bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 02: Does Pokemon Go Help Players be More Active? An Evaluation of Pokemon Go and Physical Activity
Authors: Xu Hanzhang , Xian Ying , Xu Haolin , Liang Li , Hernandez Adrian F , Wang Tracy Y , Peterson Eric D
Published: July 2021

Objective:
Pokémon Go is a location-based augmented reality game for mobile devices. Leveraging GPS and camera on the smartphone, Pokémon Go requires the player to travel around an area capturing animated creatures. This study aimed to evaluate physical activity associated with Pokémon Go.

Methods:
We recruited 167 iPhone users who had played Pokémon Go in July 2016. Study participants provided screenshots of their daily “steps” reported on their iPhone Health app between June 15, 2016 and Jul 31, 2016. The primary outcome measures were average daily “steps” and % of days > 10,000 steps/day before and after playing Pokémon Go.

Results:
Of 167 volunteers, the mean age were 26±6 years. The average daily steps was 5678±2833 (median 5718 [IQR 3675-7279]) before the participants played Pokémon Go and this number increased to 7654± 3616 (median 7232 IQR [5041-9744]) after they started playing the game. On average, we observed an increase of 1976 (95% CI 1494-2458, p<0.001) in daily steps (
Figure
). Additionally, participants were more likely to achieve 10,000 steps/day goal after playing Pokémon Go (15.3% before vs. 27.5% after; OR 2.06, 95% CI 1.70-2.50). Results from subgroup analyses also showed significant increased level of physical activity after Pokémon Go. Participants who spent more time playing (2-2.5 hours/day 2861 more steps, 95% CI 1884-3837; >2.5 hours/day 2238 more steps, 95% CI 1008-3467), overweight/obese (3031 more steps, 95% CI 2132-3929), or with a lower baseline physical activity level (lowest quartile, 2,899 more steps, 95% CI 2030-3767) had the largest increase after the initiation of the game.

Conclusion:
We observed a significant increase in physical activity associated with Pokémon Go. Games like Pokémon Go may provide an alternative way to encourage exercise, especially among young adults with low baseline physical activity levels and/or overweight/obesity.
Abstract 20: Cardiovascular Health Trends in Electronic Health Record Data (2010-2015): the Guideline Advantage
Authors: Foraker Randi , Patel Sejal , Khan Yosef , Bauman Mary Ann , Bower Julie
Published: July 2021

Background:
Electronic health records (EHRs) are an increasingly valuable data source for monitoring population health. However, EHR data are rarely shared across health system borders, limiting their utility to researchers and policymakers. The Guideline Advantage™ (TGA) program, a joint initiative by the American Heart Association (AHA), American Cancer Society, and American Diabetes Association, brings together data from EHRs across the country to support disease prevention and management efforts in the outpatient setting.

Methods:
We analyzed TGA EHR data from >70 clinics comprising 281,837 adult patients from 2010 to 2015. We used the first available measure per patient for each calendar year to characterize trends in the proportion of patients in “ideal”, “intermediate”, and “poor” CVH categories for blood pressure (BP), body mass index (BMI) and smoking. Total cholesterol and fasting glucose values were not reported to TGA. Thus, we used low-density lipoprotein (LDL) and hemoglobin A1c (A1c) treatment guidelines to classify patients into CVH categories for the respective metrics.

Results:
Patients were an average of 50 years old, and 57.4% were female. Of records with complete data on race, 70.9% of patients were white. Over 6 years of observation, we documented increases in the proportion of patients at ideal levels for BP, smoking, LDL, and A1c, but decreases in the proportion of patients at an ideal level for BMI (Figure).

Conclusions:
TGA data provide a large-scale perspective of outpatient CVH, yet we acknowledge limitations associated with using EHR data to assess trends in CVH. Specifically, EHR data entry is clinically-driven - BP and BMI values are likely to be updated at each visit for each patient, while smoking status, LDL, and A1c are not. Our analysis lays the groundwork for EHR analyses as these data become less siloed and more accessible to stakeholders.

Figure. Trends in CVH from 2010 to 2015: The Guideline Advantage™
Abstract MP035: The Clinical Epidemiology of Fatigue in Newly Diagnosed Heart Failure
Authors: Williams Brent
Published: July 2021

Introduction:
Fatigue is a common and distressing, but poorly understood symptom among patients with heart failure (HF). The underlying mechanisms of fatigue in HF have not been clearly elucidated, but may lie in both psychologic and physiologic factors. Whether fatigue remains associated with mortality independent of other common clinical attributes also remains unresolved. Accordingly, the current study sought to evaluate the prevalence, predictors, and prognostic value of clinically documented fatigue in newly diagnosed HF patients.

Methods:
This retrospective cohort study consisted of 12,285 newly diagnosed HF patients receiving health care services through the Geisinger Health System, with passive data collection through electronic medical records (EMR). Incident HF, fatigue, and other study variables were derived from coded data within EMRs. A collection of 87 candidate predictors were evaluated to ascertain the strongest independent predictors of fatigue using logistic regression. The collection of candidate variables was drawn from several domains including demographics, physical examination findings, medical history, laboratory results, and medications. Patients were followed for all-cause mortality for an average of 4.8 years. The associations between fatigue and six-month, 12-month, and overall mortality were evaluated with Cox proportional hazards regression.

Results:
Clinically documented fatigue was found in 4827 (39%) newly diagnosed HF patients. Among the 87 candidate predictors, 18 were independently associated with fatigue at a multivariable p-value threshold of 0.001. Depression was the strongest predictor of fatigue. Fatigue was often part of a symptom cluster, as other HF symptoms including dyspnea, chest pain, edema, syncope, and palpitations were significant predictors of fatigue. Volume depletion, low body mass index, and abnormal weight loss were also strong predictors of fatigue. Though fatigue was significantly associated with 6-month (HR=1.49, p<0.01), 12-month (HR=1.39, p<0.01), and all-cause mortality (HR=1.20, p<0.01) in unadjusted models, effect sizes were attenuated and non-significant after adjustment for clinical variables with HRs of 1.12 (p=0.16), 1.07 (p=0.26), and 1.00 (p=0.89), for 6-month, 12-month, and overall mortality, respectively.

Conclusions:
Fatigue is a commonly documented symptom among newly diagnosed HF patients with likely origins in both psychologic and physiologic factors. Though fatigue provided a prognostic signal in the short-term, this was largely explained by physiologic confounders.
Abstract MP079: Coronary Artery Calcium Incidence and Progression Among South Asians: Results From the MASALA Study
Authors: Kanaya Alka M , Kandula Namratha , Herrington David , Liu Kiang , Budoff Matthew
Published: July 2021

Background:
South Asians have a high burden of cardiovascular disease. We have reported that South Asians have similarly high prevalence of coronary artery calcium (CAC) compared to non-Hispanic Whites, and higher CAC than other U.S. ethnic minority groups. No studies have determined the incidence or progression of CAC among South Asians.

Methods:
We used data from a community-based cohort of South Asians (MASALA) and calculated change in CAC Agatston score between Exam 1 (2010-2013) and Exam 2 (2015-2016) among 379 South Asians. We calculated the average annual incident CAC for those with no CAC at Exam 1, and CAC progression among those with CAC at Exam 1. We compared these findings to the previously reported CAC incidence and progression in the Multi-Ethnic Study of Atherosclerosis (MESA). We also determined factors associated with a ≥100 change in CAC score.

Results:
We used data from 240 men and 139 women with repeat CAC measured after 4.5±0.7 years of follow-up. Among those with no detectable CAC at baseline, 6.8% developed incident CAC annually (9.2% of men and 4.4% of women), which was similar to MESA race/ethnic groups. Among those with known CAC at baseline, the median annual CAC progression was 23 (interquartile range, 8-56). The table shows the distribution of annual CAC progression. South Asians overall, but particularly South Asian men, had significantly higher annual CAC progression compared to the reported average in MESA (overall median 18, 4-53). Established risk factors (age, male sex, diabetes and hypertension), pericardial fat volume and visceral fat area were associated with greater CAC progression.

Conclusions:
These preliminary results suggest that South Asian men have significantly greater CAC progression compared to other race/ethnic groups. Longer follow-up of MASALA will determine whether CAC score or CAC progression are important predictors of cardiovascular disease events.
Abstract MP091: Hypertension is Associated With Increased Risk of Adverse Clinical Outcomes in Women With Peripartum Cardiomyopathy
Authors: Imran Tasnim F , Mohebali Donya , Lopez Diana , Bello Natalie , Truong Sandy , Defilippis Ersilia , Gilstrap Lauren , Semigran Marc , Gaziano J Michael , Djousse Luc , Kociol Robb
Published: July 2021

Background:
Peripartum cardiomyopathy (PPCM) is a rare condition that carries a high morbidity and mortality among young women. Studies examining the association of modifiable risk factors such as hypertension with outcomes in this population are sparse.

Methods:
We conducted a multi-center retrospective study across three major centers (BWH, BIDMC, MGH) to identify subjects with PPCM using the following criteria: ejection fraction < 40%, development of heart failure within the last month of pregnancy or within 5 months of delivery and no other identifiable cause of heart failure with reduced ejection fraction. We defined adverse clinical outcome as a composite of heart failure hospitalizations, need for extra-corporeal membrane oxygenation, ejection fraction <35%, cardiac transplantation or death during the follow-up period.

Results:
In all, 237 women met criteria for PPCM across the three centers between April 1995 and November 2015. Participants had a median age of 33.1 years (IQR: 28.6-38.0), gravida 2.0, para 2.0, mean left ventricular ejection fraction at diagnosis of 30%; 25% had chronic hypertension and 14% had preeclampsia. After a median follow-up of 3.2 years (IQR: 1.0-7.8), 59 events occurred. In a logistic regression model adjusting for age, number of prior pregnancies and number of deliveries, women with preeclampsia had an OR of 1.34 (95% CI: 1.05-1.72), p=0.02 as compared to those without preeclampsia. A similar association was observed for hypertension (Table). In sensitivity analysis, the association between preeclampsia and adverse outcomes persisted for blacks and other races, but not for whites.

Conclusion:
Our study suggests that hypertension or preeclampsia at diagnosis is associated with increased risk of heart failure hospitalizations, need for extra-corporeal membrane oxygenation, poor left ventricular function recovery, cardiac transplantation and death on follow-up in women with PPCM. Clinicians should consider aggressive treatment of hypertension in women of childbearing age.
Abstract P041: New Biomarkers for Detecting and Subtyping Insulin Resistance
Authors: Cistola David P , Mishra Ina , Patel Vipulkumar , Patel Rinkal , Deodhar Sneha
Published: July 2021

Introduction:
The metabolic abnormalities that precede type 2 diabetes progress slowly and in stages. Current evidence-based diabetes prevention programs target individuals in Stage 2 (impaired glucose tolerance or prediabetes). However, by that stage, 70% of pancreatic beta-cell insulin secretory capacity has been lost irreversibly. Thus, it is imperative to identify individuals in Stage I (early insulin resistance syndrome) in order to preserve pancreatic insulin secretion and prevent both diabetes and prediabetes. Early insulin resistance syndrome is characterized by compensatory hyperinsulinemia, dyslipidemia, sub-clinical inflammation and acid-base abnormalities. The nature of the association between these elements is unclear, and different subtypes of insulin resistance syndrome may exist.

Hypothesis:
We have developed two novel and unconventional biomarkers for characterizing insulin resistance in non-diabetic subjects. One approach is based on dynamic light scattering (DLS) of human serum. The second approach measures the T
2
relaxation time of water in human plasma using compact time-domain NMR relaxometry (TD-NMR). We hypothesize that these methods can detect subtypes,
i.e.
, insulin resistance with or without inflammation, hypercholesterolemia, or acid-base abnormalities.

Methods:
Seventy-two asymptomatic non-diabetic human subjects were recruited through an IRB-approved biomarker discovery protocol. Medical histories, anthropomorphic measurements and fasting blood samples were obtained, and over 1300 blood biomarkers were measured on each subject along with DLS and TD-NMR parameters. Bi-variate correlation analyses and multiple regression models were used to analyze continuous variables, and categorical variables were established for insulin resistance, inflammation, acid-base abnormalities and lipid abnormalities. Multiple means comparisons were performed using one-way ANOVA and Tukey-Kramer testing.

Results:
Plasma water T
2
from TD-NMR was strongly correlated with markers of early insulin resistance syndrome. Multiple regression analysis showed independent contributions from markers of hyperinsulinemia, hypercholesterolemia and inflammation. Multiple means comparisons showed significant differences for insulin resistance with and without inflammation. By contrast, DLS parameters were strongly correlated with insulin markers, but could not distinguish the inflammatory subtypes.

Conclusions:
Both TD-NMR and DLS are able to detect early insulin resistance in individuals who do not meet the criteria for prediabetes or metabolic syndrome. However, TD-NMR has the unique ability to distinguish inflammatory vs. non-inflammatory subtypes of insulin resistance. Subtyping and risk stratification are important for the design of personalized interventions to prevent diabetes, prediabetes and cardiovascular disease.
Abstract P089: Early CVD Events by Race and Sex: Does Risk for Atherothrombotic- and Hypertension-related Events Differ by Race and Sex? The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Lewis Cora E , Kiefe Catarina I , Jacobs David R , Goff David C , Shikany James M , Sidney Stephen , Duprez Daniel , Lloyd-Jones Donald , Reis Jared , Schreiner Pamela J , Durant Raegan , Kim Young-il , Kershaw Kiarri
Published: July 2021

African Americans (AA), both men (M) and women (W), have higher CVD mortality rates than European Americans (E), but AAM have lower prevalence of coronary calcified plaque than WM. AAs also have higher blood pressure (BP) and HDL-C than W; HDL-C is lower in M than W. We tested the hypotheses that AA race is related to higher risk of hypertension (HTN)-related events, and being male is related to higher risk of atherothrombotic (ATH)-related events, placing AAM at particularly high risk for CVD.

Methods:
We used baseline risk factor data, and adjudicated events through 28 years of follow-up from the CARDIA study which recruited 5,115 participants aged 18-30 years at baseline (1985-6). ATH-related events included acute coronary syndrome with or without MI, coronary revascularization, and CHD and other atherosclerosis death. HTN-related events included heart failure, end-stage renal disease (ESRD), stroke, and death due to cardiomyopathy. CVD events excluded ESRD and included peripheral artery disease procedures. We analyzed time to first event censoring at death without incident CVD and at follow-up end. We built adjusted Cox models with forward selection including race, sex, age, education, and smoking status as forced predictors and selecting among physical activity, anthropometry, glycemia, lipid, and blood pressure risk factors.

Results:
In unadjusted analyses, risk of HTN-related events was related to race (p<0.01) but not sex (p=0.35), ATH-related events to sex (P<0.01) but not race (p=0.44), and CVD events to race (p<0.01) and sex (P<0.01). Unadjusted, all risk factors were associated with both HTN- and ATH-related events, except physical activity was not related to ATH and CVD events. After adjustment (table), AAM had higher risk of HTN- and ATH-related events, EM had higher risk of ATH-related events, AAW had higher risk of HTN-related events, and all had higher risk of CVD events than EW.

Conclusion:
Race and sex are differentially associated with early HTN- vs ATH-related events, and AAM were at increased risk for both.
Abstract P106: Epigenetic Age Acceleration and Postprandial Lipemia in the Genetics of Lipid Lowering Drugs and Diet Network Study
Authors: Irvin Marguerite R , Hidalgo Bertha , Zhi Degui , Aslibekyan Stella , Tiwari Hemant K , Absher Devin , Arnett Donna K
Published: July 2021

Background:
Calculated ‘epigenetic age,’ a novel biomarker based on DNA methylation levels of 353 CpGs, has been demonstrated to accurately predict chronological age across a broad spectrum of tissues and cell types. Recently epigenetic age acceleration or older epigenetic age in comparison to chronological age has been robustly associated with all-cause mortality independent of chronological age in multiple human cohorts. However, accelerated epigenetic aging has not been associated with lipids levels, including postprandial lipid levels which are linked to prothrombotic and proinflammatory processes that may precipitate aging. In the current study we aimed to evaluate the association between epigenetic age acceleration and lipid levels.

Methods:
We used the Horvath DNA methylation age calculator to estimate epigenetic age in 988 Caucasian participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) using Illumina Infinium HumanMethylation450 BeadChip array data derived from CD4+ T-cell DNA. GOLDN participants did not take lipid lowering drugs for at least four weeks prior to enrollment and underwent a standardized high fat meal challenge after fasting for at least 8 hours followed by timed blood draws at 3.5 and 6 hours following the meal. Epigenetic age acceleration was calculated as the residual from regressing methylation age on chronological age. We used linear mixed models to examine the association of age acceleration quartiles with fasting and postrandial (3.5 and 6 hour time points) low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride (TG) levels after adjusting for age, study site, sex, fasting lipid level (if applicable), deconvolution estimated T-cell type percentages and a random effect of family relationship.

Results:
The correlation between calculated methylation age and chronological age was 0.91. The difference between methylation age and chronological age (methylation age - chronological age) was on average -5.8 (5.9), -0.5 (4.7), 2.9 (4.3), and 7.8 (5.0) years for the first through fourth quartiles of age acceleration, respectively. After adjustment for covariates neither fasting nor postprandial lipids were associated with age acceleration quartile.

Conclusions:
Evidence from the current study suggests lipid levels in the fasting and postprandial state are not related to accelerated epigenetic aging, however given the association between epigenetic age acceleration and mortality observed in previous studies the relationship of other metabolic parameters with age acceleration may be worthy of investigation.
Abstract P128: Serum Lipid Levels at Adolescence can Predict Adult Dyslipidemia in South Korea - The Kangwha Study
Authors: Lee Jung H , Kim Hyeon C , Kang Dae R , Suh Il
Published: July 2021

Introduction:
Several studies have examined tracking pattern of lipid profile level during long follow-up periods in Western countries. However, there have been few such studies in East Asia.

Hypothesis:
We assessed the hypothesis that there exists tracking pattern of lipid profile level from adolescence to adulthood, and lipid measurements in adolescence can predict adult dyslipidemia in South Korea.

Methods:
The Kangwha Study was a community-based prospective cohort study that started in 1986 in Kangwha County, South Korea
.
A total of 400 participants (54% women) whose serum total cholesterol, triglyceride, and high density lipoprotein (HDL) cholesterol level were measured at least once during adolescence (1992-1996), and repeatedly measured at least once during adulthood (2005-2015) were enrolled in our study. Body mass index, waist circumstance, and blood pressure were measured at all measurements. Family history of cardiovascular disease, smoking history, and presence of adult dyslipidemia were checked at adulthood. The tracking pattern of lipid profile level was determined by tracking coefficients (low: <0.30; moderate: 0.30-0.59; moderately high: 0.60-0.89; high: ≥0.90). The tracking coefficients were calculated by Generalized Estimating Equation. The predictability of adult dyslipidemia was assessed by multiple logistic regression and area under curve (AUC) value. Additional analyses were performed to find out whether repeated lipid measurements during adolescence can enhance the predictability of adult dyslipidemia or not.

Results:
The presence of adult dyslipidemia was 26.3% (105 of 400). Mean age of study participants at enrollment is 13.8 years (SD, 1.6 years), and that at adulthood is 30.1 years (SD, 3.7 years). When adjusted for age, body mass index, waist circumstance, and blood pressure, the tracking coefficient of total cholesterol was 0.59 (95% confidence interval (CI), 0.54-0.63), that of triglyceride was 0.39 (95% CI, 0.28-0.49), and that of HDL cholesterol was 0.51 (95% CI, 0.46-0.55). The AUC value of our multiple logistic regression model on adult dyslipidemia without lipid profile levels at adolescence was 0.77 (95% CI, 0.72-0.83), and that with lipid profile levels at adolescence was 0.80 (95% CI, 0.75-0.85). P value for AUC comparison was significant (p=0.02). In additional analyses, using the average lipid profile levels in multiple lipid measurements at adolescence did not significantly improve the AUC value (p>0.09).

Conclusion:
In conclusion, moderate tracking patterns of serum lipid profile level were shown in this study. Serum lipid profile measurements at adolescence could help the prediction of adult dyslipidemia. The results of this study supported the need of lipid profile screening at adolescence.
Abstract P156: Assessing the Effect of the Heart of New Ulm Project: a Population-Based Program to Reduce Cardiovascular Disease
Authors: Sidebottom Abbey C , Sillah Arthur , Vock David M , Miedema Michael M , Pereira Raquel , Benson Gretchen , Lindberg Rebecca , Boucher Jackie L , Knickelbine Thomas , VanWormer Jeffrey J
Published: July 2021

Background:
Despite a highly recognized priority for public health and healthcare to implement population-level strategies to reduce the burden of cardiovascular disease (CVD), limited evidence exists on the most effective strategies. Data collection and evaluation of large scale, community based-prevention programs can be challenging and costly to achieve. The Heart of New Ulm (HONU) Project, begun in 2009, is a population-based initiative with healthcare, community, and workplace interventions addressing multiple levels of the social-ecological model designed to reduce modifiable CVD risk factors in rural New Ulm, MN. The community is served by one health system, enabling the use of electronic health record (EHR) data for surveillance.

Objective:
To assess trends for CVD risk factors, events, and healthcare utilization for New Ulm residents compared to a matched control population.

Methods:
We matched New Ulm residents (n = 4,077) with controls (n = 4,077) from a regional community served by the same health system using refined covariate balance techniques to match on baseline demographics, CVD risk factors, and health care utilization. Mixed effects longitudinal models with adjustment for age and gender, and an interaction for time by community, were run. Model based estimates were constructed for the entire cohort at each time period.

Results:
Over the first 6 years of the HONU Project,blood pressure, LDL, total cholesterol, and triglycerides were managed better in New Ulm than the matched comparison community. The proportion of New Ulm residents with controlled blood pressure increased by 6.2 percentage points while the control group increased by 2 points. 10-year ASCVD risk scores showed less decline for New Ulm residents than controls (16 vs. 18.4). The intervention and control groups did not differ with regard to inpatient stays, CVD events, smoking, or glucose.

Conclusions:
Compared to a matched control population, we found improved control of CVD risk factors in the New Ulm Population exposed to the HONU Project.
Abstract P170: High Intake of Dietary Protein is Associated With Increased Risk of Heart Failure With Preserved Ejection Fraction
Authors: Eaton Charles B , Barbour Mohamad F , Ashraf Farhan , Roberts Mary , Martin Lisa W , Allison Matthew A , Johnson Karen C , Valdiviezo Carolina I
Published: July 2021

Background:
Heart Failure with preserved ejection fraction(HFpEF) is growing and common problem in elderly women with high morbidity and mortality. The role of diet in its prevention is under-researched.

Objective:
To evaluate calibrated and uncalibrated dietary protein, energy adjusted animal and vegetable protein and their association with incident HFpEF.

Methods:
Study participants in Women’s Health Initiatve (n=14,184) with valid FFQ data, free of baseline HF or missing covariates had urinary nitrogen calibrated total protein, energy calibrated using doubly labelled water animal and vegetable protein determined. Cox models adjusted for age, education, race/ethnicity, CHD, diabetes,waist to hip ration,hypertension, physical activity, systolic blood pressure, anemia, atrial fibrillation evaluated prospective association with HFpEF. HFpEF was defined as ejection fraction >45%.

Results:
Over 13.2 years of follow-up, there were 513 cases of HF, 268 cases of HFpEF, 162 of HFrEF and 83 of undetermined ejection fraction. Increasing levels of calibrated total protein showed a linear dose response relationship with an increased risk of HFpEF whereas uncalibrated total protein did not. Higher intake of animal protein demonstrated an increased risk , while vegetable protein showed a trend towards and inverse relationship. (see table)

Conclusion:
HIgher levels of calibrated total protein are associated with increased risk of HFpEF with animal protein appearing to be the most deleterious. Plant based diets with high levels of vegetable protein may be protective. Further studies should evaluate this.
Abstract P171: Potential Mortality Reduction with Optimal Usage of sacubitril/valsartan Therapy for the Treatment of Heart Failure in Canada
Authors: McKelvie Robert , White Michel , Vaillancourt Marc , Haddad Paola , Zaour Nancy
Published: July 2021

Background:
Despite well-recognized standard of care therapies, heart failure (HF) continues to be characterized by high mortality rates. Sacubitril/valsartan, a first-in-class treatment for HF with reduced ejection fraction (HFrEF) provided incremental cardiovascular and overall survival benefit in PARADIGM-HF, the largest clinical trial ever conducted in HF patients. We hypothesized that optimal use of sacubitril/valsartan in the treatment of HFrEF in Canada would be associated with potential benefits in terms of deaths avoided.

Objective:
The objective of this analysis was to quantify the number of potential deaths avoided with optimal usage of sacubitril/valsartan in the treatment of HFrEF in Canada.

Methods:
Data from Statistics Canada was used to quantify the population above 18 years of age. A literature search was then conducted to determine the prevalence of HF in Canada, the proportion of these with NYHA class II and III, and finally the proportion of patients with HFrEF. The number needed to treat (NNT) to avoid one death, standardized to 12 months was derived from the PARADIGM-HF trial. The NNT using product limit survival rates and actual follow-up times from the PARADIGM-HF trial was also derived. The potential number of deaths prevented as a result of optimal usage of sacubitril/valsartan as per current approved usage in Canada (HFrEF patients with NYHA class II or III) were estimated along with multiple-way sensitivity analysis using the analysis-of-extremes method. The main outcome and measure was all-cause mortality.

Results:
A Canadian prevalence of 2.31% was applied to determine the number of HF patients. From those, 64% were classified as NYHA Class II and III of which 56% were considered as rEF. It was estimated that in Canada, approximately 242,200 patients are affected with HFrEF with NYHA class II and III. Based on a NNT of 80, optimal usage of sacubitril/valsartan therapy was estimated to prevent 3,014 deaths per year (range, 1,930 – 4,331 per year). Based on the alternate NNT (71.3) using the product limit survival rates and actual follow-up times from PARADIGM-HF, a total of 3,397 patient deaths could be potentially prevented each year (range, 2,718 – 4,076 per year).

Conclusion:
Standard of care treatment for HF is well-established and has shown important mortality reduction but there is still a need for additional therapies to further improve survival rates for patients living with HFrEF. The findings from this analysis suggest that a substantial number of deaths in Canada could potentially be avoided by optimal usage of sacubitril/valsartan therapy. This analysis supports the importance of rapidly implementing evidence-based therapy, in this case sacubitril/valsartan, into routine clinical practice to improve clinical outcomes for HFrEF patients in Canada.
Abstract P208: The Joint Association of Low Vitamin D and Vitamin K Status with Blood Pressure and Hypertension
Authors: van Ballegooijen Hanne , Brouwer Ingeborg A , Visser Marjolein , van Schoor Natasja , Beulens Joline W
Published: July 2021

Introduction:
Low vitamin D and vitamin K status are both associated with cardiovascular risk. New evidence from experimental studies on bone health suggest an interaction between vitamin D and K, however a joint association with vascular health outcomes is largely unknown.

Hypothesis:
We assessed the hypothesis that the combination of low vitamin D and low vitamin K status is associated with higher systolic and diastolic blood pressure in 402 participants and with incident hypertension in 231 participants free of hypertension at baseline.

Methods:
We used data from a subsample of the Longitudinal Aging Study Amsterdam (LASA), a population-based cohort of Dutch participants 55-65 years. Vitamin D and K status were assessed by measuring 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix gla protein (dp-ucMGP). High dp-ucMGP is indicative of a low vitamin K status. Generalized estimating equation and Cox proportional hazard models were used for the association of vitamin D and vitamin K status with blood pressure and incident hypertension (systolic blood pressure ≥140 or diastolic blood pressure ≥90 mmHg or using anti-hypertensive medication).

Results:
During a median follow-up of 6.4 years, 62% of the participants (n=143) developed hypertension. Vitamin D and vitamin K status were categorized in groups: 25(OH)D <50/≥50 mmol/L and median dp-ucMGP <323/≥323pmol/L. The combination of low 25(OH)D <50 nmol/L and high dp-ucMGP ≥323 pmol/L was associated with increased systolic 4.8 mmHg (95% CI 0.1-9.5) and diastolic 3.1 mmHg (0.5-5.7) blood pressure compared to 25(OH)D ≥50 mmol/L and dp-ucMGP <323 pmol/L, after adjusting for age and sex, BMI, alcohol consumption, smoking, education, season of blood collection, total cholesterol and estimated glomerular filtration rate. A similar trend was seen for incident hypertension HR:1.62 (0.96-2.73).

Conclusions:
The combination of low vitamin D and K status was associated with increased blood pressure and might play a role in the development of hypertension.
Abstract P224: Association of Nonalcoholic Fatty Liver Disease With Left Ventricular Geometry and Remodeling: the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: VanWagner Lisa B , Wilcox Jane E , Ning Hongyan , Lewis Cora E , Shah Sanjiv J , Carr John J , Rinella Mary E , Lima Joao A , Lloyd-Jones Donald M
Published: July 2021

Background:
Nonalcoholic fatty liver disease (NAFLD) is associated with high cardiovascular mortality, including heart failure (HF). Left ventricular hypertrophy (LVH) increases the risk of future HF. The relationship between NAFLD and LV geometry is unknown. In a large prospective population-based sample of black and white adults free from liver or heart disease, we examined the relationship between NAFLD and markers of LV remodeling.

Methods:
Participants from the CARDIA study (Y25 exam; age 43-55 years) with concurrent CT quantification of liver fat and tissue Doppler echocardiography were included (n=2,576). Echocardiography was repeated at Y30 follow up (age 47-62 years). LV geometry was classified into normal and abnormal geometry by integrating relative wall thickness and LV mass index. NAFLD was defined as CT liver attenuation ≤ 40 Hounsfield units after excluding other causes of liver fat. Logistic and polytomous regression models were used to test associations.

Results:
NAFLD prevalence was 9.6%. NAFLD participants were more likely to be male (57.7% vs. 40.0%), white (57.3% vs. 50.2%), and had higher BMI (36.0 vs. 29.9 kg/m
2
) than non-NAFLD. At Y30 NAFLD participants had higher LV mass, left atrial diameter, and LV relative wall thickness compared to non-NAFLD (p<0.01). Those with NAFLD had higher prevalence of LVH (31.9% vs. 18.2%), concentric remodeling (15.3% vs. 13.1%), concentric hypertrophy (12.9% vs. 7.9%) and eccentric hypertrophy (18.9% vs. 10.1%, p<0.0001). In multivariable analyses NAFLD was independently associated with prevalent LV remodeling (Table). Associations were attenuated after adjustment for HF risk factors. In contrast, NAFLD was associated with incident LVH independent of HF risk factors. Adjustment for BMI attenuated this association. There was no interaction by race or sex.

Conclusion:
NAFLD is associated with subclinical changes in LV geometry and remodeling, a precursor to HF. The role of NAFLD in LV remodeling as a potential therapeutic target warrants further investigation.
Abstract P246: Long-term Optimal Lifestyle and Clinical Factors and Progression in Arterial Stiffness in the Multiethnic Study of Atherosclerosis
Authors: Tedla Yacob , Delaney Joseph , Liu Chia-Ying , Stein James , Carnethon Mercedes , Greenland Philip
Published: July 2021

Introduction:
Optimal cardiovascular health (CVH), based on lifestyle and clinical factors, is associated with lower risk of CV events and this may occur partly by preventing progression of arterial stiffness. We assessed the association of optimal lifestyle and clinical factors with changes in arterial stiffness in the Multi-Ethnic Study of Atherosclerosis.

Methods:
Among 2,729 participants (aged 44-84 years, 46.5% male), number of optimal lifestyle factors (BMI <25 kg/m2, never smoker, never drinkers, exercised >500 METS minutes/week) and optimal clinical factors (systolic BP <140 and diastolic BP <90mmHg, fasting glucose <100mg/dL, and total cholesterol <200mg/dL), across 5 visits, were summed to create an overall optimal score for lifestyle and clinical factors. Carotid arterial stiffness was measured using distensibility coefficient (DC) and Young’s elastic modulus (YEM) at baseline and after a mean of 9.5 years (visit 5). In separate multiple linear regression models, percent changes in DC and YEM between visits 1 and 5 were regressed on quartiles of overall optimal score for lifestyle and clinical factors.

Results:
On average, DC decreased by 5.3% and YEM increased by 24.4% over ten years. Mean optimal lifestyle score was 10.2 (range: 0-19) and optimal clinical score was 9.1 (range: 0-15) across 5 visits. There was no difference in arterial stiffness progression between individuals in the upper quartiles of optimal lifestyle score and those in the lowest quartile. A higher score on optimal clinical factors was inversely associated with progression in arterial stiffness. Linear trends in the increase of DC (P-trend<0.001 in all) and decrease of YEM (P-trend<0.002 in all) were observed across the quartiles of optimal clinical score and quartiles of CVH score (i.e. combining lifestyle and clinical factors) (Table 1).

Conclusion:
Optimal CVH was associated with less arterial stiffening, but only the clinical factors were predicting arterial stiffness and lifestyle factors had no influence on arterial stiffness.
Abstract P258: Racial Disparity in 90-Day Post-Stroke Readmission - An MUSC Perspective
Authors: Chhatbar Pratik Y , Obeid Jihad S , Zhao Yujing , Lackland Daniel T , Adams Robert J
Published: July 2021

Background:
Readmissions after acute hospitalizations are a cause of both risk and expense, and many of them are potentially preventable. Importantly, risk-standardized hospital readmission rates are sometimes used as a yardstick of the quality of care offered. However, racial variability in readmissions might involve factors beyond quality of care and has not been studied extensively.

Objective:
To identify differences in readmissions between African Americans and other races and determine preventable readmissions from a pragmatic viewpoint.

Methods:
We obtained deidentified data from Medical University of South Carolina (MUSC) Electronic Data Warehouse (EDW) on adult admissions with index diagnosis considered as an ischemic stroke (or closely related) using International Classification of Diseases, Ninth Revision (ICD-9) codes 433.x, 434.x, 436.x, 437.x between January 2011 and June 2014. Of these, we determined readmission and reason for readmission over 90-day period. Readmission can be hospital or emergency room readmission. We obtained race as the only linked demographic.

Results:
Of the 1953 patients admitted with index diagnoses of stroke, 765 (39%), 1148 (59%) and 50 (1%) were African Americans, Caucasians and others, respectively. At 90-days, 256 patients were readmitted as in-patient, of which 128 (50%), 126 (49%) and 2 (1%) were African Americans, Caucasians and others, respectively. On the other hand, 241 patients visited Emergency Room, of which 175 (73%), 65 (26%) and 1 (1%) were African Americans, Caucasians and others, respectively. On adjusting readmissions to index admissions, 17%, 11% and 4% of African Americans, Caucasians and others, respectively, were readmitted in hospital, while 23%, 6% and 2% of African Americans, Caucasians and others, respectively, visited Emergency Room over 90-days period.

Conclusions:
90-days readmission rates involve African Americans in a disproportionate manner. This demands further investigation on the etiology of readmission and the care offered.
Abstract P293: The Effect of Diet Beverage Intake on Measures of Diabetes Control: A Pilot Study
Authors: Odegaard Andrew , Hirahatake Kristin
Published: July 2021

Introduction:
Diet beverages are calorie free beverages sweetened with non-nutritive sweeteners (NNS). People with diabetes are at high macro and microvascular risk and are the highest per capita consumers of diet beverages as they tend to consume them directly in place of sugar sweetened beverages. This behavior has been endorsed by dietetic and scientific organizations; and diet beverages are marketed synonymously with better health, suitable for weight loss, and thus advantageous for diabetes control. The underlying public health concern is the lack of data to support or refute this concept. To begin addressing this evidence gap we carried out a randomized, two period crossover trial testing the effect of habitual diet beverage intake compared to habitual bottled water intake (avoidance of all NNS) on clinical markers of diabetes control and potential mechanistic pathways.

Hypothesis:
Habitual diet beverage intake will raise glycemia, lower kidney function, and lower diet quality compared to water intake.

Methods:
We carried out a randomized, two period crossover trial of 12 adults with type 2 diabetes who were being treated with oral medications and were free of other major chronic disease. In two separate 4 week periods with a washout period between them, participants were randomized to consume 24 oz. a day of a diet beverage (DB) of choice in 1 period and 24 oz. a day of bottled water (H2O) in the other while maintaining usual lifestyle habits and diabetes treatment regimens across periods. The primary outcome was change in glycemia (fructosamine). Secondary outcomes were kidney function (eGFR via serum creatinine) and diet quality (healthy eating index score, HEI-2010). All clinical measures were collected by standardized protocol and laboratory measurement. Diet was assessed by 3 random 24 hour recalls each period (1 weekend, 2 weekday) using a web based automated self-administered platform and diet quality was calculated by estimating the HEI-2010. Mixed-model repeated measures linear regression was used to analyze the continuous outcomes data.

Results:
10 women and 2 men, mean (SD) age 58.3 (7.9) years with mean (SD) HbA1c % of 7.1 (1.4) at baseline were randomized and completed the study. Glycemia (fructosamine) was reduced, mean (SE) of -3.9 (3.2) umol/L during the H2O period and increased 0.6 (3.2) umol/L during the DB period, p=0.36. The results for kidney function (eGFR) were: H2O: -0.4 (3.7) v. DB: -2.3 (-3.7) mL/min/1.73m
2
, p=0.72. Diet quality was lower during the DB period relative to the H2O period (58.0 v. 61.5, p=0.25).

Conclusion:
Although the magnitude and precision of the treatment effects limits the inference, these results suggest the need for larger and longer trials to more definitively test this hypothesis and inform the role diet beverages may have in diabetes control.
Abstract P298: Associations Between Time-varying Physical Activity and Physical Performance Measures in Postmenopausal Women: the Women’s Health Initiative
Authors: Laddu Deepika , Wertheim Betsy C , Garcia David O , Brunner Robert , Shadyab Aladdin H , Groessl Erik , Going Scott B , LaMonte Michael J , Cannell Brad , LeBoff Meryl , Cauley Jane A , Thomson Cynthia A , Stefanick Marcia L
Published: July 2021

Introduction:
Maintaining regular physical activity (PA) may delay the onset of functional disability and preserve mobility later in life. Whereas many population-based studies have reported the prospective relationship of initial PA levels to later-life functional status, few studies have examined the longitudinal relationships between changes in PA to changes in physical functioning. This study examined associations between changes in PA and changes in standard physical performance measures (PPM) over 6-years in older women.

Methods:
Recreational PA was reported using the WHI questionnaire; gait speed, timed chair stand, and grip strength were assessed in clinic using standardized protocols. Exposures were assessed at baseline, years 1, 3 and 6 of the Women’s Health Initiative Clinical Trials (n=5092 women; mean age = 69.8 y). Mixed effects linear regression models were used to evaluate the association between time-varying PA and change in each PPM. Potential interactions between time-varying PA and race and age (<70 y; ≥70 y) were also tested.

Results:
At baseline, 23.0% women were categorized as sedentary (SED; <100 MET-min/wk), 30.4% as light PA level (100- <500 MET-min/wk), 27.5% as moderate (500- <1200 MET-min/wk); and 19.1% as high PA (≥ 1200 MET-min/wk). Significant, dose-response associations between PA and improvements in all PPMs were observed over the 6 y follow-up after adjusting for demographic, lifestyle, and clinical factors. Compared to SED, women in the high PA groups showed better grip strength (0.48 kg higher;
P
<0.01), more chair stands (0.35 more;
P
<0.001), and faster gait speeds (0.06 m/s faster
; P
<0.001). Older women (≥70 y) benefited more from higher levels of PA than the younger women (P
interaction for age
=0.014), as reflected by their greater increase in chair stands (
P
<0.001); however, interactions between PA and race were not significant.

Conclusions:
These findings provide evidence that, in post-menopausal women, maintaining higher PA levels over time is associated with benefits in lower extremity function, as compared to being sedentary. These data are consistent with the view that regular PA plays an important role in maintaining functional status during aging, particularly in older women.
Abstract P321: Pregnancy Loss is Associated With Subclinical Cardiovascular Disease in Mexican Women
Authors: Hartasanchez Sandra A , Flores Mario , Monge Adriana , Yunes Elsa , Cantu-Brito Carlos , Espinosa Luis , Lopez-Ridaura Ruy , Lajous Martin
Published: July 2021

Introduction:
Cardiovascular disease (CVD) in women often develops in the absence of conventional risk factors. Prenatal loss, a common pregnancy outcome, may result in physiologic changes that could affect future risk of myocardial infarction. Little is known about the impact of pregnancy loss on early markers of CVD risk.

Hypothesis:
Pregnancy loss affects carotid artery intima-media thickness (CIMT).

Methods:
We conducted a cross-sectional analysis among 1,769 disease-free women from the Mexican Teachers’ Cohort who had been pregnant to evaluate the relation between pregnancy loss and CIMT. In 2008 participants answered a baseline questionnaire on reproductive history, risk factors for chronic disease and medical conditions that was updated in 2011. We defined pregnancy loss as abortion and/or stillbirth. Between 2012 and 2016, CIMT was measured by trained neurologists using ultrasound in three clinical sites. We log-transformed CIMT and defined carotid atherosclerosis as CIMT ≥0.8mm or plaque. We used multivariable linear and logistic regression models to assess the relation between pregnancy loss, CIMT and carotid atherosclerosis.

Results:
Mean age of participants was 49.8 (SD ± 5.1) years. The prevalence of pregnancy loss was 22% (394 of 1769) , while we observed carotid atherosclerosis in 23% (405 of 1769) of participants. Comparing participants who reported a pregnancy loss to those who did not, the multivariable-adjusted odds ratio for carotid atherosclerosis was 1.52 (95% CI 1.12, 2.06). Women who experienced a stillbirth had 2.32 higher odds (95% CI 1.03, 5.21) of carotid atherosclerosis than those who did not. Mean CIMT appeared to be higher in women who reported a pregnancy loss relative to those who did not, however, in multivariable analyses, pregnancy loss and stillbirth were not significantly associated with CIMT.

Conclusions:
Abortion and stillbirth may be associated with a higher risk of CVD. Additional investigation on potential underlying mechanisms for this association is required.