bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3347: Sirolimus Eluting Stents In Single Vessel Versus Multi-vessel Percutaneous Coronary Intervention: Results From The Matrix Registry
Authors: Atmakuri Satya R , Mehran Roxana , Obunai Kotaro , Gupta Anuj , Syros George , Kreps Edward M , Collins Michael B , Gray William A , Moses Jeffrey W , Leon Martin B , Stone Gregg W , Dangas George D
Published: July 2021

Background
The efficacy of sirolimus eluting stents (SES) to reduce in-stent restenosis compared to bare metal stents has been studied in single coronary vessels. However, the long-term efficacy and safety of SES implantation in multiple coronary vessels has not been well studied. We compared the efficacy and safety of SES implanted in single vessel versus multi-vessel PCI.

Methods
The MATRIX registry prospectively evaluates the efficacy and safety of SES in a “real world” population. In this registry, SES was implanted in single vessel PCI in 1103 patients and in multi-vessel PCI in 321 patients. Dual anti-platelet therapy with aspirin and clopidogrel was recommended for at least one year. All clinical events are source-documented and adjudicated by an independent committee.

Results
The multi-vessel PCI group had more patients with diabetes (38.4% vs. 32.4%, p=0.04), but less patients with prior PCI (37.7% vs. 46.6%, p=0.006) and prior CABG (17% vs. 22.3%, p=0.04). The mean number of stents implanted was 1.7 ± 0.9 vs. 3.1 ± 1.1 with procedural success of 96.7% vs. 95.6% in single and multi-vessel PCI groups respectively. The two-year clinical outcomes are shown in the table

.

Conclusions
We documented no significant differences in single vs. multi-vessel PCI with sirolimus DES. Therefore, with appropriate patient selection and PCI technique, the treatment with multi-vessel PCI appears to be as safe and effective as single vessel PCI.
Abstract 3354: Increase of Telomere Gap between Granulocytes and Lymphocytes in Patients with Previous Myocardial Infarction: A Novel Measure for Accelerated Telomere Erosion
Authors: Spyridopoulos Ioakim , Erben Young , Brummendorf Tim H , Haendeler Judith , Seeger Florian , Kissel Christine , Martin Hans , Hoffmann Jedrzej , Assmus Birgit , Zeiher Andreas M , Dimmeler Stefanie
Published: July 2021

Individuals with age-corrected reduction of total leukocyte telomere length have been shown to exhibit a remarkable increase in mortality from cardiovascular and infectious complications. Given the considerable interindividual variability of telomere length in healthy adults due to genetic differences already present at birth and the heterogeneity in composition of the total leukocyte compartment, extensive study populations are required to detect accelerated telomere shortening between age-matched groups. With this study, we intended to identify a parameter to improve prediction of individual telomere erosion in patients (pts) with coronary artery disease and previous myocardial infarction (CAD).

Methods:
Mean telomere length (mTL) was measured in 63 CAD pts (mean age 65±4 years, mean ejection fraction 31±9%) and 23 age-matched healthy controls (65±4 years). Using the flow-FISH method, we were able to distinguish between myeloid and lymphoid cell populations in peripheral blood cells as well as in bone marrow mononuclear cells (BMC).

Results:
The difference between mTL of the granulocyte and lymphocyte population (ΔTEL
Gr-Ly
) was significantly increased from 742 ± 396 base pairs (bp) in the control group to 1055±570 bp in CAD pts (p=0.018). Age was the only independent predictor for telomere length of BMCs. Lymphocytes, but not granulocytes, demonstrated significant telomere shortening between BMCs and peripheral blood in CAD patients (−444 ± 624 bp) as opposed to an increase in a young and healthy control group (+307 ± 372 bp) (p<0.001). Using immunomagnetic cell sorting, telomerase activity (TA) was determined in freshly isolated white blood cell subpopulations. Surprisingly, TA could not be detected in peripheral blood granulocytes (CD15
+
granulocytes) from CAD pts. In contrast, CD4
+
T-lymphocytes contained the highest amount of TA, compared to CD8
+
cells and B-lymphocytes.

Conclusions:
Our results suggest that primarily peripheral blood lymphocytes - and not granulocytes - can develop stress-induced telomere erosion in CAD. Therefore the base pair length difference between the two populations provides a valuable parameter to detect telomere erosion in patients with CAD, largely independent of the hereditary influence on mTL.
Abstract 3365: MRI Delayed Enhancement Identifies Cardiac Fibrosis after Myocardial Infarction at the Cellular Level in
ex vivo
Rat Heart
Authors: Schelbert Erik B , Mohanty Bibhu D , Anderson Stasia A , Hsu Li-Yueh , Karim Syed M , Aletras Anthony H , Kellman Peter , Arai Andrew E
Published: July 2021

Background:
Delayed enhancement MRI imaging detects chronic myocardial infarction (MI) but some have questioned the accuracy of “non-specific extracellular contrast agents.” Using a resolution 1000 fold higher than previous validation studies we investigated whether MRI could detect fibrosis from chronic MI at an image resolution approaching the size of a cardiomyocyte.

Methods and Results:
Eight week old Sprague Dawley rats underwent coronary ligation to create myocardial infarction; 2 months later rats were given gadolinium-DTPA (0.3 mmol/kg) intravenous and were euthanized 10 minutes later. Myocardial delayed enhancement MRI images were acquired ex vivo at 7 Tesla with a 3D gradient echo sequence using voxel dimensions of 50 micron = to identify areas of fibrosis. Histologic sections of rat myocardium 50 microns apart were stained with Masson’s trichrome and digitally photographed. Using computerized planimetry, MRI correlated well with regions of fibrosis as determined by histological specimens stained with Masson’s trichrome (y = 0.99x − 0.007; R
2
= 0.99; p<0.0001). From a perspective of image resolution, MR images routinely detected clefts of viable cardiomyocytes 2– 4 cells thick that separated bands of fibrous tissue.

Conclusions:
Using MR microscopy at 7T, ex vivo delayed enhancement images were obtained with a spatial resolution roughly equivalent to three cardiomyocytes. Gadolinium-DTPA accurately identified cardiac fibrosis following myocardial infarction. These data provide important validation of the delayed enhancement technique for detection of post myocardial infarction fibrosis at an unprecedented level of detail.6
Abstract 453: The S1p2 Receptor Is Expressed In Human Platelets,is Linked To The Rhoa-rho Kinase Pathway And Is Degraded By μ-calpain In Type 2 Diabetes
Authors: Randriamboavonjy Voahanginirina , Badenhoop Klaus , Busse Rudi , Fleming Ingrid
Published: July 2021

Sphingosine-1-phosphate (S1P) is a bioactive lipid involved in multiple biological processes; it is stored in platelets and released upon activation. Although S1P is known to exert extracellular effects on platelets such as shape change and aggregation, the receptor that mediates these effects and the molecular mechanisms involved are poorly understood. The aim of the present study was to characterize the S1P receptor expressed in platelets as well as the molecular mechanism underlying S1P-mediated platelet activation and eventual changes associated with the development of type 2 diabetes. We found that washed human platelets from healthy volunteers expressed mainly the S1P2 receptor and to a lesser extent the S1P1 receptor. Stimulation of these platelets with exogenous S1P led to a concentration-dependent increase in intracellular calcium as well as to platelet aggregation. The latter response was accompanied by the translocation of RhoA to the membrane and was inhibited (by 50%, P<0.01) by the Rho kinase inhibitor Y27632 (1 μmol/L). Neither the PKC inhibitor, Ro-318220, the MAPK inhibitor, PD98059, nor the tyrosine kinase inhibitor, tyrphostin A-23, affected the S1P-mediated platelet aggregation. Serum obtained from patients with type 2 diabetes contained 1.5-fold higher levels (P<0.01) of S1P that from healthy individuals. However, platelets from patients with type 2 diabetes demonstrated an attenuated aggregability to S1P as well as decreased levels of the S1P2 protein. The latter was found to be a target of the calcium-dependent protease μ-calpain which we found to be highly activated in platelets from patients with type 2 diabetes. Finally, stimulation of platelets from healthy donors with high concentration of S1P led to the activation of μ-calpain. Taken together, our results show that S1P can elicit platelet aggregation by activating the S1P2 receptor and the RhoA-Rho kinase pathway. In platelets from patients with type 2 diabetes, in which the circulating concentration of S1P is elevated, responses to S1P are damped, via a phenomenon that correlates with the activation of μ-calpain and the subsequent degradation of the S1P2 receptor. The latter may represent an auto-protective mechanism against exaggerated platelet activation in diabetes.
Abstract 3367: Prospective Testing of Isoproterenol and Adenosine After Pulmonary Vein Isolation: Acute Results
Authors: Callahan Thomas D , Zakaib John S , Meulet John , Barrett Conor , Phillips Karen , Wasson Sanjeev , Elayi Claude , Ching Chi Keong , Dresing Thomas , Schweikert Robert , Martin David , Burkhardt J D , Cummings Jennifer , Wazni Ousama , Kanj Mohamed , Saliba Walid , Natale Andrea
Published: July 2021

Background: Pulmonary vein isolation (PVI) offers an estimated cure rate from atrial fibrillation (AF) of 60 to 80% after the first procedure. While some data suggest that lack of inducibility of AF by electrical stimulation after atrial fibrillation ablation may predict improved outcomes, chemical induction of AF during PVI has not been well-studied. In an on-going prospective study, we seek to determine if chemical induction of AF after PVI with subsequent ablation of elicited triggers improves overall success. Herein, we report acute results of attempted re-induction of AF using adenosine and isoproterenol in patients undergoing PVI.

Methods: Fourty-three consecutive patients with symptomatic AF presented for PVI. Following initial isolation and while catheters were still in place in the left atrium, 18 to 24 mg of IV adenosine was administered as a single bolus. Subsequently, infusion of isoproterenol was administered at up to 20 mcg/min. After administration of each drug, patients were observed for induction of AF or other atrial arrhythmias, focal firing including frequent monomorphic PAC’s or focal atrial tachycardias or evidence of recovery of conduction from the pulmonary veins.

Results: Adenosine administration induced atrial fibrillation in 3 of 43 patients. Notably, no arrhythmias or focal firing were seen with isoproterenol in these three patients. Adenosine did not uncover recovery of conduction from the pulmonary veins in any patient or induce focal firing. Isoproterenol administration induced atrial fibrillation in 3 patients. Focal firing was induced in 18 patients. Recovery of conduction into pulmonary veins was observed after isoproterenol in 6 of 43 patients resulting in application of additional lesions to achieve re-isolation in each case.

Conclusions: Our initial data suggests atrial fibrillation may be chemically re-induced with adenosine and isoproterenol administration in a minority of patients undergoing PVI. Focal firing may also be induced with isoproterenol. Isoproterenol but not adenosine uncovered recovery of conduction into the pulmonary veins in several patients. The mechanism by which arrhythmias and AF initiate may differ with adenosine versus isoproterenol.
Abstract 3387: The Effects of Restrictive Annuloplasty on Mitral Leaflet Coaptation and The Mechanism Regulating Functional Mitral Regurgitation: Simplified Echocardiographic Study
Authors: Shudo Yasuhiro , Taniguchi Kazuhiro , Toda Koichi , Matsue Hajime , Hata Hiroki , Fujita Shinichi
Published: July 2021

Objectives: The effects of restrictive annuloplasty on mitral leaflet coaptation in a clinical setting have not been fully elucidated. We developed a novel simplified method for assessing the actual degree of coaptation and investigated changes caused by its use. Based on our findings, we evaluated the direct effects of restrictive annuloplasty on mitral leaflet coaptation and the mechanism regulating mitral regurgitation.

Methods and Results: We studied 23 patients (mean 60 years old) with functional mitral regurgitation (grade 3 to 4+) with congestive heart failure (LV ejection fraction 32±10%) due to idiopathic (n=8) or ischemic (n=15) who underwent mitral valve repair with restrictive annuloplasty and 20 normal control subjects. We measured the septal-lateral diameter, tenting height, tenting area, and coaptation length of the mitral valve in 4-chamber, 2-chamber, and long-axis views at mid-systole before and after surgery using transthoracic and transesophageal echocardiography procedures. Coaptation length was calculated with the following formula: Ad-Ac, where Ad equals the whole length of the anterior leaflet during the diastolic phase and Ac equals the length of the non-coaptation free portion of the anterior leaflet at mid-systole. Coaptation length index was defined as the ratio of coaptation length to septal-lateral diameter.

Results: Tenting height and tenting area were significantly decreased, while coaptation length and coaptation length index were significantly increased (Table

). In multivariate analysis, coaptation length index showed a statistically significant negative correlation with degree of residual MR (r=0.77, p<0.0001) and was found to be the most reliable predictor of MR grade.

Conclusion: Our novel simplified method provided quantitative and morphological descriptions of mitral leaflet coaptation, and can also provide important information for developing a surgical strategy for regulation of MR.

Table
Abstract 3391: Prevalence Of Hypertrophic Cardiomyopathy In Elite Athletes
Authors: Basavarajaiah Sandeep , Wilson Mathew , Chlebinska Agnes , Yavari Arash , Jackson Gordon , Whyte Gregory , Shah Ajay , Sharma Sanjay
Published: July 2021

Objectives:

The prevalence of HCM in the general population is estimated to be around 1 in 500. The exact prevalence of HCM in athletes has never been reported and has important implications with regards to potential future national pre-participation screening programme in countries such as United Kingdom, where currently there is no such programme for junior athletes.

Methods:

Between 1996 and 2006, 3500 asymptomatic and normotensive elite athletes (70% males) aged between 14–35 years (mean: 20.5±5.80) and a mean body surface area of 1.86±0.16 m
2
(range1.36–2.29) underwent 12-lead EKG and 2D-echocardiography. Cardiac dimensions and function were measured using conventional methods.

Results:

Of the 3500 athletes, 53 (2%) had maximal left ventricular wall thickness (LVWTd) > 12 mm (mean: 13.6 ± 0.9, range: 13–16). All 53 were male athletes and all except 3 of them had associated dilated LV cavity (58.5 ± 5.14 mm, range 52– 65) implying physiological left ventricular hypertrophy (LVH). This was also supported by normal indices of diastolic function and absence of family history of HCM or sudden cardiac death (SCD). However, there were 3 athletes with LVWT > 12mm who had a relatively non-dilated LV cavity (range:45– 46) and bizarre EKG changes (deep T-wave inversion) that that raised the suspicion of HCM. But none of them exhibited any other phenotypic feature of HCM on further testing with 48-hour EKG recording, cardiopulmonary exercise testing and assessment of their first-degree family members. Only one of the 3 athletes agreed to detrain for 12-weeks, which resulted in regression of LVH and complete resolution of EKG changes.

Conclusion:

In our study, only 3 athletes had echocardiographic findings that could have been consisted with the diagnosis of HCM but further investigations failed to support the diagnosis. These results indicate that the prevalence of HCM in highly trained athletes is extremely rare. The structural and functional changes associated with HCM precludes generation of large amounts of cardiac output that are required during exercise selecting out most of these individuals from competitive sports. Our findings also questions the validity of previous data which proposes that HCM is the commonest cause of exercise related SCD in young athletes.
Abstract 3403: Heart Failure Patients Improve their Exercise Capacity after Cardiac Rehabilitation Irrespective of having a Preserved or Depressed Ejection Fraction
Authors: Franco Veronica , Brown Todd M , Tallaj Jose A , Sanderson Bonnie , Bittner Vera A
Published: July 2021

Background: Whether exercise training reduces morbidity and mortality in heart failure (HF) patients is unknown. The objective of this study was to determine if cardiac rehabilitation (CR) outcomes differ in HF patients with and without systolic dysfunction.

Methods: We included the 152 patients completing CR from 1996 to 2006 with HF listed as the primary diagnosis or as a co-morbidity. Based on left ventricular ejection fraction (LVEF) at enrollment, we divided patients into 2 groups: those with LVEF ≥ 45% (51/152, 34%) and those with LVEF < 45% (101/152, 66%). At baseline, we compared distance, perceived exertion (Borg Scale), shortness of breath (Dyspnea Scale), and maximum heart rate (MHR) during a 6 minute walk test (MWT);self reported physical activity (total metabolic hours); depressive symptoms (Beck Depression Inventory [BDI]); and quality of life (physical component score [PCS] and mental component score [MCS] of the SF-36) between the 2 groups. Within each group, we compared changes from baseline to CR completion for each parameter. We compared differences between groups with multivariate linear regression to assess the association between LVEF classification and changes in each parameter, controlling for age, race, gender, and baseline value of the parameter.

Results: Mean age (61 vs. 62 years), race (43% vs. 43% non-white), and gender (36% vs. 37% women) were similar in the 2 groups. At baseline, both groups had similar 6 MWT values, depressive symptoms, and quality of life, although Borg scores were higher in the LVEF ≥ 45% group. At CR completion, the 2 groups showed improvement in all parameters (all p<0.05) except MHR on 6 MWT, which was unchanged in both groups. After adjusting for age, race, gender, and baseline value of each parameter, there was no difference in the magnitude of the improvement between the 2 groups (table

).

Conclusions: Patients with clinical heart failure symptoms, regardless of ejection fraction, benefit from exercise training.
Abstract 3414: Mortality Incidence and the Severity of Coronary Atherosclerosis Assessed by CT Angiography
Authors: Ostrum Matthew P , Yang Eric , mao SongShou , gopal Ambarish , Ahmadi Naser , Budoff Matthew J
Published: July 2021

Objectives:
This study was performed to investigate the relationship between the degree of coronary artery disease (CAD) and incidence of mortality in patients who were referred for Cardiovascular Computed Tomographic Angiography (CTA) in an outpatient setting.

Background:
Non invasive coronary angiography is being increasingly performed by CTA to assess for significant obstructive CAD. While there is extensive literature on mortality incidence with respect to degree of CAD defined by conventional coronary angiography and coronary artery calcification, no such outcome data exists for coronary CTA.

Methods:
We observed over a mean follow-up of 5±2 yrs, 2971 consecutive patients who underwent cardiac CTA. Significant CAD, defined as greater or equal to 50% luminal narrowing of an epicardial vessel, was determined by CTA. All cause mortality was detected through a search of the national death registry by patient’s social security number. Multivariable Cox proportional hazards models were developed to predict all-cause mortality.

Results:
Among this cohort, we detected a total of 102 deaths (3.4%). We observed the following mortality rates among patients with varying degrees of atherosclerotic disease burden; 3 vessel disease 18.8% (3/16), 2 vessel disease 6.1% (6/99), 1 vessel disease 3.5% (12/347), non obstructive disease 2.1% (22/1062), no detectable disease 1.8% (15/849). Patients with increasing severity of both non-obstructive and obstructive disease were more likely to die over the subsequent 5 years (Table 1

).

Conclusions:
The severity of coronary artery disease assessed by noninvasive CT angiography independently correlates with all cause mortality.
Abstract 3433: The Effect of Normal Pulmonary Arterial Bed Bubble Contrast Conductance and Latency on Bubble Contrast Echocardiography: Does “Any Bubbles” in the left atrium always mean Patent Foramen Ovale (PFO)?
Authors: Sorensen Sherman G , Barraclough Royce , Ketterer Jeremy , Turnbaugh Todd , May Heidi T , Muhlestein Joseph B
Published: July 2021

BACKGROUND:
The presence of a PFO remains a controversial possible mechanism for a significant number of cryptogenic strokes. However, unvalidated and arbitrary criteria of left heart contrast-bubble appearance on echocardiography form the basis for PFO diagnosis, treatment, and research. We postulated that variable conductance of contrast bubbles through the pulmonary artery (PA) vascular bed, as well as bubble latency can result in the misdiagnosis of PFO.

METHODS:
Consecutive pts (N=50) undergoing PFO closure by intra-cardiac echocardiography (ICE) guided imaging and right heart catheterization were studied.
PULMONARY CONDUCTANCE:
Prior to septal closure, ICE imaging of the left atrium was performed during selective PA bubble contrast injections (BCI) at baseline and after injection of 200micrograms of nitroprusside (NP). The appearance of left atrial bubbles was quantified by a validated 1–5 grading system (5–100 bubbles) at rest and following NP. A definite NP response was determined to be present if 2 observers agreed there was at least one grade level increase in bubble conductance from rest.
PULMONARY LATENCY:
120 seconds after right atrial BCI, trans-tricuspid ICE pulmonic valve imaging was performed for count of residual bubbles as a correlate of bubbles remaining in the PA at rest.

RESULTS:
Age was 42 ± 18 years; 70% were female. Pulmonary conductance was present in most pts (84% =grade 1–2, 8% =grade 3– 4). Residual bubbles at the pulmonic valve at 2 minutes were common (range 0 –30 bubbles, mean 6.2 ± 6.5; 42% >5 bubbles). “Definite” increase in conductance after NP was present in 38% of pts. The difference between baseline and NP grade agreed with subjective “definitive” change and “no change” readings (1.26 vs −0.03; p=0.0001). Augmentation of pulmonary conductance by NP was significant (grade 1.32 ±.79 vs 1.74 ± 1.1; p=0.0001) and definitive change was more likely in women than in men (45.7% vs 20.0%; p=0.08).

CONCLUSION:
We conclude that:

pulmonary conductance of bubbles is common, variable, modifiable, and more common in women.

Bubble latency in the pulmonary system may erroneously augment Valsalva shunt evaluation.

Caution should be exercised when equating lower bubble counts on echocardiography with the diagnosis of PFO.
Abstract 464: Membrane Microparticles From Ischemic Muscle Induce In Vitro Progenitor Cells Differentiation And In Vivo Neovascularization.
Authors: Leroyer Aurelie S , Ebrahimian Teni G , Vilar Jose , Levy Bernard I , Tedgui Alain , Boulanger Chantal M , Silvestre Jean-Sebastien
Published: July 2021

Postischemic neovascularization is mediated, at least in part, by the homing of progenitor cells to sites of injury and their differentiation into endothelial cells (EC). However, the mechanisms of in situ progenitor differentiation remain for the most part unknown. We hypothesized that miproparticles (MPs) released following ischemia-induced cell activation or apoptosis are the endogenous signal of postischemic vasculogenesis. MPs were detected by electron microscopy as vesicles of 0.1 to 1 μm in diameter in mice ischemic hindlimb muscle, 48hrs after unilateral femoral artery ligation. After isolation by sequential centrifugations, flow cytometry analyses showed that AnnexinV+ MPs concentration in ischemic calf was 3.5-fold higher than in control muscle (1392±406 vs. 394±180 AnnV+MPs/mg, p<0.005) and mainly originated from endothelial cells (47% of MPs are CD144+). MPs isolated from ischemic muscles induced a more potent in vitro bone marrow-mononuclear cells (BM-MNC) differentiation into EPC, than those isolated from control muscle (6.1±1.0% vs. 3.5±0.7% Dil-LDL/BS1lectin+ cells/field, p<0.05). Moreover, MPs isolated from GFP+ ischemic muscles colocalized with differentiated BM-MNC. MPs isolated from atherosclerotic plaque were uneffective whereas those isolated from apoptotic or IL-1 activated EC also promoted BM-MNC differentiation. Interestingly, MPs from ischemic muscles produced more reactive oxygen species and expressed significantly higher levels of NADPH oxidase p47 (6 fold ; p<0.05) and p67 subunits (16 fold ; p<0.005) than those from control, whereas gp91 subunit expression was unchanged. The MPs-induced BM-MNC differentiation was reduced by two fold with MPs isolated from gp91-deficient mice (p<0.05). MPs effect on post-ischemic vasculogenesis and revascularization was examined in the ischemic hindlimb model. MPs isolated from ischemic muscles were injected into ischemic legs in parallel with venous injection of BM-MNC. MPs increased the pro-angiogenic effect of BM-MNC transplantation and this effect was blunted with MPs from gp91−/− mice. These results demonstrate that MPs produced after tissue ischemia stimulate progenitor cell differentiation and subsequently promote postnatal neovascularization.
Abstract 3452: The Common Variant Rs9939609 In The FTO Gene Is Associated With Myocardial Infarction In Two Large German Populations (German Family MI Study And KORA-B)
Authors: Erdmann Jeanette , Götz Anika , Bruse Petra , Medack Anja , Lieb Wolfgang , Fischer Marcus , Baessler Andrea , Stark Klaus , Hengstenberg Christian , Ziegler Andreas , Schunkert Heribert
Published: July 2021

Very recently, a genome-wide search for type 2 diabetes susceptibility genes identified a common variant in the FTO gene that predisposes to diabetes through an effect on body mass index (BMI). The A allele of rs9939609 (frequency 39%) was associated with increased BMI with a median per-allele change of ~0.36 kg/m2. Obesity (BMI >30) is a major risk factor for cardiovascular disease, especially for myocardial infarction (MI). We aimed to identify the role of rs9939609 in two large German MI populations with markedly different ascertainment strategies. Two different MI populations were studied. The first case group (Cases A) consists of 762 MI patients ascertained by a strong family history of MI. The second case group (Cases B) included 589 patients suffering from sporadic (non familial) MI from the German KORA register (KORA-B). The control group (Controls) consisted of participants of the WHO MONICA survey in Germany (n=1,644). The genotypes were either extracted from data of a genome wide scan using the 500K Affymetrix Gene Chip Array (Cases A and Controls) or by Taqman assay (Cases B). First, there was a non-significant trend towards higher BMI in carriers of the TA or AA genotype of rs9939609 in all populations under study (table 1

). Second, rs9939609 was associated with MI in both MI populations (table 2

). Our data suggest that rs9939609 within the FTO gene is related to the risk for MI in these two large German MI study samples. The function of FTO is mostly unknown. Hence, the mechanisms underlying the association between the FTO gene product and energy balance as well as the risks of diabetes and MI are unknown and require additional investigation.

Table 1

Table 2
Abstract 3460: Liver-type Fatty Acid-binding Protein Is A Promising Predictive Marker Of Contrast-induced Nephropathy
Authors: Manabe Kenichi , Kamihata Hiroshi , Senoo Takeshi , Yoshida Susumu , Sakuma Takao , Isono Tsuyoshi , Yamamoto Satoshi , Iharada Yoshiji , Motohiro Masayuki , Sugaya Takeshi , Iwasaka Toshiji
Published: July 2021

Contrast-induced nephropathy (CIN), a well-known complication of contrast media exposure for the patients with chronic kidney disease (CKD), may results from acute tubular necrosis. Although 4 to 11 percent with mild to moderate renal insufficiency develop CIN, there were no biological markers to more accurately predict the occurrence of CIN than the existing makers such as serum creatinine (sCr). Liver-type fatty acid-binding protein (L-FABP) as a novel maker, is an intracellular carrier protein of free fatty acids that marked upregulated and expressed abundantly in proximal tubules after renal ischemia.We prospectively investigated whether urinary L-FABP is an alternative maker of predicting CIN.

Methods: We enrolled sixty-five patients (46 male, 71.8 ± 8.2years) undergoing scheduled coronary angiography who had mild kidney disease with CKD stage3 (glomelurar filtration ratio (GFR) <60 ml/1.73 m
2
or albuminuria (u-Alb)≥ 300 mg/gCRE), treated with one-half isotonic (0.45 percent) saline between 12 hours before and after the procedure. We measured urinary L-FABP, u-Alb,β
2
-microglobulin, α
1
-microglobulin, sCr and NAG(
N
-acetyl-β-d-glucosaminidase). CIN was defined as an increase of sCr of >25% or 0.5 mg/dl (44.2micromol/l) within 2 days of contrast. The cohort was divided into two groups according to occurrence of CIN; CIN-G and nonCIN-G.

Results:
CIN occurred in 4 of 65 patients (6%). Demographics, the pre-procedural level of makers (β
2
-microglobulin, α
1
-microglobulin, sCr, NAG) and used contrast volume are no significant differences between the two groups. Pre-procedural urinary L-FABP levels were significantly greater in CIN-G than in nonCIN-G(112.5 ± 81.4μg/g Cr;19.7 ± 43μg/g Cr;
P<
0.01) as well as u-Alb (CIN-G;1711.3 31386.6 mg/gCRE nonCIN-G; 192.3 3482.3 mg/gCRE Cr;
P <
0.01). On the basis of ROC curve of urinary parameters , u-Alb and urinary L-FABP had the significantly high predictive value than other markers(p<0.05).

Conclusion:
Urinary L-FABP combined with u-Alb can be more accurate markers to predict the risk of CIN than other existing urinary parameters.
Abstract 3464: Gender Differences In Coronary Revascularization Rates Following Acute Myocardial Infarction
Authors: Sedlak Tara , Pu Aihua , Aymong Eve , Gao Min , Khan Nadia , Quan Hude , Humphries Karin
Published: July 2021

Objective(s):

Studies suggest that early revascularization following an AMI is equally important in both genders. We examined coronary revascularization (PCI or CABG) rates in men and women following an AMI.

Methods:

We studied a cohort of 7 728 patients >20 years with an AMI admission between January 1, 1999, and September 30, 2002 who underwent catheterization within 90 days of their index AMI. Demographic, clinical, and procedural data were obtained from the British Columbia (BC) Cardiac Registry, a prospective registry of all cardiac procedures performed in BC. Patients without 180 days of available follow-up and patients with a normal angiogram were excluded. Our primary objective was to examine gender differences in the odds of undergoing coronary revascularization within 180 days of the index coronary catheterization. We also examined time trends in revascularization rates by gender from 1999 to 2002.

Results:

Of the 6 726 eligible patients, 68.2% of women and 78.4% of men underwent revascularization within 180 days of their index catheterization following an AMI (p<0.0001). After adjusting for age, extent of vessel disease, hyperlipidemia, LVEF, DM, CHF, CRF, HTN, PVD, CVA, COPD, liver disease, cancer, case complexity, ICU/CCU use, and catheterization year, women were still less likely to undergo revascularization (OR 0.80, 95% CI 0.70 – 0.93). There was no interaction between gender and year of catheterization post-AMI (Figure 1

).

Conclusion:

Conditional on receiving coronary catheterization within 90 days following an AMI, women were less likely to undergo coronary revascularization within 180 days compared to men. The gender difference persisted from 1999 to 2002.
Abstract 3482: Prevalence and Progression of Subclinical Atherosclerosis in Younger Adults with Low 10-Year Risk but High Lifetime Risk for Cardiovascular Disease: Findings from the CARDIA and MESA Studies
Authors: Berry Jarett D , Liu Kiang , Folsom Aaron R , Polak Joseph F , Lewis Cora E , Shea Steven , Sidney Stephen , Carr J. J , O’Leary Daniel H , Chan Cheeling , Lloyd-Jones Donald M
Published: July 2021

Objective
: The Adult Treatment Panel (ATP) III recommends estimating
10-year
risk for cardiovascular disease (CVD), but this strategy identifies few individuals age ≤ 50 years as high risk. Many individuals have a
lifetime risk
up to 70% despite a low 10-year risk (<10%) for CVD. We hypothesized that individuals with low 10-year/high lifetime risk would have a greater burden of subclinical atherosclerosis compared to individuals with low 10-year/low lifetime risk.

Methods
: We included individuals age ≤ 50 from two multiethnic NHLBI-sponsored studies designed to assess the importance of risk factors in the development of CVD [2988 from Coronary Artery Risk Development in Young Adults (CARDIA) study;1076 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA)]. The ATP III 10-year risk and lifetime risk for CVD were estimated for each participant, permitting stratification into three groups: low 10-year (<10%)/low lifetime (<39%) risk, low 10-year (<10%)/high lifetime risk (≥ 39%), and high 10-year risk (≥ 10%). Diabetics were considered to have high 10-year (≥ 10%) risk in all analyses. Baseline levels (CAC, IMT) and change in levels of subclinical atherosclerosis (CAC progression) were compared across the 3 risk strata for both cohorts.

Results
: As expected, those with high 10-year risk (≥ 10%) had the greatest burden of subclinical atherosclerosis in both studies. Among individuals with low 10-year risk (91% of all participants) in CARDIA, individuals with a high lifetime risk had significantly greater carotid IMT, higher CAC prevalence, and greater incidence of CAC progression compared to individuals with low lifetime risk (see table

). A remarkably similar pattern of results was observed in MESA.

Conclusions
: Individuals with low 10-year but high lifetime risk for CVD have a greater subclinical disease burden and greater incidence of atherosclerotic progression compared to individuals with low 10-year but low lifetime risk.

Baseline Carotid Intima-Media Thickness (IMT), Coronary Artery Calcium (CAC) Prevalence and Progression among CARDIA Participants
Abstract 3497: Low Serum Estradiol and Cardiovascular Disease Mortality in Older Men: The Rancho Bernardo Study
Authors: Laughlin Gail A , Barrett-Connor Elizabeth , Bergstrom Jaclyn
Published: July 2021

Context: The traditional view that the male excess in cardiovascular disease (CVD) mortality is due to harmful effects of testosterone has been challenged. In older men, low, rather than high, testosterone predicts atherosclerotic disease progression, and serum estradiol, not testosterone, is prospectively associated with CVD events.

Objective: To determine the association of endogenous sex hormones with cardiovascular disease mortality in older community-dwelling men.

Methods: Prospective population-based study of 858 men aged 50 to 91 years (median 73) who had serum estradiol and testosterone measurements at baseline (1984 – 87) and were followed for mortality through July, 2006.

Results: Median (95% interval) hormone levels were 300 (175, 505) ng/dl for testosterone and 20 (11, 32) pg/ml for estradiol. During the 22 year (average 12.6) follow-up, 559 deaths occurred; 281 (50%) were due to CVD. Age-adjusted Cox regression analyses using hormone quintiles showed testosterone was not related to CVD mortality, but suggested a threshold effect for lower levels of estradiol (P < .001). The risk of CVD death was 1.77 (95% CI 1.32, 2.38) for men in the lowest estradiol quintile (< 15 pg/ml) compared to those with higher levels (P < .001), adjusting for age, BMI, current smoking, physical activity and alcohol intake. This association was independent of the metabolic syndrome, diabetes and prevalent cardiovascular disease. Additional adjustment for lipids, lipoproteins, blood pressure, insulin resistance, CRP, IL-6, leptin, adiponectin or androgen deficiency (total testosterone < 250 ng/dl) had minimal effect on results. Exclusion of deaths that occurred during the first 2 years (to minimize the effect of occult disease) or adjustment for a combination of health status markers also had no effect. Men with low estradiol had lower BMI, smaller waist girth, and were more likely to have lost 10 pounds in the previous 10 years (all P < .001); adjusting for these factors did not influence results.

Conclusions: Low serum estradiol in older men is associated with increased risk of cardiovascular death, independent of age, adiposity, and lifestyle choices. This relationship does not appear to be due to pre-existing disease and is not related to androgen deficiency.
Abstract 3503: Low Dose Aspirin and Incident Diabetes Mellitus in Apparently Healthy Middle-Aged American Women - the Women’s Health Study
Authors: Pradhan Aruna , Cook Nancy , Manson JoAnn , Ridker Paul , Buring Julie
Published: July 2021

Introduction: Inflammation is linked with the development of type 2 diabetes. Epidemiologic data suggest this association may be stronger in women and clinical studies demonstrate that short-term high-dose aspirin has a prominent hypoglycemic effect. However, to date, no randomized trials have directly evaluated the efficacy of aspirin in the prevention of type 2 diabetes at doses acceptable for use in routine clinical practice.

Hypothesis: We assessed the hypothesis that treatment with low-dose aspirin reduces the incidence of type 2 diabetes among initially healthy middle-aged American women.

Methods: Subjects were enrolled in the Women’s Health Study, a randomized clinical trial of aspirin and vitamin E for primary prevention of cardiovascular disease and cancer in which subjects were also monitored for the clinical occurrence of type 2 diabetes. Between 1992 and 1995, 38,716 women aged ≥ 45 years and free of diabetes, cancer, and cardiovascular disease were randomized to either low-dose aspirin (100 mg on alternate days) or placebo. During the randomized treatment period (median follow-up = 10 years), 1,696 cases of confirmed clinical type 2 diabetes accrued.

Results: There were 849 cases in the aspirin group and 847 in the placebo group (HR 1.01; CI 1.00 to 1.02). Stratification of the population by diabetes risk factors including age, BMI, physical activity, postmenopausal hormone use, family history of diabetes, and high-sensitivity C-reactive protein levels (n = 27,167) had no effect on this main finding. Analyses accounting for adherence to randomized treatment also failed to show a beneficial effect.

Conclusions: Chronic low-dose aspirin does not prevent the development of type 2 diabetes in apparently healthy middle-aged and older American women.
Abstract 3506: Cost Effectiveness of Adding PCI to Optimal Medical Therapy in Patients with Stable Coronary Artery Disease: Economic Outcomes from the COURAGE Trial
Authors: Weintraub William S , Goeree Ron , Zhang Zefeng , Teo Koon , Kolm Paul , Spertus John A , Maron David , O’Rourke Robert , Hartigan Pamela , Culler Steven , Becker Edmund , Boden William E , Barnett Paul G
Published: July 2021

Background:
The main results of COURAGE showed no differences in all-cause mortality or non-fatal MI (primary endpoint), the composite of death, MI or stroke, or hospitalization for ACS (secondary endpoints) during 4.6 year median follow-up in the 2,287 patients with stable coronary artery disease (CAD) randomized to optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). There was a benefit to PCI in quality of life measured with the Seattle Angina Questionnaire. This study focuses on cost-effectiveness of PCI.

Methods:
Resource utilization including initial and follow-up hospitalizations were assigned a DRG and then costs assigned from Medicare reimbursement. Medication costs were assessed from Redbook average wholesale price. Survival was estimated for patients from Framingham data. Survival was quality adjusted from utility measured by standard gamble. Cost and outcome were discounted 3%. Costs after the trial period are Medicare average costs. Cost-effectiveness is expressed as an incremental cost effectiveness ratio (ICER), of cost per life year (LY) or quality adjusted life year (QALY) gained. The distribution of the ICER was assessed by bootstrap.

Results:
The added cost of PCI is approximately $10,000, without significant gain in LY or QALYs. The ICER varied from just over $150,000 to just under $300,000 per LY or QALY gained with PCI. A large minority of the distributions of the ICERs found PCI to be dominated by OMT, that is OMT offering better outcome at lower cost.

Conclusions:
The addition of PCI to OMT as an initial management strategy costs significantly more without offering an advantage in survival or QALYs. The ICER is high compared to conventional benchmarks, and the distribution includes infinity and low probability of being below $50,000/QALY gained. PCI in addition to OMT is not a cost-effective initial management strategy for symptomatic, chronic coronary artery disease.
Abstract 3513: Induction of Apoptosis in Endothelial Progenitor Cells by the Adipokine Resistin
Authors: Zhang Yanhua , Zhang Yanmin , Mather Kieren J , Ingram David A , Rehman Jalees
Published: July 2021

Introduction:
The risk for atherosclerosis is higher in patients with significant obesity and is partly mediated by higher circulating levels of detrimental adipokines released by the adipose tissue. One such adipokine is resistin, which increases endothelial dysfunction and inflammation. Little is known about its effect on endothelial progenitor cells (EPCs), which participate in endothelial repair and angiogenesis. We therefore studied the effects of resistin on apoptosis and oxidative stress in EPCs.

Methods:
Human EPCs were obtained from umbilical cord blood by culturing mononuclear cells and identifying highly proliferative endothelial colonies. Mature human aortic endothelial cells (HAECs) were obtained from Cambrex (Baltimore, MD). Cells were exposed to varying doses of resistin. Apoptosis was measured by caspase-3 activation using the EnzCheck Caspase-3 Assay Kit (Molecular Probes, OR). Since oxidative stress is a pro-apoptotic pathway, we quantified oxidative stress using the fluorescent dye Dichlorofluorescein. Values for apoptosis and oxidative stress are given as relative fluorescence units.

Results:
Even a low dose of resistin (10 ng/ml) induced apoptosis in EPCs (Baseline vs 10 ng/ml: 977 ± 100 vs 1112 ± 129, p=0.03). However, at 100 ng/ml resistin the effect was more pronounced (1337 ± 92, p=0.02). Interestingly, this pro-apoptotic effect of resistin could not be observed in mature HAECs (Baseline: 1160 ± 277 vs. Resistin 10ng/ml: 964 ± 160), even at 100 ng/ml (1168 ± 138). Resistin treatment also increased oxidative stress in EPCs, and the peak effect occurred at the dose of 50 ng/ml (Baseline: 2053 ± 237 vs. Resistin 50 ng/ml: 4261 ± 1262). Similar to the apoptosis resilience, mature endothelial cells did not increase oxidative stress with resistin.

Conclusion:
Circulating levels of resistin can range from 10 ng/ml to 25 ng/ml, in lean subjects while levels found in obesity range from 40 –100 ng/ml. Our data shows that resistin in this physiologic and pathophysiologic range can affect the survival EPCs. Progenitor cells also appear to be more vulnerable to resistin that mature cells. We believe these findings will lead to new insight into the detrimental effects of resistin on the vasculature and develop vasculoprotective therapies.
Abstract 475: Relationship Between Oxidized Phospholipid Content On Apolipoprotein B-100 Particles, Statin Therapy and Atheroma Volume: Observations From The REVERSAL Study
Authors: Choi Seung-Hyuk , Chae Andrew , Miller Elizabeth R , Ntanios Fady , DeMaria Anthony N , Nissen Steven E , Witztum Joseph L , Tsimikas Sotirios
Published: July 2021

Background:
Increased levels of oxidized phospholipids on apolipoprotein B-100 particles (OxPL/apoB) are associated with angiographically defined coronary artery disease, progression of carotid atherosclerosis and predict new cardiovascular events. Interestingly, OxPL/apoB levels increase in response to low-fat diets or therapy with different statins. Furthermore, during dietary-induced atherosclerosis regression in animals, increases in plasma OxPL/apoB levels are associated with reduced OxPL content in atheromatous plaques, suggesting a flux of OxPL from the vessel wall to the lumen.

Methods:
In a subgroup of 220 patients from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, we measured several biomarkers of oxidized LDL (OxLDL), including OxPL/apoB and IgG and IgM apoB-100 immune complexes (apoB-IC) and OxLDL autoantibodies, at baseline and after 18 months of treatment with atorvastatin (AT) 80mg/d or pravastatin (PR) 40mg/d. Measures of total atheroma volume (TAV) and vessel remodeling with intravascular ultrasound (IVUS) were analyzed.

Results:
Compared to baseline values, OxPL/apoB levels increased 58.5% (P<0.0001) in response to AT and 32.7% (P<0.0001) in response to PR. In contrast, IG apoB-IC, IgM apoB-IC and IgM OxLDL autoantibodies were significantly reduced by both AT and PR (p-value: range 0.04 – 0.0001). However, no differences in OxLDL biomarkers were noted between the AT and PR groups. In the entire group, there were no correlations between TAV and vessel remodeling with any OxLDL biomarkers at baseline or 18 months.

Conclusion:
Statin therapy results in significant increases in OxPL/apoB and decreases in immune complexes and OxLDL autoantibodies. However, these measures do not correlate with atheroma volume or vessel wall remodeling measured by IVUS. Whether statin-induced changes in plaque characteristics, such as the lipid core, correlate with plasma OxLDL biomarkers remains to be determined.
Abstract 3539: Low Inflammatory Activity Evidenced By hsCRP Predicts A Benefit From Clopidogrel Treatment In Patients With High Risk For Cardiovascular Events. - A Substudy From The CHARISMA Trial
Authors: Weber Michael W , Hamm Christian W , Bhatt Deepak L , Topol Eric J
Published: July 2021

Aims
We investigated the impact of clopidogrel treatment on the inflammatory activity as evidenced by a change of hsCRP levels in a broad population of high risk for atherothrombotic events. Further, the prediction of hsCRP levels for a treatment benefit of clopidogrel was explored.

Methods
This study included 8021 patients with overt atherosclerotic disease or multiple cardiovascular risk factors enrolled in the CHARISMA trial. Patients were randomized either to clopidogrel plus aspirin or placebo plus aspirin. HsCRP was measured at study entry and at study termination (median 28 months). The predefined primary endpoints were myocardial infarction, stroke and death from cardiovascular causes.

Results
There was a stepwise increase in the event rate of the combined primary endpoint with increasing quartiles of hsCRP (4.0%, 6.1%, 7.4% and 8.7% in the highest quartile). In both treatment groups the changes of hsCRP levels over time were identical. In patients with low hsCRP levels (<3 mg/l) clopidogrel treatment was associated with a lower event rate as compared to placebo (4.0% vs. 6.0%, Log-rank p=0.005). In contrast no treatment effect could be observed in patients with high hsCRP levels (8.1% vs. 8.0%, ns).

Conclusions
Surpisingly, the reduction of cardiovascular events by antiplatelet treatment with clopidogrel occurred in patients with low levels of hs-CRP