomized to adaptive goals with immediate reinforcement (Ad+Im) would have greater improvements in cardiovascular health measures than participants assigned to static goals and/or delayed reinforcement conditions (active controls).

Methods:
Inactive adults (Age = 41.8 ± 6.7yrs; BMI = 34.5 ± 6 kg/m2) were randomized to an adaptive/static goal intervention with either immediate micro-incentives or delayed incentives in a 4-month factorial RCT to improve steps/day. Additionally, all four groups received daily text-message prompts-to-action and Fitbit ZipTM activity monitors. Pre and post VO2peak (n=81) were estimated using a modified, sub-maximal Balke treadmill protocol while central blood pressures, augmentation index (Aix@75) (n=70) and carotid-femoral pulse wave velocity (cf-PWV) (n=64) were assessed with the Sphygmocor XCELTM device. Between- and within-group differences were examined using linear mixed models, adjusted for sex, age, race/ethnicity, and smoking history. Alpha was set at 0.05, and data are presented as estimated marginal means ± standard errors (SE).

Results:
All groups improved from pre to post, but we found no significant between-group differences in the degree of improvement. Across all groups, we found the following: VO2peak and all vascular markers improved significantly pre to post intervention (p<0.05). VO2peak improved by ~5% (pre = 24.9 ± 0.65 vs. post = 26.3 ± 0.66 ml/kg/min). Central systolic blood pressures (cSBP) decreased (cSBP pre = 117.5 ± 2.1 vs. post = 113.1 ± 2.2 mmHg). Cf-PWV (pre = 7.5 ± 0.18 vs. post = 7.3 ± 0.18 m/sec) and AIX@75 (pre =14.1 ± 2.2 vs. post = 11.4 ± 2.2) decreased.

Conclusion:
Cardiorespiratory fitness and markers of vascular health improved when participants were simply provided a Fitbit and prompted daily to be more physically active, regardless of incentive or goal-setting approach. Implications for designing behavioral interventions for cardiovascular risk reduction will be discussed.
Abstract MP66: Significant Positive Association of Progression in Arterial Stiffness with Accelerated Increase in Aortic Calcification Among Multi-ethnic Middle-aged Men (ERA JUMP Study)
Authors: Guo Jingchuan , Fujiyoshi Akira , Masaki Kamal , Abhishek Vishnu , Barinas-Mitchell Emma , Hisamatsu Takashi , Ahuja Vasudha , Willcox Bradley , Miura Katsuyuki , Rodriguez Beatriz , Ueshima Hirotsugu , Kuller Lewis H , Sekikawa Akira
Published: March 2022

Background:
Cross-sectional data suggest that aortic calcification (AC) is independently associated with arterial stiffness, yet no previous study has examined the association prospectively. We hypothesize that increase in AC has a positive association with the progression of arterial stiffness assessed by brachial-ankle pulse-wave velocity (baPWV). To test our hypothesis, we examined data from our population-based samples of healthy middle-aged men (ERA JUMP Study).

Method:
Participants (n=635) aged 40-49 at baseline (207 White American, 45 African American, 142 Japanese American and 241 Japanese in Japan, all men) were examined for AC, baPWV, and other factors at baseline and repeated 4-7 years later. The associations of baPWV progression (relative annual change) with annual change in AC were analyzed using general linear models and logistic regression, after adjusting for age, race, blood pressure and other risk factors.

Results:
Annual change in AC was significantly associated with baPWV progression. Fully-adjusted means (standard error) of relative annual change in baPWV(%) from the 1st to 4th quartile (Q) of annual change in AC were 0.26(0.15), 0.44(0.16), 0.88(0.14) and 0.96(0.16), respectively (trend p=0.002) (Table). Similarly, fully-adjusted odds ratios (95% confidence interval) for baPWV progression > 0 comparing annual change in AC Q2 to Q4 versus Q1 were 1.04 (0.62-1.77), 1.83 (1.06-3.16) and 3.10 (1.60-5.99), respectively (trend p=0.004) (Table).

Conclusion:
AC, which primarily represents calcification in the medial arterial layer or combination of media and intima, was strongly and progressively associated with increasing arterial stiffness, suggesting that calcification may casually link to arterial stiffness progression.
Abstract MP71: Undetected Disease and Low Medication Adherence are Major Determinants of Poor Cardiovascular Risk Factor Control in Rural India
Authors: Khetan Aditya K , Purushothaman Raghunandan , Gupta Rishab , Agarwal Sushil , Mohan Sri Krishna Madan , Josephson Richard A
Published: March 2022

Background:
Cardiovascular disease is the leading cause of mortality in India. Since it is largely driven by risk factors such as hypertension, diabetes and smoking it is important to study diagnosis, treatment and control patterns for these conditions, and identify areas for improvement.

Methods:
Project SEHAT (ClinicalTrials.gov number, NCT02115711) is a cluster RCT with a long term goal of improving the control of cardiovascular risk factors in a rural community in West Bengal, India. For the baseline data, 3575 adults, between the ages of 35 and 70, were screened for hypertension, diabetes and smoking. For hypertension and diabetes, an elevated reading was confirmed on a repeat visit.

Results:
Risk factors were common, with hypertension, diabetes and smoking evident in 18.3% (654 of 3575), 9.0% (321 of 3575) and 15.1% (540 of 3575) of adults, respectively. Overall, 34.5% (1233 of 3575) of adults had at least one risk factor. There was a huge burden of undetected disease, with only 45.2% (296 of 654) of hypertensives and 59.8% (192 of 321) of diabetics previously aware of their disease. Linkage to care was high with 72.0% (213 of 296) of previously diagnosed hypertensives and 86.0% (165 of 192) of previously diagnosed diabetics on treatment. Control rates were, however, low with 8.2% (54 of 654) of hypertensives controlled (BP <140/90 mmHg) and 13.7% (44 of 321) of diabetics controlled (fasting blood sugar <126 mg/dl). This may be partly explained by a low medication adherence rate, with the adherence (medium and high) being 35.5% (76 of 213) in hypertensives and 20.6% (34 of 165) in diabetics, as measured by the Morisky Medication Adherence Scale-8.

Conclusions:
In our population in rural India, 1 in 3 adults have a major cardiovascular risk factor, with abysmal control rates. Barriers to risk factor control primarily exist at the points of diagnosis and medication adherence. Over the next 2 years, a community health worker led intervention, with an aim to improve the control of hypertension, diabetes and smoking will be tested in this cohort.
Abstract MP74: Hnf1a Variant, Energy-reduced Diets, Weight Loss and Insulin Resistance: The Pounds Lost and Direct Trials
Authors: Huang Tao , Wang Tiange , Zheng Yan , Ivey Kerry , Durst Ronen , Schwarzfuchs Dan , Stampfer Meir , Bray George , Sacks Frank , Shai Iris , Qi Lu
Published: March 2022

Background:
Macronutrients regulate the gene expression of hepatic nuclear factor 1 alpha (HNF1A) which plays a key role in in the normal function of pancreatic beta cells and development of insulin resistance.

Objective:
We aimed to determine whether weight loss diets varying in macronutrients modulate the effect of HNF1A genetic variant on weight loss and improvement of insulin resistance.

Methods:
We analyzed the interaction between a diabetes-associated common variant in the HNF1A gene (rs7957197) and weight-loss diets on body weight and insulin resistance among 722 overweight/obese adults from a 2-year randomized weight-loss trial (POUNDS Lost). We then sought to validate the findings in an independent 2-year weight-loss trial (Dietary Intervention Randomized Controlled Trial; DIRECT), which involved 280 different overweight/obese adults.

Results:
In the POUNDS LOST, we found fat diet significantly modified the genetic effect of HNF1A such that greater decreases in body weight and waist were observed in participants with the T allele than others among high-fat diet group (P <0.04 for both, P for interaction <0.006, We observed borderline significant interactions for improvement of fasting insulin and insulin resistance (P for interaction=0.07 and 0.06, respectively). We found similar gene-fat interactions in the DIRECT.

Conclusions:
The consistent findings from two independent randomized intervention trials provide strong evidence that individuals with the HNF1A rs7957197 T allele may experience enhanced weight loss and improved insulin sensitivity as a result of hypocaloric, high-fat diets.
Abstract MP80: Genome-wide Meta-analysis of SNP-by-antihypertensive Treatment Class Effect on Serum Potassium in Cohorts of European and African Ancestry From Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
Authors: Irvin Marguerite R , Zhi Degui , Sitlani Colleen , Limdi Nita , Bis Joshua A , Floyd James , Avery Christy , Whitsel Eric , Lange Leslie , Smith Albert , Noordam Raymond , Arnett Donna , Psaty Bruce
Published: March 2022

Thiazide diuretics (TD) lead to hypokalemia and angiotensin-converting enzyme inhibitors (ACE) and angiotensin receptor blockers (ARB) lead to hyperkalemia more frequently than other antihypertensives. Inter-individual variation in serum potassium on antihypertensive treatments exist and we hypothesized genetic markers may modify the association of treatment class with serum potassium levels. We separately evaluated interactions of SNP-by-TD as well as SNP-by-ACE /ARB on serum potassium levels among users of antihypertensive medication (anti-HTN). Our study included 7 European-ancestry cohorts (EA, N = 1673 TD exposed; N=1262 ACE /ARB exposed; N=1998 reference, users of other anti-HTN) and 4 African-American ancestry cohorts (AA, N = 482 TD exposed; N =411 ACE/ARB exposed; N=1182 users of other anti-HTN). Models were adjusted for age, sex, BMI, potassium supplementation, and ancestry at the cohort level. We filtered results based on an estimated degrees of freedom filter that incorporated SNP imputation quality, minor allele frequency (MAF), and the number of exposed participants. We performed race-stratified fixed effects inverse variance weighted meta-analyses of 2.5 million SNP-by-drug interaction estimates. ACE /ARB data uncovered eleven significant (P<5x10-8, Figure top line) SNPs (smallest P=1.1х10-8; MAF 0.37-0.40) at a single locus among EAs with consistent direction of effect across the 7 cohorts. The SNPs are located between the genes for NR2F1 antisense RNA 1 (NR2F1-AS1) and arrestin domain containing 3 antisense RNA 1 (ARRDC3-AS1) on chromosome 5 (Figure). The ACE /ARB interaction meta-analysis in AAs highlighted a SNP in insulin-like growth factor 1 receptor (IGF1R). The TD interaction analysis did not yield significant results in either race group. In conclusion, genome-wide SNP-by-ACE /ARB interaction analyses for serum potassium uncovered loci that could have future implications for the prevention of arrhythmias due to high potassium levels on a common antihypertensive treatment.
Abstract MP88: Sodium, Sugar and Fat Content in Commercial Infant and Toddler Foods, 2015
Authors: Maalouf Joyce , Cogswell Mary E , Bates Marlana , Scanlon Kelley , Gunn Janelle P , Yuan Keming , Merritt Robert
Published: March 2022

Introduction:
Early intake of foods with excess sodium, sugar, and saturated fat can influence later dietary habits and health, potentially increasing the risk of cardiovascular disease. A 2012 analysis indicated that 72% of commercial toddler meals were high in sodium (average: 361 mg per serving) and 32% of toddler meals and >70% of infant and toddler snacks, desserts, and juice drinks contained one or more added sugars. Given manufacturer reported changes in commercial infant and toddler foods the study objective is to determine the sodium, sugar and fat content of commercial infant and toddler foods sold in the U.S. in 2015.

Methods:
Major brands of infant and toddler food products were identified. Nutrition information was collected from manufacturer websites and grocery stores (e.g. private label products) from May to July, 2015. A total of 1,045 food products were categorized according to main ingredients, target eater and serving sizes. Serving sizes were standardized to the FDA Reference Amount Customarily Consumed (RACC) per eating occasion for the specific category. Mean sodium, sugar and saturated fat content was computed per serving, per 100g, and in relation to calories (mg/1000 Kcal for sodium and as a percent of calories for sodium and fat). High sodium content was defined as >210 mg/serving or >200 mg/100g, the CODEX standard used by manufacturers. Presence of added sugar and industrially produced trans fat was determined from the ingredients list.

Results:
Mean sodium content ranged from 4 mg/serving (mixed grains and fruits) to 290 (toddler meals) and 73 mg/1000 Kcal (cereals, dry/instant) to 997 mg/1000 Kcal (savory snacks).Mean percent of calories from sugar ranged from 7% (savory snacks) to 82% (juices/drinks), and percent of calories from saturated fat from 0% (infant vegetables, dinners, fruits, dry cereals) to 7.5% (toddler meals). Almost all infant foods were low in sodium. Few infant foods contained added sugars except 44% of infant pureed fruits and 27% of mixed grains with fruits. Eighty-one percent of toddler meals exceeded 210 mg/serving, while 5% were >200 mg/100 g with an average of 170 mg/100g. More than 70% of toddler’s meals, cereal bars/breakfast pastries, and infant/toddler desserts and dairy products contained added sugar. None of the products contained industrially produced trans fat.

Conclusions:
In 2015 average sodium content of commercial toddler meals was about 20% lower than in 2012, with the majority meeting the CODEX standard, but still above 210 mg per serving. Commercial toddler meals, infant mixed grain with fruits and infant or toddler cereal bars/breakfast pastries and desserts remain of concern due to added sugars. Commercial infant and toddler foods are generally low in their saturated fat content with no industrially produced trans fat.
Abstract MP91: Habitual Sleep Duration and Health: A Possible Role for Exercise
Authors: Hall Christine M , Forbush Sierra , Youngstedt Shawn , Killgore Scott , Barilla Holly , Gehrels Jo-Ann , Alfonso-Miller Pamela , Palmer William , Carrazco Nancy , Grandner Michael
Published: March 2022

Introduction:
Habitual sleep duration is associated with cardiometabolic disease risk and poor mental health. Exercise has been shown to improve cardiometabolic disease risk and mental health. Further, insufficient/excessive sleep is associated with sedentary behavior. It is plausible that benefits of exercise may mitigate some negative effects of insufficient or excessive sleep.

Methods:
Data from the 2013 Behavioral Risk Factor Surveillance System, a phone-based survey conducted by the CDC, was used. All participants were asked to report habitual 24-hour sleep, which was recorded as whole numbers and categorized as Very Short (≤4h), Short (5-6h), Normal (7-8h, reference), and Long (≥9h). Participants reported their primary source of physical activity. For this analysis, the following groups were included: None (N=125314), Walking (N=179,996), Running (N=23,153), Gardening (N=26,637), and Yoga/Pilates (N=3370). Outcomes of interest were obesity, depressed mood, and history of hypertension and diabetes. Population-weighted binary logistic regression models evaluated relationships between sleep duration and these outcomes, stratified by activity group. Covariates included age, sex, race/ethnicity, and education.

Results:
See Table 1. Relationships between sleep duration and health outcomes differed by activity group. Associations with very short sleep were generally maintained across groups. However, relationships with short sleep were somewhat mitigated in running and yoga, and relationships with long sleep were seen less in running and gardening.

Conclusions:
The relationship between sleep duration and health may be modified by activity. It is possible that activities such as running and yoga may mitigate some of the negative health effects of insufficient or excessive sleep, as long as sleep duration is not extremely short. Also the obesity relationship was particularly unaffected by exercise.
Abstract MP95: Should Habitual Sleep Duration be Added to “Life’s Simple 7?”
Authors: Grandner Michael A , Patterson Freda , Kohl Malone Susan , Hanlon Alexandra , Haynes Patricia , Petrov Megan , Parthasarathy Sairam
Published: March 2022

Introduction:
The AHA introduced the “Life’s Simple 7” guidelines. Sleep is not mentioned in these guidelines. The present analyses examine whether sleep duration is associated with each of the “Simple 7,” and whether sleep duration contributes unique variance to health over and above the “Simple 7.”

Methods:
Pooled data from the 2005-2008 NHANES was used. NHANES is a nationally-representative survey conducted by the CDC. High blood pressure and high cholesterol were assessed as self-reported history. High blood sugar was assessed as measured fasting glucose ≥100 mg/dL. Low physical activity was assessed as 2000 kcal for women and >2500 kcal for men. Measured obesity was defined as ≥30 kg/m2. Current smoking was self-reported. Habitual sleep duration was assessed as self-reported weeknight sleep and categorized as Very Short (≤4h), Short (5-6h), Normal (7-8h), and long (≥9h). Overall health was rated on a 5-point scale, with Excellent, Very Good and Good coded as “Good,” and Poor and Very Poor coded as “Poor.” All analyses were weighted and adjusted for age, sex, race, education, and body mass index (except obesity analyses).

Results:
Habitual sleep duration was associated with each of the components of the “Simple 7,” including high blood pressure, high cholesterol, high blood sugar, low physical activity, high calorie diet, obesity, and smoking (see Table). Further, even after adjusting for all 7 components as well as covariates, sleep duration was related to overall health, such that overall poor health was associated with both very short (OR=1.81, 95% CI[1.31-2.49], p<0.001) and short (OR=1.23, 95%CI[1.00-1.51],p<0.05) sleep duration.

Conclusions:
Habitual sleep duration is a key lifestyle health behavior. It is associated with each of the components of the “Simple 7” and contributes unique variance to overall health beyond these other key indicators. Adequate sleep duration should be considered when drafting lifestyle health guidelines.
Abstract P004: Estimating the Mortality Benefits of Ideal Cardiovascular Health: A Dose-response Meta-analysis
Authors: Aneni Ehimen C , Crippa Alessio , Younus Adnan , Osondu Chukwuemeka U , Veledar Emir , Nasir Khurram
Published: March 2022

Background:
Studies have shown that individuals with higher levels of Ideal Cardiovascular Health (ICVH) metrics have favorable health outcomes. However, none of these studies quantify the reduction in the risk of death per unit increase in ICVH. In this study, we estimated the reduction in CVD and all-cause mortality attributable to per unit improvement in ICVH.

Methods:
Five studies identified through a literature search were included. Major differences in the re-categorization of the 7 ICVH metrics were noted, with studies having between 3-6 groups. Reference groups also ranged from 0 to ≤2 ideal CVH metrics. Because of these differences, risk reduction per unit increase in ICVH was not comparable across studies. To overcome these challenges, we quantified association between ICVH metrics and all-cause/CVD mortality using a dose-response meta-analysis, so all exposure categories contribute to a defined pooled association and heterogeneity is reduced by accounting for values assigned to these qualitative metrics.

Results:
Original data and meta-analysis model of studies assessing CVD mortality are shown in the figure. There was a significant linear trend ( p < 0.001) with moderate heterogeneity (Q test = 12, p = 0.02 and I2 = 66 %). Each unit increase in ICVH metric was associated with 18% (95% CI: 12, 23) reduction in HR. In all-cause mortality analysis (graph not shown), there was also a significant linear trend (p < 0.001) with moderate heterogeneity (Q test = 18, p = 0.003, and I2 = 72 %). Each unit increase in ICVH metric was associated with a 10% (95% CI: 6, 13) reduction in HR for all cause mortality.

Conclusion:
Our study is the first meta-analysis to demonstrate a dose-response impact of ICVH on mortality. The novel dose-response design allowed us to investigate strength, direction and type of association as well as overcomes challenges posed by heterogeneity ICVH metrics categorization while preserving the statistical control for confounding variables that was conducted in the individual studies.
Abstract P007: Association of Plasma Lactate with Incident Atrial Fibrillation in the ARIC Study
Authors: Misra Satish , Matsushita Kunihiro , Sang Yingying , Chen Lin , Coresh Josef , Schmidt Maria Ines , Hoogeveen Ron , Ballantyne Christie , Alonso Alvaro , Young J. Hunter
Published: March 2022

Introduction:
Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting up to six million persons in the United States. The mechanism underlying AF has been extensively investigated in recent years. Reduction in oxidative capacity has been described as a contributor to several aging-related diseases including hypertension and diabetes mellitus. In vitro studies of atrial myocardium have described mitochondrial dysfunction related to reduced oxidative capacity in patients with AF. We sought to evaluate the association of plasma lactate, a marker of impaired oxidative capacity, with incident AF in a large population-based cohort.

Methods:
The Atherosclerotic Risk in Communities (ARIC) study has followed 15,792 men and women from 4 US communities since 1987. We identified 11,191 participants at the 4
th
visit (1996-1998) without prevalent AF for whom plasma lactate levels were available. Incident AF was identified using hospital discharge codes and death certificates. The association of plasma lactate with incident AF was evaluated using Cox proportional hazards models.

Results:
During a mean follow-up of 13.1 years, there were 1498 cases of incident AF. In unadjusted analysis, there was a statistically significant difference in incident AF when comparing plasma lactate by quartiles and continuously (Model 1). This association remained significant in adjusted models including age, gender, race, body-mass index, smoking, alcohol use, history of cardiovascular disease, aspirin use, statin use, total cholesterol, and glomerular filtration rate (Models 2 and 3). When adjusting for diabetes or hypertension alone, potential mediators to which reduced oxidative capacity may contribute, this association was strongly attenuated (HR per standard deviation of log(lactate) 1.04, 95% CI: 0.99, 1.10 and 1.04, 95% CI: 0.99, 1.09 respectively).

Conclusion:
Plasma lactate is independently associated with incident AF, and its contribution to AF may be, at least in part, mediated by diabetes and/or hypertension.
Abstract P015: Associations of Activated Coagulation Factor VII-Antithrombin Complex (FVIIa-AT), a Novel Coagulation Biomarker, with Genetic Variants in the F7/F10 Locus and Risk of Cardiovascular Disease Mortality: The Cardiovascular Health Study
Authors: Olson Nels C , Lange Leslie A , Longstreth W.T. , Reiner Alex P , Tracy Russell P
Published: March 2022

Introduction:
Circulating activated factor VII (FVIIa; ~ 1-2% of total FVII) needs to bind tissue factor (TF) to initiate coagulation. This is a rare event in a healthy person, with the FVIIa-TF complex almost immediately inactivated by antithrombin (AT). Therefore, the FVIIa-AT complex reflects the amount of recent TF-FVIIa formation and may be a biomarker of thrombotic risk. We hypothesized that FVIIa-AT would be associated with single nucleotide polymorphisms (SNPs) in genes involved in the activation and regulation of coagulation and with incident cardiovascular disease (CVD) events.

Methods:
FVIIa-AT, FVIIa (ELISA and truncated TF-based clot rate assay, both Diagnostica Stago, Inc.), and FVII clotting activity (FVIIc) (in-house clot rate assay) were measured in citrated plasma samples from ~3,500 older adults from the Cardiovascular Health Study (CHS) during the Year 5 CHS exam. Associations of FVIIa-AT with ~50K SNPs in CVD-related genes were evaluated using the IBCv2 genotyping array. Cox proportional hazards models were used to evaluate associations of FVIIa-AT with incident coronary heart disease (CHD), ischemic stroke, and CVD event-related mortality over a median 14.5 years of follow-up.

Results:
FVIIa-AT was moderately correlated with FVIIa (Pearson
r
2
=0.48) and FVIIc (
r
2
=0.28; both p-values <0.0001). Mean FVIIa-AT was higher in women (152 pM, standard deviation (SD)= 54 pM) than men (128 pM, SD= 49 pM) and higher in European-Americans (EAs) (142 pM, SD= 53 pM) than African-Americans (124 pM, SD= 57 pM) (both p-values <0.0001). Among EAs, 11 SNPs in the
F7
/
F10
locus and 5 SNPs in the
PROCR
locus, which encodes the gene for endothelial protein C receptor (EPCR), were significantly associated with FVIIa-AT. The most significant association was rs488703 located in an intron of the
F7
gene (p=3.7x10
-85
); each copy of the minor allele was associated with 24.6 pM lower FVIIa-AT. The most significant SNP in the
PROCR
locus was rs867186 (3.3x10
-10
) associated with 9.0 pM higher FVIIa-AT per minor allele. After adjustment for CVD-risk factors, the hazard ratio for CVD-related mortality among participants in the highest FVIIa-AT quintile was 1.24 (95% confidence interval=1.01, 1.54; p=0.04) compared with those in the lowest quintile. FVIIa-AT was not significantly associated with risk of incident CHD or ischemic stroke independently of traditional CVD risk factors.

Conclusions:
These results are consistent with a role of common
F7
/
F10
and
PROCR
genetic variants on the extent of FVII activation and support a role for recent TF-FVIIa formation in CVD-related mortality among older adults.
Abstract P020: High-sensitivity Cardiac Troponin T is an Independent Predictor for Coronary Artery Disease in Japanese Population: The Circulatory Risk in Communities Study
Authors: Imano Hironori , Yamagishi Kazumasa , Okada Takeo , Kitamura Akihiko , Iso Hiroyasu ,   CIRCS Investigators
Published: March 2022

Background:
Coronary heart disease (CHD) has become No.1 cause of death in the world. Therefore, it is important to seek new predicting indicators to capture high risk individuals of CHD. Cardiac Troponin T in healthy individuals may be a candidate of predictor.

Hypothesis:
High-sensitivity cardiac Troponin T (hs-cTnT) is an independent predictor for incident CHD in general population.

Methods:
We conducted a nested case-control study in four Japanese communities of the Circulatory Risk in Communities Study (CIRCS). We investigated 120 cases (81 men and 39 women, aged 38-86 years) of first incident CHDs between 2001 and 2011, and 240 controls matched with age, sex, communities and the year of examination. Serum hs-cTnT levels were measured by electrochemiluminescence immunoassay. We used the serum storing at –80°C. The median (range of) period until the incidence of CHD was 2.0 years (4 days to 9.5 years) among cases. The incidence of CHD was ascertained by systematic active surveillance. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of incident CHD were calculated with conditional logistic regression analyses. We calculated the ORs for each quartile of hs-cTnT against the lowest quartile as a reference. The adjustment variables included body mass index, systolic blood pressure, antihypertensive medication use, diabetes mellitus, serum total cholesterol, serum high-density lipoprotein cholesterol, and drinking status.

Results:
The distribution of hs-cTnT was from ≤0.003 ng/mL (measurement limit) to 0.155 ng/mL. The percentage of cases in each quartile of hs-cTnT was 24.7% (23/93) in the lowest quartile (≤0.004 ng/mL), 30.5% (29/95) in the second quartile (0.005 to 0.007 ng/mL), 38.4% (33/86) in the third quartile (0.008 to 0.011 ng/mL) and 40.7% (35/86) in the highest quartile (≥0.012 ng/mL). The ORs for incident CHD were 1.73 (95%CI: 0.83 to 3.58) for the second quartile, 2.63 (1.21 to 5.68) for the third quartile, and 2.90 (1.33 to 6.32) for the highest quartile against the lowest quartile. Each multivariable OR was 1.59 (0.74 to 3.45), 2.50 (1.08 to 5.77), and 2.61 (1.10 to 6.20), respectively.

Conclusions:
In conclusion, hs-cTnT was an independent predictor for CHD in Japanese general population.
Abstract P025: Trimethylamine N-oxide Not Associated with Coronary Artery Calcium in Healthy, Young Adults with Normal Kidney Function: Coronary Artery Risk Development in Young Adults Study, 2000-2011
Authors: Meyer Katie A , Benton Thomas Z , Bennett Brian , Jacobs David R , Lloyd-Jones Donald M , Gross Myron D , Gordon-Larsen Penny , Zeisel Steven H
Published: March 2022

Objective:
Trimethylamine N-oxide (TMAO), a gut microbiota-dependent nutrient metabolite, has been implicated in the development of cardiovascular disease (CVD). TMAO is excreted in the urine and high levels may reflect poor kidney function, an independent risk factor for CVD. We tested the association between TMAO and coronary artery calcium (CAC) in a young, healthy sample of US adults with normal kidney function.

Methods:
Study participants were from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter cohort of black and white Americans established in 1985/86 (baseline n=5,115; ages 18-30). CAC was measured at follow-up years 15, 20, and 25 with computed tomography (CT). Among a subsample of participants with no detectable CAC at year 15 who had complete CAC data (years 15, 20, 25) and covariate data (year 15) (n=746), we measured TMAO (uM) in year 15 stored plasma (-70 C) and defined incident CAC as having total Agatston units ≥ 0 across all arteries at year 20 or 25. TMAO was measured by using liquid chromatography mass spectrometry. Multivariable-adjusted logistic regression was used to estimate the 10-year incidence of CAC (% who developed any CAC) across quartiles of year 15 TMAO.

Results:
Among 746 participants without CAC at year 15, 184 developed CAC over the 10-year study period. TMAO was not associated with incident CAC in multivariable-adjusted logistic regression models, controlling for demographic, behavioral, and biologic covariates (see Table). Comparing quintiles 1 and 5 of TMAO, the multivariable-adjusted risk (%) of the cohort who developed CAC over the 10-year period was 26% (95% CI: 18%-36%) and 22% (16%-31%), respectively.

Conclusion:
In this population-based cohort of healthy middle-aged US adults with normal kidney function (99% eGFR≥60 ml/min/1.73 m2), TMAO was not associated with incident CAC over 10 years of follow-up. These findings do not support a role for TMAO in the progression of atherosclerosis among young (33-45 y) healthy individuals with normal kidney function.
Abstract P028: The Prognostic Utility of Vitamin D Across Continents in Patients with Suspected Acute Coronary Syndrome
Authors: Naesgaard Patrycja A , Pönitz Volker , Leon de la Fuente Ricardo , Brugger-Andersen Trygve , Nilsen Stein Tore , Grundt Heidi , Brede Cato , Staines Harry , Nilsen Dennis W
Published: March 2022

Background:
Several studies have demonstrated a correlation between low vitamin D levels and cardiovascular risk. Vitamin D is a fat soluble vitamin that can either be ingested (mainly from fatty fish), or created in the skin on exposure to sun.

Objectives:
To assess the collected prognostic utility of vitamin D measured as 25-hydroxyvitamin D [25(OH)D] in 1852 patients hospitalized with chest pain and suspected acute coronary syndrome (ACS) recruited from two continents located at opposite sides of the Equator; coastal-Norway and inland Northern-Argentina, where the vitamin D source is either a combination of diet and sun exposure or mainly sun exposure, respectively. Data from both areas were collected in a similar registry and pooled in the present analysis.

Methods:
2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death (SCD) in the total- as well as in the troponin T (TnT) positive (TnT > 0.01 ng/mL) patient population were analyzed in quartiles of 25(OH)D, applying univariate and multivariable analysis. Variables included in the Cox regression model were country, TnT, hs-CRP, BNP, creatinine, age, gender, BMI, recruitment seasons and 14 other conventional risk factors for coronary heart disease.

Results:
At follow-up, 292 patients had died. 859 patients were TnT positive and of these 186 died. In multivariable Cox regression models for all-cause mortality, cardiac death and SCD in the total patient population, the adjusted hazard ratios (HR) for 25(OH)D in the highest quartile (Q4) as compared to the lowest quartile (Q1) were 0.52 (95% confidence interval (CI), 0.34-0.80), p=0.003, 0.54 (95% CI, 0.31-0.96), p=0.037 and 0.42 (95% CI, 0.18-0.98), p=0.045, respectively. In the TnT positive patient population the respective HRs were 0.43 (95% CI, 0.26-0.72), p=0.001, 0.47 (95% CI, 0.25-0.90), p=0.023 and 0.32 (95% CI, 0.12-0.87), p=0.025.

Conclusion:
Vitamin D status may serve as a prognostic indicator in chest pain patients with suspected ACS.
Abstract P033: Estimating the Impact of Risk Factors for Hypertrophic Cardiomyopathy-related Mortality Among Persons Aged 12-35: United States, 1999-2013
Authors: Fatunde Olubadewa A , Ritchey Matthew D
Published: March 2022

Background:
Hypertrophic cardiomyopathy (HCM), with an estimated prevalence of 1 in 500, is hereditary and often remains asymptomatic and undiagnosed. Although potentially treatable, HCM is a leading cause of sudden cardiac death among adolescents and young adults. While previous HCM-related mortality estimates were extrapolated from cohort studies, this study applies two definitions to death certificate data to estimate national mortality rates and identify at-risk groups.

Methods:
Death certificates of 12-35 year olds with HCM-related deaths in 1999-2013 were obtained from the National Vital Statistics System. Two definitions were applied: 1) specific—underlying-cause-of-death (UCD) ICD-10 code for HCM (I42.1, I42.2); and 2) sensitive—deaths that met the specific definition; had a UCD code for cardiomyopathy, unspecified (I42.9); or had a contributing cause code of I42.1, I42.2, or I42.9 and a HCM-related UCD (Figure). Deaths with external injury (V01-Y89) or congenital (Q00-Q99) codes were excluded. Ratios comparing rates by age (12-19, 20-35), gender (male, female), time (1999-2003, 2004-2008, 2009-2013), and race (non-Hispanic (NH) white, NH black) were calculated.

Results:
During 1999-2013, 2,735 specific and 8,390 sensitive HCM-related deaths occurred among 12-35 year olds. Mortality rates were 1.84 and 5.64 per million, respectively. Mortality rates were higher in 20-35 vs 12-19 year olds (specific mortality ratio 1.69, sensitive mortality ratio 5.66); males vs females (5.09, 2.55), and NH blacks vs NH whites (2.66, 3.24), and decreased over time (Figure).

Discussion:
The HCM-related mortality estimates and at-risk groups (e.g. males, blacks) described here are consistent with findings from previous studies. HCM-related deaths are potentially avoidable through implementation of screening and treatment interventions; however, ideal screening parameters have not been identified. Ongoing surveillance can inform screening improvement efforts and assess for continued rate decreases.