bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP42: Do Adult Ambulatory BP Cut-points Predict Target Organ Damage Better Than Pediatric ABP Percentiles?
Authors: Urbina Elaine M , Ferguson Michael A , Lande Marc B , Meyers Kevin , Rosner Bernard , Samuels Joshua A , Flynn Joseph T ,   and the SHIP AHOY Investigators
Published: March 2020

Ambulatory hypertension (HT) is more strongly related to cardiac target organ damage (TOD) than clinic BP. Therefore, correct classification of ambulatory blood pressure (ABP) phenotype is needed to determine which patients to refer for imaging. Pediatric ABPM interpretation is based on percentiles of ABP while adult ABPM interpretation is based on static cut-points. We sought to determine which ABP classification system was the best predictor of TOD in adolescents. We measured adiposity, LV mass index (LVMI), systolic and diastolic function (strain, E/e’ ratio) in 315 adolescents (15.9 + 1.4 years, 64% white, 59% male). BP phenotype was determined by mean of 6 casual aneroid SBPs, and 24-hour SBP on ABP (Spacelabs Inc., Snoqualmie, WA) 1) by age, sex and height specific pediatric cut-points and 2) by adult ABPM cut-points (day <130, night < 110, 24-hour < 125 mmHg). We evaluated concordance in classification and prevalence of TOD with Chi square and kappa statistic for agreement. For daytime SBP, 5% of all subjects (16 of 315) reclassified from normotensive (NT) to masked hypertension (MH) and 8% (24 of 315) reclassified from white coat (WC) to HT. Results were similar for night and 24-hour ABP. Fewer NT and WC subjects had any form of TOD by adult vs pediatric cut-point (NT 32 vs 36%, WC 8 vs 13%; chi square < 0.0001, kappa 0.73). The only significant differences in cardiac TOD by ABP phenotype were found using adult ABP cut-points (LVMI higher and strain lower HT vs NT, diastolic E/e’ higher HT and MH vs NT all p <=0.05). We conclude that classification of ABP by adult cut-points is superior in identifying adolescents at risk for cardiac TOD. These findings may inform future pediatric ABP guidelines.
Abstract MP43: Urine And Plasma Metabolome of Healthy Adults Consuming the Dietary Approaches to Stop Hypertension Diet: A Pilot Study
Authors: Pourafshar Shirin , Nicchitta Mira , Tyson Crystal C , Svetkey Laura P , Corcoran David , Bain James , Muehlbauer Michael , Ilkayeva Olga , O’Connell Thomas M , Lin Pao-Hwa , Scialla Julia
Published: March 2020

The mechanisms of the Dietary Approaches to Stop Hypertension (DASH) diet on various health markers remain unclear. The objective of this study was to identify plasma and urine metabolites altered by DASH that may elucidate mechanisms of benefit and suggest biomarkers to facilitate research and monitoring. We tested metabolomics differences in a controlled feeding study of 20 people consuming a Control diet for one wk followed by 2 wks of random assignment to Control or DASH. Fasting plasma and 24-hour urine samples collected at the end of each wk were profiled for metabolites using non-targeted GC/MS and amino acids and acylcarnitines were measured in plasma using a targeted panel. Linear models compared metabolite levels between DASH and Control during the final two randomized feeding wks [nominal p<0.05 and false discovery rate (FDR) adjusted p<0.2]. Compared to Control, DASH is designed to be lower in total fat and saturated fat, but higher in protein, fiber, potassium, magnesium and calcium. Overall, we found 161 identifiable urine metabolites. In FDR adjusted tests, urine excretion of a variety of polyphenolic acids were higher on DASH. In plasma, gamma tocopherol, acylcarnitine C5 from branched chain amino acid (BCAAs) metabolism, and amino acids including BCAAs leucine/isoleucine and valine were lower on DASH (Table 1). Several small and medium chain dicarboxylic acylcarnitines were higher on DASH. Consumption of DASH increases urine levels of a set of polyphenolic compounds many of which have been linked to lower blood pressure in animal and small human studies. In plasma, BCAAs are lower on DASH despite higher protein intake. Further research is needed to investigate these metabolites as a panel for dietary monitoring in hypertension.
Table 1.
Nontargeted and targeted metabolites (Selected metabolites are shown here) in DASH and Control.
Abstract MP55: Protein Intake is Associated With Lower Risk of Type 2 Diabetes in the Framingham Offspring Study
Authors: Pickering Richard T , Yuan Mengjie , Singer Martha R , Lara Castor Laura , Moore Lynn L
Published: March 2020

Introduction:
Diet and exercise are key prevention strategies for type 2 diabetes (T2DM). Few longitudinal studies have examined separate effects of animal and plant proteins on T2DM risk and results are conflicting. The goal of this study was to evaluate the association between usual intake of dietary protein (total, animal, and plant) and T2DM risk.

Methods:
Data from middle-aged men and women in the longitudinal Framingham Offspring Study (FOS) with approximately 20 years of follow-up were used. Diet was assessed using three-day diet records (exams 3 and 5); protein intake was adjusted for body weight using the residuals from a linear regression model. Glucose was measured after an overnight fast; impaired fasting glucose (IFG) was defined as a FG >100; diabetes was diagnosed using a standardized and validated FOS protocol. To estimate the hazards ratios) (HR) for IFG or T2DM, Cox proportional hazards models were used to adjust for confounding by age, sex, education level, physical activity, cigarette smoking, height, energy intake, and weight-adjusted carbohydrate intake.

Results:
Subjects with the highest total protein intakes (≥100 g, men, ≥90 g women) had 34% reduced risks of IFG/T2DM (HR: 0.66; 95% CI: 0.51, 0.85). In this cohort, intakes of animal protein were more than double those of plant protein. The highest intakes of animal protein (≥65 g, men; ≥55 g, women) vs. lower intakes (<55 g, men; <40 g, women) were linked with 33% reduced risks of IFG/T2DM (95% CI: 0.55, 0.82) while intermediate levels of intake were linked with 29% lower risks. In contrast, moderate and higher intakes of plant protein (20-25 g and ≥25 g vs. <20 g) led to non-statistically significant 6-12% risk reductions. Beneficial effects of total protein were stronger for women (HR: 0.53; 95% CI: 0.36, 0.80) than for men (HR: 0.80; 95% CI 0.57, 1.13). In secondary analyses, we evaluated effect modification by other dietary and lifestyle factors. In particular, both men and women with higher intakes of protein and higher levels of physical activity had statistically significant reductions in long-term risk of IFG/T2DM (31%, 39%, and 22% risk reductions among active adults with higher intakes of total, animal, and plant protein, respectively) compared with more sedentary adults who had lower intakes of protein. In contrast, higher physical activity levels alone (among those with lower protein intakes) were associated with non-statistically significant 13-14% lower risks of IFG/T2DM.

Conclusions:
This prospective study of middle-aged men and women provides important evidence to suggest that dietary protein when combined with an active lifestyle, may be a strategy for lowering long-term risk of diabetes. In this study, animal protein had stronger beneficial effects, but future studies are needed in population groups with higher intakes of plant protein to determine whether these effects would be comparable.
Abstract MP56: Progression of Hyperglycemia in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Rooney Mary R , Rawlings Andreea , Pankow James S , Echouffo Tcheugui Justin , Coresh Josef , Sharrett A Richey , Selvin Elizabeth
Published: March 2020

Introduction:
Despite the high prevalence of prediabetes and diabetes in old age, the progression of hyperglycemia in older adults is not well-characterized.

Objective:
To characterize prevalence and predictors of hyperglycemia progression during 5 years of follow-up among 2894 older adults without diabetes (mean age 76, 60% female, 18% black).

Methods:
Using data from the ARIC Study, we report according to hyperglycemia (normal or prediabetes) status at baseline (visit 5, 2011-13) the incidence of visit 6 (2016-17) outcomes (normoglycemia, prediabetes, diabetes, or mortality). Multinomial logistic regression was used to identify predictors of these outcomes stratified by baseline hyperglycemia status. In a sensitivity analysis, we applied inverse probability of attrition weights (IPAW) to account for informative missingness.

Results:
Most participants (64%) with normal HbA1c at baseline had normal HbA1c at the follow-up visit, 19% progressed to prediabetes, 16% died, and 1% developed diabetes (HbA1c ≥6.5% or diabetes medication use or self-report diagnosis). Among participants with prediabetes at baseline, most remained prediabetic 5 years later (61%), 18% died, 14% reverted to normoglycemia, and 7% developed diabetes. Black participants, men, and those with hypercholesterolemia had a higher risk of hyperglycemia progression (
Table
). Physical activity was inversely associated with risk of progression. Body mass index (BMI) in older age was not associated with hyperglycemia progression and BMI was inversely associated with mortality. Results were similar when we used IPAW.

Conclusions:
In this community-based population of older adults, progression from prediabetes to diabetes was relatively uncommon over the 5 year period. Risk factors for hyperglycemia progression and mortality, such as BMI, may differ when measured in older adulthood. We also identified subgroups with higher risk of hyperglycemia progression in older age and who may benefit from targeted diabetes prevention efforts.
Abstract MP59: Serum Sphingolipids and Incident Diabetes in US Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Chai Jin Choul , Chen Guochong , Yu Bing , Grove Megan , Fretts Amanda M , DAVIGLUS Martha L , Garcia-Bedoya Olga L , Thyagarajan Bharat , Schneiderman Neil , Cai Jianwen , Kaplan Robert , Boerwinkle Eric , Qi Qibin
Published: March 2020

Introduction:
Genetic or pharmacological inhibition of sphingolipid synthases prevented diabetes in animal studies. Scanty of cohort studies that examined circulating sphingolipids and incident diabetes yielded disparate findings.

Hypothesis:
Specific sphingolipids are associated with elevated risk of diabetes beyond traditional risk factors.

Methods:
Untargeted metabolomics profiling was performed using fasting serum samples collected from 2010 adult participants of the Hispanic Community Health Study/Study of Latinos, who were free of diabetes and other major chronic diseases at baseline (2008 to 2011). A total of 43 sphingolipids were quantified and 6 sphingolipid scores were derived considering subclasses and chemical structures. Survey Poisson regressions were applied to estimate relative risk (RR) and 95% confidence interval (CI) of incident diabetes associated with individual sphingolipids and the scores.

Results:
Over ~6 years of follow-up, 224 incident diabetes cases were identified using the ADA criteria. After adjustment for socioeconomic and lifestyle factors, 8 sphingolipids were associated with higher risk of diabetes significantly at the FDR-adjusted level (
Figure
). After further adjusting for general and central adiposity, blood pressure, CRP, HDL cholesterol, and triglycerides, only associations for three saturated sphingomyelins (SMs),36:0 (RR =1.41 [95% CI 1.17-1.69]), 38:0 (RR =1.32 [1.11-1.56]), and d18:0/22:0 (RR =1.45 [1.24-1.71]) remained. Of the 6 scores, only a score comprising 5 saturated SMs was associated with higher risk of diabetes (RR =1.31 [1.12-1.53]) after the full adjustment. An addition of the saturated SM score to the full model including traditional risk factor lead to a modest improvement in diabetes risk classification (net reclassification improvement = 22.0%; 95% CI: 7.8%-36.1%).

Conclusions:
Our findings suggest that a cluster of saturated SMs may be associated with higher risk of diabetes beyond traditional risk factors in US Hispanics/Latinos.
Abstract MP64: Associations of Pre-pregnancy BMI and Maternal Glycemia in Pregnancy With Maternal and Child Microbiome Five Years After Birth: Results From the Genetics of Glucose Regulation in Gestation and Growth (Gen3G) Prospective Cohort
Authors: Jia Fan , Differding Moira K , Doyon Myriam , Perron Patrice , Bouchard Luigi , Guérin Renée , Massé Eric , Hivert Marie-France , Mueller Noel T
Published: March 2020

Introduction:
Maternal pre-pregnancy obesity and gestational diabetes increase future risk of obesity in the mother and child. Obesity and diabetes have been associated with lower gut microbiome diversity. To our knowledge, no studies have examined if maternal pre-pregnancy body mass index (ppBMI) and maternal glycemia during pregnancy are prospectively associated with gut microbiome diversity in mothers and their children in mid-childhood.

Hypothesis:
We hypothesized that higher maternal ppBMI and maternal glycemia are associated with lower gut microbiome diversity in mothers and their children 5 years after birth.

Methods:
Gen3G is pre-birth cohort of mother-child dyads, >18 yrs who visited a pregnancy clinic in Sherbrooke, Canada. Oral glucose tolerance tests (OGTT) were administered in second trimester of pregnancy. A total of 178 mother-child pairs (not on antibiotics in the month prior to visit) provided stool, anthropometric measurements and lifestyle information 5 years after birth. Maternal overweight and obesity were defined as 25-30 kg/m
2
and >=30 kg/m
2
respectively. From the stool, we extracted microbial DNA and sequenced the V4 region of the 16S ribosomal subunit. We used linear regression to model the association of ppBMI and glucose values during OGTT with maternal and child gut microbiome Shannon diversity, adjusted for confounders (
see footnote of Figure
).

Results:
Maternal ppBMI showed U-shaped associations with gut microbiome diversity of both mothers and children 5 years after birth (
Figure, left panels
). Higher 1h-glucose post-OGTT was associated in a dose-response fashion with lower gut microbiome diversity in mothers (p for trend <0.001) and children (p for trend <0.001) 5 years after birth (
Figure, right panels
).

Conclusion:
Higher glycemia in pregnancy, and to a lesser extent ppBMI, was prospectively associated with lower gut microbiome diversity in mother-child pairs 5 years after birth, even after adjustment for confounders and mother and child BMI measured 5 years after birth.
Abstract MP71: Socioeconomic Status, Guideline Directed Medical Therapy, and Prognosis in Heart Failure With Reduced Ejection Fraction: The Atherosclerosis Risk in Community (ARIC) Study
Authors: Mathews Lena , Ding Ning , Collison Amira , Mok Yejin , Shin Jung-Im , Crews Deidra , Rosamond Wayne D , Kucharska-Newton Anna , Chang Patricia , Ndumele Chiadi E , Coresh Josef , Matsushita Kunihiro
Published: March 2020

Introduction:
Current research suggests racial differences exist in the utilization of guideline directed medical therapy (GDMT) and prognosis in heart failure with reduced ejection fraction (HFrEF). Whether individual and community level socioeconomic status (SES) impacts prescription patterns of GDMT and prognosis in HFrEF has not been studied.

Methods:
We studied 669 ARIC participants with incident HFrEF (EF<50%) (mean age 77.6 (SD 6.5) years; 39% black; 46% women) during 2005-2017 (median 1.8 years of follow-up). We assessed the proportion of patients on optimal GDMT (defined as ß-blockers [BB] and ACE inhibitors [ACEI] or angiotensin receptor blockers [ARB]) or adequate GDMT (one of either BB, ACEI/ARB, aldosterone antagonists [AA], or hydralazine and nitrates [H-ISDN]) at hospital discharge by individual SES (education and income), neighborhood SES (area deprivation index: ADI) and their combination (Table). We also examined the contribution of GDMT prescription to prognosis overall, and by SES. Subsequently, we quantified the association of SES with mortality and re-hospitalization for HFrEF.

Results:
The proportion of patients prescribed optimal and adequate GDMT was 54% and 81%, respectively. BB were most frequently prescribed (83%), followed by ACEI/ARB (61%), AA (11%), and H-ISDN (9%). Overall, BB were associated with lower mortality, while H-ISDN were associated with higher mortality, compared to their non-use counterparts. ACEI/ARB were associated with lower re-hospitalization, compared to non-users of ACEI/ARB. The prescription of GDMT and the effect of GDMT on prognosis did not significantly differ by SES. Despite that, lower SES was independently associated with higher risk of mortality and re-hospitalization (Table).

Conclusions:
Overall, optimal GDMT was low at discharge, but did not differ by SES. Despite that, there were significant differences in death and re-hospitalization by SES, suggesting a potential need for tailored approaches to HFrEF management for low SES individuals.
Abstract MP72: Using Non-HDL-C/Triglyceride Ratio To Screen For Direct LDL-C Testing: Improving LDL-C Estimates At A Cost
Authors: Vasquez Nestor , Quispe Renato , Jones Steven R , Martin Seth S , Joshi Parag H , Muthukumar Alagarraju
Published: March 2020

Introduction:
Despite more accurate low-density lipoprotein cholesterol (LDL-C) estimates by the Martin (mLDL-C) method, most laboratories still use the Friedewald (fLDL-C) equation. Low non-high density lipoprotein (non-HDL-C) and high triglycerides (TG) drive inaccuracy in LDL-C estimation. We compared a strategy of identifying errors in fLDL-C using non-HDL-C/TG ratios with subsequent reflex direct LDL-C testing to a strategy of using mLDL-C.

Methods:
We included 4,939,542 individuals (2/3 derivation, 1/3 validation dataset) with TG <400 mg/dL with lipid profiles directly measured via Vertical Auto Profile from the Very Large Database of Lipids. We compared directly measured LDL-C with estimated fLDL-C and mLDL-C. The direct LDL-C assay has an allowable error of 12% which was used as the threshold for accuracy assessment. LDL-C estimates above and below non-HDL-C/TG cutpoints (range 0-2.0) were evaluated for accuracy from the derivation dataset and the 4 best performing ratios were tested in the validation set. Individuals with non-HDL-C/TG ratios below the cutpoints were assumed to require direct LDL-C measurement. Medicare costs ($17 lipid panel; $12 direct LDL-C) were used to estimate added costs of direct LDL-C measurement.

Results:
Nearly 8% of fLDL-C results deviated >12% from direct LDL-C compared with only 2.5% of mLDL-C results in the entire population. Non-HDL-C/TG ratios of 0.6-0.9 performed best in the derivation dataset. In the validation dataset, a non-HDL-C/TG ratio of 0.7 had the highest area under the curve for identifying >12% error in fLDL-C estimates (Table). At this ratio, 14.5% of fLDL-C samples would need direct LDL-C measurement at an increase in costs of lipid testing by 10%.

Conclusions:
Use of non-HDL-C/TG ratio <0.7 as screening for direct LDL-C measurement can improve the accuracy of LDL-C estimates in labs using the Friedewald equation. However, such an approach is significantly costlier than using mLDL-C.
Abstract P102: Potential U.S. Population Impact Of Low Cardiovascular Health In Terms Of Preventable Loss Of Life-span And Health-span
Authors: Khan Sadiya S , Ning Hongyan , Allen Norrina B , Bundy Joshua D , Wilkins John T , Lloyd-Jones Donald M
Published: March 2020

Introduction:
Individuals who maintain optimal cardiovascular health (CVH) live a longer, healthier life without cardiovascular disease (CVD). In order to quantify the population burden of sub-optimal CVH, we estimated potential loss of health- and life-span in a nationally representative sample of middle-aged US black and white adults.

Methods:
We first calculated individual-level composite CVH scores (range 0-14 points), including all 7 AHA-defined CVH metrics (smoking, diet, physical activity, body mass index, blood pressure, glucose, and cholesterol) using data from middle-aged participants (40-49 years) from 3 population-based cohorts. We categorized participants into low (0-6), moderate (7-9), and high (10-14) CVH and used Irwin’s restricted means to estimate years lived free of and with CVD. Next, we determined the contemporary prevalence of low, moderate, and high CVH in middle-aged black and white adults (40-59 years) pooled from 3 NHANES survey cycles (2011-2016). Finally, we generated estimates of CVD-free and overall years of life lost in moderate and low CVH compared to high CVH subgroups, weighted to the US population accounting for the NHANES complex survey design.

Results:
Of 12,906 participants in the pooled cohort, 23% were black and 56% women. Low and moderate CVH were associated with 4.41±0.02 and 1.86±0.01 fewer healthy years lived without CVD and 2.43±0.02 and 1.09±0.01 fewer overall years of life, respectively. This resulted in a greater proportion of life lived with CVD across all race-sex groups
(FIGURE).
When weighted to the US population, we estimate that approximately 230.8 (203.5, 258.0) and 97.1 (95% CI 85.6, 108.6) million healthy life years will be lost due to low and moderate CVH, respectively, in middle-aged adults.

Conclusions:
The projected loss of healthy CVD-free years and total life years due to low and moderate CVH is substantial. Maintenance of optimal CVH into mid-life may represent a significant opportunity to extend healthspan and mitigate disparities in the US population.
Abstract P114: Association of Atrial Fibrillation With Incidence of Extracranial Systemic Embolic Events (SEE) in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Shi Mengyuan , Chen Lin Yee Y , Bekwelem Wobo , Norby Faye L , Soliman Elsayed Z , Alam Aniqa , Alonso Alvaro
Published: March 2020

Objectives:
Embolic stroke is a major complication of atrial fibrillation (AF). Mechanisms that lead to elevated stroke risk in AF are also likely to increase risk of extracranial systemic embolic events (SEE). However, little is known about the magnitude of the association of AF with SEE, needed to fully characterize the impact of AF on cardiovascular outcomes. We evaluated the association of AF with SEE and the prediction of SEE among persons with AF in a community-based cohort.

Methods:
We included 14,941 participants of the ARIC study (mean age, 54 ± 6, 55% women, 74% white) without AF at baseline (1987-89) and followed through 2017. AF was identified from study electrocardiograms, hospital discharges, and death certificates. SEE was defined as the presence of hospitalization discharge codes ICD-9-CM 444.xx or ICD-10-CM I74.x (Arterial embolism and thrombosis) in any position. CHA2DS2-VASc score, a predictor of stroke risk in AF, was calculated at the time of AF diagnosis. Cox models adjusting for fixed and time-varying covariates were used to estimate associations of incident AF with SEE risk and between CHA2DS2-VASc score and SEE risk in those with incident AF.

Results:
Among eligible participants, 3,114 developed AF and 270 had a SEE event. Incident AF was associated with increased risk of SEE [hazard ratio (HR) = 3.6, 95% confidence interval (CI) 2.6 - 5.0], after adjusting for baseline and time-dependent covariates (Table). The association of incident AF with SEE was stronger in women (HR 5.3, 95% CI 3.3 - 8.4) than in men (HR 2.7, 95% CI 1.7 - 4.3) (p for interaction = 0.002). In participants with incident AF, we identified 59 SEE events. Higher CHA
2
DS
2
-VASc score was associated with increased SEE risk (HR per 1-point increase = 1.2, 95% CI 1.1 - 1.5).

Conclusions:
AF is associated with more than a tripling of the risk of SEE, with a stronger association in women than in men. CHA
2
DS
2
-VASc is associated with SEE risk in AF patients, highlighting the value of the score to predict outcomes and guide treatments in persons with AF.
Abstract P120: Women With Menopause After Age 45 and Take Hormone Therapy After Age 60 Increase the Risk of Cardiovascular Disease
Authors: Zhu Dongshan , Chung Hsin-Fang , Dobson Annette , Pandeya Nirmala , Mishra Gita
Published: March 2020

Introduction:
Evidence from clinical trials and observational studies on the relationship between menopausal hormone therapy (MHT) and cardiovascular disease (CVD) risk has been discordant.

Hypothesis:
We hypothesized that the association between MHT and risk of CVD might be affected by both age at menopause and age when initiated MHT.

Methods:
We harmonised and pooled individual-level data from 15 studies across five countries/regions (Australia, Scandinavia, USA, Japan, and UK). Postmenopausal women who had reported their MHT status (user or non-user) and CVD status (occurred or not, including coronary heart disease (CHD) and stroke) were included. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for the association between MHT use and incident CVD. We stratified the analyses by age when initiated MHT and age at natural menopause to examine the interaction between MHT, age initiated MHT, and age at menopause on incident CVD.

Results:
Overall, 190 625 postmenopausal women were included. We identified 10 601 incident CVD events, including 7615 CHD and 3543 strokes. Around 39% (74 585) women were MHT users. Compared to non-users of MHT, women who were MHT users had 10% higher risk of incident CVD (HR 1.10, 95% CI 1.06-1.14), with HR (95% CI) of (1.15, 1.10-1.20) for CHD and (1.02, 0.96-1.09) for stroke. After stratifying by age at natural menopause, women who experienced menopause after age 45 years and took MHT had around 15% higher risk of CHD, while the significant association with incident stroke was only observed in women who had menopause after 55 years (1.16, 1.01-1.33). After a further stratification by age initiated MHT, we found the significant associations between MHT users and incident CVD were only observed in women who experienced menopause after age 45 years and took MHT at age 60 years or old (Table 1).

Conclusions:
Postmenopausal women who experienced natural menopause after age 45 years and took MHT after age 60 years had increased risk of incident CVD.
Abstract P124: The Impact of Combined Prediabetes and Prehypertension on Cardiovascular Morbidity
Authors: Sjöli Annie , Daka Bledar , Lindblad Ulf , Hellgren Margareta
Published: March 2020

Introduction:
Cardiovascular disease (CVD) is often preceded by prediabetes (pre-DM) and/or prehypertension (pre-HT), but few studies have investigated the effect of concurrent pre-DM and pre-HT on cardiovascular risk.

Hypothesis:
We assessed the hypothesis that concurrent pre-DM and pre-HT increases the risk of CVD. Furthermore, we examined if the estimated cardiovascular risk differs with sex and with the definition of pre-DM.

Methods:
In 2002-2005, 2816 randomly selected individuals from two Swedish municipalities were enrolled in a health survey. The participants’ cardiometabolic profiles, including blood pressure (BP) and glucose tolerance, were examined. Individuals with diabetes mellitus and/or hypertension were excluded, leaving 2330 persons for analyses. Out of these, 150 had co-existing pre-DM (IFG and/or IGT) and pre-HT (WHO 2013 criteria), while 1250 had simultaneous normal glucose tolerance (NGT) and optimal BP (< 120/80 mmHg). Outcomes were assessed in 2011 using national Swedish registers. Hazard ratios (HR) for CVD were calculated for pre-DM, pre-HT and pre-HT combined with pre-DM, all versus NGT/optimal BP. Analyses were adjusted for age, BMI, sex, smoking and earlier CVD.

Results:
A total of 80 CVD events occurred during 8.1±0.9 years of follow-up. The unadjusted HR for CVD for combined pre-DM/pre-HT was 22.5. The association was attenuated after adjustments but persisted in the full model, see Figure 1. A test for interaction between combined pre-DM/pre-HT and sex on the outcome of CVD was non-significant (p = 0.6). IFG/pre-HT predicted CVD in all adjustment models (HR 3.2, p = 0.005) while IGT/pre-HT did not.

Conclusions:
Combined pre-DM and pre-HT substantially increases the risk of CVD. Those with pre-DM defined by IFG might be at particularly high risk, while the risk is likely the same in both sexes. Intensified treatment strategies should be considered in those with concomitant pre-DM and pre-HT.
Abstract P125: Interaction Effects of Diabetes and Subclinical Hypothyroidism on Heart Rate Variability. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Hoshi Rosangela , Santos Itamar S , Dantas Eduardo , Andreao Rodrigo , Duncan Bruce , Schmidt Maria , Mill Jose-Geraldo , LOTUFO Paulo A , Bensenor Isabela M
Published: March 2020

Background:
Diabetes and subclinical hypothyroidism are frequently coexisting conditions. The separated effects of each one on the cardiovascular system and cardio autonomic function are known. However, it has not been investigated yet whether the presence of both diseases has a joint influence on the cardiac autonomic system. As the autonomic nervous system is involved in cardiovascular, endocrine, and metabolic control, the association of diabetes and subclinical hypothyroidism might have combined effects, leading to cardio autonomic impairment and rising cardiovascular risk.

Aim:
To analyze the interaction effects of diabetes and subclinical hypothyroidism on Heart Rate Variability parameters among adults. using the participants enrolled at the baseline data of t

Methods:
The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a cohort of 15015 men and women aged 35 to 74 years-old recruited in 2008-10. Participants were categorized into four groups: non-diabetes with normal thyroid function (controls), non-diabetes with subclinical hypothyroidism; diabetes with normal thyroid function; and diabetes with subclinical hypothyroidism. Heart Rate Variability analyses were performed in time and frequency domains: Standard Deviation of NN interval (SDNN); Root of the Mean of the Sum of the Squares of Differences between adjacent NN intervals (RMSSD, Low-Frequency (LF) and High-Frequency (HF) on 5-minute time series collected in the supine position. For each Heart Rate Variability parameter, we divided the sample into quartile groups, using the fourth quartile as reference. We analyzed the associations with the highest quartile group for each Heart Rate Variability parameter using additive and multiplicative terms in logistic models.

Results:
Point Odds Ratio, and 95% Confidence Intervals (95%CI) estimates for the first quartiles of all Heart Rate Variability measures were higher for subjects with the combination of both, “diabetes plus subclinical hypothyroidism” than for people with only the diagnosis of diabetes: SDNN: 2.61 (95%CI = 1.13 to 6.05) vs. 1.52 (95%CI =1.25 to 1.85); RMSSD: 2.70 (95%CI =1.18 to 6.18) vs. 1.48 (95%CI =1.21 to 1.80); LF: 2.82 (95%CI =1.05 to 7.56) vs. 1.73 (95%CI =1.40 to 2.13); HF: 3.07 (95%CI =1.21 to 7.75) vs. 1.41 (95%CI =1.16 to 1.71). Nonetheless, no significant multiplicative interaction terms between diabetes and subclinical hypothyroidism were found for the association with HRV variables.

Conclusion:
There is a potential joint impact on Heart Rate Variability showed by additive effects between diabetes and subclinical hypothyroidism.
Abstract P134: PR Interval Length is Associated With Presence of the White Matter Lesions: Insights From the Epidemiological LIFE-Adult Study
Authors: Kornej Jelena , Friedrich Katrin , Schroeter Matthias L , Witte Veronika , Villringer Arno , Löffler Markus , Zeynalova Samira
Published: March 2020

Background:
PR interval prolongation is associated with increased risk for atrial fibrillation (AF). AF is a known risk factor for cerebrovascular complications including microbleeds and stroke. This might explain the occurrence of white matter lesions (WML) and consequent cognitive dysfunction. The aim of the current study was to analyze the relationship between PR interval and WML in an epidemiological study.

Methods:
The LIFE-Adult-Study is a population-based cohort study of randomly selected participants from Leipzig, Germany. In this cross-sectional analysis, individuals without AF, with available brain MRI and ECG were included. The Fazekas scale was used to quantify the amount of WML and was graded into four Fazekas stages: 0=none; 1=punctate foci; 2= beginning confluence; 3=large confluent areas. Stages 2-3 were considered as advanced WML.

Results:
The study population comprised 2421 individuals (age 59±15 years, 1287 (53.2%) males). The median PR interval was 160 ms (IQR 143; 179). There were 319 (13.2%) individuals with advanced WML (stages 2 and 3). These probands were significantly older, had more often cardiovascular comorbidities, diabetes and stroke than patients without WML (all p<0.005). On univariable analysis, PR interval (OR 1.012, 95%CI 1.008-1.016, p≤0.001) and PR interval ≥160 ms (OR 2.1, 95%CI 1.6-2.7, p≤0.001) were significantly associated with advanced WML. On multivariable analysis, age, arterial hypertension, stroke and PR interval (OR 1.005, 95%CI 1.000-1.009, p=0.044) demonstrated significant association with advanced WML. Furthermore, in other multivariable model PR interval ≥160ms demonstrated significant association with WML (OR 1.431, 95%CI 1.089-1.881, p=0.010).

Conclusions:
The PR interval is associated with advanced WML.
Abstract P148: Sex Differences in the Genetic Predisposition of Coronary Artery Disease
Authors: Huang Yunfeng , Hui Qin , Gwinn Marta , Hu Yijuan , Quyyumi Arshed A , Vaccarino Viola , Sun Yan
Published: March 2020

While coronary artery disease (CAD) is the leading cause of death for both men and women, sex differences in CAD risk are widely observed. Genetic susceptibility for CAD may be modified by sex and contribute to sex disparities in CAD. However, whether such modification exists is not clear given the limited sample size of previous studies. Using the UK Biobank, we constructed a CAD genetic risk score (CAD-GRS) based on 161 known loci, and assessed the sex-specific effect of the CAD-GRS on CAD incidence in ~307,147 men and women of European ancestry without previous history of CAD. During an average follow-up of 6.1 years 9,847 incident CAD events were identified using hospitalization data and the national death registry. To examine if certain intermediate trait contributes more predominantly on sex differences in CAD risk, we constructed three risk factor-based CAD-sub-GRSs after removing pleiotropic SNPs: 1) 26 loci associated with blood pressure (BP) and CAD (BP-sub-GRS); 2) 17 loci associated with lipids and CAD (lipids-sub-GRS); and 3) 16 loci associated with body mass index (BMI) and CAD (BMI-sub-GRS). Sex-specific effects of CAD-sub-GRSs were examined. Cox models were implemented to assess sex-specific genetic effects of CAD adjusted for age, smoking, alcohol drinking, history of hypertension and diabetes, BMI, cholesterol medication, education and SES, and population stratification. To avoid over-adjustment, history of hypertension, cholesterol medication and BMI were not controlled for in the analyses of BP-sub-GRS, lipids-sub-GRS and BMI-sub-GRS, respectively. Both CAD-GRS and CAD-sub-GRSs were categorized using quintiles into “low” (quintile 1), “intermediate” (quintile 2 - 4), and “high” (quintile 5) groups. We observed a strong sex discrepancy in the effect of the overall CAD-GRS on CAD incidence (HR
high GRS vs. low GRS
= 2.4 (95% CI: 2.2, 2.6) for males vs. HR
high GRS vs. low GRS
= 1.8 (95% CI: 1.6, 2.0) for females, interaction p-value = 0.002). A similar gene-sex interaction was observed for CAD-sub-GRS driven by BP-associated loci (HR
high GRS vs. low GRS
= 1.5 (95% CI: 1.4, 1.7) for males vs. HR
high GRS vs. low GRS
= 1.2 (95% CI: 1.1, 1.3) for females, interaction p-value = 0.0005) but not lipids or BMI-associated loci. The SNP-based analysis revealed significant gene-sex interaction (p=0.0001) at one CAD locus (21q22.11). The lead SNP (rs28451064) is a
cis
-eQTL for several neighboring genes’ expression (
MRPS6
,
SLC5A3
,
KCNE2
and
AP000318.2
) in aorta and tibial artery tissues. Previous genome-wide association studies reported significant associations between rs28451064 and bone mineral density, waist-hip ratio as well as pulse pressure. These results suggest that genetic predisposition of CAD based on known loci is stronger in men than in women. Future investigations of genetic risk and mechanism for CAD need to consider sex-specific effects.
Abstract P158: USING CHA
2
DS
2
- VASC SCORE TO PREDICT CLINICAL OUTCOMES IN PATIENTS WITH INFECTIVE ENDOCARDITIS
Authors: Abe Temidayo , Mather Paul J , Olowu Banjo
Published: March 2020

Background:
The CHA
2
DS
2
- VASC score is a well-validated stroke risk stratification tool in patients with non-valvular atrial fibrillation. Most of the clinical variables used have been associated with poor outcomes in patients with infective endocarditis (IE). We aim to determine its usefulness in predicting outcomes in patients with IE.

Methods:
We included 35,570 patients with IE from the national inpatient sample (2009 - 2012). CHA
2
DS
2
- VASC score was calculated for each patient. Hierarchical two-level logistic and linear models were used to estimate outcomes for CHA
2
DS
2
- VASC scores 1 to 8, using score 0 as the referent score. Outcomes of interest were overall in-hospital mortality, cardiogenic shock, atrioventricular block (AVB) and valve replacement. All clinical characteristics were defined per the ICD-9-CM codes.

Results:
The mean age of the sample was 59.81 +/- 18 years. Of the 35570 patients with IE, overall mortality rate was 11.4% (n= 4038/35570), cardiogenic shock 2.6 % (n=912/35570), AVB 4% (n=1426/35570) and 10.3% (n=3652/35570) required valve replacement. Higher CHA2DS2-VASc score were associated with increased mortality from 8.1 % for a score of 0 to 21.7 % for score of 8. Cardiogenic shock increased from 5.2% for a score of 0 to 24 % for a score of 3. AVB increased from 5.5% for score of 0 to 17.5% for score of 4. While valve replacement surgery increased from 1.3% for score of 0 to 3.8% for score of 5. Figure, 1 revealed the adjusted odds ratios for outcomes per CHA
2
DS
2
- VASC score 1 to 8, using 0 as the referent score, a higher score was significantly associated with increased odds for overall mortality, cardiogenic shock, AVB, and valve replacement.

Conclusion:
In patients with infective endocarditis, CHA2DS2-VASc score can serve as a risk assessment tool to predict outcomes. 
Abstract P164: Urban-rural Disparities Amongst Heart Failure Patients With Reduced Ejection Fraction
Authors: Khadanga Sherrie , Silverman Daniel N , Plante Timothy B , Cubberly Charles , Steiner Johannes
Published: March 2020

Intro:
Differences in health care delivery between urban and rural populations have been described, but the extent to which this impacts treatment and outcomes in patients with heart failure with reduced ejection fraction (HFrEF) within a large, rural HF referral network has not been evaluated to date.

Objective:
To describe differences in guideline directed medical therapy (GDMT) usage and cardiovascular (CV) mortality in urban vs rural dwelling individuals with HFrEF in Vermont.

Methods:
A retrospective analysis was performed on adult HFrEF patients residing in Vermont referred to University of Vermont Medical Center between January 1, 2015-2017. The study included all patients with a documented EF
<
35% on echo. Demographics, risk factors, use of GDMT, and all-cause CV mortality were obtained. Urban and rural designations were based on the ZIP code version of the Rural-Urban Commuting Area (RUCA) classification system. Poisson regression analysis was used to compare the relative risk for mortality and use of GDMT by rurality.

Results:
838 patients were identified (mean age 71.4
+
12.9 years old; 66.5% male) and divided into 3 RUCA groups (urban, rural, isolated). Adjusting for age, sex, hypertension, diabetes mellitus, atrial fibrillation and smoking status, no difference was seen in GDMT (table 1) between urban and rural patients (relative risk [RR], 1.03; 95% CI, 0.64-1.67). Urban patients were less likely than isolated patients to use GDT (RR, 0.75; 95% CI 0.52-1.08). There was a CV mortality benefit for those in rural (RR, 0.50; 95% CI 0.34-0.73) or isolated areas (RR, 0.74; 95% CI 0.62-0.89) compared to those in urban areas.

Conclusion:
While GDMT reduces morbidity and mortality in HFrEF patients, it was underutilized throughout Vermont. Findings from this state-wide cohort of decreased CV mortality in rural and isolated areas are contrary to prior studies. This finding highlights the unique socioeconomic environment of Northern New England and has important implications for CHF management and resource allocation.
Abstract P175: Systolic Blood Pressure Trajectory Across Childhood to Adolescence Predicts Self-reported Htn in Adults:
I3c CV Outcomes Study
Authors: Urbina Elaine M , Khoury Philip R , Hu Tian , Bazzano Lydia A , Burns Trudy , Dwyer Terence , Juonala Markus , PRINEAS Ronald J , Raitakari Olli T , Sinaiko Alan R , STEINBERGER Julia , Venn Alison , WOO Jessica G , Jacobs David R
Published: March 2020

Levels of systolic blood pressure (SBP) in youth tend to predict adult SBP levels, but whether the trajectory of SBP over time predicts adult HTN is not known. In the International Childhood CV Cohort (i3C) Consortium, we constructed SBP trajectories in 9515 participants who had ≥2 SBPs in youth, and who reported HTN status (by questionnaire) at mean age 47 years. We used measured SBP from age 3-19 years to form trajectories using a mixed model with spline for age and random intercept and slope. The intercept and slope form personal trajectories during age 3-19 after removing the overall curve (spline) common to all participants. Trajectory groupings were formed by stratifying the intercept and slope by tertiles, forming 9 nearly equal sized groups, each having a consistent intercept and slope combination, among either a low, mid or high intercept and low (declining), mid (flat) or high (increasing) slope. The average SBP for all measurements in 6 age categories characterized the trajectories (Figure left panel). This characterization is reiterated using ages 3-11 and 12-19 years in the right panel which displays the adult HTN prevalence across the trajectories. Logistic models evaluated whether SBP trajectory group predicted adult HTN after adjustment for age and year at first childhood SBP measurement, age and BMI at adult HTN, smoking, sex, cohort, and race. Overall adult HTN prevalence was 30.9% increasing across SBP trajectories. All SBP trajectories compared to the highest intercept/slope group remained significant predictors of adult HTN even after adjustments (odds ratios 0.24 for lowest intercept/slope trajectory and 0.75 for highest intercept/intermediate slope trajectory both compared to highest intercept/highest slope, all P<0.0001). We conclude that baseline (intercept) and slope of SBP changes from childhood to adolescence can assist providers in identifying potential for modifying the development of hypertension in adulthood.
Abstract P186: Obstructive Sleep Apnea and Risk of Chronic Kidney Disease in the ARIC Sleep Heart Health Study
Authors: Full Kelsie M , Jackson Chandra , Rebholz Casey M , Matsushita Kunihiro , Lutsey Pamela L
Published: March 2020

Background:
Obstructive sleep apnea (OSA) is a prevalent sleep disorder and may be associated with the development of chronic kidney disease (CKD) through hypoxia, inflammation, and oxidative stress. However, the prospective relationship between OSA and incident CKD remains unknown. In this study, we leveraged in-home polysomnography (PSG) data from a large community-based cohort of adults to examine the association between OSA and risk of incident CKD in late-midlife.

Methods:
Participants in the Atherosclerosis Risk in Communities (ARIC) study (N=1,525; mean age=62.5 ± 5.4 years, 52.4% female) completed in-home PSG assessments as part of the Sleep Heart Health Study. OSA severity was defined according to apnea-hypopnea index (AHI) (events/hour): normal <5.0, mild 5.0-14.9, moderate 15.0-29.9, and severe ≥30.0. Incident CKD was defined according to estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m
2
and at least 25% decline in eGFR from baseline, CKD-related hospitalization or death, or end-stage renal disease. Cox proportional hazards regression was used to estimate OSA severity with risk of incident CKD. Models were adjusted for demographics, health behaviors, BMI, and other markers of cardiometabolic conditions.

Results:
Among 1,525 participants, a total of 461 CKD events occurred over an average of 19 years of follow-up. After adjustment for demographics and health behaviors, severe OSA (AHI ≥30.0) was associated with increased risk of CKD (Hazard Ratio (HR): 1.51; 95% Confidence Interval (CI): 1.08, 2.10). This association was attenuated after additional adjustment for BMI (HR; 1.07, CI: 0.75, 1.52).

Conclusions:
Overall, OSA was linked to greater CKD risk. The association was attenuated after adjusting for obesity, a risk factor for both conditions. Due the high prevalence of OSA and CKD in the US adult population, more investigation is needed.

Figure 1. Estimated probability of years free of Chronic Kidney Disease (CKD) by obstructive sleep apnea (OSA) severity in the ARIC Sleep Heart Health Study:
Abstract P198: Connected Health Remote Monitoring in Atrial Fibrillation Care Management
Authors: Scales Robert , Lew Kathryn , Parker Colin , Raad Aasaf , Lester Steven
Published: March 2020

Background:
Avoiding early hospital readmission after a diagnosis of atrial fibrillation (AF) lowers healthcare costs.

Purpose:
This investigation pilot tested the process of using a Connected Health (CH) communication platform in AF care management.

Subjects:
A self-selected group of patients (n=18, 56% male, mean age=69 years,
SD
=12.6) diagnosed with hemodynamically stable AF and an uncontrolled ventricular response with heart rates > 110 bpm were recruited.

MethodS:
Eligibility criteria included a recent AF related emergency department or outpatient clinic visit and the new prescription of a rate control medication. This included AV node modifying medications (either a beta blocker or nondihydropyradine calcium channel blocker) at a starting dose determined by the supervising physician. A care management team (CMT) coordinated by a nurse practitioner provided individualized telephone medical management with no planned clinical visits during a period of early recovery. Patients were equipped with the AliveCor
TM
Kardia electrocardiogram (ECG) home monitoring device and a supporting mobile device application. Patients returned home with medical guidance from the CMT and ECG recording instructions. Heart rate and rhythm were monitored remotely by the NP and the medication dose was adjusted to reach a target resting heart rate <110 bpm. Patients were managed for 3-weeks before being discharged back to primary care or outpatient cardiology for consideration of a rate versus rhythm control strategy if spontaneous restoration of sinus rhythm had not occurred.

ResultS:
Patients recorded an average of 50 (
SD
=40.0) ECG tracings with a mean of 13 (
SD
=3.79) related CMT telephone contacts. The mean resting heart rate was significantly lower (
p
<0.05) at the completion of the intervention (72.9 bpm,
SD
=17.31) compared to baseline (102.3 bpm,
SD
=27.17). All of the AF patients achieved adequate heart rate control or spontaneously returned to sinus rhythm. However, 4 patients (22%) required a related emergency room visit and unplanned hospitalization.

Conclusion:
In this small feasibility study, an electronic healthcare device (biosensor) paired with a mobile-heath application provided a practical remote monitoring communication platform to support tele-management, but the intervention did not prevent hospital readmission.

Future Directions:
Further research is needed to identify factors that will improve the process of applying CH to AF care management.