bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3522: Transfer Patients With Acute Myocardial Infarction Do Not Impact Hospital Quality Measurements, Despite Being Sicker Than Directly Admitted Patients
Authors: Don Creighton , Stewart Douglas , Heckbert Susan , Maynard Charles , Goss Richard
Published: July 2021

BACKGROUND
Studies of hospital quality and national performance measures for acute myocardial infarction (AMI) frequently exclude transfer patients. Little is known about the clinical characteristics and outcomes of patients with AMI transferred for revascularization.

HYPOTHESIS
Transfer patients have greater clinical comorbidity and worse hospital survival than non-transfer patients, and negatively impact hospital quality measures.

METHODS
A retrospective-cohort study was performed using all patients with ST-elevation myocardial infarction who underwent coronary intervention or coronary artery bypass grafting (CABG) in Washington State from 2002 – 2005. Data on clinical and procedural characteristics, medications, and complications were obtained from the Clinical Outcomes Assessment Program. Hospitals were compared by rates of death and discharge with aspirin, beta-blockers, lipid lowering agents, and ACE inhibitors. Logistic regression was used for adjusted analysis.

RESULTS
Of patients undergoing revascularization for AMI, 7080 were directly admitted and 2910 were transferred. Diabetes (23.4 v. 19.7%, p<0.01), hypertension (61.3 v. 55.7%, p<0.01), and thrombolysis (32.3 v. 3.4%, p <0.01) were greater among transfers. Transfers presented with a higher rate of left main and three-vessel disease, intra-aortic balloon pump use (6.4 v. 3.6%, p<0.01) and underwent CABG more frequently (15.4 v. 5.5%, p <0.01). Transfer patients had a lower risk of death (3.9 v. 4.9%, p=0.03), but no difference in discharge medication prescription. Adjusting for major risk factors, procedure, and hospital type, transfers had a similar risk for in-hospital death compared to non-transfers (OR 0.9, CI 0.5 – 1.6). Hospitals with a high percentage of transfers treated higher-risk patients, but had similar outcomes to those with few transfers. Excluding transfers from the hospital-level analysis did not appreciably change these results.

CONCLUSION
Transfers were higher-risk, but had similar in-hospital mortality and were equally likely to receive appropriate medication at discharge compared to directly admitted patients. Inclusion of transfers did not affect hospital-level inpatient mortality or measurements of adherence to quality guidelines.
Abstract 3524: Implementation of the American Heart Association Get With the Guidelines Heart Failure Program (GWTG-HF) Reduces Length of Stay and Decreases Cost for Hospitalized Heart Failure Patients at St. Joseph’s Regional Medical Center (SJRMC)
Authors: Faillace Robert T , Siegrist Richard B , Duchensky Steven , Marut Lorraine , Matza Ilene , Sarimento Lucena , Cahill Kathleen , Bogdanowitz Eileen , Sabatino Michele
Published: July 2021

Hospitalized heart failure patients (HF) may not consistently receive standards of care and hospitals frequently realize a financial loss in the care of HF patients. GWTG-HF makes it more likely to ensure optimal care, decrease direct cost and increase hospital profit in the management of HF patients.

HYPOTHESIS:
Utilization of GWTG-HF with a multi-disciplinary team would be associated with a consistent application of standards of care, shorter duration of hospitalization and less direct cost for hospitalized HF patients.

METHODS:
GWTG-HF was fully operational in 2006 with a multi-disciplinary team consisting of a Physician Champion, Advanced Practice Nurses (APNs), Case Managers and RNs. APNs utilized GWTG-HF at the point of service and worked collaboratively with attending physicians. We compared the average length of stay, total number of hospitalized days, patient revenue, total direct cost, contribution margin, and the profit/loss for hospitalized HF patients in 2005 to those in 2006.

RESULTS:
There were 773 cases of HF admissions in 2005 as compared to 781 in 2006. Overall compliance with GWTG-HF Core Measures in 2006 was 98% (HF-1 D/C Instructions 99%; HF-2 Left ventricular systolic (LVS) function evaluation 96%; HF-3 ACEI/ARB for LVS dysfunction 98%; HF-4 Smoking cessation advice 100%; Beta Blocker Use 95%). The average length of stay (LOS) in 2005 was 6.7 days as compared to 6.3 days in 2006 (p <0.02). The total number of hospital days in 2005 was 5,145 as compared to 4,880 in 2006 (p<0.02). Between 2005 and 2006 patient revenue increased by $279,847 (p<0.01), direct cost decreased by $348,014 (p<0.05), contribution margin increased by $627,861 (p=0.06) and the full cost profit margin increased by $309,460 (NS).

CONCLUSION:
Utilization of GWTG-HF at SJRMC is associated with a high compliance with standards of hospitalized HF care, decrease in average LOS, decrease in total number of hospital days and decrease in direct cost. Although not statistically significant, hospital contribution margin and profit increased for acutely decompensated HF patients.
Abstract 3526: Medication Non-adherence Is Associated With A Broad Range Of Adverse Outcomes In Patients With Coronary Artery Disease
Authors: Ho P. Michael , Magid David J , Shetterly Susan M , Olson Kari L , Maddox Thomas M , Peterson Pamela N , Masoudi Frederick A , Rumsfeld John S
Published: July 2021

Background:
Little is known about the effect of non-adherence among coronary artery disease (CAD) patients on a broad spectrum of outcomes including cardiovascular mortality, cardiovascular hospitalizations or revascularization procedures.

Methods:
This was a retrospective cohort study of 15,767 patients with CAD in a managed care organization. Medication adherence was calculated as proportion of days covered (PDC) for filled prescriptions of β-blockers, ACE-inhibitors, and statin medications. Multivariable Cox regression assessed the association between medication non-adherence as a time-varying covariate and mortality (all-cause and cardiovascular), adjusting for demographics and clinical characteristics. Median follow-up was 4.1 years.

Results:
Across the three classes of medications, non-adherent patients were more likely to be younger and have a diagnosis of COPD or depression. In unadjusted analysis, non-adherence to each individual class of medication was associated with higher all-cause and cardiovascular mortality. In multivariable analysis, non-adherence remained significantly associated with increased all-cause mortality risk for β-blockers (HR 1.50; 95% CI 1.33–1.71), ACE-inhibitors (HR 1.74; 95% CI 1.52–1.98), and statins (HR 1.85; 95% CI 1.63–2.09). In addition, non-adherence remained significantly associated with higher risk of cardiovascular mortality for β-blockers (HR 1.53; 95% CI 1.16 –2.01), ACE-inhibitors (HR 1.66; 95% CI 1.26 –2.20), and statins (HR 1.62; 95% CI 1.124 –2.13). The findings of increased risk associated with non-adherence were consistent for cardiovascular hospitalization and revascularization procedures.

Conclusions:
Non-adherence to cardioprotective medications is associated with a broad range of adverse outcomes. These findings support the importance of non-adherence in clinical practice and suggest that medication non-adherence should be a target for future interventions.
Abstract 3529: Feasibility, Effectiveness and Safety of Intensive Glucose Control in Critically Ill Hyperglycemic Patients Hospitalized With Acute Coronary Syndromes
Authors: Kosiborod Mikhail , Inzucchi Silvio , Hamburg Mitchell , Riggs Lisa , Koshy Sindhu , Krumholz Harlan M , Xiao Lan , Khalid Adnan , Spertus John A
Published: July 2021

Background: Elevated blood glucose (BG) is associated with higher mortality and complications in patients (pts) hospitalized with AMI. While current ACC/AHA guidelines recommend “normalization” of BG in critically ill AMI pts, experience with implementation of intensive BG control protocols in this population is extremely limited.

Methods: We implemented an intensive BG control protocol at the Mid America Heart Institute (MAHI) CCU beginning 08/2006, with the purpose of evaluating its feasibility, safety and effectiveness. All ACS patients with admission BG >140 mg/dL received a modified Yale-MAHI intravenous insulin infusion protocol, with a target BG range of 90–120 mg/dL. Demographic, clinical and laboratory data were abstracted from medical records of 94 consecutive pts that received the protocol (post-intervention), and compared with data on 138 consecutive ACS pts with admission BG >140 mg/dL hospitalized in CCU immediately prior to the protocol implementation (pre-intervention).

Results: There were no significant differences between pre and post-intervention pts in age (64 vs. 66, p=0.2), female gender (40 vs. 39%, p=0.8), known diabetes (57 vs. 51%, p=0.3), or admission BG (218 vs. 203 mg/dL, p=0.13). Mean 24 hour BG was markedly reduced in post-intervention vs. pre-intervention pts (132 vs. 181 mg/dL, p<0.001). The protocol was very effective in both rapid attainment and maintenance of BG targets (Figure

). The rate of hypoglycemia (BG <60 mg/dL) was 0.72%, and none of the hypoglycemic events were symptomatic.

Conclusions: Intensive BG control in critically ill ACS patients with the modified Yale-MAHI protocol is feasible, effective and safe.
Abstract 154: Hydrogen Peroxide-Induced Contractile Dysfunction is Mediated Through Oxidation of SERCA on Cysteine-674
Authors: Lancel Steve , Zhang Jingmei , Kuster Gabriela M , Ying Jia , Pimentel David R , Trucillo Mario P , Weinberg Ellen O , Siwik Deborah A , Cohen Richard A , Colucci Wilson S
Published: July 2021

Background:
Reactive oxygen species (ROS) are critical mediators of cardiomyocyte contractile dysfunction. We previously reported that H
2
O
2
induces thiol oxidative post-translational modifications of the calcium handling protein sarco/endoplasmic reticulum calcium ATPase (SERCA), leading to a reduction of its activity and contractile dysfunction. Here, we tested the hypothesis that cysteine-674 of SERCA is critical for H
2
O
2
-induced contractile dysfunction in adult rat ventricular myocytes (ARVM).

Methods:
Overexpression of wild-type (WT) or mutant SERCA, in which cysteine-674 was mutated to serine (C674S), was accomplished by 36 hours of adenoviral infection. ARVM were paced at 5Hz and superfused with 100μM H
2
O
2
. Cell shortening and calcium transients were measured over 20 minutes using video-edge detection and fura-2 fluorescence. Thiol oxidation of SERCA was assessed using biotinylated iodoacet- amide (BIAM)-labeling.

Results:
After 14min of H
2
O
2
exposure, cell shortening was markedly reduced in WT-SERCA overexpressing ARVM (−43 ± 21%) but not in C674S-SERCA overex-pressing ARVM (−49% ± 31%, p<0.05 vs WT-SERCA, n=21–24/group). Time of 50% cell relengthening was prolonged by 15 ± 5% in WT-SERCA ARVM (p<0.05 vs time 0) but not in C674S-SERCA cells (+1 ± 4%, NS vs time 0). Compared with WT-SERCA ARVM, expression of C674S-SERCA attenuated the H
2
O
2
-induced reduction in calcium transient amplitude (−51 ± 11% vs −87 ± 6%, p<0.05 C674S-SERCA vs WT-SERCA). The 50% calcium reuptake time was prolonged in WT-SERCA compared with C674S-SERCA ARVM (60 ± 3ms vs 46 ± 3ms, p<0.05), reflecting a decrease in SERCA activity in WT-SERCA but not in C674S-SERCA ARVM. H
2
O
2
decreased BIAM-labeling in ARVM overexpressing WT-SERCA by 40% ± 7% (p<0.01,n=3) but failed to decrease BIAM-labeling in ARVM overexpressing C674S-SERCA.

Conclusion:
Increased thiol oxidative post-translational modification was correlated with a reduced SERCA activity and calcium handling abnormalities, and these effects were attenuated in ARVM overexpressing mutated SERCA modified at Cys674. These findings suggest that oxidation on Cys674 of SERCA is responsible for H
2
O
2
-induced reduction in its activity leading to contractile dysfunction.
Abstract 473: Aldose Reductase Expression In Foam Cells As Possible Link Between Diabetes, Hyperlipidemia And Atherosclerosis
Authors: Gleissner Christian A , Sanders John M , Ley Klaus
Published: July 2021

Aldose reductase (AR) is the rate-limiting enzyme of the polyol pathway, which under normoglycemic conditions detoxifies aldehydes. With increased glucose levels, however, AR uses glucose as substrate, resulting in increased osmotic and oxidative stress as shown in diabetic microvascular complications like polyneuropathy or nephropathy. Recently, overex-pression of human AR has been shown to increase atherosclerotic lesions in LDL receptor knock out mice. We hypothesized that AR is expressed in foam cells and contributes to atherosclerosis in humans. To evaluate the relevance of AR expression in human foam cells, monocytes were isolated from peripheral blood by gradient centrifugation and negative isolation. Macrophages were generated by treating monocytes with either macrophage colony-stimulating factor (M-CSF) or CXCL4 (platelet factor-4) for 6 days. To induce foam cell formation, macrophages were treated with oxidized low density lipoprotein (oxLDL, 100 μg/ml) or medium for 0, 2, 4, 6, 8, 12, 24, or 48 hours. AR expression was assessed by real-time RT-PCR. AR activity was determined photometrically by measurement of NADPH consumption. At 4 hours, AR gene expression was found increased about 1.4- (M-CSF) and 1.8-fold (CXCL4), respectively. In accordance with these findings, AR activity was significantly increased in macrophages stimulated with oxLDL and could be inhibited by treatment with the AR inhibitor epalrestat. oxLDL-dependent upregulation of AR was further elevated under hyperglycemic conditions (30 mM glucose) supporting a synergistic effect of hyperlipidemia and diabetes mellitus. Inhibition of AR by epalrestat resulted in reduction of oxLDL-dependent IL-6 upregulation suggesting that pro-inflammatory effects of oxLDL are at least partly mediated by AR. The in-vivo relevance of AR expression was demonstrated by immunohistochemistry showing expression AR in human atherosclerotic plaque. In summary, we demonstrate oxLDL-dependent upregulation of AR in human macrophages as a novel pro-inflammatory mechanism in foam cells. AR might represent a potential link between hyperlipidemia, diabetes mellitus and atherosclerosis and might be a relevant therapeutic target.
Abstract 3543: Long-Term Benefits of Cardiac Rehabilitation in Patients With Incomplete Revascularization: 5-Year Follow-up.
Authors: Belardinelli Romualdo , Lacalaprice Francesca , Piccoli GianPiero , Iacobone Gianfranco , Piva Roberto
Published: July 2021

There is evidence that cardiac rehabilitation (CR) determines important benefits in patients with coronary artery disease(CAD). However, it is unclear whether CR may improve the outcome of pts with incomplete revascularization (IR) after PTCA/stenting and/or coronary artery bypass surgery (CABG). From 1/1/2002 to 30/11/2004, we prospectively studied 259 patients with CAD who underwent PTCA after a SCA or CABG in 1(10/7%, respectively), 2(20/19%) and 3 major coronary arteries (70/74%). Patients were randomized into 2 homogeneous groups on the basis of the results of cardiopulmonary exercise stress testing(CPET) performed twice one week apart: a group with a positive CPET for inducible ischemia (P, n=129), and a group with a negative CPET (N, n=130). Patients were further randomized into 2 groups. The intervention group(Group CR) received CR combining exercise training (60%peak VO2, 3 times a week for 8 weeks)+ nutrition counseling+ standard medications (65P+65N, 25% women, mean age 56±8 years), while the control group (Group C) had no CR (65P+64N, 25% women, mean age 58±8 years). On entry and at 8 weeks all patients underwent CPET, brachial artery flow-mediated dilation (BA-FMD) and blood chemistry. Group CR-N had more marked improvements in peak VO2 and FMD than CR-P (P<0.001 for both). However, CPET became negative in 22% post PTCA CR-P patients and 28% post CABG CR-P (P<0.001 vs initial). After 8 weeks, group CR was recommended to continue a home program of exercise training with periodic supervision at the hospital’s gym, while group C was not. At 5 years, both peak VO2 and FMD were significantly higher in CR (P<0.01 vs C) with no differences between CR-P and CR-N. Cardiovascular risk profile (CVRP) was significantly improved in CR (P<0.01 vs C). Cardiac events were significantly lower in CR than C : new acute coronary syndrome (P<0.001); new PCI (P<0.0001); new CABG(P<0.001); hospital readmission: (P<0.0001); cardiac death (P<0.05). Multivariate analysis demonstrated that the lower rate of events in CR was not collinear with changes in CVRP. In conclusion, IHD patients with IR take advantage from CR and maintain a higher functional capacity and a better control of CVRP at 5 years. These benefits were associated with a better outcome.
Abstract 3544: One year follow-up after acute Coronary Artery Disease (CAD) - Immediate hospital discharge vs. cardiac rehabilitation
Authors: Schwaab Bernhard , Waldmann Annika , Katalinic Alexander , Poppe Britta , Sheikhzadeh Abdolhamid , Raspe Heiner
Published: July 2021

Background:
The evidence of cardiac Rehab is not fully settled as meta-analysis mostly included studies without acute revascularisation and modern preventive medication.

Method:
In a multicentre randomised controlled trial, 1.474 patients (pts.) with acute CAD were included to investigate the impact of telemedicine on chronic CAD: 679 pts. were included immediately at discharge from the hospital (Hosp), 795 pts. after three week in-patient Rehab. All pts. had acute coronary angiography and were followed for one year. As Hosp pts. were included 11,3 ± 3 days (median 11) earlier than Rehab pts., events in the Hosp group were counted from day 12.

Results:
Rehab pts. were older (64 ±10 vs. 62 ±10 years; p<.001), had more congestive heart failure (64 vs. 40%, p<.001), renal insufficiency (10 vs. 7%, p=.036), hypercholesterolemia (79 vs. 74%, p=.023), and carotid stenosis (8 vs. 4%, p=.004). Telemedicine device prescription, gender, atrial fibrillation, peripheral artery disease, diabetes, hypertension, education and social status were similar in groups. After one year, Rehab pts. had more β-blockers (88 vs. 75%, p<.001), ACE-inhibitors (81 vs. 70%, p<.001), lower LDL-C (102 ±35 vs. 121 ±47 mg/dl, p<.001) and a higher proportion of non-smokers (62 vs. 56%, p=.024). There was no difference in platelet inhibition, anticoagulation and statin therapy (81 vs. 79%). The primary combined endpoint of all-cause mortality, acute myocardial infarction (AMI), coronary revascularisation and hospitalisation occurred in 32.6% of Rehab pts. and in 38.7% of Hosp pts. (p=.014; absolute risk reduction (ARR) 0.0615, relative risk reduction (RRR) 16%, number needed to treat (NNT) 17). AMI (1.8 vs. 3.8%, p=.015; ARR 0.0207, RRR 54%, NNT 49) was reduced. Revascularisation (4.2 vs. 5.4%), hospitalisation (33.6 vs. 38.0%) and all-cause mortality (2.1 vs. 2.4%) were similar between groups. After multivariate analysis, the primary endpoint was still significant: OR 0.716 (95% CI 0.575–0.892; p=0.003) giving a RRR of 28% in favour of Rehab therapy.

Conclusion:
Although Rehab pts. were sicker at entry, cardiac Rehab substantially reduced relevant clinical endpoints within one year. With a very low NNT, Rehab is highly effective and should be advised to all suitable patients with acute CAD.
Abstract 3554: Metabolic Syndrome in Non-Obese Population: A Growing Concern
Authors: Martins Susana , Cortez-Dias Nuno , Fiuza Manuela
Published: July 2021

Context:
There is general consensus that prevalence of metabolic syndrome (MS) increases with body mass index (BMI), but less is known in normal weight individuals.

Objectives:
To determine the prevalence and likelihood of MS and its components in normal weight (NW: 18.5–24.9 kg/m
2
), overweight (OW: 25–29.9 kg/m
2
) and obese individuals (OB: ≥30 kg/m
2
). NW parameters were further divided in the following: 18.5–20.9; 21–22.9; 23–24.9 kg/m
2
.

Methods:
Descriptive cross-sectional study representative of all regions of Portugal. Individuals ≥18 years visiting their general practicioner, irrespective of their reason for consulting, were asked to participate after informed consent in the national registry of MS prevalence (VALSIM). MS was defined by NCEP-ATP III criteria. Overall MS, each of its components, as well as gender and age-specific prevalences were estimated. Multivariate regression analysis was used to estimate the odds ratio (OR) of MS by age, gender and BMI.

Results:
A total of 16333 adults was analysed (mean age: 59±14 years; 61% women). The overall prevalence of MS was 29.4%. Risk of MS was higher in women and rose with age. The OR for MS in OW and OB was three and nine times, respectively. However, even non-obese population had an unexpected high prevalence of MS, particularlly in upper NW and OW Individuals. The analysis of each MS-component according to BMI showed that high blood pressure is highly prevalent in these Individuals, with relevance for those in lower NW. The occurence of fasting hyperglicemia (>110mg/dL) in NW and OW Individuals was 13.6% and 25.1%, respectively.

Conclusions:
Individuals in the upper normal-weight and overweight BMI range have a high prevalence of high blood pressure, fasting hyperglicemia and MS. Therefore, screening individuals with normal or slightly elevated BMI is important in the prevention of diabetes mellitus and cardiovascular disease.

Prevalence of MS and individual components according to BMI
Abstract 3564: A Multi-Stage Evaluation of Genetic Association with Early-Onset Coronary Artery Disease in
MYLK
Gene
Authors: Wang Liyong , Hauser Elizabeth R , Crosslin David , Nelson Sarah , Hale A B , Gregory Simon , Shah Svati H , Kraus William E , Goldschmidt-Clermont Pascal J , Vance Jeffery M
Published: July 2021

Background:
Consistent linkage evidence has been found for coronary artery disease (CAD) at chromosome 3q13–21. To fine map the region, we previously conducted a peak-wide association survey using single nucleotide polymorphisms (SNPs) evenly spaced at 100 kb intervals. While strongest association was found at Kalirin gene, multiple genes displayed evidence for association with early-onset CAD, including the myosin light chain kinase (MYLK) gene. MYLK is a member of the Kalirin-RhoGTPase pathway that we have proposed previously to be important in CAD.

Methods:
To thoroughly evaluate the association at
MYLK
, we examined 46 tagging and functional SNPs across the gene in a case-control dataset with early-onset CAD (N=750), resulting in an average density of one SNP every 6 kb. Significant results were then validated in families with early-onset CAD (N=2954). As a third evaluation, the probands (N=560) of the families were compared to the controls (N=291) from the case-control dataset. Finally, validated SNPs were examined for correlation with atherosclerosis in 145 aorta specimens.

Results:
Multiple SNPs were significant in the initial screening in the case-control dataset (p=0.001 to 0.038). However, only three of them were validated in all datasets (p=0.001 to 0.046). In addition, the risk alleles of the three SNPs were correlated with higher atherosclerosis burden in aortas (p=0.007 to 0.040). The three SNPs are in linkage disequilibrium with each other (r
2>
0.9) and span over 50 kb region near the 5’ end of the gene.

Conclusions:
Our multi-stage evaluation strongly supports
MYLK
as a novel CAD susceptibility gene. MYLK regulates smooth muscle cell contraction and endothelial cell permeability through catalyzing the phorsphorylation of the regulatory myosin light chain. The known functions of MYLK provide a plausible mechanism for its involvement in the development of atherosclerosis.
Abstract 3566: Confirmed Influence Of The
LPIN1
Gene On Traits Of The Metabolic Syndrome In Human
Authors: Wiedmann Silke , Fischer Marcus , Koehler Martina , Neureuther Katharina , Doering Angela , Riegger Günter , Hengstenberg Christian , Baessler Andrea
Published: July 2021

Lipin, a molecular protein expressed by adipocytes, has marked effects on adipose tissue mass, insulin sensitivity, and glucose homeostasis. Genetic variants within the lipin gene,
LPIN1
, may be associated with traits of the metabolic syndrome (MetS) as we have shown previously in a sample of the general population.

Methods: 15 SNPs densely covering the
LPIN1
gene region were genotyped in an age- and sex- stratified sample of the general population (MONICA study Augsburg, DNA and phenotypes of 1,416 Caucasians). Ten of these SNPs were also genotyped for replication in an independent sample of 1,030 subjects recruited throughout Germany. The MetS was defined via the sum of its core components and additionally by a factor score derived from factor analysis. Permutation based methods were used to test the association between genetic
LPIN1
variants and metabolic traits for empirical significance.

Results: Linkage disequilibrium (LD) analysis revealed three LD blocks encompassing
LPIN1
. We identified three associated three-marker haplotypes: one common haplotype (26.8% frequency) increases the risk for the MetS (OR=1.6, 95% CI[1.2–2.2]), while the other two being less common (5.7% and 4.0%) are strongly associated with lower blood pressure (p<0.0001), a lower BMI and waist circumference (p<0.0001), lower HbA1c (p<0.01) as well as a lower MetS factor score (p<0.0001). Furthermore, the frequencies of arterial hypertension (p<0.0001), obesity (p<0.0001), diabetes (p<0.05), and the presence of ≥3 MetS components (p<0.0006) were significantly lower than in subjects not carrying one of these protective haplotypes. These findings could be largely confirmed in the replication sample. Specifically, the same haplotypes were significantly associated with fasting triglyceride levels (p=0.00008), HDL cholesterol levels (p=0.00012), diabetes (p=0.00007), and the MetS factor score (p=0.002).

Conclusion: These data confirm that allelic variants of the
LPIN1
gene have significant effects in human metabolic traits and highlight the importance of lipin in the pathophysiology of the MetS. Permutation-based low p-values and the consistent findings in several populations across multiple phenotypes of the MetS reflect the robustness of these results.
Abstract 3570: Common Mitochondrial Haplogroups Do Not Predict Risk of Ischemic Cardiovascular Disease, Mortality, or Longevity in the General Population
Authors: Benn Marianne , Schwartz Marianne , Nordestgaard Børge G , Tybjćrg-Hansen Anne
Published: July 2021

Recently there have been numerous reports suggesting a role for mitochondrial haplogroups, defined by common polymorphisms in the mitochondrial genome, in the pathogenesis of common multifactorial disease such as ischemic cardiovascular disease, and in longevity. These studies have in common that they are all case-control studies with a very limited number of participants, and therefore are prone to selection bias and have very limited power. In the present study, we therefore tested the hypothesis that mitochondrial haplogroups predict risk of ischemic cardiovascular disease, mortality, and longevity in a large prospective study of a general population of Northern European descent. We genotyped 9,254 individuals from the Danish general population, The Copenhagen City Heart Study, for six polymorphisms (mt7028, mt10398, mt11719, mt12308, mt12612, mt15607) defining eight mitochondrial haplogroups, and determined the ability of these haplogroups to predict risk of ischemic cardiovascular disease, mortality, and longevity with, respectively, 25 and 11 years follow-up. Haplogroup frequencies were: H(45.9%), U(15.9%), T(9.9%), J(9.1), K(6.2%), V(4.5%), W/I(3.8%), and Z(3.5%). Multifactorially adjusted hazard ratios for hospitalization due to ischemic heart disease and ischemic cerebrovascular disease as a function of haplogroups were not significantly different from the most common haplogroup H. Furthermore, multifactorially adjusted hazard ratios for death of all causes as well as for major causes of death including ischemic cardiovascular disease as a function of haplogroups were also not significantly different from haplogroup H. Finally, on survival plots, longevity defined as percent surviving as a function of age by haplogroups did not differ when comparing each haplogroup with haplogroup H. In conclusion, in this large prospective study of a general population of Northern European descent mitochondrial haplogroups did not predict risk of ischemic cardiovascular disease, mortality, or longevity. Thus, our results suggest that mitochondrial haplogroups are not major predictors of ischemic cardiovascular disease, overall mortality, mortality from ischemic cardiovascular disease, or longevity in the general population.
Abstract 3577: Thickness of mitral annular calcification is directly associated with cardiovascular morbidity and mortality. The Northern Manhattan Study.
Authors: Kohsaka Shun , Sacco Ralph L , Jin Zhezhen , Liu Rui , Rundek Tatjana , Boden-Albala Bernadette , Homma Shunichi , Di Tullio Marco R
Published: July 2021

BACKGROUND: Mitral annular calcification (MAC) is common in the elderly, and is associated with atherosclerotic risk factors. We sought to determine the magnitude of association between MAC and vascular events in the multiethnic prospective cohort of northern Manhattan.

METHODS: MAC was assessed by transthoracic 2D-echocardiography as binary (yes/no) and continuous (mm) variable. Subjects were aged ≥40 years at enrollment, and were free of prior myocardial infarction (MI) and stroke. The association between MAC and MI, ischemic stroke, and vascular death was examined, adjusting for established cardiovascular risk factors and for carotid artery stenosis (>60%) by means of Cox regression analysis.

RESULTS: Of 1,958 subjects, 502 (25.7%) had MAC. MAC was significantly associated with age, systolic blood pressure, male gender and history of atrial fibrillation. During a mean follow-up of 7.4 ± 2.5 months, there were 100 MI, 104 ischemic stroke and 156 vascular deaths recorded. After adjustment for other risk factors, MAC was associated with an increased risk of MI (HR 1.72, 95%CI 1.13–2.63; p=0.012) and vascular death (HR 1.57, 95%CI 1.12–2.20; p=0.008), but not of ischemic stroke (HR 1.36, 95%CI 0.89 –2.06; p=0.16). When MAC was categorized into mild to moderate (1– 4mm, n=253; 13.1%) or severe (≥4mm, n=245; 12.7%), severe MAC remained as a strong and independent predictor of vascular events, but not stroke (Table

).

CONCLUSION: MAC was a strong and independent predictor for MI and vascular death in this multiethnic cohort especially when its thickness is more than 4mm. Its predictive value for ischemic stroke was not independent of other cardiovascular risk factors.

Table.

Association of MAC severity with clinical vascular outcomes.
Abstract 477: Selective Heart Rate Reduction Via Inhibition Of The
I
F
-current Prevents Atherosclerosis And Improves Endothelial And Erectile Function In Apoe −/− Mice
Authors: Custodis Florian , Baumhaekel Magnus , Schlimmer Nils , List Franka , Gensch Christoph , Boehm Michael , Laufs Ulrich
Published: July 2021

Introduction
: Elevated resting heart rate (HR) is associated with increased risk for cardiovascular morbidity and mortality. Erectile dysfunction is associated with endothelial dysfunction and atherosclerosis due to similar risk factors. We hypothesized that HR reduction may influence endothelial- and erectile function and tested the effects of the
I
f
-current inhibitor ivabradine in ApoE−/− mice.

Methods and Results:
Male ApoE−/− mice fed a high-cholesterol diet were treated with ivabradine (iva) (10 mg/kg/d p.o.) or vehicle (n=10 per group) for 6 weeks. Treatment with ivabradine reduced HR by 13.4% (iva 472±9 bpm vs vehicle 545±11 bpm, p<0.01). High cholesterol feeding led to severe atherosclerosis in the aortic sinus and the aorta. Ivabradine reduced atherosclerotic plaque size in the aortic root from 32±4% to 18±2% and in the ascending aorta from 26±4% to 7±1% (p<0,05). Endothelium dependent relaxation of aortic rings and corpora cavernosa to carbachol was significantly improved in ivabradine fed ApoE−/− mice compared to controls (p<0.01). Aortic eNOS mRNA expression, quantified by real time PCR with the TaqMan system was upregulated to 156±11% (p<0.05) in aortic rings after treatment with ivabradine. HR reduction led to attenuation of NADPH oxidase activity to 48±6% as measured by a lucigenin-enhanced chemiluminescence assay and decreased L-012 chemiluminescence to 24±9% (both p<0.05). Lipidperoxidation was reduced to 65±8% in the vasculature of the iva group compared to vehicle treatment (p<0.05). DHE fluorescence microscopy in aortic sections detected reduction of ROS release to 62±4% in ivabradine treated mice (p<0.01).

Conclusions
: Selective HR reduction improves endothelial as well as erectile function and reduces atherosclerotic plaque formation in ApoE−/− mice. Those functional effects are mediated by decreased oxidative stress and upregulation of endothelial NOS (eNOS). These results identify HR as a risk factor for vascular disease and support the importance of heart rate reduction in vascular prevention.
Abstract 3586: Alcohol Consumption and One-Year Angina Risk After Myocardial Infarction
Authors: Buchanan Donna M , Mundluru Surya , O’Keefe James H , Reid Kimberly J , Tang Fengmeng , Dawood Nazeera , Peterson Eric D , Spertus John A
Published: July 2021

Background:
Prior studies show light to moderate alcohol use is associated with reduced mortality and cardiovascular events, whereas heavy use increases mortality and cardiovascular risks. The association of alcohol use and post-myocardial infarction (MI) symptoms is unknown. We explored the association between alcohol use and risk of having angina 1 year after an MI.

Methods:
Upon enrollment in the 19-center prospective PREMIER registry, acute MI patients (n=2481) were asked about alcohol use. Angina (any vs. none) was assessed at 1 year with the Seattle Angina Questionnaire. The association of alcohol use and 1-year angina was modeled using a hierarchical multivariable modified Poisson regression model.

Results:
Overall, 47% reported never drinking and others reported having the following # of drinks/day: 42% < 1; 6% 1 to 2; 3% > 2 to 4; 2% > 4. After adjusting for demographic, clinical, and treatment variables, patients that reported never drinking were 45% more likely to have angina than moderate drinkers (1 to 2 drinks/day). However, > drinks/day was associated with an 81% greater risk of angina than moderate alcohol use. Those drinking < 1 drink/day or > 2 to 4 per day had similar angina risk compared to moderate drinkers. Results did not vary by gender (p > .05 for interaction).

Conclusions:
This study extends prior evidence of a dose-dependent relationship between alcohol use and other cardiovascular benefits/risks to post-MI angina. Moderate alcohol consumption (1 to 2 drinks/day) was associated with reduced risk of angina 1 year after MI compared to abstinence or heavy alcohol consumption. Excessive alcohol use (>4 drinks/day) was associated with increased risk of angina.
Abstract 3589: Warfarin Therapy, Anticoagulation Intensity and Outcomes in Older vs. Younger Patients with Atrial Fibrillation: The ATRIA Study
Authors: Go Alan S , Fang Margaret C , Chang Yuchiao , Borowsky Leila H , Pomernacki Niela K , Singer Daniel E
Published: July 2021

Background.
Warfarin is highly efficacious for stroke prevention in atrial fibrillation (AF) in selected randomized trial populations. However, controversy exists about its effectiveness and safety and the target INR range in the old and oldest old AF patients in usual clinical care.

Methods.
We examined anticoagulation-related outcomes associated with older vs. younger age among 13,559 patients with AF within Kaiser Permanente of Northern California between July 1996 and September 2003. Longitudinal warfarin use was characterized using a validated algorithm from filled prescriptions and INR tests found in pharmacy and lab databases. Anticoagulation intensity was characterized using linear interpolation from outpatient INR tests. Risk factors for stroke and bleeding were obtained from clinical and administrative databases. Thromboembolic (TE) and intracranial hemorrhage (ICH) events were identified from hospitalization databases and confirmed by chart review.

Results.
During 66,754 person-years of follow-up, a large fraction was contributed by older patients: <60 (12.3%), 60 – 69 (18.5%), 70 –79 (37.8%), 80+ (31.4%) years. Older patients were more likely to be women and have a higher prevalence of stroke and bleeding risk factors. Among warfarin users, the proportion of time in therapeutic INR range was similar across age groups (64 – 66%, P=NS). We validated 1041 TE and 279 ICH events. Absolute event rates were higher with older age, but the relative effectiveness of warfarin for preventing TE increased and relative harm due to ICH decreased between ages 60 – 69 and 80+ years (Table

). In separate multivariable analyses, INR 2.0 –3.0 provided the optimal risk-benefit ratio for TE and ICH events across each age category.

Conclusion.
Among persons with nonvalvular AF, the net clinical benefit of warfarin was greater at older ages. INR 2.0 –3.0 is the optimal target anticoagulation range across the spectrum of age to maximize TE prevention at an acceptable risk of ICH.
Abstract 3592: Early Detection Of CD4-positive Lymphocytes In Adipose Tissue During The Development Of Insulin Resistance
Authors: Hess Katharina , Marx Nikolaus , Wabitsch Martin , Skurk Thomas , Hauner Hans , Hartge Martin , Kintscher Ulrich
Published: July 2021

Background: Adipose tissue inflammation may play a critical role in the pathogenesis of insulin resistance (IR) and arteriosclerosis. Previous work has mainly focused on the role of macrophages in human adipose tissue, but little is known about pro-inflammatory T-lymphocytes. Therefore the present study examined the role of CD4-positive lymphocytes in adipose tissue inflammation and IR.

Results: Both, CD4-positive lymphocytes and macrophages are present in human visceral adipose tissue as determined by immunohistochemical staining. Most macrophages were HLA-DR positive, reflecting activation through IFNγ, a cytokine released from CD4-positive lymphocytes. Furthermore, SDF-1α, a T-cell chemotactic protein, was also detectable in human adipose tissue. RT-PCR analyses confirmed the expression of IFNγ and SDF1α in visceral adipose tissue. Freshly isolated human adipocytes as well SGBS adipocyte cells express SDF-1α with a down regulation of its expression during adipocyte differentiation in both cell types. In a mouse model of IR, high fat diet induced IR already after 5 weeks which was associated with a marked lymphocyte infiltration in visceral adipose tissue as determined by immunohistochemical staining and RT-PCR. In contrast, macrophages were absent after 5 weeks of diet but could be detected at week 10, suggesting early infiltration of lymphocytes during the development of IR.

Conclusion: Pro-inflammatory T-lymphocytes are present in visceral adipose tissue and may contribute to local inflammatory cell activation before the appearance of macrophages. These data suggest that lymphocytes may play an important role in the initiation and perpetuation of adipose tissue inflammation as well as the development of insulin resistance.
Abstract 3611: Cardiovascular risk factors and venous thromboembolism: A meta-analysis
Authors: Kamphuisen Pieter , Becattini Cecilia , Brighton Timothy , Selby Rita , Ageno Walter
Published: July 2021

Background:
The concept that venous thromboembolism (VTE) and atherosclerosis are two distinct entities has recently been challenged. Patients with spontaneous VTE had more asymptomatic carotid atherosclerotic lesions and a higher incidence of cardiovascular disease than patients with VTE secondary to known risk factors and controls. However, no clear relationship between cardiovascular risk factors and VTE has ever been determined. We performed a meta-analysis to assess the potential association between well known cardiovascular risk factors and VTE.

Methods:
Medline and EMBASE databases were searched to identify studies that evaluated the prevalence of major cardiovascular risk factors in VTE patients and in controls. The studies were selected using a priori defined criteria and each study was reviewed by two authors who abstracted data on study characteristics, study quality and outcomes. Odds Ratio (OR) or weighted mean differences and 95% confidence intervals (CI) were calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated using the I
2
statistic.

Results:
Twenty-one case-control and cohort studies with a total of 63.552 patients met the inclusion criteria. Compared to controls, the risk of VTE was 2.33 for obesity (95% CI 1.68 –3.24), 1.51 for hypertension (1.23–1.85), 1.42 for diabetes (1.12–1.77), 1.18 for smoking (0.95–1.46), and 1.16 for hypercholesterolemia (0.67–2.02). Weighted mean HDL cholesterol levels were significantly lower in VTE patients compared to controls, whereas no difference was observed in total cholesterol and LDL cholesterol levels. Significant heterogeneity among studies was detected in all subgroups, except for diabetes. Higher quality studies were more homogeneous and, except for hypertension, the significant associations remained unchanged.

Discussion:
Common cardiovascular risk factors are associated with an increased risk of VTE. This association between VTE and atherothrombosis has obvious clinical implications with respect to screening, risk factor modification and future therapy. Future prospective studies could investigate underlying mechanisms of this two-way relation.
Abstract 3614: Anticonceptive Drug Use And Increased Carotid and Femoral Plaque Prevalence: Population Data From Asklepios
Authors: Rietzschel Ernst , De Buyzere Marc , De Baquer Dirk , Bekaert Sofie , Segers Patrick , Cassiman Peter , Verdonck Pascal , De Backer Guy , Gillebert Thierry C
Published: July 2021

Purpose: Combination therapy with the female hormones estrogen (E) and progestins are very frequently used with approximately 100 million women worldwide taking oral contraceptives (OC). Recent trials have cast doubt on the cardiovascular safety of hormonal replacement therapy (HRT). In contrast to the HRT-controversy, little attention has been focused on OC, a therapy using 10 –100 fold higher levels of E than HRT. We describe population correlates of long-term OC use.

Methods: The Asklepios study is a representative sample (2524 M/F volunteers, 35–55 years) from the Belgian general population free from overt cardiovascular disease. Vascular echography of the carotid and femoral arteries was systematically performed and atherosclerosis was defined by presence of carotid or femoral plaque.

Results: Of 1301 women (median age 45.7 y), 27.4% were taking OC and 10.0% were taking HRT. In contrast, past OC-use is far more prevalent: 81% of women having taken OC for at least 1 year, with a median exposition of 13 years. After multivariate adjustment for age, smoking, blood pressure, lipids, obesity, diabetes, physical activity, fruit, vegetable and alcohol intake, educational level and drug therapy (lipid-lowering, antihypertensive, aspirin), use of OC was associated with a significant increase in carotid or femoral unilateral plaque. Odds ratio’s (OR) per 10 years of OC exposure were: carotid plaque 1.17 (1.00 –1.33) and femoral plaque 1.28 (1.10 –1.47). We also looked at prevalence of bilateral disease (involvement of right and left carotid/femoral artery) as a more stringent phenotype of atherosclerosis. OR per 10 years OC exposure were: carotid plaque 1.42 (1.03–1.84); femoral plaque 1.34 (1.05–1.63).

Interpretation : Use of contraceptive therapy is very common and associated with an unexpected increase in the prevalence of carotid and femoral atherosclerosis in otherwise young, apparently healthy women. Our data suggest a 20 –30% increased prevalence of plaque in the carotid and femoral arteries per 10 years of OC exposure. In the light of widespread (>80% of our population sample; > 100 million women globally) and usually prolonged OC use (>10 years) these results suggest OC use could be an important factor in the global atherosclerotic burden.
Abstract 3616: Left Atrial Size Association with Incident Ischemic Stroke and All-Cause Mortality in African Americans: the Atherosclerosis Risks in Communities (ARIC) Study
Authors: Nagarajarao Harsha S , Penman Alan D , Taylor Herman A , Mosley Thomas , Butler Kenneth , Skelton Thomas N , Samdarshi Tandaw , Fox Ervin R
Published: July 2021

Background: The association between left atrial (LA) size, ischemic stroke and mortality has been investigated in non-Hispanic whites but not in African Americans despite their disproportionately higher rates of stroke and cardiovascular mortality. Purpose: We examined the association of LA size assessed by echocardiogram with the incidence of ischemic stroke and all-cause mortality in a large population-based cohort of African Americans.

Methods: Participants in the Jackson cohort of the ARIC study have been extensively evaluated including echocardiograms during the third examination (1993–1995) and have been followed for incident cardiovascular events including stroke.

Results: The study population consisted of 1,887 participants of which 660 (35%) were men with a mean age of 58.9 ± 5.7 years. LA diameter by tertile was significantly related to hypertension, diabetes and body mass index (BMI) (p<0.0001 for each). Over a median follow-up period of 8.8 years, there were 103 incident strokes (6.47 per 1,000 person-years) and 206 deaths (13.3 per 1,000 person-years). Adjusting for age, sex, hypertension, smoking, diabetes, total cholesterol:HDL ratio, and BMI, LA size was associated with stroke (HR per 10 mm increment of LA diameter 1.44; 95% CI: 0.99, 2.08, p = 0.05) and significantly associated with mortality (HR 1.38; 95% CI: 1.06,1.79 p < 0.02). After further adjustment for prevalent CHD and congestive heart failure, only the association with mortality remained statistically significant (p < 0.03).

Conclusions: In this middle-aged population based cohort of African Americans, LA size was significantly associated with all-cause mortality independent of traditional cardiovascular risk factors.