bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 5993: One-Year Clinical Outcomes of Sirolimus-Eluting vs. Paclitaxel-Eluting Stents in Unselected Patients: Results from the Multicenter EVENT Registry
Authors: Novack Victor , Cutlip Donald , Kleiman Neal , Pencina Michael , Mauri Laura , Cohen David
Published: July 2021

Background:
Several randomized trials have demonstrated that PCI with sirolimus-eluting stents (SES) compared with paclitaxel-eluting stents (PES) is associated with lower rates of angiographic restenosis and target lesion revascularization (TLR). Since many of these trials have included angiographic follow-up, the generalizability of these results to routine clinical practice remains controversial.

Methods and Results:
We used data from the EVENT Registry a multicenter, observational study of unselected patients undergoing PCI in more than 40 US centers to compare in-hospital and 1-year clinical outcomes among patients treated with SES (n=3443) or PES (n=2592). The primary endpoint was the composite of cardiac death or MI at one year. Secondary endpoints included TLR and ARC definite or probable stent thrombosis. Logistic regression or Cox proportional hazards models were used to adjust for baseline clinical and demographic characteristics, lesion characteristics, procedural characteristics, and site characteristics (proportion SES use).

Results:
Baseline characteristics were generally similar between the 2 groups; however patients receiving PES were more likely to have undergone PCI in the setting of an ACS. Intervention in LAD lesions and totally occluded lesions were more common in the SES group. At 1-yr there was no difference in the composite primary end-point between the groups (SES 9.1% vs. PES 10.0%; see Table

). Incidence of death, MI and stent thrombosis did not differ between the groups. TLR rates were higher in the SES group (4.4% vs. 3.3%, p=0.048), but this difference was no longer significant after adjustment for baseline covariates including site characteristics.

Conclusions:
Among unselected patients undergoing non-emergent PCI, SES and PES appear to be comparable in terms of clinical outcomes at 1 year. These findings suggest that previously observed differences in TLR may be largely related to the “oculostenotic reflex”.

Unadjusted and Risk-Adjusted 1-Year Clinical Outcomes
Abstract 6072: Waitlist Mortality for Infants Awaiting Heart Transplantation in the United States in the Current Era: Analysis of Data from the United Network for Organ Sharing
Authors: Mah Doug , Singh Tajinder , Thiagarajan Ravi R , Gauvreau Kimberlee , Piercey Gary E , Fynn-Thompson Francis , Almond Christopher S
Published: July 2021

BACKGROUND UNOS (United Network for Organ Sharing) data suggest that of all pediatric transplant candidates, infants awaiting heart transplantation face the highest waitlist mortality. We sought to determine the mortality rate for waitlisted infants in the current era and to identify the risk factors associated with waitlist mortality.

METHODS In this multi-center cohort study using the US Scientific Registry of Transplant Recipients, we analyzed all infants <12 months of age listed for first heart transplant between January 1999 and July 2006. Clinical and demographic characteristics were recorded at the time of listing. Multivariate logistic regression modeling was used to identify predictors of waitlist mortality.

RESULTS In this six year period, 1133 patients less than 12 months of age were identified with a median age of 1 month (IQR 0 to 5 mo) and median weight of 4.0 kg (IQR 3.2 to 5.6 kg). 516 (45%) were female, 438 (39%) were non-white, 724 (64%) had congenital heart disease (CHD) and 910 (80%) were listed status 1A. Overall, 250 (22%) died while waiting including 179 (72%) listed at age <3 mo, 190 (76%) with CHD, 89 (35%) listed on mechanical ventilation, and 68 (27%) on ECMO. In multivariate analysis, risk factors for waitlist mortality (reported as hazard ratio, 95% CI) included age <3 months (1.5, 1.1–2.0), CHD (2.0, 1.5–2.7), ventilator support (2.0, 1.5–2.7), ECMO support (5.0, 3.6 –7.0) and non-white race (1.7, 1.4 –2.2).

CONCLUSION Mortality of infants waiting for heart transplantation remains high with a 22% waitlist mortality in the current era. ECMO support, ventilator support, CHD, age less than 3 months, and non-white race were independently associated with waitlist mortality whereas listing status was not. Measures to improve donor availability for this age group and refinements in organ allocation to lower waitlist mortality are urgently needed.
Abstract 6087: Fragmented QRS Complex on 12-lead ECG Developed During the First 48 Hours after Acute Myocardial Infarction Predicts Mortality
Authors: Das Mithilesh K , Michael Mark A , Suradi Hussam
Published: July 2021

Fragmented QRS complex (fQRS) signifies myocardial infarction (MI) scar. Myocardial scar acts as a substrate for ventricular arrhythmias and a risk for death. We postulated that the development of new fQRS during the first 48 hours after an acute MI signifies mortality. Serial ECGs of 896 pts with acute coronary syndrome (ACS) and their mortality during follow-up were studied. MI was diagnosed by history, ECG and elevated cardiac enzymes. Serial ECGs were recorded at presentation, 8 hours, 16 hours and 24 – 48 hours. The fQRS on 12-lead ECG was defined by the presence of fragmented QRS, notched R or S wave, or RSR′ pattern without any bundle branch block, in at least 2 contiguous leads in one of the coronary artery territories (LAD: lead V1 to V6, LCx: lead I, aVL and V6, and RCA: lead II, III and aVF). The MI group (n =441, 98.4% males, age 63±11 yrs) and the control (unstable angina) group (n=455, 97.1% males, age 61±11 yrs, P=NS). 104 (24%) patients had STMI and 337 (76%) patients had NSTMI. fQRS developed in a significantly higher number of patients in the MI group as compared to the control group (224 [50.8%] vs. 17 [3.7%], p<0.001), respectively. New Q-waves developed in 122 (27.7%) and 2 (0.4%) patients in MI group and control group, respectively. fQRS was a multivariate predictor of mortality in ACS group as well as in the MI group, whereas Q wave did not predict mortality during a 23+/−17 months of follow-up. Kaplan-Meier survival curve revealed a significantly higher mortality in fQRS vs. non-fQRS group (p=0.001),. The development of fQRS within the first 48 hours of ACS patients predicts mortality during follow-up in patients with MI.
Abstract 6088: Clinical and Angiographic Predictors of 30-Day and One-Year Cardiac Ischemic Events in Patients with Non-ST Elevation Acute Coronary Syndromes: Results from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) Trial
Authors: Lansky Alexandra , Goto Kenji , Cristea Ecatarina , Fahy Martin , Mehran Roxana , Stone Gregg W
Published: July 2021

An early invasive strategy is of clinical benefit in moderate and high-risk acute coronary syndromes (ACS). Clinical predictors of short and long-term ischemic outcomes in pts with ACS have been well studied, whereas the extent, location and characteristics of angiographic coronary disease in predicting outcome is not well defined. The ACUITY trial randomized 13,819 pts with moderate and high risk ACS to unfractionated heparin or enoxaparin + GP IIb/IIIa inhibitors (GPI), versus bivalirudin + GPI, vs. bivalirudin alone. The angiographic substudy of ACUITY included the first 7000 consecutive randomized US patients. All angiograms were reviewed by an independent core laboratory for complete 3 vessel assessment of CAD extent and burden (total mm length of lesions>30%DS), as well as baseline and final lesion and flow characteristics. Clinical and angiographic predictors of ischemic outcomes at 30 days and 1 year (death, MI, or ischemic target vessel revascularization) were identified by univariate and multivariable analysis using logistic regression analysis. Of 6921 pts with interpretable angiograms, 3826 pts (55.3%) were treated with PCI, 755 (10.9%) with CABG, and 2340 (33.8%) with medical therapy. Composite ischemia occurred in 595 (8.6%) pts at 30 days and 1153 (17.4%) pts at one year. Independent predictors of 30 day and 1 year ischemic cardiac events by multivariable analysis are shown in the table

. Among moderate- to high-risk ACS patients, beyond the well recognized clinical risk factors of renal insufficiency and diabetes mellitus, angiographic manifestations of coronary atherosclerosis including greater burden and severity of disease, and presence of calcified lesions, are important independent predictors of 30 day and 1 year adverse outcomes.

Table.

Multivariate Predictors of Composite Ischemia
Abstract 6115:Assessment of Circumferential and Longitudinal Strain using Speckle Tracking Echocardiography. Comparison With Tagged Cardiac Magnetic Resonance
Authors: Goffinet Celine , Montant Patrick , Chenot Fabien , Vancraeynest David , Pasquet Agnes , Gerber Bernhard L , Vanoverschelde Jean-Louis
Published: July 2021

Background.
Speckle tracking echocardiography (STE) is a new method that allows to quantitalively measure myocardial deformation in an angle-independent manner. The aim of this study was to evaluate the accuracy of STE-derived estimates of circumferential and longitudinal strains, in patients with variable degrees of LV dysfunction, using tagged cardiac magnetic resonance (cMR) as the reference standard.

Methods.
A total of 80 patients (66 men, mean age 54 ± 16 years) with a variety of cardiac diseases underwent STE and cMR on the same day. For circumferential strain, data were analyzed on matched short-axis cross-sections (at basal and apical levels) using either the QLab software (for STE) or HARP (for tagged cMR). For longitudinal strain, data were analyzed on similar 4-, 3- and 2-chamber views using either QLab (for STE) or a custom-made program that allows for tracking of cMR tags in long-axis projections (for tagged cMR).

Results.
87% of myocardial segments could be analyzed. Correlation and limits of agreement between STE and cMR were good for both global (r = 0.95, p<0.001 and 1.2 ± 5.1%, respectively) and segmental circumferential strain (r=0.84, p<0.001 and 1.1 ± 9.9%, respectively, figure1

). Correlation and limits of agreement between STE and cMR were similarly good for global (r =0.96, p<0.001 and −0.1 ± 3.0%, respectively) and segmental longitudinal strain (r = 0.77, p<0.001 and 0.2 ± 9.6%, respectively, figure1

).

Conclusions.
STE provides accurate measurements of segmental circumferential and longitudinal strains and thus offers the opportunity to routinely assess these parameters in daily clinical practice.
Abstract 6133: Microvascular Dysfunction and Chronic Inflammation in Patients without Cardiovascular Risk Factors
Authors: Recio-Mayoral Alejandro , Mason Justin C , Kaski Juan C , Rubens Michael B , Harari Olivier A , Camici Paolo G
Published: July 2021

Premature coronary atherosclerosis, which is actually seen as an active inflammatory process, is an established complication of systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We hypothesized that exposure to chronic inflammation, even in the absence of classical cardiovascular risk factors (CVRF), could result in coronary microvascular dysfunction (CMD), an early marker of coronary atherosclerosis. By means of positron emission tomography in combination with oxygen-15 labeled water, myocardial blood flow (MBF) was measured at rest and during iv adenosine infusion (140 μg/kg/min) in 13 SLE and 12 RA patients (mean [±SD] age 44±10 years) without CVRF. All patients underwent coronary angiography using multi-slice (64 slices) computed tomography and only those with none or trivial coronary artery disease (<30% luminal stenosis) were included. A group of 25 age- and gender-matched controls were also studied. There were no differences between patients and controls regarding body-mass index, blood pressure and lipid parameters. RA and SLE patients showed similar mean disease duration (16±11 and 11±7 years, respectively; p=0.12). Resting MBF was similar in patients and controls (1.25±0.27 vs 1.15±0.24 ml/min/g, p=0.15). However, during adenosine stress patients had lower MBF compared with controls (2.94±0.83 vs 4.11±0.84 ml/min/g, p<0.001). As result, coronary flow reserve (CFR; adenosine/resting MBF) was significantly reduced in patients (2.44±0.78) compared with controls (3.81±1.07; p<0.001). Seven patients showed ischemic electrocardiographic changes during adenosine and had a more severe reduction in CFR (1.76±0.81) and more years of disease (21±7 years) compared with those patients without ischemic changes (CFR 2.49±0.54; p=0.006; duration of disease 14±5 years; p=0.03). CFR was inversely correlated with years of disease (r=−0.65, p<0.001), but not with corticosteroid cumulative dose (r=0.20, p=0.39). Chronic inflammation in the absence of traditional CVRF is characterized by severe CMD. This may represent an early marker of disease which precedes and contributes to premature coronary artery disease in patients with RA and SLE.
Abstract 6143: Regression of Aortic Valve Stenosis by ApoA-I Mimetic Peptide Infusions in Rabbits
Authors: Busseuil David , Shi Yanfen , Mecteau Mélanie , Brand Geneviéve , Avram Teodora , Kernaleguen Anne-Elen , Thorin Eric , Latour Jean-Gilles , Rhéaume Eric , Tardif Jean-Claude
Published: July 2021

Purpose
: Aortic valve stenosis is the most common valvular heart disease, and standard curative therapy remains open-heart surgical valve replacement. The aim of our experimental study was to determine if ApoA-I mimetic peptide infusions could induce regression of aortic valve stenosis.

Methods
: Twenty-seven New-Zealand White male rabbits received a cholesterol-enriched diet and vitamin D
2
until significant aortic valve stenosis was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were randomized to receive saline (control group,
n
=14) or an ApoA-I mimetic peptide (treated group,
n
=13), 3 times per week for 2 weeks. Serial echocardiograms and post mortem valve histology were performed.

Results
: Aortic valve area improved significantly in the treated group compared to controls after 7 days (20.9±0.9 mm
2
vs. 18.2±0.6 mm
2
,
P
<0.0001) (corresponding to increases of 15.9% and 1.9%), 10 days (21.5±1.0 mm
2
vs. 19.5±0.6 mm
2
,
P
=0.0032) (increases of 19.2% vs. 9.1%), and 14 days of treatment (22.4±0.9 mm
2
vs. 20.4±0.6 mm
2
,
P
=0.0028) (increases of 24.4% vs. 14.2%). Likewise, aortic valve thickness decreased by 19% after 14 days of treatment in the treated group (0.951±0.070 mm at baseline vs. 0.768±0.074 mm at follow-up) whereas it was unchanged in controls (
P
<0.0001). Histological analysis revealed that lesion extent at the base of valve leaflets and sinuses of Valsalva was smaller in the treated compared to control group (52.8±12.5% vs. 66.7±9.9%,
P
=0.032). The ApoA-I mimetic peptide treatment also leads to a reduction in aortic valve calcifications as revealed by the loss of the positive relationship observed in the control group (
r
=0.87,
P
=0.004) between calcifications area and aortic valve thickness.

Conclusions
: Infusions of an ApoA-I mimetic peptide lead to regression of experimental aortic valve stenosis. These positive results justify the further testing of HDL-based therapies in patients with valvular aortic stenosis. Regression of aortic stenosis, if achieved safely, could transform our clinical approach of this disease.
Abstract 5813: Vascular Function Measured By Digital Thermal Monitoring Strongly Correlates with the Severity of Coronary Artery Disease Diagnosed by 64 Slice Multidetector Computed Tomography
Authors: Ahmadi Naser , Nuguri Vivek , Tirunagaram Sumithra , Saeed Anila , Hajsadeghi Fereshteh , Usman Nudrat , Hecht Harvey , Naghavi Morteza , Budoff Matthew
Published: July 2021

Background:
Digital Thermal Monitoring (DTM) of vascular reactivity is a new test of vascular function that correlates well with the Framingham Risk Score and subclinical coronary artery disease measured by the coronary calcium score. This study evaluates whether DTM correlates with the severity of coronary artery disease (CAD) measured by 64 slice multidetector computed tomography (MDCT).

Methods:
151 patients, mean age 64±9 years, 69% male, were studied. Each underwent DTM during a 5 minute supra systolic arm-cuff occlusion and MDCT. Post-cuff deflation fingertip temperature rebound (TR) was correlated with CAD severity assessed by MDCT.

Results:
After adjusting for age, gender and CAD risk factors using logistic regression analysis, the odds ratio for TR in the lowest tertile vs. upper 2 tertiles was 1.3 (95% CI 0.89 –1.6, p=0.4) for mild CAC (luminal stenosis<30%), 2.7 (95% CI 1.2–3.9, p=0.0001) for moderate CAD (30 –70% luminal stenosis) and 6.94 (95% CI 2.2–10.7, p=0.0001) for severe CAD (luminal stenosis>70%) compared to normal coronaries. Additionally, TR was lower in coronary segments with mixed plaque compared to calcified plaque (0.43±0.17 vs. 0.91±0.19, p=0.001).

Conclusions:

Vascular dysfunction measured by DTM strongly correlates with the severity and characteristics of coronary plaques measured by MDCT, independent of age, gender and cardiac risk factors.

DTM may be a useful tool for the identification of high risk patients, additional studies are warranted.
Abstract 5815: Effects of Atorvastatin on F-18 Fluorodeoxyglucose Accumulation on Positron Emission Tomography in Atherosclerotic Plaques: The EARDROP Study
Authors: Ishii Hideki , Toriyama Takanobu , Aoyama Toru , Takahashi Hiroshi , Tanaka Miho , Nishio Masami , Tamaki Tsuneo , Miyagi Motohiro , Amano Tetsuya , Uetani Tadayuki , Matsubara Tatsuaki , Murohara Toyoaki
Published: July 2021

In atherosclerosis, plaque vulnerability is strongly related to rupture, and vulnerable plaques contain numerous inflammatory cells, particularly macrophages, suggesting that inflammation is closely associated with plaque instability. Recently, it has been suggested that F-18 fluorodeoxyglucose (FDG) on positron emission tomography (PET) is a useful technique for detection of local inflamed atherosclerotic lesions. We therefore examined the effects of atorvastatin on F-18-FDG accumulations in atherosclerotic plaques at common carotid and ascending aorta. A total of 20 patients with dyslipidemia but not treated with medication were enrolled and imaged using F-18-FDG -PET and CT for baseline measurement. They were randomized to receive 20-mg or 5-mg atorvastatin after imaging and F-18-FDG -PET and CT were checked again 6 months later. Changes in the standard uptake value (SUV) of F-18-FDG-accumulation rate (plaque/integral plasma) between baseline and follow-up were evaluated. After atorvastatin treatment, serum C-reactive protein (CRP) levels, low-density lipoprotein (LDL) cholesterol levels and malondialdehyde-modified LDL (MDA-LDL) cholesterol levels were significantly reduced (CRP levels: from 1277±704 mg/dl to 609±314 mg/dl, p < 0.0001, LDL cholesterol levels: from 154±29 mg/dl to 98±29 mg/dl, p < 0.0001, MDA-LDL cholesterol levels: 178.4±70.8 IU/l to 125.4±49.7 IU/l, p < 0.0001, respectively). The maximum SUV significantly decreased at follow-up (common carotid arteries: from 1.36 ±0.13 g/dl to 1.28 ±0.22 g/dl, p = 0.047, ascending aorta: from 1.63 ±0.20 g/dl to 1.53 ±0.16 g/dl, p = 0.032, respectively). Notably, the decrease in the SUV was well correlated with reduction of serum CRP levels (common carotid arteries: r = 0.52, ascending aorta: r = 0.47, respectively), LDL cholesterol levels (common carotid arteries: r = 0.46, ascending aorta: r = 0.43, respectively) and MDA-LDL cholesterol levels (common carotid arteries: r = 0.47, ascending aorta: r = 0.43, respectively). Six-month atorvastatin treatment had anti-inflammatory effects and decreased SUV detected by F-18-FDG -PET, which might represent regression of aortic vulnerability.
Abstract 1266: Do Gender Differences Exist in the Relation of Physical Activity with Changes in Body Mass Index and Waist Circumference over 20 years: the CARDIA Study
Authors: Hankinson Arlene L , Daviglus Martha L , Lewis Cora E , Schreiner Pamela J , Sidney Stephen , Permanente Kaiser , Liu Kiang
Published: July 2021

Public health guidelines recommend physical activity to minimize weight gain. Yet, the data are ambiguous; some studies show weaker associations between activity and adiposity/weight changes in women perhaps due to inability to control for gender differences in energy intake and fat distribution. We hypothesized that after accounting for energy intake and fat distribution, associations between high activity levels and changes in weight, body mass index (BMI) or waist circumference over 20 years would not differ by gender. Black and white adults ages 18 –30 from the CARDIA Study, an NHLBI sponsored multi-center longitudinal study, had anthropometric measures taken and activity habits assessed using an interviewer-based questionnaire at 7 exams over 20 years (n=3555). Generalized estimating equations were used to calculate average annual changes in weight (pounds), BMI (kg/m
2
), and waist circumference (cm) by long-term activity level over 20 years, stratified by sex and baseline overweight status. High activity was associated with smaller gains in weight, BMI and waist circumference in men and women over 20 years (Table

, weight data not shown). Formal interaction tests by sex and baseline overweight status were significant (p<0.05). When comparing high versus low activity, women showed larger differences in weight change than men. Compared with low activity, normal weight women with high activity gained 16.8 fewer pounds over 20 years while normal weight men gained 5.6 fewer pounds. Consistently high activity during young adulthood is associated with smaller gains in weight, BMI and waist circumference. The difference in weight gain between high and low activity is greater in women and persists after adjustment for energy intake. These results suggest that weight gain in young adults, particularly women, may be slowed by incorporating high activity into daily life in a manner that can be maintained over many years.

Table:

Average annual changes in BMI and waist circumference by long-term activity categories, stratified by gender and baseline overweight status
Abstract 3124: The Magnitude of Reclassification Indices for Individual Predictors of Global Cardiovascular Risk
Authors: Cook Nancy R , Ridker Paul M
Published: July 2021

Methods based on risk stratification have recently been proposed to evaluate and compare predictive risk models, but their performance in clinically relevant populations has not been demonstrated, including for well-known cardiovascular risk predictors. We fit models including traditional risk factors as well as high-sensitivity C-reactive protein (hsCRP) and parental history of myocardial infarction in prospective data from 24,558 women in the Women’s Health Study who experienced 766 cardiovascular events over an average 10-year follow-up. Fit of models with and without each risk factor was evaluated using both traditional methods, including the C index and goodness-of-fit test, and newly proposed methods for reclassification, which compare predicted risk strata for two models. Reclassification calibration compares observed to predicted risk for each model within reclassified risk strata; the net reclassification improvement (NRI) estimates the net proportion of cases moving to higher vs. lower risk strata; the clinical NRI estimates the NRI among those at intermediate risk; and the integrated discrimination improvement (IDI) compares the mean difference in predicted probabilities between cases and controls for two models. For each model set, the reclassification calibration statistic showed a significant lack of fit in models excluding each of these predictors, indicating that the predicted risk did not fit that observed in reclassified strata. Values of the NRI were 20% for age, 8–11% for hemoglobin A1c in diabetics, smoking, and systolic blood pressure, and 3–5% for lipids, hsCRP, and parental history. The clinical NRI for those initially at intermediate risk was 46% for age and ranged from 9–29% for other risk factors. The IDI was less than 2% for all predictors, including age. These data demonstrate the magnitude of several newly proposed reclassification measures for well-known cardiovascular risk factors. These measures can demonstrate the potential of new models and markers to change risk strata and alter treatment decisions, and should be considered as another means to compare models and assess the accuracy of absolute risk estimates and risk strata.
Abstract 3136: Lipid-Lowering Medication Modifies The Gene-Diet Association Between 5-Lipoxygenase Promoter Polymorphisms And Carotid Artery Atherosclerosis
Authors: Roth Nitzan C , Vikman Susanna , Allayee Hooman , Mack Wendy J , Hodis Howard N
Published: July 2021

Background:
5-Lipoxygenase (5-LOX) is the rate-limiting enzyme in the biosynthesis of leukotrienes from arachidonic acid (Ara), an n-6 polyunsaturated fatty acid (PUFA). Previous studies suggest that polymorphisms in the number of tandem Sp1 binding sites in the promoter of the 5-LOX gene may have an atherogenic effect due to a heightened inflammatory state when dietary Ara is high and dietary long-chain n-3 PUFAs (eicosapentaenoic acid, EPA, plus docosahexaenoic acid, DHA) are low.

Methods:
We determined 5-LOX genotypes in 1,663 adults participating in one of five randomized controlled atherosclerosis trials using carotid artery intima-media thickness (CIMT) as the outcome. Baseline data on participant characteristics and clinic and laboratory measurements, including fasting lipids and CIMT, were obtained using the same methods in all trials. Diet was measured using 3-day records and intake of each PUFA was categorized as above or below the median. We used linear regression to examine the cross-sectional associations between 5-LOX genotype, dietary PUFAs, and CIMT.

Results:
Alleles were classified as wild-type (W, with 5 repeats), deletion (D, with 2– 4 repeats), or addition (A, with 6–9 repeats). The frequencies of the six genotypes were: 60.6% WW, 27.1% WD, 4.9% WA, 4.9% DD, 2.2% DA, and 0.4% AA. Among participants using lipid-lowering medication, mean CIMT was significantly elevated by 79.1 μm (95% CI = 5.3–152.9) in DD individuals compared to WW individuals after adjustment for sex, race, age, trial, and BMI >25 kg/m
2
. High dietary EPA+DHA blunted the gene-CIMT association (p for interaction = 0.007). In contrast, DD genotype was not associated with CIMT among non-users of lipid-lowering medication.

Conclusion:
The atherogenic effect of the shorter promoter alleles is modulated by dietary intake, especially in individuals using lipid-lowering medication, indicating a complex mechanism involving both inflammation and lipids.
Abstract 3138: The Effect of Interactions among Variants of CD36 on Hypertensive Heart Disease Phenotypes
Authors: de las Fuentes Lisa , Gu C. Charles , Waggoner Alan D , Juang Jyh Ming , Davila-Roman Victor G
Published: July 2021

Alterations in myocardial metabolism are implicated in mediating hypertensive heart disease (HHD). We hypothesize that variants in CD36 modulate HHD phenotypes both individually and collectively via interactions among CD36 variants and with those in other metabolic regulatory genes. Cardiovascular (CV) phenotypes were characterized by echocardiography and carotid artery ultrasonography. The association between race-specific CD36 tagSNPs (r
2
>0.8) and HHD traits were tested in Caucasian (C, n=608) and African-American (AA, n=228) adults. Association between dependent variables and individual SNPs were tested by regression analysis adjusting for known confounding covariates. Tests for interaction were carried out by first examining within-gene
cis
-interactions by regression against haplotypes in CD36, followed by exploratory analysis of cross-gene interactions between CD36 and PPARα, PPARγ, and PGC1α using Bayesian network (BNT) analyses. A total of 14 and 52 CD36 SNPs in C and AA, respectively, were evaluated. In C, no significant main effects for individual CD36 SNPs were detected while 3 CD36 haplotypes were associated with LV diastolic function, LV mass, and LV ejection fraction suggesting a role for interaction of
cis
-acting elements. In AA, 15 individual SNPs and 17 CD36 haplotypes were associated with HHD-related traits. Exploratory BNT analyses including significant haplotypes from the 4 genes identified meaningful gene-gene interactions in both races, highlighting the complex nature of interactions among CD36 and metabolic regulatory genes in the etiology that deserves further investigation.

Figure.

BNT of all significant (p=0.05) haplotypes from CD36, PGC1α, PPARα, PPARγ in the African-American cohort. Dependent variable (LVM/HI
27
) and body mass index (potential covariate) shown in orange.
Abstract 3176: Differerential Impact Of Acute Myocardial Risk Factors And Chronic Comorbidities On Use Of Guideline-recommended Therapies In Patients Presenting With Acute Coronary Syndromes
Authors: Joynt Karen E , Huynh Luan , Amarena John , Brieger David , Coverdale Steven , Rankin Jamie , Soman Ashish , Chew Derek P
Published: July 2021

Background: Prior investigations show that patients presenting with ACS with high-risk features are less likely to receive evidence-based therapies (EBT). Current risk stratification tools combine acute and chronic risk factors (RF); these may contribute differently to receipt of proven therapies.

Methods: Using data from a prospective audit of 2600 patients in Australia, the impact of acute myocardial RF (biomarker elevation, ECG changes, cardiac arrest, Killip class ≥ 2), chronic co-morbid RF (prior CHF, chronic lung disease, malignancy, prior CVA, GFR < 60, age > 75), and traditional RF on patient management were examined using logistic regression.

Results: the best predictor of receipt of EBT was the number of myocardial RF; the best predictor of a low likelihood of receipt was the number of co-morbid RF (Table

). The presence of three or more myocardial RF conferred an OR of 2.21 for receiving clopidogrel and 4.3 for undergoing angiography, while the presence of four or more co-morbid RF lowered the OR to 0.47 for clopidogrel and 0.09 for angiography (Figure 1a

/b

).

Conclusions: High-risk patients may be less likely to receive EBT than low-risk patients, but this is driven by comorbid conditions rather than markers of severity of illness. Research is needed to validate these therapies in high-risk patients, and ongoing efforts at quality improvement should focus on high-risk populations.

Figure 1a.

Odds of receiving clopidogrel during hospitalization

Figure 1b.

Odds of receiving angiography during hospitalization

Application of management recommendations within 24 hours of admission and at discharge, adjusted for cardiovascular risk factors and prior coronary artery bypass grafting.
Abstract 3203: The role of Neprilysin in the Development of Insulin Resistance, Type 2 Diabetes and Cardiovascular Disease
Authors: Standeven Kristina F , Carter Angela M , Balmforth Anthony J , Wheatcroft Stephen B , Hooper Nigel M , Grant Peter J
Published: July 2021

Neprilysin (NEP) cleaves several bioactive peptides involved in the regulation of vascular function. In human microvascular endothelial cells, fatty acids and glucose increase NEP activity, and inhibition of NEP in animal studies results in increased insulin sensitivity, suggesting that NEP may be related to the metabolic syndrome. We tested this hypothesis in cell, animal and human based models. Microarray analysis of mRNA expression in differentiated human adipocytes (Affymetrix Human Genome U133 Plus 2.0 arrays) showed NEP expression to be an order of magnitude higher than the average gene signal, suggesting that human adipocytes express high endogenous levels of NEP mRNA. Real time PCR confirmed high levels of NEP mRNA in preadipocytes which increased 28 fold during differentiation and reached levels equivalent to the endogenous control, GAPDH, by 14 days. We created a diet induced model of obesity by feeding male C57BL/6J mice a high-fat diet, which resulted in decreased glucose tolerance and insulin resistance in obese mice. Plasma NEP levels measured after 15 weeks of feeding were significantly higher in obese mice (1642 [± 529]) pg/μl) compared to lean mice (820 [± 487] pg/μl) (p < 0.01). NEP levels increased 4- and 9-fold in epididymal and mesenteric fat in obese, compared to lean, mice. In a study of 318 healthy white European males, plasma NEP measured by activity assay was significantly higher in subjects with the metabolic syndrome (MetS) and levels increased progressively with increasing number of MetS components, being ~8-fold higher in those with 5 MetS components compared with those with none. NEP correlated with insulin, HOMA and BMI in all subjects. In conclusion, we have generated cell, murine and human data which suggest that NEP may have an important role in cardio-metabolic risk associated with insulin resistance, with the adipocyte as a major source of NEP. These findings indicate that NEP is a novel adipokine that links insulin resistance to vascular risk.
Abstract 4986: A Physiology-Based Mathematical Model of Coronary Heart Disease Accurately Predicts CHD Event Rates in Real Populations
Authors: LaBute Montiago , Dziuba Julia , Waksman George , Peskin Barbara
Published: July 2021

The high societal burden of coronary heart disease (CHD) and prohibitive costs associated with clinical trials mandate the need for other methods to investigate new diagnostic protocols, disease management strategies and treatments. The Archimedes Model is a clinically detailed simulation model of human physiology, disease progression, and healthcare systems designed to support such investigations. The model has been validated against more than 50 of the most important clinical trials involving both primary and secondary prevention populations. The model includes emerging biomarkers and conventional CHD risk factors. Here we assess the accuracy of the model by simulating the evolution of CHD events in two primary prevention populations: the Atherosclerosis Risk In Communities (ARIC) and the Framingham Heart Study (FHS) prospective observational studies. Initial populations were created by matching the baseline information in FHS (N=4960) and ARIC (N=12800), and individual-level outcomes of incident and recurrent CHD events (non-fatal and fatal myocardial infarction) were tracked over time. These data were used to calculate Kaplan-Meier curves. Two-tailed p-values were derived from comparison of the simulated and actual survival curves using the log-rank test. P-values for incident (ARIC: p=0.349; FHS: p=0.811) and recurrent (ARIC: p=0.879; FHS: p=0.951) events indicate that there are no significant differences between the simulated and real populations. In conclusion, the Archimedes Model is capable of predicting both incident and recurrent CHD events with a high degree of accuracy in general populations, making it a valuable tool for healthcare applications.

First myocardial infarctions (fatal and non-fatal). Dashed red lines are computed from study data. Solid blue lines are Archimedes Model simulation results.
Abstract 4992: Cardiovascular Disease Risk Prediction with and without Knowledge of Genetic Variation at Chromosome 9p21.3: The Women’s Genome Health Study
Authors: Paynter Nina P , Chasman Daniel I , Buring Julie E , Shiffman Dov , Cook Nancy R , Ridker Paul M
Published: July 2021

Background
: While genetic variation at chromosome 9p21.3 is associated with incident cardiovascular disease (CVD), it is unclear whether screening for this polymorphism improves risk prediction. We sought to determine whether knowledge of variation at chromosome 9p21.3 adds to the information provided by traditional risk factors using data from a prospective cohort study of female Caucasian health professionals in the United States.

Methods
: 22,129 initially healthy participants in the Women’s Genome Health Study were prospectively followed over a median of 10.2 years for incident CVD. We determined genotype for rs10757274 in chromosome 9p21.3 as well as blood pressure, smoking status, diabetes, blood levels of cholesterol, high sensitivity C-reactive protein (hsCRP), and family history of premature myocardial infarction (MI). Models were compared overall using the C-index and for reclassification across commonly used categories of 10-year CVD risk (<5%, 5% to <10%, 10% to <20%, 20+%).

Results
: Genotype for rs10757274 was associated with an adjusted hazard ratio (HR) for incident CVD of 1.25 (95% CI 1.04 – 1.51) for the AG genotype (present in 49% of the women) and 1.32 (95% CI 1.07 – 1.63) for the GG genotype (present in 24% of the women) compared to the AA genotype. However, the addition of the genotype to traditional CVD risk factors had no effect on the C-index (0.805 to 0.807) with correct reclassification of 526 women (2.4%). When the genotype was added to previously validated prediction models that additionally included hsCRP and family history of premature MI, there was again no effect on the C-index (0.809 to 0.807), and only 214 women (1.0%) were reclassified correctly.

Conclusion
: In this large prospective cohort of Caucasian women, genetic variation in chromosome 9p21.3 was associated with incident CVD but did not improve discrimination or classification of predicted risk.
Abstract 5010: Determining the Plasticity of Cardiovascular Risk in the Elderly: A role for serial NT-proBNP measurement
Authors: Defilippi Christopher , Christenson Robert , Gottdiener John , Kop Willem J , Seliger Stephen L
Published: July 2021

In the elderly, with decades of exposure to cardiovascular (CV) risk factors, CV prognosis is often considered static. We hypothesized that CV risk is dynamic reflected by changes in NTproBNP over time. We measured NTproBNP at baseline and after 2–3 years in the Cardiovascular Health Study. Long-term risk of CV death according to change in NTproBNP was estimated with the Kaplan-Meier method. We used Cox models to test if effect of change in NTproBNP was independent of demographic and CV risk factors, baseline NTproBNP, renal function, coronary disease, and CV medications. Participants were categorized at baseline as < (low) or >=190pg/mL (high) levels, based on an observed increase in risk above this level. A significant change in NTproBNP category was defined as a change of >25% to a level above or below this cut-point, based on the reported biological variability of NTproBNP. Change in NTproBNP was also evaluated as a continuous measure. Serial NTproBNP levels were measured in 2,975 (86%) of 3,469 participants (age 75±5 years) without heart failure and who had a follow-up visit. CV death was different between those with low levels that remained low (n=1,774) vs. those with low levels that became high (n=468) (1.1 vs. 2.7 per 100 person-yrs, p<.001) and those with high levels that remained high (n=621) vs. those with high levels that became low (n=112) (4.2 vs. 1.6 per 100 person-yrs, p<.001) (figure

). As a continuous measure, change in NTproBNP was linearly associated with CV mortality risk after adjustment (per Ln-fold increment: RR=1.47, p<.001). Dynamic changes in NTproBNP levels reflect dramatic change in CV prognosis in the elderly.

Proportion without Cardiovascular death, by initial and follow-up NT-proBNP
Abstract 5020: The Association between Different Measures of Blood Pressure and Coronary Artery Calcium in Postmenopausal Women
Authors: Allison Matthew A , Manson JoAnn , Langer Robert , Aragaki Aaron , Smoller Sylvia , Lewis Cora , Thomas Asha , Lawson William , Cochrane Barbara , Hsia Judith , Hunt Julie , Robinson Jennifer
Published: July 2021

Background: The aim of this study was to determine the magnitude and significance of the associations between coronary artery calcium (CAC) and different measures of blood pressure among postmenopausal women.

Methods: Subjects were a subset of women aged 50 to 59 at baseline in the Women’s Health Initiative (WHI) clinical trial of conjugated equine estrogen (CEE) who underwent a one-time computed tomography (CT) scan of the chest following the end of the trial to determine CAC. At the baseline WHI clinic visit, CEE trial participants provided data on a wide range of factors to include blood pressure measurements which were measured twice with the participant in the seated position using a conventional mercury sphygmomanometer and appropriately sized cuffs.

Results: The sample consisted of 1,064 women with a mean age of 55.1 (2.8) years at WHI randomization and 64.8 (2.9) years at CAC ascertainment. The prevalence of a CAC score > 0 was 47%, while the prevalence of a CAC score >= 10 and > 100 was 39 and 19%, respectively. There was a linear association between the log-odds of any CAC and SBP while there was a curvilinear and inverse association with DBP that was independent of CVD risk factors and blood pressure medication status. For any value of diastolic blood pressure, the probability of CAC increased with higher levels of SBP. Conversely, for any given value of SBP, the probability of any CAC decreased with higher levels of DBP. Those with a PP >= 55 mmHg had nearly a two-fold higher odds for having any CAC (Odds Ratio: 1.95, 95% CI: 1.24 – 3.06) while individuals with isolated systolic hypertension (SBP >= 140 and DBP < 90) had a 73% higher odds for CAC (95% CI: 1.03 – 2.90, p = 0.04) independent of other risk factors and blood pressure medication status. There was no significant associations between mean arterial pressure and CAC.

Conclusions: In postmenopausal women over the age of 50 years, both SBP and DBP are relevant for determining the risk for coronary artery calcium. Notably, higher levels of pulse pressure and systolic blood pressure were strong determinants of CAC, while diastolic blood pressure was inversely related. Consequently, isolated systolic hypertension may be relevant in women. These results may be of clinical relevance for the prevention of coronary artery disease.

This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 5021: The Paradox of Gender in Long-Term Survival Following AMI: A Comparison of the 1995 and 2001 Minnesota Heart Survey Cohorts
Authors: Berger Alan K , Duval Susan J , Barber Cheryl , Smith Lindsay , Luepker Russell V
Published: July 2021

Improved mortality following acute myocardial infarction (AMI) has been observed in recent decades. We sought to identify how improved adherence to standard pharmacologic therapies and widespread use of percutaneous coronary intervention (PCI) impact mortality in men (M) and women (W). The Minnesota Heart Survey (MHS) abstracted a random sample of all medical records from patients age 30 –74 hospitalized with an AMI in the Minneapolis metro area in 1995 and 2001. Hospital mortality was ascertained from the medical record and verified using death certificates. General linear models were used to compare the outcomes of M and W between the 1995 and 2001 surveys. Survival curves were estimated using Cox proportional hazard models incorporating demographic factors and baseline characteristics. We identified 1313 AMI patients (764 M, 549 W) in 1995 and 1518 AMI patients (630 M, 888 W) in 2001. W were younger in 2001 compared to 1995; there was no significant age difference in M. The prevalence of hypertension and diabetes in AMI patients increased between 1995 and 2001. The use of aspirin, beta-blockers and ACE inhibitors during hospitalization as well as coronary angiography and PCI significantly increased between 1995 and 2001. There was a significant decline in hospital length of stay for M (2.0 days) and W (1.5 days). There was a significant decline in 3-year adjusted mortality for M but a nonsignificant increase in mortality in W [Figure

]. Improved utilization of recommended AMI pharmacologic therapies and coronary revascularization between 1995 and 2001 in M and W have only translated into improved survival among M in a population-based study.
Abstract 5054: Apolipoprotein B, but not Low-Density Lipoprotein Cholesterol is Associated with Coronary Atherosclerosis Beyond Total Cholesterol in Diabetics and Non-Diabetics
Authors: Martin Seth S , Qasim Atif N , Rader Daniel J , Reilly Muredach P
Published: July 2021

Introduction:
Accumulating evidence suggests that apolipoprotein B (apoB) is superior to low-density lipoprotein cholesterol (LDL-C) in prediction of cardiovascular events. Yet, an important outstanding question is whether apoB, relative to LDL, is an enhanced marker for subclinical atherosclerosis, particularly in diabetics where LDL levels may underestimate atherogenic lipid burden due to increased proportion of small, dense LDL.

Hypothesis:
We hypothesized that plasma apoB would be a better predictor than LDL-C of coronary artery calcification (CAC) scores in type 2 diabetics and non-type 2 diabetics.

Methods:
We performed cross-sectional analyses of asymptomatic Caucasians in (1) The Study of Inherited Risk of Coronary Atherosclerosis (434 men and 383 women; median age 48, non-diabetics) and (2) The Penn Diabetes Heart Study (580 men and 261 women; median age 60, type 2 diabetics).

Results:
Levels of apoB and LDL-C were correlated in diabetics (r=0.78, p<0.001) and non-diabetics (r=0.77, p<0.001). There was no association between LDL-C and CAC in diabetics. In non-diabetics, an association of LDL-C was lost after adjustment for total cholesterol. In contrast, after controlling for age, gender, statin therapy, and total cholesterol, levels of apoB were positively associated with CAC in diabetics [tobit regression ratio for 30 mg/dl increase in apoB 2.94 (95% CI 1.62 – 5.53), p=0.001) and had a more modest association with CAC in non-diabetics [1.67 (95% CI 1.16 – 2.32), p=0.005].

Conclusions:
ApoB, but not LDL-C, predicted CAC scores, a measure of coronary atherosclerotic burden. The strength of this association was greater in diabetics than non-diabetics. Relative to LDL-C, plasma apoB levels may be particularly useful in assessing CVD risk in type 2 diabetes.
Abstract 5061: Long-Term Treatment with Eicosapentaenoic Acid Suppresses Ischemia-Induced Ventricular Fibrillation: Potential Involvement of ATP-Sensitive Potassium (KATP) Channel
Authors: Tsuburaya Ryuji , Yasuda Satoshi , Ito Yoshitaka , Shiroto Takashi , Gao JunYi , Ito Kenta , Shimokawa Hiroaki
Published: July 2021

Although epidemiologic studies demonstrated that eicosapentaenoic acid (EPA) reduces sudden cardiac death in patients with coronary artery disease, the mechanisms remain to be examined. It was reported that during early myocardial ischemia, activated KATP channels could cause fatal ventricular arrhythmia. We thus hypothesized that long-term treatment with EPA suppresses ischemia-induced ventricular fibrillation (VF) by inhibiting myocardial KATP channels. Male pigs were treated with either a control chow or EPA (600 mg/kg/day, PO) for 3 weeks (n=8 each). They were subjected to myocardial ischemia (90 min) by occlusion of the left circumflex coronary artery and monophasic action potential (MAP) that reflects electrical activity of the LV in vivo was measured. In the EPA group, EPA content in red blood cells was increased to 4.5±0.3 mol%, a comparable level in the clinical studies (~5.8 mol%). The EPA treatment significantly reduced the occurrence of VF and the need for DC cardioversion, with a resultant marked improvement in mortality (EPA 0% vs. control 50%, P<0.05). Furthermore, the EPA treatment significantly inhibited ischemia-induced shortening of MAP duration (measured at 90% repolarization) (EPA −19.5±3.0% vs. control −27.6±8.1%, P<0.05). Importantly, the beneficial effect of EPA on MAP was abolished by pre-treatment with diazoxide, a KATP channel opener (5 mg/kg/min for 20 min, IC) (EPA+diazoxide −27.9±6.4%, P<0.05 vs. EPA) (

Figure

). These results indicate that long-term treatment with EPA stabilizes ventricular electrical property during myocardial ischemia partly through suppression of KATP channels in vivo.

Representative Recordings of Monophasic Action Potential(MAP) in Pigs